The diagnostic process in patients after painful total knee arthroplasty (TKA) is challenging. The more clinical and radiological information about a patient with pain after TKA is included in the assessment, the more reliable and sustainable the advice regarding TKA revision can be. The primary aim was to investigate the position of TKA components and evaluate bone tracer uptake (BTU) using pre-revision SPECT/CT and correlate these findings with previously published pain patterns in painful patients after TKA.p < 0.05).A prospectively collected cohort of 83 painful primary TKA patients was retrospectively evaluated. All patients followed a standardized diagnostic algorithm including 99m-Tc-HDP-SPECT/CT, which led to a diagnosis indicating revision surgery. Pain character, location, dynamics and radiation were systematically assessed as well as TKA component position in 3D-CT. BTU was anatomically localized and quantified using a validated localization scheme. Component positioning and BTU were correlated with pain characteristics using non-parametric Spearman correlations (Based on Spearman’s rho, significant correlations were found between pain and patients characteristics and SPECT/CT findings resulting in nine specific patterns. The most outstanding ones include: Pattern 1: More flexion in the femoral component correlated with tender/splitting pain and patella-related pathologies. Pattern 3: More varus in the femoral component correlated with dull/heavy and tingling/stinging pain during descending stairs, unloading and long sitting in patients with high BMI and unresurfaced patella. Pattern 6: More posterior slope in the tibial component correlated with constant pain.The results of this study help to place component positioning in the overall context of the "painful knee arthroplasty" including specific pain patterns. The findings further differentiate the clinical picture of a painful TKA. Knowing these patterns enables a prediction of the cause of the pain to be made as early as possible in the diagnostic process before the state of pain becomes chronic.Level IIIThe online version contains supplementary material available at 10.1007/s00167-021-06567-y. The causes for recurrent pain after total knee arthroplasty (TKA) are manifold and range from knee joint-related factors such as infection, arthrofibrosis, patellofemoral problems, malposition or malalignment, loosening or instability to non-knee joint-related causes such as psychological disorders, vascular pathologies, back or hip problems , 23.The diagnostic process is challenging. Besides a detailed patient history, a thorough clinical examination, radiological, serological and microbiological investigations are part of a standardized diagnostic algorithm for unhappy patients after TKA , 35. As In 2020, this study group was able for the first time to identify pain characteristics in unhappy patients after TKA and link these to specific underlying pathologies. Based on this, pain patterns were found  Fig. 1)1). HowevOver the past 10 years, SPECT/CT has become an increasingly recognized and appreciated diagnostic imaging modality in patients with pain after TKA. A considerable number of studies have been published proving its beneficial clinical use in establishing the diagnosis and providing guidance for further treatment , 14, 31.To date, there exists no study that links findings of SPECT/CT to specific pain patterns in patients with pain after TKA. The more clinical and radiological information about a patient with pain after TKA is included in the assessment, the more reliable and sustainable the advice regarding TKA revision can be .Therefore, the primary aim of this study was to assess the position of TKA components and evaluate BTU using pre-revision SPECT/CT and correlate these findings with previously published pain patterns in painful patients after TKA. It was hypothesized that specific TKA component positioning and BTU patterns can be correlated with recently identified pain patterns.N = 46).This study was approved by the local ethical committee 2017-02048) and was performed in accordance with the ethical standards of the responsible committee and with the guidelines of the Helsinki Declaration of 1975, as revised in 2008. A written informed consent was signed by every patient. A consecutive number of 83 patients, who underwent primary TKA from 1993 to 2017 and complained about unilateral persistent knee pain and who underwent a revision surgery after completing the diagnostic algorithm including SPECT/CT were prospectively collected and then included in this retrospective cohort study. The cohort is mostly consistent  with that in the previously published study on TKA pain patterns . Data we017-02048Within the framework of the consultations at the knee centre, all the variables listed in Table All patients underwent 99m-Tc- hydroxymethyl diphosphonate (HDP) SPECT/CT imaging following a standardized and highly reliable protocol , 15, 31.Mechanical alignment and TKA position were assessed using a customized validated 3D-software which has been proven highly accurate . A post hoc analysis using G*Power, version 3.1.9  tested that, for the given N = 83, a correlation of rho = 0.28 can be found with a power of 80%. For the number of patients with pain characteristic values (N = 59), the same correlation has to be rho = 0.35.Results are presented as means, ranges and standard deviations (SD) or with numbers and percentages. To correlate binary variables, phi coefficients were calculated. Because the cut angles values and some BTU values are not normally distributed, ordinal Spearman correlations (rho) were used for all correlations. Two-sided Patient demographics and TKA characteristics of all 83 patients included are shown in Table N < 4) were excluded from the statistical analysis  were identified .P2: More valgus in the femoral TKA component is associated with constant pain (p < 0.001), in particular at night (p < 0.05), and instability-related pathologies.P3: More varus