Lumbar herniated disc (HNP) is mainly treated by conservative management. Epidural steroid injection (ESI) has been an option to treat failed cases prior to surgery. Triamcinolone has been widely used due to its efficacy in bringing about pain reduction for up to three months. However, several reports have shown some severe adverse events. Platelet-rich plasma (PRP) is made from blood through centrifugation. Several studies supported the potential short to long-term effects, and safety of PRP injection in treating HNP. The study objective was to evaluate the efficacy of PRP in treatment of single-level lumbar HNP in comparison to triamcinolone.Thirty patients were treated by transforaminal epidural injections. PRP was obtained from 24 ml venous blood through standardized double-spin protocol. Participants included fifteen patients each being in triamcinolone and PRP groups. The same postoperative protocols and medications were applied. The visual analogue scale of leg (LegVAS), collected at baseline, 2, 6, 12, and 24 weeks, was the primary outcome. The BackVAS, Oswestry Disability Index (ODI), adverse event, and treatment failure were the secondary endpoints.Platelet ratio of PRP in fifteen patients was 2.86 ± 0.85. Patients treated by PRP injections showed statistically and clinically significant reduction in LegVAS at 6, 12, and 24 weeks, and in ODI at 24 weeks. It demonstrated comparable results on other aspects. No adverse event occurred in either group.Noncommercial epidural double-spin PRP yielded superior results to triamcinolone. Due to its efficacy and safety, the procedure is recommended in treating single level lumbar HNP.https://clinicaltrials.gov/ct2/show/record/NCT05234840.NCT, NCT05234840. Registered 1 January 2019, The online version contains supplementary material available at 10.1186/s12891-023-06429-3. Lumbar radicular pain is usually caused by mechanical compression of nerve root, and by inflammatory responses –3. ConsePlatelet-rich plasma (PRP) has recently gained a name as an adjuvant component in the orthopedics field . PRP proThe study aims were to compare the results of transforaminal PRP injection and traditional ESI on lumbar radicular leg pain by VAS (LegVAS), back pain (BackVAS), functional score , adverse event, and percentage of treatment failure in HNP patient.The study was a triple blinded, randomized controlled trial in level I referral center. The study was conducted between April 2019 to May 2021. After the assessment of eligibility was accomplished. The inclusion criteria were patients aged 20–55 years, having failed conservative treatment of unilateral HNP undergone for at least 6 weeks, with visual analogue scale (VAS) of greater than 30, and confirmed a single-level HNP, corelated to clinical, by MRI. The exclusion criteria included previous spine surgery or epidural injection, progressive neurological deficit, cauda equina, coagulopathy-related conditions, associated cervical myelopathy, systemic bone and joint diseases. All patients had full conservative management including rest, activity modification, oral medication, and physical therapy by rehabilitation team. Patients with no improvement in VAS and greater than 30 were defined as failed conservative management. All patients had to have been exempted from NSAIDs for at least one week. The study was approved by the Ethics Committee of Queen Savang Vadhana Memorial Hospital , and receipt of the ClinicalTrials.gov ID was NCT05234840. All participants provided informed consent.n= [(r + 1)(Z1−β+Z1−α)2σ2]/r[(µA-µB)−dNI]2 was used. Previous similar study’s data were used for this calculation [Based on the non-inferiority formula, culation . Togethen= [r + (Z1−β+Z1−26 ml of blood was obtained from each patient (6ml each in 4 CPDA (citrate phosphate dextrose adenine) and 2ml in EDTA (ethylene diamine tetra acetic acid tube) for CBC).First-spin of 900 g for 5 min .Three layers formed: transfer top layer (platelet poor plasma) and middle layer (platelets and WBC) to another sterile tube (about 3.3 ml), discard bottom layer (RBC).Second-spin of 1000 g for 10 min.The upper one third was discarded (platelet poor plasma) by pipet, the remaining was mixed by turning 10 times.Final product was 4 ml of PRP .All treatments were performed by a single, experienced orthopedic surgeon. Patients were placed in the prone position. Using a sterile technique, epidural injections were performed under a C-arm fluoroscopy . Briefly, the transforaminal approach through Kambin’s triangle was used to minimize risk of nerve injury. The position of the needle , was guided and confirmed under anteroposterior and lateral fluoroscopic views. Once the needle-end was located and checked by contrast media, either 2 mL of PRP followed by NSS 0.5 ml, or total of 2ml of 1% lidocaine with 40 mg triamcinolone was injected. The syringe was covered with a large sterile strip to mask the substance. The patient was observed for 30 min after the procedure to monitor for any undesirable reaction. All patients were asked to avoid strenuous activities in the ensuing 3 days. Cold compression and paracetamol were provided for pain relief.Primary outcome was radicular leg pain evaluated by LegVAS. A diagram was presented to the patient with a score of 0 denoting “no pain”, and a score of 100 denoting “pain as bad as it could be.” BackVAS, ODI adverse event, and failure of treatment were also addressed at baseline, 2, 6, 12, 24 weeks. Patients were observed for acute postoperative complications for at least 4 to 6 h. Medication prescribed was paracetamol and tolperisone. All patients used ice pack for 1 day and lumbar support for 3 days after the injection. Patients were advised of acute complications such as soreness, itching, neurological deficits, and infection. Limited back activities were recommended for 1 week. There was no drop out, and no cross-over group. Treatment failure was defined as persistent or deteriorated pain. MRI was requested when there was persistent pain or new onset of pain.An independent t-test, Fisher’s Exact test, and Chi-square test were used for demographic data, presented as mean ± SD, and percentage. Repeated ANOVA was used to compare the mean of quantitative variables over time. The Chi-square test was used to assess failure of treatment. The p value < 0.05 was considered statistically significant. Data were analyzed with STATA 17. All study parameters were analyzed according to the intention-to-treat (ITT) principle.A total of 30 patients (15 patients in each group) were enrolled in this study. No significant differences were found in the demographic data, as shown in Table According previous studies , the valNo adverse events such as local inflammation, infection, and neurological deficit occurred in either group. Two patients in triamcinolone group needed later operation due to persistent pain at 6 weeks follow-up. There was no statistical difference in treatment failure between the two groups Table .Prolotherapy uses a method of inflammatory induction to recruit cytokines and growth factors, which later promote healing cascade. However, the rationale of using PRP is it contains high concentration of cytokines and growth factors which are released overtime . The othPRP usage has been studied in orthopedic spine surgery, mainly in treating degenerative disc disease. Prior to PRP usage, Becker’s RCT reported superior results of PRP to triamcinolone on LegVAS by using of Autologous Conditioned Serum (ACS), another type of orthobiologics, in treating HNP by multiple injections . RecentlPatients treated with PRP showed significant improvement in VAS, ODI, and other functional scores. PRP showed high potential in regeneration and healing via several mechanism such as inflammatory regulation pathway, cellular stimulation, and tissue regeneration pathway in both animal model and human . PRP areAccording to the meta-analysis about spontaneous disc resorption, the overall incidence is about 67% in conservative patients . MoreoveWe concurred with Zhen Xu et al.’s study on efficacy of PRP compared to betamethasone in treating lumbar HNP in term of pain score and functional score . Our stuOur research conducted RCT, with similar demographic data with single experience surgeon, represented an emerging substitute, PRP, in treating single-level HNP. The drawback for PRP is injection time which is within one hour after final product. PRP production protocol takes about 30 min for overall process. This protocol can be done in any hospital because it requires simple centrifuge with easy-to-follow protocol and laboratory staff with sterile technique due to an open-system. Our limitations were short time follow-up, subjective primary outcome as VAS, and too small sample size to detect the statistically significant of treatment failure.The present study showed that alternative PRP injection provided a superior result to triamcinolone on LegVAS, and comparable results on BackVAS, ODI, adverse event, and treatment failure. The prolonged and superior effect with potentially lower rate of treatment failure supports the usage of PRP in HNP treatment. Noncommercial PRP protocol is safe, reproducible and effective in the treatment of lumbar HNP. We encourage using PRP protocol , insteadBelow is the link to the electronic supplementary material.Supplementary Material 1