in the femoral TKA component is associated with dull/heavy and tingling/stinging pain during descending stairs, unloading and long sitting (p < 0.05) in patients with high BMI (p < 0.01) and unresurfaced patella (p < 0.05).P4: More internal rotation of the tibial TKA component is associated with tugging/wrenching pain during unloading (p < 0.05) and radiation to the spine (p < 0.01).P5: More varus in the tibial TKA component is associated with starting pain (p < 0.05) in patients with high BMI (p < 0.05).P6: More posterior slope in the tibial TKA component is associated with constant pain (p < 0.05).P7: More tibiofemoral valgus alignment is associated with constant pain, in particular at night, and by walking downhill and with low BMI (p < 0.05).P8: More tibiofemoral varus alignment is associated with patients with high BMI (p < 0.001).P9: Increased BTU laterally at the stem and tip of the tibial component is associated with constant pain (p < 0.05), whereas increased BTU in the area of the tray is associated with patients with pain aggravation in flexion (p < 0.01).Based on the correlations found the following patterns  followed by patella-related problems (56.6%) and instability (51.8%). This is in contrast to most register data published in recent years –22. In mtender/splitting pain and patella-related pathologies (P1). More valgus in the femoral component and in the tibiofemoral alignment correlated with constant pain, in particular at night , whereas more varus in the femoral component correlated with dull/heavy and tingling/stinging pain during long sitting, descending stairs and by unloading in patients with unresurfaced patella (P3). Femoral component positioning in valgus (P2) and internal rotation was associated with instability-related pathologies, however, not significantly. More internal rotation of the tibial component correlated with tugging/wrenching pain during unloading and radiation to the spine (P4), whereas increased posterior slope in the tibial component caused constant pain (P6). Interestingly, a strong correlation was found between arthrofibrosis (other problems) and valgus positioning of the tibial component —tibiofemoral valgus alignment with lower BMI. The association between obesity and increased risk of varus malalignment post-surgically has been described in literature in the past [Second, correlations were found between TKA component positioning, pain and TKA characteristics and other pathologies. More flexion in the femoral component was significantly associated with nt Table . A clearght P2, P, whereastender/splitting pain character was also found in P1. Anterior slope of the tibial TKA component may lead to a tight flexion gap and subsequent flexion deficit. Generally, it is aimed for a posterior slope of 0°–7° [tugging/wrenching pain character, aggravation when unloading and radiation to the spine.These findings play a crucial role in the diagnostics of patients with painful TKA. Component positioning represents a major challenge in this process and often confronts the clinician with the question whether a specific component position is considered as pathological or within the range of the “norm”. It is generally agreed, that TKA component positioning should not be viewed in absolute terms, but in the context of the complaints as a whole within the diagnostic process. However, reference values, which were also used in this study for statistical purposes to distinguish between conspicuous and inconspicuous TKA component positioning, are provided in the literature as follows , 17, 36:of 0°–7° . Thus, tHowever, there is an individual range of TKA component position in each direction, which is accepted by the patient, which we call the “envelope of TKA position” . AwengenA significant correlation between TKA component positioning and pain localisation could not be demonstrated in this study. However, this is not surprising as in the previously published pain patterns by Mathis et al., the anatomical location has been proven no being helpful in localizing the underlying problem .Third, highest mean BTU in SPECT/CT was found in supero-lateral areas of the femur and patella, and in the postero-lateral tibial tray. Areas in the patella and around the tibial tray showed almost twice as high mean BTU values than femoral or stem and tip areas of the tibia. Therefore, one could argue that increased BTU at femoral areas and areas around the tibial stem or tip are more specific for identification of pathologies in patients with TKA. These findings are consistent with previous results of Awengen et al. who compared BTU distribution patterns in asymptomatic and symptomatic TKA patients . HoweverSeveral limitations of the present study have to be acknowledged. This was a retrospective series of prospectively collected 83 TKAs assigned to a specialized knee centre, operated by a team of different surgeons from various hospitals. Thus, a prospective study design including only painful TKAs from one surgeon would improve the comparability of the patient significantly. Another limitation is the restriction of underlying pathologies to anatomical and mechanical nature. It is a well-known fact, that psychological and social determinants play an important role in the perception of pain in patients after TKA . HoweverThe painful TKA remains a challenge for the surgeon . RevisioThe findings of this study add significant value to the previously published TKA pain patterns and further differentiate the clinical picture of a painful knee after TKA. Knowing these pain patterns to its utmost extent enables a prediction of the cause of the pain to be made as early as possible in the diagnostic process. If the causes of the described complaints are known, a decision for a necessary therapy can be made reliably and sustainably at an early stage before the state of pain becomes chronic.Supplementary file1 (PDF 67 KB)Supplementary file2 (PDF 67 KB)Supplementary file3 (PDF 66 KB)Below is the link to the electronic supplementary material.


Are greater Central Sensitization Inventory scores associated with worse pain outcomes after endometriosis surgery?In this longitudinal presurgery and postsurgery cohort study of 239 people with endometriosis, higher Central Sensitization Inventory scores at baseline were statistically significantly associated with higher chronic pelvic pain scores at follow-up.These findings suggest that the Central Sensitization Inventory may be used preoperatively by gynecologists to counsel patients on expected postoperative pain outcomes and identify people who may have persistent pain after surgery. This cohort study explores the association between Central Sensitization Inventory scores and persistent pain after endometriosis surgery. A subset of people who undergo surgery for endometriosis have persistent pain, suggesting that other factors besides the endometriosis, such as central sensitization, may play a role in this pain. The Central Sensitization Inventory, a validated self-reported questionnaire of central sensitization symptoms, may identify individuals with endometriosis who have more pain after surgery due to pain sensitization.To examine whether greater baseline Central Sensitization Inventory scores are associated with postsurgical pain outcomes.This prospective, longitudinal cohort study performed at a tertiary center for endometriosis and pelvic pain in British Columbia, Canada, included all patients aged 18 to 50 years with diagnosed or suspected endometriosis and a baseline visit between January 1, 2018, and December 31, 2019, who underwent surgery after the baseline visit. Individuals who were menopausal, had a prior hysterectomy, or were missing data for outcomes or measures were excluded. Data analysis was performed from July 2021 to June 2022.The primary outcome was chronic pelvic pain at follow-up measured on a scale of 0 to 10, with 0 to 3 indicating no pain or mild pain, 4 to 6 indicating moderate pain, and 7 to 10 indicating severe pain. Secondary outcomes were deep dyspareunia, dysmenorrhea, dyschezia, and back pain at follow-up. The main variable of interest was baseline Central Sensitization Inventory score .P = .02), deep dyspareunia , dyschezia , and back pain  at follow-up, when controlling for baseline pain scores. The Central Sensitization Inventory scores themselves decreased slightly from baseline to follow-up ; however, individuals with high baseline Central Sensitization Inventory scores still had high scores at follow-up.A total of 239 patients  identified as White mixed with another ethnicity], 1 [0.4%] Black or African American, 29 [12.1%] Asian, 2 [0.8%] Native Hawaiian or Pacific Islander, 16 [6.7%] other, and 2 [0.8%] mixed race or ethnicity) with follow-up data at more than 4 months after surgery were included in this study (71.0% follow-up rate). The mean (SD) baseline Central Sensitization Inventory score was 43.8 (18.2), and the mean (SD) follow-up was 16.1 (6.1) months. Higher baseline Central Sensitization Inventory scores were significantly associated with higher chronic pelvic pain (odds ratio [OR], 1.02; 95% CI, 1.00-1.03; In this cohort study of 239 patients with endometriosis, higher Central Sensitization Inventory scores at baseline were associated with worse pain outcomes after endometriosis surgery, when controlling for baseline pain scores. The Central Sensitization Inventory could be used to counsel patients with endometriosis on their expected outcomes after surgery. However, surgery is not adequate for complete resolution of symptoms in some people.8 Reoperation rates after conservative fertility-sparing surgery can reach 50% within 5 years, suggesting that pain mechanisms beyond the endometriosis lesions themselves may be involved.9 In addition, recurrent pain and reoperation can occur in patients undergoing hysterectomy.10 Pain mechanisms in endometriosis are multifactorial.11Endometriosis is characterized by the presence of endometrial-like tissue outside the uterine cavity.11 It is characterized by long-lasting hyperexcitability of the central nociceptive system that can amplify and perpetuate the perception of pain, even after medical or surgical treatment of the endometriotic tissue.16 An increasing body of evidence for central sensitization in endometriosis involves the use of neurophysiologic testing, such as quantitative sensory testing (QST), and magnetic resonance imaging (MRI). Studies using QST have shown that patients with endometriosis have significantly altered pain thresholds after stimulation of both endometriosis sites and extrapelvic locations, suggesting the amplification of central pain processing.19 Brain MRI studies have identified regional changes in brain morphology and function, such as thalamic gray matter volume reduction and alterations in functional connectivity in endometriosis-associated CPP.21 Such changes in brain function and morphologic mechanisms may contribute to the development of chronic pain and associated comorbidities, such as mood disorders and cognitive impairment.21 A limitation of QST and MRI is that they are less