Breast cancer surgery is usually managed using opioid-inclusive anesthesia (OIA), although opioids are associated with several adverse events, including nausea, vomiting, and constipation. Multimodal opioid-free anesthesia (OFA) has been introduced to reduce the incidence of these side effects. In this single-center retrospective study, we investigated whether ketamine, combined with magnesium and clonidine, could effectively control postoperative pain in patients undergoing quadrantectomy, while reducing postoperative nausea and vomiting (PONV).p <0.05). Patient satisfaction was comparable in the two groups.A total of 89 patients submitted to quadrantectomy were included and divided into an OFA group (38 patients) and an OIA group (51 patients) according to the received anesthetic technique. Analgesia in the OIA group was based on an intraoperative infusion of remifentanil, and analgesia in the OFA consisted of an intraoperative infusion of ketamine and magnesium sulfate. Postoperative pain in both groups was managed with nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol. Postoperative pain, assessed with the numeric rating scale (NRS), requirements for additional analgesics, the incidence of PONV, and patient satisfaction evaluated using a QoR-40 questionnaire were compared between the two groups. Levels of pain at 30 min and 6, 12, and 24 h after surgery; number of paracetamol rescue doses; and the incidence of PONV were lower in the OFA group (A combination of ketamine, magnesium, and clonidine could be more effective than opioid-based analgesia in reducing postoperative pain and lowering PONV occurrence after quadrantectomy for breast cancer. Breast cancer is the most commonly diagnosed neoplasm in women and accounts for nearly a third 29%) of all malignancies, representing the leading cause of cancer death among women worldwide % of all . BecauseAcute postoperative pain after breast surgery stems both from direct damage to peripheral nerve fibers and from changes in neuro-endocrine profiles . HoweverBreast cancer surgery is typically carried out using either balanced anesthesia or total intravenous anesthesia, which involves the administration of intraoperative opioids , either in boluses or by target-controlled infusion. Opioids’ intraoperative administration is burdened by side effects such as acute tolerance and postoperative paradoxical hyperalgesia . The latThe most commonly reported side effects of opioids are postoperative nausea and vomiting (PONV) and constipation , 38. PONN-methyl-d-aspartic acid (NMDA) receptors, some of which also have anti-inflammatory activity [Two anesthesia techniques, opioid-free anesthesia (OFA) and opioid-sparing anesthesia, have been introduced in order to avoid the adverse effects of opioids. Both techniques have been proven to be effective in decreasing opioid consumption in acute postoperative pain management . In OFA,activity . Analgesactivity , all of activity .We hypothesized that OFA, using a combination of ketamine, magnesium, and clonidine, might provide better postoperative pain relief than OIA for patients submitted to quadrantectomy. The main aim of this retrospective study was to determine whether pain reported through a numerical rating scale (NRS) in the 24 h following surgery was lower in a group of patients receiving OFA than in a group of patients receiving OIA. Secondary objectives included evaluating differences in the incidence of PONV, the number of doses of rescue analgesics needed, and perception of the quality of care during the hospital stay until final discharge using a QoR-40 questionnaire.This retrospective study was approved by the Bioethics Committee of Sapienza University of Rome (no. 7028_2020). The patients involved in the study underwent quadrantectomy, without axillary lymph nodes dissection, from October 1, 2017, to March 30, 2018.Data were extracted from anesthesiologic and nursing reports. The quality of life was evaluated using a QoR-40 questionnaire, which is routinely completed by all inpatients. Pain scores, assessed using NRS, were entered in anesthesiologic and nursing reports immediately after surgery, during the stay in the post-anesthesia care unit (PACU), and during hospitalization in the assigned ward. The NRS is an 11-point scale for self-reporting of pain where 0 = no pain and 10 = extreme pain/worst possible pain. Pain assessments were recorded at 30 min and 6, 12, and 24 h after surgery. The total use of analgesics after surgery, the need for “rescue doses,” the occurrence of PONV, and hemodynamic or respiratory instability were also recorded, both immediately after surgery and during the hospital stay.Incomplete or incorrect records  were excluded from the study. The exclusion criteria were the history of opioid, alcohol, or drug abuse; chronic pain; the use of analgesics before surgery; and psychiatric illness.This anesthesia department has a group of anesthetists dedicated to breast surgery. One of the anesthetists regularly uses OFA, whilst the rest of the group uses OIA. The patients were divided into two groups based on the employed method of anesthesia. OFA and OIA were both administered by target-controlled infusion, following the protocols shown in Table Remifentanil infusion was stopped 30 min before the end of the surgery, then morphine 0.05mg/kg and ondansetron 4 mg were administered in the OIA group. Anesthesia reports were completed as usual during each surgery, with non-invasive blood pressure readings, heart rate, and peripheral capillary oxygen saturation (%) recorded every 5 min, from the start until emergence.Postoperative analgesia was based on a 24-h intravenous continuous infusion of ketorolac  and metoclopramide (10 mg), using an elastomeric pump. A rescue dose of intravenous paracetamol (1 g) was administered for pain with an NRS score ≥ 5.After emergence from anesthesia, the patients were monitored in the PACU for at least 30 min; hemodynamic parameters, respiratory function, and postoperative pain values were fully assessed and recorded on a specific chart.Once the patients were discharged from the PACU to the assigned ward, pain was re-assessed using the NRS and the values were recorded, together with the presence or absence of PONV, in specific nursing reports. The nursing staff was also able to record hemodynamic, respiratory, and other clinically significant events, such as postoperative delirium (POD) episodes and postoperative cognitive dysfunction (POCD). PONV was treated with intravenous ondansetron (4 mg) in all patients without a history of intolerance to the drug.Immediately before being discharged from the hospital, all patients completed another QoR-40 questionnaire. Basing on the individual score difference of questionnaires, the patients were divided into three different groups: ≤10 (group A), 10–30 (group B), and >30 (group C). Only the QoR-40 score that differed by more than 10 points from baseline values (in either a positive or negative direction) was considered as a significative change.T test for unequal variances. PONV was considered to be a dichotomous variable (presence/absence of PONV episodes) and studied using Yates’s chi-squared test. The total administration of rescue therapy was analyzed using the Mann-Whitney U test for independent samples. The QoR-40 questionnaire was analyzed in qualitative terms, without a quantitative measure of variations. Data are presented as average with standard deviation or median values with a confidence interval of 95%. P values <0.05 were considered to be statistically significant. Data were analyzed using the software program MedCalc, version 19.0.7Descriptive analysis was performed using percentages of binary variables, average and median values for continuous variables, and by calculating their respective dispersion values. Normality was tested using the Kolmogorov-Smirnov test. An ANOVA test was used for repeated measures to evaluate postoperative pain values reported through the NRS at the chosen time intervals . A statistical comparison of postoperative pain at different time points between groups was made using Welch’s adjusted N=98 patients were submitted to quadrantectomy without axillary lymph nodes dissection during the period study, as shown in Fig. n=4), history of chronic pain (n=2), and analgesic use before surgery (n=3). Patients were divided into two groups based on the method of anesthesia. The OFA group contained 38 patients, and the OIA group contained 51 patients. There were no statistically significant differences in the demographic or clinical data between the two groups, as illustrated in Table c pain n=, and anaIn both groups, adequate depth of anesthesia was achieved and maintained throughout surgery. Intraoperative hemodynamic stability was maintained in both groups during surgery and no vasoactive drugs were required.Lower NRS scores and PONV incidence were reported in the OFA group compared with the OIA group, as shown in Table p= 0.006).The OIA group needed the highest number of paracetamol rescue doses, 77 in total, with a median of 2.0 administrations (CI 1–2). The OFA group required only 29 rescue doses in total, with a median of 1.0 (CI 0–1). The difference was statistically significant . The vast majority of patients in both groups had no significant change in QoR-40 score during their hospital stay, suggesting no difference in perception of hospitalization quality between the OFA group and the OIA group. It is worth noting that five patients in both the OIA and OFA groups had a change in QoR-40 score of 10–30 points (subgroup B), whereas two patients in the OIA group and no patients in the OFA group had a difference greater than 30 points (subgroup C).Either group reported any adverse reactions to drugs, and no patient required any analgesics other than paracetamol as rescue therapy.Any patient experienced no POD or POCD, and no major cardiac, respiratory, or hemodynamic events were reported.This study showed that the OFA regimen, based on continuous intravenous infusion of ketamine and magnesium, significantly reduced postoperative pain and PONV than the OIA regimen. OFA is possible by the intravenous administration of nonopioid drugs that block surgical stress and sympathetic reactions.Only qualitative analysis was carried out on the data gathered through the QoR-40 questionnaire since 24 h was not viewed as a long enough time to speculate about reasons for improvement or worsening of the quality of life. Nevertheless, in both groups, 87% of patients showed changes of ± 10 points in QoR-40 scores at discharge from the hospital, showing that an opioid-free treatment did not worsen patients’ overall satisfaction or comfort when compared with an opioid-inclusive approach.Although adding to OFA a locoregional block can be a valuable choice during thoracoabdominal surgeries, OFA can be very effective by combining several medications without a locoregional analgesic technique .Few studies evaluated OFA technique in breast cancer surgery. In agreement with the results of the presenting study, an OFA approach demonstrated favorable results and appears to be associated with the reduction of postoperative pain scores, opioid consumption, and PONV , 34, 43.Studies in other surgeries also showed that OFA may result in reduced postoperative opioid requirements, as well as decreased PONV incidence, hospital length of stay, and risk for intraoperative complications , 17, 46.However, in a recent randomized trial in gynecological laparoscopy, OFA demonstrated to be feasible and easy to perform, but no obvious advantages were provided in this setting over OIA with regard to PONV, pain scores, and morphine consumption .p = 0.03) [A recent meta-analysis, including 33 RCTs and 2209 participants, showed no clinically significant benefits in terms of pain and opioid use after surgery, but a clear benefit with respect to a reduction in PONV was demonstrated when intraoperative opioids were avoided . In a pr = 0.03) . HoweverNMDA receptors have a central role in the mechanisms of OFA. These ionotropic, calcium-permeable, and receptors are activated by both glutamate and voltage changes and are involved in the transmission and modulation of pain. They also contribute to