feasible for implementation into clinical practice.Of note, central sensitization has been increasingly recognized as a crucial component in the pathogenesis of endometriosis-associated pain, occurring alongside the peripheral nociceptive contributors on a continuum.25 This questionnaire assesses systemic pain and pain-related symptoms and mental health but is not a neurophysiological measure and thus not a direct marker of central sensitization.26 A previous study27 found that the number of CSSs was significantly correlated with increasing pain scores and CSI scores in endometriosis. Although the CSI is not a direct or exclusive measure of central sensitization,30 it is able to discriminate between patients with CSSs, such as fibromyalgia, and healthy controls.32 The CSI’s measurement properties indicate excellent internal consistency (0.87-0.91), good test-retest reliability (0.82-0.97), and high construct validity (r = 0.46 for larger regions of pain).34The Central Sensitization Inventory (CSI) is a validated self-reported questionnaire that is used to assess symptom severity and identify people with central sensitivity syndromes (CSSs), also referred to as chronic overlapping pain conditions, where central sensitization may be part of the underlying cause.35 and at a tertiary center, patients with pelvic pain reported up to 20 operations before referral, with a possible explanation being unrecognized and untreated central sensitization and overreliance on surgery.36 Thus, an important clinical problem in the management of endometriosis is the ability to identify individuals who may not benefit from surgery in order to prevent unnecessary additional operations. Currently, there is a lack of clinical tools to counsel patients with endometriosis on their probable pain response to surgery. Therefore, an easy-to-use tool for clinicians to assist them in identifying symptoms that may indirectly reflect central sensitization may help prevent unnecessary interventions for endometriosis.Endometriosis costs approximately $16 000 annually per patient in the US,In this prospective, longitudinal study, the association between CSI and persistent pain after endometriosis surgery was explored, with a primary outcome of CPP and secondary outcomes of dysmenorrhea, deep dyspareunia, dyschezia, and back pain. We hypothesized that higher baseline CSI scores would be associated with worse pain outcomes. In a corollary analysis, we also measured the change in CSI score after surgery to assess the association of surgery with symptoms of central sensitization.36 After patients provide consent to EPPIC, the following data sources are entered prospectively and in real time into the registry: (1) patient-reported questionnaires at baseline and follow-up and (2) clinician-reported data for the baseline physical examination and the subsequent index surgery. Research ethics approval for this study was granted by the University of British Columbia and the British Columbia Children’s and Women’s Research ethics boards. All people included in this study consented to their data being used for research as part of the EPPIC data registry; therefore, reconsent was not required for data analysis in this study (approved by the Children's and Women's Research Ethics Board). All data were deidentified. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies.Prospective, longitudinal data from a patient registry, the Endometriosis Pelvic Pain Interdisciplinary Cohort (EPPIC), were analyzed at a tertiary center for endometriosis and pelvic pain. The EPPIC registry has been described previously.The study cohort was selected from registry participants who met the following inclusion criteria: (1) 18 to 50 years of age; (2) endometriosis based on a previous surgical diagnosis , current endometrioma on imaging or current deep infiltrating nodule on palpation or imaging, or clinically suspected endometriosis; and (3) new or additional referral baseline visit to the center between January 1, 2018, and December 31, 2019, among patients who consented to inclusion in the registry and who prospectively underwent an index surgery (approximately 6 months after baseline visit) by an endometriosis specialist surgeon with advanced training in laparoscopic surgery at our center. We included both conservative (fertility-sparing) surgery, which primarily involved excision of endometriosis lesions, and hysterectomy . The sample size was too small to divide hysterectomies by oophorectomy status; thus, hysterectomies were considered a single group. Our group aims to excise all visually suspected lesions, both typical and atypical, for all stages (I-IV) and anatomical subtypes .The exclusion criteria for participants included (1) postmenopausal status ; (2) previous hysterectomy and/or bilateral salpingo-oophorectomy (before the baseline visit); (3) missing CSI or CPP scores; (4) follow-up completed less than 4 months after surgery; and (5) withdrawn consent. Follow-up questionnaires are sent 1 and 2 years after baseline, although there is variability in when participants actually