central sensitization and a phenomenon known as “wind-up,” both of which play a role in chronic pain mechanisms. Repeated stimulation of spinal C-fibers increases the spontaneous activity of NMDA receptors  and leadMany studies have shown that ketamine is effective as an analgesic both during and after different types of surgery, including abdominal, thoracic, orthopedic, and bariatric surgery. Ketamine acts as an NMDA receptor antagonist, both centrally and peripherally and is also used as an adjuvant in patient-controlled analgesia to ease PONV and to prevent CPOP , 46.Several meta-analyses and randomized controlled trials have shown that magnesium sulfate, another drug commonly used in OFA, is very effective in reducing acute postoperative pain , 27. MagOur results agree with those of Laskowski et al.  which clThe incidence of PONV was reduced in patients who received OFA. Complications that might arise from PONV include inhalation of gastric contents, bleeding, surgical wound re-opening, dehydration, electrolyte imbalance, and a general delay in healing and discharge from the hospital , 30. ThePrincipal limitations to our study are its monocentric and retrospective nature, its relatively small sample size, and the restriction of re-evaluation time to 24 h after surgery. In addition, the bispectral Index (BIS) was not performed during anesthesia. Such a short follow-up time made it impossible to effectively assess the effect of either method of anesthesia on the patients’ quality of life in the long term. Lack of quantitative measures for PONV, POCD, and POD and the non-application of a risk score for PONV  further limited our investigation since these conditions could be scored only as either present or absent. Lastly, a regional anesthetic technique such as paravertebral block or pectoral nerves block could have been considered for additional pain relief and OFA regimen implementation.In conclusion, this retrospective analysis of two different anesthesia methods, one with opioids (OIA) and one without opioids (OFA), showed that an opioid-free approach based on concomitant administration of ketamine and magnesium as a continuous intravenous infusion is safe and effective. OFA was associated with reduced postoperative pain in the first 24 h after surgery, lower need for additional analgesic drugs, and reduced incidence of PONV. The patients’ comfort levels were comparable to those of patients receiving OIA.


Although opioids have been shown to be effective for cancer pain, opioid-induced adverse events (AEs) are common. To date, little is known about the differences in risks of AEs by opioid type. This study was performed to compare the prevalence of AEs across opioids commonly used for analgesic treatment in Japan.This study was conducted as a preplanned secondary analysis of a multicenter prospective longitudinal study of inpatients with cancer pain who received specialized palliative care for cancer pain relief. We assessed daily AEs until termination of follow-up. We rated the severity of AEs based on the Common Terminology Criteria for Adverse Events version 5.0. We computed adjusted odds ratios for each AE  with the following variables: opioid, age, sex, renal dysfunction, and primary cancer site.n = 25, 6.3%) was the most frequent, followed by drowsiness , nausea and vomiting , and constipation . The multivariate logistic analysis showed that no single opioid was identified as a statistically significant independent predictor of any AE.In total, 465 patients were analyzed. Based on the descriptive analysis, the top four most commonly used opioids were included in the analysis: oxycodone, hydromorphone, fentanyl, and tramadol. With respect to the prevalence of AEs among all analyzed patients, delirium (There was no significant difference in the prevalence of AEs among oxycodone, fentanyl, hydromorphone, and tramadol, which are commonly used for analgesic treatment in Japan. Cancer pain has a significant impact on patients’ quality of life . One stuTo date, no study has been conducted to investigate the prevalence of AEs among Japanese patients with advanced cancer who received specialized palliative care. We hypothesized that understanding the characteristics of AEs can improve the quality of analgesic treatment using opioids. This study was performed to compare the prevalence of AEs  across opioids commonly used for analgesic treatment in Japan.This study was a preplanned secondary analysis of a multicenter prospective longitudinal study conducted in Japan from 1 November 2020 to 30 June 2021. Five specialized palliative care consultation teams and four palliative care units in tertiary care hospitals in Japan participated in the study. The original study assessed the time to achieve cancer pain management by specialized palliative care provided by certified palliative care physicians, advanced practice nurses, and multidisciplinary palliative care staff . We defined cancer pain in this study as pain associated with cancer invasion and metastasis; the definition of cancer pain excluded pain related to anticancer treatments such as surgery, chemotherapy, and radiotherapy. In patients with multiple cancer pain, we focused on the cancer pain that was most severe and interfered with daily life. We enrolled consecutive eligible inpatients who received specialized palliative care. All observations were performed within the range of routine clinical practice. The inclusion criteria for the patients in the original study were 1) receipt of specialized palliative care, 2) cancer pain, and 3) requirement for further cancer pain management. In this study, we added the inclusion criteria: the patients who were used opioids for cancer pain management. We excluded patients 1) whose most severe pain was not cancer pain, 2) who were admitted for surgery, and 3) who could not evaluate their symptoms and therapeutic interventions because of a severe symptom burden, serious psychological distress, or cognitive disorders preventing us from evaluating their symptoms or treatment. All patients were followed up until they indicated that there was no need for further cancer pain management because the management was sufficient, they developed other types of cancer pain that required more intervention, or they were discharged without adequate pain management. Although the patients had been previously registered, they were re-registered each time if they required further cancer pain management because of worsening or new pain.2), concomitant drugs , opioids, and daily morphine milligram equivalents. AEs were assessed every day until termination of follow-up.Palliative care physicians prospectively recorded the data collection sheets every day to determine whether the enrolled patients considered their cancer pain management successful and whether they needed further management. We collected the following patient data at enrollment (baseline): age, sex, primary cancer site, organ dysfunction  for each AE with the following variables: opioid (reference group = oxycodone), age (per 10 years), sex , renal dysfunction (reference group = absent), and primary cancer site . As for opioid, we selected oxycodone because of the most frequency prescription in the analyzed patients. Opioids prescribed to less than 30 patients were excluded from the analysis because they would destabilize the logistic model. Potential confounding variables were identified based on previous studies –11.p value between 0.01 and 0.05 was considered to be a weak indication of the finding, and a p value of < 0.01 was considered to be a clear indication of a finding.All analyses were performed using JMP version 16 for Windows . A The present study was conducted in accordance with the ethical standards of the Declaration of Helsinki and the ethical guidelines for medical and health research involving human subjects presented by the Ministry of Health, Labour and Welfare, Japan. This study was approved by the institutional review board of each participating institution and by the Independent Ethics Committee of Tohoku University School of Medicine . Japanese law does not require individual informed consent from participants in a noninvasive observational trial such as the present study. Therefore, we used an opt-out method rather than obtaining written or verbal informed consent. All patients could receive information on the study through the instructions posted on the ward or institutional website and had the opportunity to decline participation.n = 189, 40.9%) was the most commonly used, followed by hydromorphone , fentanyl , tramadol , tapentadol , and morphine . The median observation duration was 3.0 days . The patients’ characteristics are shown in Table In total, 522 patients were enrolled during the study period. Fifty-seven patients were excluded because of no opioid use. Thus, we analyzed 465 patients, including 265 (57.7%) men and 194 (42.2%) women . Among the opioids, oxycodone  was the most frequent, followed by drowsiness , nausea and vomiting , and constipation . With respect to the prevalence of AEs for the four analyzed opioids, delirium  was the most frequent, followed by drowsiness , nausea and vomiting , and constipation . After controlling for age (per 10 years), sex, renal dysfunction, and primary cancer site , no single opioid was identified as a statistically significant independent predictor of any AE. However, the following trends were shown: the risk of constipation was decreased with fentanyl  compared with oxycodone, and the risk of nausea and vomiting was increased with tramadol  compared with oxycodone. Additionally, the risk of constipation was clearly increased in patients with renal dysfunction .The OR for each AE is shown in Table The current study showed that the prevalence of AEs was relatively low in the participating patients with advanced cancer. The multivariate logistic analysis showed that no single opioid was a statistically significant independent predictor of any AE.Among the analyzed participants, 4.6% to 6.3% showed any AEs during the observation period. A Cochrane review reported that the prevalence of AEs was 17% to 30% for constipation, 14% to 23% for nausea, and 7% to 15% for vomiting . A systeThere was no significant difference in the prevalence of AEs among tramadol, oxycodone, hydromorphone, and fentanyl. These results are consistent with previous investigations in which there was very little evidence suggesting that any one opioid agonist has a substantially better AE profile than any other . Our mulOur study had a larger sample size than most prior studies , 16. HowThere was no significant difference in the prevalence of AEs among oxycodone, fentanyl, hydromorphone, and tramadol, which are commonly used for analgesic treatment in Japan.