complete the questionnaires. We used the most recently completed follow-up questionnaire available. Our predetermined goal was to follow up patients through approximately 18 months after surgery. The study cohort is presented in The primary outcome was CPP at follow-up. The secondary outcomes were deep dyspareunia, dysmenorrhea, dyschezia, and back pain. All the pain scores were rated on an 11-point numeric rating scale , and because assumptions of linear regression were not met , we then categorized the pain scores as none to mild , moderate , and severe  for ordinal regression. In the registry, follow-up questionnaires are sent at specific intervals , but there is variability when individuals complete the questionnaire: for each participant, we used the most recent follow-up questionnaire available .25 Each of the questions targets a different component of downstream symptoms, such as feeling depressed or having low energy, muscle stiffness, poor sleep, and light sensitivity. A higher score indicates greater symptom severity that may be indirectly related to conditions with underlying central sensitization. The CSI is in the public domain and is freely available.37The main variable of interest was the CSI score at baseline measured from 0 to 100, consisting of 25 self-reported questions rated from 0 to 4 .39 and (5) painful bladder syndrome41 via diagnostic criteria; (6) bladder or pelvic floor tenderness42 and (7) abdominal wall pain36 via physical examination; (8) anxiety symptoms measured by Generalized Anxiety Disorder 7 (GAD-7)43; (9) depressive symptoms measured by Patient Health Questionnaire 9 (PHQ-9)44; and (10) magnification, rumination, and helplessness measured by the Pain Catastrophizing Scale.45Other variables considered included demographic characteristics , type of surgery , and number of CSSs. Patient self-reported race from the EPPIC data registry was included as a variable in this study because there is potential clinical variation by race in endometriosis. As previously reported, we assessed 10 CSSs and pelvic pain-related comorbidities: (1) fibromyalgia, (2) chronic fatigue syndrome, and (3) migraines (each self-reported); (4) irritable bowel syndromeP > .05 and/or by running separate binomial logistic regressions on cumulative dichotomous-dependent variables). Significant variables on univariable ordinal regressions were put into a multivariable model, followed by backward elimination. Bivariate associations (2-tailed) were performed using an unpaired, independent t test or paired-sample t test (continuous variables) or a χ2 test, Fisher exact test, or Wilcoxon signed rank test . Effect sizes were calculated as follows: (z divided by the square root of B) for the Wilcoxon signed rank test and (mean divided by SD) for the paired-sample t test Cohen d. SPSS Statistics, version 24 (IBM Corp) was used for analysis. Significance was set at a 2-sided P < .05. Missing data were excluded on a per analysis basis.Data analysis was performed from July 2021 to June 2022. The outcomes were examined for associations with baseline CSI scores, as well as with other variables of interest, using ordinal logistic regression and controlling for baseline pain score. Ordinal regression was performed due to failure to meet the normality assumption of linear regression when the 0 to 10 values were used for the primary and secondary outcomes. The assumption of proportional odds was met for all ordinal logistic regression models  identified as White mixed with another race or ethnicity], 1 [0.4%] Black or African American, 29 [12.1%] Asian, 2 [0.8%] Native Hawaiian or Pacific Islander, 16 [6.7%] other, and 2 [0.8%] mixed) with follow-up of more than 4 months after surgery, the mean (SD) baseline CSI score was 43.8 (18.2). The mean (SD) number of days between baseline  and the index surgery was 227 (143)  days. For the index surgery, 168 patients (70.3%) underwent conservative surgery, and 71 (29.7%) underwent hysterectomy. A total of 122 (51.0%) had stage I/II endometriosis, whereas 97 (40.6%) had stage III/IV endometriosis. The 239 patients had a mean (SD) follow-up of 16.1 (6.1) months  after the index surgery, with 97 patients lost to follow-up (leaving 239 of 336 patients for a follow-up rate of 71.0%) . Other sP = .04), higher anxiety , and depressive symptoms , as well as painful bladder syndrome  and bladder or pelvic floor tenderness  compared with the study cohort  and the secondary outcomes of dysmenorrhea , deep dyspareunia , dyschezia , and back pain  . However, there remained variability in the pain scores at follow-up, with some individuals having persistently high pain (eTable 3 in Pain scores significantly decreased from baseline to follow-up after surgery (eTable 3 in P = .02), controlling for baseline CPP . We repeated the analyses after removing the 8 people with bilateral salpingo-oophorectomy, and the results were similar (eTable 4 in Older age and hysterectomy (vs conservative surgery) were associated with less severe CPP scores at follow-up. Stage of endometriosis was not significantly associated