Low back pain (LBP) is a painful condition affecting 80% of word population at some point in their life. Lumbar intervertebral discdegeneration and reduced muscle force is one the major cause of LBP. Sixty-two patients with LBP undergoing discectomy were recruitedafter receiving consent. Lumbar muscles strength and VAS  for lumbar pain were checked, MRI scan were analysed.Histological degenerative changes were analysed. The study revealed histological degeneration at intervertebral disc has direct effecton increase in pain at lumbar region, decrease in strength of lumbar flexor and extensors muscles and degenerative changes seen on MRIscan. Low back pain (LBP) is a painful condition, localized below the costal margin and above the inferior gluteal fold, with or withoutreferred pain to the lower limbs -2. It isThis analytical study was conducted in Department of Anatomy in collaboration with Department of Radiology, Department ofOrthopaedics and Department of Neurosurgery, at RL Jalappa Hospital and Research Centre, a teaching hospital of Sri Devaraj UrsMedical College, a constituent of Sri Devaraj Urs Academy of Higher Education and Research, Kolar, Karnataka, India.Sample size calculation was done by using SPSS, version 22.0, with 90% power and 95% confidence interval [Patients within the age group of 20-45 year, male and female with the history of low back pain, with or without radiating pain tothe lower limb, having grade III, IV and V on pfirrmann grading on MRI scan was included in the study groupPatients with cervical or thoracic intervertebral disc degeneration, malignancy, pregnancy, history of other joint pains, historyof prior discectomy, smokers, patients having abdominal trauma, known case of rheumatoid arthritis or spinal infection were excludedfrom the study.62 patients who were recruited as study group which fulfils the inclusion criteria, after which consent from the patients was takento enrol the patients for the study. Patients were than clinically examined, level of pain at lumbar region was recorded on VAS, muscle strength for the lumbar flexor and extensors muscles was recorded by manual muscle testing method, MRIscan was done and was graded according to pfirrmann grading system and lumbar intervertebral disc biopsy sample was collected duringdiscectomy surgery which was stored in buffered 10% formaldehyde and was later processed for histopathological analysis.Patients recruited for the study was analysed for pain at the lumbar region by using Visual Analogue Scale (VAS). A Visual AnalogueScale (VAS) is one of the pain rating scales  the scorPatients included in the study group were tested for the muscle strength of lumbar spine (flexor and extensor muscles) by usingmanual muscle testing method.Patient was asked to lie in prone position with hand clasped behind head and was instructed to raise head, shoulder, and chest offthe table.Patient was asked to lie in supine position with hand clasped behind head and was instructed to raise head, Shoulder, and thoracicspine off the table.62 patients recruited in the study group were scanned for degenerative changes at lumbar intervertebral disc by MRI and were gradedaccording to Pfirrmann grading system. The Pfirrmann grading system  is widelLumbar intervertebral disc biopsy sample were collected during discectomy surgery from the patients recruited as study group.Biopsy tissue was collected in 10% buffered formalin. Tissue sample were than processed by using tissue processing steps whichincludes fixation, dehydration and clearing, impregnation and embedding, paraffin block making, paraffin blocks were than sectioned at4-6 µ m thickness by using microtome. Tissue sections were stained by using Haematoxylin and Eosin stain to identify chondrocytecluster and granular changes in annulus fibrosus and nucleus pulposus, massion's tricrome stain to identify misalignment of thecollagen fibres in annulus fibrosus and nucleus pulposus and alcian blue stain to identify mucous degeneration and histologicalvariables were selected for further analyses  Table 2Table 2.Descriptive statistics such as frequency & proportion was calculated for categorical data and mean, standard deviation wascalculated for continuous data. Chi square test was used to compare gender of study and control group, Paired t test was used tocompare between group variable, p value <0.05 was considered as statistically significant.The patients with history of low back pain, within the age group of 20-45 years, both male and female undergoing for discectomysurgery after receiving consent from the patients were included in the study group. Our study revealed 58.06% were male and 41.64%were female among the patients and most prevalent age group was between 41-50 years with 59.68% followed by age group 31.40 with32.26% patients respectively and the mean age of the patients was 40±5.75 respectivelyand meanFlexor and extensor muscles strength of lumbar spine were checked by manual muscle testing method before discectomy surgery inpatients. Our study showed that there was no significant correlation between flexor and extensor muscle strength. The stuDisc section from the patients undergoing surgery for back pain showed increased number and size of chondrocyte cells, which wererounded or elongated, with territorial matrix and chondrocyte cells were arranged in a group of two or three cells at places. PresencThe study revealed that there was highly significant correlation between flexor strength with mucous degeneration and granularchanges with p value (<0.0001) and there was significant correlation with No. of cells, concentric tear & radial tear with flexorstrength  of study participants .Our study revealed that there was significant correlation between granular changes and mucous degeneration with extensor strength,also concentric tear showed significant correlation with extensor strength and no. of cells and radial tear showed no significantcorrelation with extensor strength .The study revealed that there was statistically significant correlation between mucous degeneration and pfirrmann grades with pvalue (<0.0001) and other histological criteria were not showed significant correlation Pfirrmann .The study revealed that there was statistically significant correlation between mucous degeneration and concentric tear with visualanalogous score and rest of histological criteria showed no significant correlation with visual analogous score.Our study is first of its kind as per our knowledge; where histopathological changes was correlated with muscle strength of lumbarspine in patients with clinical history of low back pain and undergoing discectomy surgery. This study examined whether lumbar MRI,lumbar VAS, lumbar muscles strength measured by manual muscle testing method in routine clinical examination in patients with low backpain undergoing disectomy surgery for proplapsed disc is correlated with histopathological changes in lumbar intervertebral disc.Studies suggest that the main cause of intervertebral disc degeneration is loss of nucleus pulposus matrix, which in turn decreasesthe proteoglycan content and results in unequal transmission of force on intervertebral disc which marks the process of degeneration.In response to which chondrocyte cells proloferate to up-lift and compensate progressive extracellular loss. In our Results from our current study demonstrates that patients with low back pain undergoing discectomy surgery, showed degenerativechanges such as increase in the number of chondrocytes, granular changes, mucous degeneration, concentric and radial tear; whichshowed significant correlation with lumbar spine flexor and extensor muscles strength, lumbar pain and degenerative changes on MRIscan. This suggests that histological degeneration at intervertebral disc has direct effect on increase in pain at lumbar region,decrease in strength of lumbar flexor and extensors muscles and degenerative changes seen on MRI scan.