with CPP at follow-up. In the multivariable model, higher CSI scores at baseline remained significantly associated with a more severe CPP score at follow-up , dyschezia , and back pain  at follow-up, controlling for baseline pain scores  and follow-up   (eTable 3 in  < .001) . As illuIn this prospective study of 239 patients with endometriosis undergoing surgery at a tertiary center, significant reductions of moderate effect size in pain scores were observed on average but with some patients experiencing persistent pain. We found that the baseline CSI score was associated with higher pain scores at follow-up after surgery (both conservative surgery or hysterectomy), including for CPP, deep dyspareunia, dyschezia, and back pain. Furthermore, there was a statistically significant but clinically small reduction in the CSI score itself after surgery; however, CSI scores remained persistently high, especially in those with multiple CSSs.46 Furthermore, Roh et al47 found that centrally mediated symptoms measured by the CSI were associated with poor functional outcome at 3 months after carpal tunnel surgery, although this association diminished at 12 months. A prospective, observational study by As-Sanie et al48 found that the odds of persistent pelvic pain at 6 months after hysterectomy for benign indications increased by 27% for every 1-point increase in central sensitization pain on the Fibromyalgia Survey. Together, these studies46 indicate that a higher degree of centralized pain may be associated with persistent chronic pain after surgery.Our findings suggest that patients with endometriosis with a higher degree of symptom severity  as measured by the CSI at baseline had worse pain outcomes after surgery compared with those with a lesser degree of symptom severity. This finding is in line with our hypothesis because surgical treatment of peripheral pain generators  may not directly treat central nervous system pain generators . Similar to our study, in people who underwent spinal surgery, higher preoperative CSI scores were associated with higher postoperative scores on the Pain Disability Questionnaire.49 using QST, which found statistically significant but relatively small changes in pain thresholds after endometriosis surgery. Of particular concern were individuals with high CSI scores and multiple CSS comorbidities for whom CSI scores remained persistently high after surgery. These observations suggest that surgery may have little effect on many symptoms of central sensitization, despite improvements in pain. It may be that systemic symptoms of central sensitization, once developed, have a tendency to persist over time despite improvements in other pain-related parameters. However, it remains possible that with longer-term follow-up there may be additional gradual reduction in CSI scores after endometriosis surgery.Although pain scores significantly decreased on average with moderate effect size after surgery in our population, there was a statistically significant, but small effect size, change in CSI scores from baseline to follow-up after surgery. This finding is consistent with studiesThis study has several strengths, including access to a large patient population from a tertiary center with a 71.0% follow-up rate. This study includes a prospective registry with validated clinical questionnaires , physical examination, and surgical findings. Endometriosis surgery was also performed by endometriosis specialist surgeons, thereby reducing the possibility of the CPP variable being influenced by significant residual disease. Of note, stage of endometriosis was not associated with the follow-up pain outcomes in our analyses. This finding suggests that inadequate excision and recurrence of disease were likely not factors, even in the high-stage group, because higher pain at follow-up was not found in the people with high-stage disease.This study also has limitations, including the fact that the CSI mainly measures indirect downstream symptoms, such as pain intensity and sleep disturbances, and that neurophysiological markers of central sensitization were not analyzed. To conclude that the CSI is a useful tool to identify pain sensitization and ultimately alter treatment decisions, the CSI should be correlated with surrogate measures of central sensitization, such as QST, in individuals with endometriosis. In addition, the study setting was a referral center for endometriosis-associated chronic pain, and research is needed to validate the findings in other settings, such as with community gynecologists. This study is also limited by its variability in time between the baseline visit  and index surgery, as well as between index surgery and completion of the follow-up questionnaire .In this cohort study of 239 patients with endometriosis, the CSI at baseline was significantly associated with persistent CPP after endometriosis surgery. These findings suggest that the CSI may be a useful tool to assist clinicians in phenotyping endometriosis-associated pain and in counseling patients on the expected outcomes after surgery.