Conclusion: Patients with early knee and/or hip OA with an active pain coping style use significantly more different healthcare services over 10 years, as opposed to those with a passive pain coping style. Further research should focus on altered treatment  in patients with an active coping style, to reduce HCU.Background: Knee and hip osteoarthritis (OA) among older adults account for substantial disability and extensive healthcare use. Effective pain coping strategies help to deal with OA. This study aims to determine the long-term relationship between pain coping style and the course of healthcare use in patients with knee and/or hip OA over 10 years. Methods: Baseline and 10-year follow-up data of 861 Dutch participants with early knee and/or hip OA from the Cohort Hip and Cohort Knee (CHECK) cohort were used. The amount of healthcare use (HCU) and pain coping style were measured. Generalized Estimating Equations were used, adjusted for relevant confounders. Results: At baseline, 86.5% of the patients had an active pain coping style. Having an active pain coping style was significantly ( Knee and hip osteoarthritis (OA) are among the most common chronic joint conditions worldwide among older adults . This prPatients with knee or hip OA are predominantly managed in primary care, e.g., by using analgesics and consulting general practitioners . Other aPain coping strategies are cognitive and behavioral reactions to chronic pain to manage the pain ,15,16. PSince it is known that having a passive pain coping style is related to higher levels of pain, it may be assumed that these patients would seek more help in healthcare to cope with their limitations. However, prior research concluded that having an active pain coping style is a significant predictor of high healthcare use (HCU) in patients with OA at 2 years ,24. It iHowever, it is currently unknown how pain coping style and HCU are related in the long term in patients with OA. Research examining this relationship in the long term is of special interest, given the chronically painful and incurable nature of OA. Therefore, this study aimed to determine the long-term relationship between pain coping style in patients with knee and/or hip OA in an early stage and the course of healthcare use over a follow-up period of 10 years.To determine the relationship between pain coping style and HCU in the long term, baseline and annually measured data for 10 years from the Cohort Hip and Cohort Knee (CHECK) cohort were used . CHECK wParticipants throughout the Netherlands were included in the CHECK cohort through convenience sampling. Participants who visited their general practitioner and potentially met the inclusion criteria were sent to one of the ten participating hospitals, where final eligibility was determined by a physician. Inclusion criteria were (1) having pain of the knee and/or hip; (2) age between 45 and 65 years, and (3) being at or within 6 months of first contact with the general practitioner for symptoms. Participants were excluded if they met any of the following exclusion criteria: (1) knee and/or hip pain was based on any other pathological condition that could explain the symptoms; (2) comorbidity precluding physical evaluation and/or follow up of at least 10 years; (3) malignancy in the past 5 years; and (4) inability to understand the Dutch language.Of the included participants in the CHECK cohort, two groups were formed at baseline by the coordinating study group based on their presenting symptoms: a variable visiting group (participants with mild symptoms) and an annual visiting group (participants with more serious symptoms) . ParticiParticipants were followed for a total period of 10 years, starting between 2002 and 2005. Participants visited the centers annually. Study visits consisted of structured interviews, self-reported questionnaires, physical examinations, X-rays, and blood and urine collection . Data frHCU was measured annually using a combined version of a self-reported questionnaire, developed for the Patient Panel Chronic Diseases by Nivel  , and theAt baseline, pain coping was identified with the Pain Coping Inventory (PCI) . The PCIThe following patient characteristics, and potential confounders, were administered at baseline: age, gender, body mass index (BMI), educational level, employment, number of comorbidities (range 0–4), and location of OA . Various®, version 25.0. The data were checked for data entry errors, outliers, and missing data. To indicate whether values were missing completely at random (MCAR) or missing at random (MAR), significant differences in baseline characteristics between participants with and without missing values at baseline were tested using independent T-tests for continuous values and chi-squared tests for categorical values. If significantly different, values were considered MAR, and imputation was conducted to reduce bias [Statistical analyses were performed using IBM SPSS Statisticsuce bias . Multipluce bias . A totaluce bias . A sensiuce bias . Descripuce bias , to takeuce bias ,24: (1) p ≤ 0.05.To determine the relationship between pain coping style and the course of the number of healthcare services used over 10 years, a longitudinal analysis was performed. To estimate the average relationship over the entire population, a General Estimating Equation (GEE) analysis was used. GEE takes into account the dependency of individual observations by specifying a working correlation structure . The litp = 0.04) and had a higher score on the WOMAC subscale physical functioning (p = 0.017).Of the 1002 participants included in the CHECK cohort, 861 met the inclusion criteria for the current study. A total of 120 participants dropped out during the study. The reason for dropping out was unknown. The average follow-up time was 9.3 years. At baseline, PCI subscales had between 2.6% and 2.9% missing values. Over the years, HCU had missing data of 2.1% at baseline to 15% at T10. Of all values, 8.8% were missing and tests showed that the values were MAR. Therefore, multiple imputation was performed. Participants with missing values were significantly more often female  in participants with an active pain coping style ranged from 1.18 (±1.75) to 1.42 (±1.49), and in participants with a passive pain coping style, from 0.99 (±1.57) to 1.35 (±1.80). p = 0.022) associated with an increase of 16.5%  in the number of the use of different healthcare services over 10 years when adjusted for confounders. The sensitivity analysis showed no remarkable differences between imputed data and original data.The analysis showed that the following variables interfered with the relationship between pain coping style and the course of the number of used healthcare services over 10 years: location of OA, NRS pain now and NRS pain past week, all WOMAC subscales, and all subscales of the SF-36, except the subscale of general health. The results of the GEE analysis on the relationship between pain coping style in an early stage of OA and the course of the number of used healthcare services over 10 years, unadjusted and adjusted for confounders, are shown in p = 0.037) associated with an increase of 18.4%  in used healthcare services in primary care. Pain coping style was not significantly associated with subgroups secondary care (p = 0.117), self-care (p = 0.118), NSAIDs (p = 0.324), and work-related care (p = 0.920).The secondary analysis , adjusteThis study aimed to examine the relationship between pain coping style in an early stage of OA and healthcare use over 10 years in patients with knee and/or hip OA. Results showed that patients with an active pain coping style use more different healthcare services over 10 years, compared to patients having a passive pain coping style. These results are independent of the change in pain and functioning over time as we adjusted for these confounders.To our knowledge, no prior studies examined the relationship between pain coping style and HCU in patients with any chronic musculoskeletal conditions over 10 years. However, there have been studies that examined factors that predict HCU in patients with knee and/or hip OA at 2 years. Hoogeboom et al.  (2012) fFrom the perspective of prevention and early intervention, a diagnosis of early OA is essential to prevent or delay the progression of OA before irreversible destruction of the joint occurs ,8. The CA surprising characteristic of the participants in the CHECK cohort was the large percentage (86.5%) of people with an active pain coping style at baseline. This may be due to several reasons. First, potential participants were excluded when they did not understand the Dutch language, whereas individuals with a non-Western background living with chronic pain and struggling with language barriers often use passive pain coping strategies . This maFurthermore, results showed that active copers in this study did not show clinically relevant improvement in health outcomes in comparison with passive copers over time . These rAn interesting finding in our study is that primary care services were used the most of all healthcare services. This is a positive finding since this is in line with the recommendations according to the Stepped Care Strategy in the management of OA . In addiStrengths of this study include the large sample size of the CHECK cohort and the participation of ten different general and university hospitals throughout the Netherlands, which generated a rich and nationally representative data sample. Also, there was only a small amount of missing data, except from HCU at the last time point. Multiple imputation was used to reduce bias. Furthermore, the data were gathered over a long period, which is suitable for the long-lasting condition of OA and resulted in the opportunity to find patterns in HCU that occurred over the period.There are also some limitations to this study. First, the HCU questionnaire only determined whether or not participants used prespecified healthcare services, and not how many times they used the services. Consequently, we were not able to present detailed data on the specific amount of utilized healthcare services. Second, self-reported HCU in patients with OA is often underreported, providing no accurate information . For futIn conclusion, the results of this study show that patients with early knee and/or hip OA with an active pain coping style use significantly more different healthcare services over 10 years, as opposed to those with a passive pain coping style. Further research is necessary to examine whether focusing on self-management skills as part of a treatment in people with an active coping style leads to a reduction in the number of used healthcare services in the long term.


High-resolution manometry (HRM) is vital in evaluating patients for surgery at the gastroesophageal (GE) junction. Previously, we reported manometry alters surgery choices at the GE junction over 50% of the time, and its components, i.e., abnormal motility and distal contractile integral (DCI), are vital in decision-making. This single-institution retrospective study examines how HRM characteristics, reported with the Chicago classification, can alter the intended surgical plans for foregut surgery.We collected data on pre-operative symptoms for patients undergoing HRM studies from 2012 to 2016, i.e., Upper GI X-rays, 48-h pH studies, DeMeester scores, upper endoscopy, and biopsy reports. HRM results were further categorized via Chicago classification . The DCI was determined; Patients not seen by a surgeon were excluded. Then a single surgeon, blinded to patient identity and HRM results, determined the planned procedure. The reviewer was then exposed to the HRM results; procedural plans were revised if needed. HRM results were then evaluated to determine which factors most influenced the surgical decisions.n = 58), with abnormal motility in 54.4% (62/114) cases. Abnormal motility findings corresponded to 70.6% (41/58) of the patients in which HRM changed the surgery decision. A DCI of < 1000 was identified in only 31.6% (36/114) of all patients, but 39.7% (23/58) of cases where the surgical decision was altered. A DCI of > 5000 was identified in only 10.5% (12/114) of all patients but 10.3% (6/58) of cases with altered surgical decisions. A DCI < 1000 and abnormal motility were generally associated with a partial fundoplication.298 HRM studies were initially identified; 114 met search criteria. Overall, HRM altered the planned procedure in 50.9% of cases (This study demonstrates the impact of identifying abnormal motility via the Chicago classification and factors like DCI on surgical choice at the GE junction. Manometry is one of the most useful adjuncts to surgery decisions at the gastroesophageal (GE) junction. This tool helps reveal how the esophagus functions, thus adding physiologic knowledge to diagnose and select potential treatment methods –4. InterIn previous studies, we examined how manometry influenced surgical decisions. We found that the manometry results changed the planned operation at least 50.9% of the time . TherefoHRM with topographical temporal spatial plotting is a powerful tool for evaluating esophageal motility and reflux. Although conventional manometry was once the gold standard, HRM is distinctly advantageous because it has more sensors and offers real-time monitoring of contractile activity over the entire esophageal length . When coSurgeons have traditionally used manometry to evaluate patients prior to anti-reflux surgery –9. When After obtaining approval from the Institutional Review Board overseeing this study, data were gathered on all HRM studies performed at a single institution from 2012 through 2016. These studies were completed by the same gastroenterology group within a single institution and utilized the Sierra Scientific Instruments HRM devices. Manometry reports included computer-generated raw data and high-resolution color graphs displaying manometry and impedance results.We identified 298 manometry studies performed within our institution during the selected time period. A chart review was then completed to collect data on pre-operative symptoms, manometry results, diagnosis, pre-operative assessment via Upper GI X-rays, 48-h pH studies, DeMeester scores, and upper endoscopy. The data were compiled into a single database and verified by a final reviewer.Table Patients evaluated by the surgeon who performs the vast majority of foregut cases at a single institution were included in the final analysis. These cases ranged from first time hiatal hernia and reflux patients, to redo paraesophageal hernias and patients presenting with achalasia. Patients who underwent manometry at outside institutions prior to presentation and those receiving further evaluation and surgery at other hospitals or by a different provider were excluded. This equaled 114 of the 298 initially identified patient cases. Only the most recent perioperative dataset was included for patients with more than one manometry study.A single surgeon analyzed the completed dataset. This surgeon was given access to the gathered data but was blinded to the patients’ identities and the manometry results. A surgical choice was then made and recorded. After the initial surgical determination, manometry results were exposed, and the procedural plans were revised as needed with subsequent correlation with the actual procedure proposed and performed for each patient. Any alterations in the surgical plans due to manometry results were then recorded. In most cases, the ultimate surgical decision is recorded as partial versus complete fundoplication.A total of 298 HRM studies were initially identified; 114 met search criteria and were reviewed by a single surgeon. As reported previously, manometry was found to have altered the planned procedure in 50.9% of cases (58 patients). In 4.4% (5 cases), the patients met the inclusion criteria, but the clinical data available upon chart review were insufficient to determine a surgery plan regardless of manometry results.Abnormal motility was identified by Chicago classification in 54.4% (62/114) of cases. The findings of abnormal motility corresponded to 70.6% (41/58) of the patients in which HRM changed the surgery decision. A DCI of < 1000 was identified in only 31.6% (36/114) of all patients, but 39.7% (23/58) of cases where the surgical decision was altered. A DCI of > 5000 was identified in only 10.5% (12/114) of all patients, but 10.3% (6/58) of cases where the surgical decision was altered.Furthermore, we found that with normal motility, complete fundoplication was more likely to be chosen than partial fundoplication 35:12; 67.3%). Conversely, abnormal motility was associated with partial fundoplication in comparison to complete fundoplication . Similarly, DCI < 1000 was associated with more likely partial fundoplication . DCI > 2000 did not seem to affect a decision for partial versus complete fundoplication , nor did DCI > 5000 . These findings are summarized in Table ; 67.3%. This study demonstrates an objective view of HRM as an integral part of the pre-operative workup for surgery at the GE junction. Furthermore, it helps delineate several components of HRM that provide valuable data for driving those surgical decisions. For instance, our data showed a strong correlation between decisions for partial fundoplication when abnormal motility was identified or if the DCI was less than 1000. Furthermore, DCI greater than 5000 did not significantly alter surgical choices in this study. These objective points helped change decisions for surgery when previous data from clinical symptoms, upper GI, or endoscopy would have led to a different surgical choice.Our study has some limitations. For example, in utilizing manometry results from only our institution, we limited the patient population to approximately a quarter of the patients who underwent foregut surgery by our designated surgeon over the study period. This approach allowed us to utilize a more standardized and consistent set of manometry results; however, the total number of patients included in the study was less than what would otherwise be expected. Importantly, we feel that even with a limited number, these patients represent the overall population undergoing foregut surgery.We also acknowledge that our results may be biased by using the expert opinion of only a single surgeon to analyze the results. As a counter argument, utilizing the experience of a single surgeon also gives our study consistency across all the patients evaluated. We sought to address this concern proactively by blinding the surgeon to manometry results and patient identity at the initial evaluation. Still, these results are significant, with HRM influencing more than half of surgical decisions. Further studies could verify these results by incorporating outside datasets or including additional surgeons in the analysis to evaluate for concordance. We intend to expand on this study and invite other experts to participate in correlating these results.Additionally, one can see a high number of abnormal manometry findings in this population that was studied. Part of this may be attributed to our broad classification of abnormal motility as any manometry finding which is outside the range of normal on the Chicago classification. However, this may also be attributed to the fact that the surgeon involved is dealing not only with reflux surgery, but also a high percentage of their practice is redo fundoplications, paraesophageal hernias, and patients being worked up for achalasia.Manometry is an essential component of surgery at the GE junction, but how it can be interpreted to help make those decisions is often up for debate. Although the debate will likely continue, this study offers insight into the decision-making process of an experienced surgeon, showing that HRM, and in particular identification of abnormal motility and defining the DCI is of great value for surgical decisions. In future studies, a closer look at other components of manometry such as integrated relaxation pressure or distal latency of the esophagus may be of additional benefit.This retrospective, single-institution study demonstrates the value of HRM and its effect on surgical decision-making at the GE junction. Furthermore, it identifies that additional factors such as low DCI and abnormal motility can also significantly influence a surgical choice.


Central sensitization is a pathophysiological cause of chronic low back pain and is linked with psychosocial factors. The association between central sensitization (CS) and body perception disturbance is currently unclear, and no prior studies have investigated this relationship in patients with acute or subacute low back pain. The objective of this study was to investigate potential factors that influence body perception disturbance using a mechanistic classification of low back pain.  This cross-sectional study was conducted at the time of initial physical therapy in patients with low back pain. During the study period, 169 patients were recruited. Pain intensity, disease duration, disability, CS, and body perception disturbance were evaluated. Patients were divided into three groups according to the pathology of low back pain, and multivariate analysis was used to examine factors affecting body perception disturbance. The dependent variable was Fremantle Back Awareness Questionnaire (FreBAQ); the independent variables were age, gender, BMI, VAS, disease duration, RDQ, and CS Inventory-9 (CSI-9). p  <  0.01). FreBAQ and RDQ scores were significantly higher in patients with CSP than those with NP (p  <  0.05). The results of multiple regression analyses indicated that CSI-9 scores were significantly associated with FreBAQ (p  <  0.01).  A total of 117 patients were included in our analysis. According to the mechanistic classification of pain, 66 (56.4%), 36 (30.8%), and 15 (12.8%) patients were categorized as having nociceptive pain (NP), peripheral neuropathic pain (PNP), and CS pain (CSP), respectively. Patients with PNP or CSP were significantly older than those with NP ( Patients with CS syndrome and low back pain tend to have higher CSI-9 scores and be older. Body perception disturbance is influenced by CS or CS syndrome, regardless of the stage of low back pain, suggesting that patients with chronic low back pain tend to have low body image. Low back pain (LBP) is associated with a high physical and economic burden . The lifCentral sensitization (CS) has been recently reported to be involved in the pathophysiology of chronic pain , 8. It iPrevious studies have described the concept of body perception disturbance (BPD) as a disease-specific factor involved in the chronicity of LBP . Body peTherefore, the purpose of this study was to examine factors that potentially influence body perception disturbance in patients with LBP, based on differences in the mechanistic classification of pain.This cross-sectional study was conducted with approval from the ethics committee of Tokyo Metropolitan University Arakawa .This study included 121 patients who received physical therapy after medical consultation at our clinic, between March and November 2021. Patients were included if they were 20–65 years old and able to provide valid responses to the administered questionnaires. LBP was defined in accordance with the criteria proposed by the Japanese medical guidelines for LBP in 2019 : “pain w2.3.The following parameters were extracted from the clinic medical records: age, gender, height, weight, body mass index (BMI), pain intensity, disease duration, FreBAQ, CSI-9, and Roland–Morris Disability Questionnaire (RDQ). All data were recorded during the first physical therapy session.The classification of pain based on its underlying mechanism was determined by the physical therapist who was in charge of the first physical therapy session for each patient. The method of classification conformed with that of Nijs et al.  who usedIn addition, the physical therapist accounted for physical examination results  and classified pain into three groups (nociceptive pain (NP), peripheral neuropathic pain (PNP), and CS pain (CSP)). Mixed or uncertain pain types were excluded. A preliminary study was conducted among 10 physical therapists to evaluate the inter-rater reliability of this classification method; the Fleiss' kappa value was 0.638, indicating substantial agreement .The primary outcomes were the Japanese versions of FreBAQ and CSI-9.The following secondary outcomes were evaluated via a questionnaire survey that was administered during the initial physical therapy session: basic patient characteristics, visual analogue scale (VAS), disease duration, FreBAQ, CSI-9, and Japanese version of RDQ. Basic patient characteristics and disease duration were obtained from the medical records.Basic patient characteristics included age, gender, height, weight, and BMI. Disease duration was defined as the number of days elapsed from the date of pain onset to the date of the first physical therapy evaluation.The VAS  was usedd = 0.21 by referencing a previous study [The target sample size was for 180 participants in our research period with an effect size as us study  which inχ2 test was used for gender. Multiple comparisons and Tukey's test were conducted as post hoc tests. The independent variable was the classification (group) of pain; the dependent variables were age, height, weight, gender, BMI, VAS, disease duration, FreBAQ, RDQ, and CSI-9. In addition, the one-way ANOVA was used to examine differences among groups for disease stage. The independent variable was disease stage ; the dependent variable was FreBAQ.The Shapiro–Wilk test was used to examine the distributional normality of a sample, and FreBAQ and CSI-9 were consistent with a normal distribution, but the other was not. The one-way analysis of variance (ANOVA) or Kruskal–Wallis test was used to examine differences among groups for demographic data, VAS, FreBAQ, CSI-9, and RDQ. The A multiple regression analysis (using the forced entry method) was conducted to examine factors that potentially influenced body perception disturbance. The dependent variable was FreBAQ; the independent variables were age, gender, BMI, VAS, disease duration, RDQ, and CSI-9.All statistical analyses were performed using IBM SPSS Statistics version 26.0 . The level of statistical significance was set at 0.05.n = 3); unable to complete the assessment due to technical problems (n = 43); and mixed pain type (n = 4). No patients were classified with an uncertain pain type. Therefore, a total of 117 patients were included in our analysis.According to the mechanistic classification of pain determined during the first physical therapy session, 66 (56.4%), 36 (30.8%), and 15 (12.8%) patients were categorized as having NP, PNP, and CSP, respectively.p ≤ 0.001). Gender, height, weight, and BMI were not significantly different among pain groups   . To clarp ≤ 0.001)   (p = 0.496) (Comparisons of outcome measures among pain groups are shown in Tables 2) Tables  and 5. A, 0.214) . Additio= 0.496) .p ≤ 0.001). The standardized partial regression coefficient, which indicates the degree of influence from independent variables, was 0.409 for CSI-9. The rate of contribution from the regression formula (R2) was 0.280. The variance inflation factor was <2 for all independent variables.The results of the multiple regression analysis using the forced entry method are summarized in According to a classification of pain based on its underlying mechanism, 66 (56.4%), 36 (30.8%), and 15 (12.8%) patients had NP, PNP, and CSP, respectively. These results were generally similar to those reported by Smart et al.  , suggesting the potential influence of other factors. LBP is a complex condition with a multifactorial etiology. A bio-psycho-social model has been previously proposed to account for the effects of psychological, social, and biophysical factors . HoweverIn the one-way ANOVA, FreBAQ scores were higher in patients with CSP than those with NP. Bogduk et al.  investigd = 0.21 by referencing a previous study that investigated the relationship between pain intensity and its pain mechanism. Second, this study was a single-institutional study, so external validity was unclear. Third, this study was a cross-sectional study, which does not provide a causal association. We need to conduct further investigation about the chronicity of LBP or CS with a longitudinal study.There were some limitations in this study. First, we could not correct sufficient sample size. The target sample size was set for 180 participants in our research period with an effect size as The results of this study suggest that patients with CS or CSS and low back pain tend to have higher CSI-9 scores and be older. Body perception disturbance is influenced by CS or CSS, regardless of the stage of low back pain, thus reflecting that patients with chronic low back pain tend to have low body image.


Background and Objectives: Total knee arthroplasty (TKA) is a commonly performed orthopedic procedure, and is often accompanied by significant postoperative pain. The supra-inguinal fascia iliaca block (SIFIB), similar to an anterior lumbar plexus block, is frequently used in hip surgeries. The interspace between the popliteal artery and capsule of the posterior knee (IPACK) block is a regional anesthesia technique that targets the posterior innervation of the knee capsule. This retrospective study aimed to compare the analgesic effects of SIFIB and SIFIB + IPACK on patients undergoing TKA under spinal anesthesia. Materials and Methods: This retrospective study revealed the data collected from a tertiary hospital. Patient data were gathered for individuals who underwent unilateral TKA under spinal anesthesia during the period between 1 January 2023 and 1 September 2023. Inclusion criteria comprised patients falling within ASA class I–III, those following a standardized perioperative analgesia regimen, and individuals receiving opioids via a patient-controlled analgesia device (PCA) as part of their postoperative pain management strategy. Patients were grouped as SIFIB and SIFIB + IPACK according to the performed regional anesthesia technique. Results: In the study, the data of 88 patients in total, 61 in the SIFIB group and 27 in the IPACK group, were analyzed. The 24 h cumulative morphine consumption was similar in the SIFIB and SIFIB + IPACK groups . The NRS scores of the groups were similar in all time frames. Conclusions: Our study reveals that combining IPACK with SIFIB in the multimodal analgesia plan does not provide additional benefits in terms of postoperative opioid consumption and pain scores in patients undergoing unilateral THA under spinal anesthesia. Total knee arthroplasty (TKA) is a surgical procedure commonly performed to restore the functionality of the knee joint. It is employed worldwide with the primary goal of enhancing patient mobility, alleviating joint discomfort, and improving the overall quality of life for individuals dealing with advanced gonarthrosis . To manaThe knee’s nerve supply is intricately derived from branches originating from both the sacral plexus and lumbar plexus, as highlighted in previous studies ,5. NerveNumerous studies and meta-analyses have provided substantial evidence regarding the efficacy of the conventional infra-inguinal fascia iliaca block in alleviating pain associated with knee arthroplasty ,4. On thHowever, there is a notable gap in the research concerning the specific application of IPACK as a complementary technique in knee arthroplasty. Our hypothesis posits that incorporating IPACK into the analgesic regimen has the potential to significantly enhance pain management, particularly when considering the neural innervation of the knee’s posterior capsule.The principal aim of this investigation is to conduct a comparative analysis of opioid consumption within the initial 24 h following surgery in patients who have undergone TKA under spinal anesthesia. Our focus will encompass the evaluation and comparison of patients who have received SIFIB alone against those who have received the combined administration of SIFIB and IPACK. Additionally, secondary objectives encompass the assessment of pain scores and diligent monitoring for the presence of postoperative complications.clinicaltrial.gov (NCT06054945).For this study, we obtained ethical approval from the Local Ethics Committee (SUKAEK 2023/16/16) and retrospectively analyzed data from patients aged 18 to 75, falling within ASA physiological classes I–III, who underwent unilateral knee arthroplasty under spinal anesthesia at Samsun University Samsun Training and Research Hospital between 1 January 2023 and 1 September 2023. Additionally, this study was registered at In our clinic, all patients who receive peripheral block techniques as part of the postoperative analgesia plan are diligently monitored and data are recorded on our forms for up to 24 h postoperatively. Detailed information regarding block performance characteristics, complications, postoperative pain intensity at specific time intervals, the presence of motor weakness, and, if PCA is employed, opioid consumption, or, if PCA is not used, rescue analgesic requirements, are meticulously documented and collected. This retrospective study is based on the analysis of meticulously collected data.The research included patients receiving either a suprainguinal fascia iliaca block (SIFIB) alone or in combination with infiltration of the posterior capsule of the knee (IPACK) for postoperative pain relief. These patients were equipped with patient-controlled analgesia (PCA) devices administering morphine as part of postoperative pain management.Exclusion criteria comprised individuals with allergies to local anesthetics, injection site infections, those under 18, ASA IV and above patients, and individuals with cognitive impairments affecting pain assessment. All patients underwent uniform spinal anesthesia, perioperative, and postoperative analgesia procedures, with the exception of variations in peripheral block or block combination.Patient demographics including age, gender, weight, height, and surgery duration were gathered from the data system. Data related to postoperative pain management, such as block concentration, time to initial analgesia request, pain intensity at specified intervals, and analgesic usage at designated time points, were routinely collected in forms, and the primary data for the study were obtained from patients’ follow-up forms. This form only includes data from the first 24 h postoperation.This study was conducted based on retrospective data analysis. In these sections, standard anesthesia/analgesia protocols applied in our clinic are described. Data from patients deviating from standard practices have been excluded.All patients are subjected to standard monitoring procedures, including noninvasive arterial blood pressure, electrocardiography, and pulse oximetry. Spinal anesthesia is induced using 12–15 mg of heavy bupivacaine, without any adjuvant, administered via a midline approach targeting the L4–L5 interval.Comprehensive preoperative, perioperative, and postoperative analgesia protocols are uniformly applied to all patients. Upon the completion of surgery, each patient receives intravenous (IV) tenoxicam (20 mg) and IV acetaminophen (1 g). The postoperative analgesic regimen comprises IV tenoxicam administered every 12 h and IV paracetamol administered every 8 h.In this retrospective study, the data were limited to patients who were exclusively administered intravenous patient-controlled analgesia (PCA) in the recovery room. In our clinical practice, the PCA system had been configured with no basal infusion and included a solution containing morphine at a concentration of 0.3 mg/mL, with a total volume of 100 mL. Patients had the option to self-administer a bolus dose of 1 mg of morphine through the PCA system, and there was a mandatory lockout period of 20 min between successive doses. PCA initiation occurred immediately following the completion of the nerve block procedure, and patients were instructed to activate the system when their numeric rating scale (NRS) pain score reached or exceeded 4.We routinely documented the total amount of opioid consumed by patients at specific intervals during the postoperative period, namely at the 1st, 3rd, 6th, 12th, 18th, and 24th hours after the surgery. In cases where, within the first 24 h, the patient reported an NRS pain score of ≥4 despite using PCA, we administered a 25 mg intravenous meperidine injection as rescue analgesia.The pain assessment in our clinic was conducted as follows: Pain levels experienced by patients were assessed under two conditions: at rest (referred to as NRS-S for static pain) and during motion (referred to as NRS-D for dynamic pain). We recorded NRS-S scores at the 1st, 3rd, 6th, 9th, 12th, 18th, and 24th hours postoperation, while NRS-D scores were documented at the 9th, 12th, 18th, and 24th hours postoperation. The NRS is a unidimensional measure of pain intensity used in adults. It involves patients rating pain on a numerical scale comprising eleven points, ranging progressively from no pain (0) to the most severe pain imaginable (10).Evaluation of Quadriceps weakness: To assess the weakness of the quadricep muscle, the patient’s knee is extended actively. This is carried out initially against the force of gravity and subsequently against applied resistance, all while keeping the hip joint flexed at a 45-degree angle and the knee joint flexed at 90 degrees. A 3-point rating scale is used to assess and score the patient’s ability to extend the knee as follows: 0 = normal strength (the patient can extend the knee against both gravity and applied resistance); 1 = mild weakness (the patient can extend the knee against gravity but struggles against resistance); 2 = severe weakness (the patient cannot extend the knee). In statistical evaluations, quadricep weakness is accepted as present  or absent (0).In this section, information is given about the application procedures of the regional anesthesia techniques applied in our clinic and the subject of this study.-Ultrasound guided IPACK blockThe ultrasound-guided IPACK block procedure is carried out within a designated regional anesthesia application section situated in a separate area within the operating room, preoperatively. Prior to the block procedure, all patients undergo standard ASA monitoring, and those considered hemodynamically suitable are administered 0.03 mg/kg of midazolam to induce sedoanalgesia. After placing the patient in a prone position, the sequential steps for the IPACK block can be succinctly delineated as follows. The initiation process entailed the scanning of the popliteal fossa using a lower-frequency ultrasound transducer . Once the femoral condyle became discernible within the US field, the probe was directed proximally until the visualization of the femoral shaft was achieved, consequently exposing the popliteal artery. Subsequently, a nerve block needle  was introduced, originating from the lateral aspect of the knee joint, targeting the region positioned between the popliteal artery and the femur, followed by the administration of 20 mL of 0.25% bupivacaine.-Ultrasound guided SIFIBIn our clinic, we apply SIFIB at the end of surgery in order to benefit from its analgesic effectiveness for a longer period of time. The US-guided SIFIB is administered postoperatively after the successful completion of a surgical procedure, once patients are transferred to the postanesthetic care unit, undergo standard ASA monitoring, and are observed to be hemodynamically stable. With the patient positioned supine, the inguinal region is aseptically prepared, and a sterile linear US transducer  is situated adjacent to the inguinal ligament, aligning its longitudinal axis parallelly to the ligament. The femoral artery and the femoral nerve are distinctly identified. Subsequently, (2) the probe is laterally repositioned to locate the sartorius muscle, ensuring that the image of the sartorius muscle is centrally displayed on the US screen. The probe is then moved cephalad, tracking the sartorius muscle until it gradually disappears while the probe traverses towards the hypoechoic anterior superior iliac spine. The US probe undergoes a 90° rotation to identify the anterior superior iliac spine, the iliacus muscle, and the abdominal muscles, all of which are visualized on the screen. The needle is introduced from the caudal aspect and directed cranially using an in-plane technique, ultimately allowing the needle tip to perforate the fascia iliaca and reach the fascia iliaca compartment. Following the confirmation of the accurate placement of the needle tip, achieved by injecting 5 mL of saline, a total of 40 mL of 0.25% bupivacaine is administered.The primary outcome of our retrospective study was the total amount of opioids required within the 24 h period following the procedure. Our secondary outcome measures encompassed the assessment of pain scores at varying intervals. Additionally, we documented ancillary factors such as episodes of nausea, vomiting, the time elapsed until the first request for analgesia, and instances of quadriceps weakness lasting more than 24 h.t-test or the Mann–Whitney U test, depending on the data distribution. Proportions were compared using the chi-square test with Yates’ correction, while Fisher’s exact test was utilized for categorical variables such as ASA classification and gender. To determine statistical significance, we set the threshold at p < 0.05. Notably, for the analysis of numeric rating scale (NRS) scores measured at five different time points, we applied the Bonferroni correction, with statistical significance defined as p < 0.001.SPSS software  was used for statistical analysis. To assess the distribution of data, we utilized the Kolmogorov–Smirnov test to evaluate normality. Descriptive data were presented using either the mean and standard deviation or the median and interquartile range (25th and 75th percentiles). Continuous variables were compared using either Student’s p: 0.163). Additionally, in terms of descriptive data such as gender distribution, ASA class, length, weight, BMI, and other parameters, the groups were similar (p > 0.05), (p > 0.05).Between the specified dates, data from 61 SIFIB and 27 SIFIB + IPACK patients who met the inclusion criteria for unilateral knee surgery were analyzed. The mean ages of the patients were 65.82 ± 4.97 years in the SIFIB group and 64.29 ± 3.95 years in the SIFIB + IPACK group, and these data were similar (> 0.05), . The patp: 0.258)  . Further: 0.258) .p < 0.05), , . In bothIn this retrospective study, we found that there was no statistical difference in opioid requirement and pain scores between the SIFIB alone and the combination of the SIFIB and IPACK as the regional component of multimodal analgesia in patients undergoing unilateral TKA under spinal anesthesia. Furthermore, there was no difference observed in terms of the time to the first analgesic request and the rate of quadricep weakness. Thus, we were unable to establish any superiority of one technique over the other in any aspect.When considering skin incision for TKA, it is observed that the entirety of sensory innervation originates from the lumbar plexus ,8. SimilAs a complementary approach to ensuring perioperative analgesia in patients undergoing knee surgery, the IPACK block can be effectively combined with other techniques. In the current literature on knee surgery, more distal blocks such as the ACB are preferred for analgesia purposes in knee surgeries—at the expense of narrowing the sensory block area—due to there being less motor blocking. When combined with an adductor canal block (ACB), it can provide high-quality perioperative analgesia in patients undergoing TKA . HoweverThe obturator nerve contributes to the posterior innervation of the knee by joining the popliteal plexus with its deep branches (articular branches) along with the sciatic nerve. Therefore, the application of SIFIB may contribute to analgesia not only in the anterior but also in the posterior aspect of the knee, facilitated by obturator nerve blockade. Given the existing research on the efficacy of ACB and IPACK combinations, there is a discernible gap to be filled via more extensive investigations into novel techniques and technical alternatives. An exploration of motor block incidence at different SIFIB volumes and concentrations represents a promising avenue for future studies. Additionally, potential research may involve a comparative analysis of quadricep weakness and analgesic efficacy between distal blocks such as ACB and ACB + IPACK, and proximal blocks such as SIFIB in TKA.Vermeylen et al.  demonstrIn TKA, instead of blocking the lumbar plexus from a high level, the general trend is to block it from a more distal level  and avoid motor weakness . In our There are some limitations of our study. Regarding the constraints of our study, it encompasses elements related to a retrospective approach, including data insufficiency, the challenge of establishing causal links, the potential for confounding factors from data sources to be present, limitations in group selection and the oversight of temporal influences, inherent design restrictions, data variability, and potential biases. These limitations underscore the need for the prudent interpretation of our results and caution regarding the definitiveness of our study’s findings. Additionally, the most crucial limitation at this point is the lack of studies in the literature demonstrating the effectiveness of the SIFIB on pain management in patients undergoing TKA. However, in a randomized controlled study conducted by our clinic very recently, it was reported that the SIFIB reduced the postoperative analgesic requirement . In thisOur study showed that adding IPACK to the SIFIB, which is a regional anesthesia technique in the multimodal analgesia plan, has no additional benefit in terms of postoperative opioid consumption, pain scores, the first analgesic request, and the rate of quadriceps weakness in patients undergoing unilateral THA under spinal anesthesia.