Objective: Postoperative assessment of patients diagnosed with binocular cataract, who underwent two phacoemulsification treatments at different times, in terms of subjective experience of the two procedures.Material and method: The investigation is a prospective study based on patients of Ophthalmology Clinic of Mária Street in Budapest and the Ophthalmology Department in Târgu Mureş, between January 2020 and April 2021. After surgery, the patients were surveyed using questionnaires. A total of 53 responses from patients who had undergone cataract removal in both eyes were processed. Data was processed using Microsoft Office Excel and GraphPad Prism 8.0.1. Results: A statistically significant difference (p = 0.0008) in pain was found between the two interventions, with patients reporting greater pain after the second surgery compared to the first treatment. The subjective increase of visual acuity was significantly different (p=0.0156) between the two surgeries. After the first treatment, 37 patients affirmed that their visual acuity met their expectations, but, by the second operation, this had dropped to 31. There was also a statistically significant difference between the individually perceived duration of the two treatments (p=0.0013), with the most frequently reported duration of the first phacoemulsification treatment being 10 minutes (43.4%), and the second eye treatment being 20 minutes (37.7%). Assessing the asymptomaticity, a significant difference (p = 0.009) was registered between the two treatments, the asymptomatic reduction for the second operation being decreased by 28.1%. Conclusion: Patients treated for binocular cataract had significantly worse subjective symptoms during the second treatment.  It is the largest protein-rich tissue in our body, with a protein content of about 35%. It does not contain blood vessels or nerves, and derives its nutrients by diffusion from the surrounding aqueous humour. The epithelial layer is on its anterior surface, concentrates the potassium and releases the sodium, the ratio of the two in the lens being nearly 10/ 1 [1].When the ratio of ions (potassium/ sodium) inside the lens is disrupted (reduced), the increase in sodium concentration causes it to attract water, which can lead to cataracts . The most common symptom is a loss of visual acuity, but depending on the anatomical location of the opacity, photophobia, monocular diplopia, myopia, color vision changes may occur. Diagnosis is made after pupil dilation, with slit-lamp examination, and the lens in the pupil area appears greyed out [3].“Cataracta” is a Greek word meaning waterfall. It is the most common disease of the lens. The accumulation of elements in its state - potassium, calcium, lipids, phosphorus - reduces or eliminates its transparency, leading to partial or total opacity [4].Cataracts are a significant cause of blindness and vision loss, affecting millions of people worldwide, and are on the rise globally. Despite the widespread use of phacoemulsification in developed countries, 20 million people are blind to the presence of bilateral cataracts [1].Because of their congenital origin, cataracts are a feature of many dermatological pathologies [Cataracts can be divided into: 1. Primary cataracta: 1].1.1. Congenital cataracta: an intrauterine pathological process, the result of genetical damage [5].1.2. Juvenile cataracts: can be diagnosed in the first decade [5].1.3. Presenilis cataracta: appears before the age of 45 [1.4. Senilis cataracta: affects older age group.6].2. Consecutive cataracta: develops because of other eye diseases [7].3. Cataract in systemic diseases: most common in endocrine diseases .Many attempts have been made to treat cataracts conservatively, but so far without success. Medication treatment includes vitamins, hormone-based supplements, essential amino acids. However, these are not effective in treating cataracts, they can only slow down the progression. The only treatment is the surgical procedure: removal of the grayed-out lens .The signs, symptoms and location determine the indication for surgery. The indication for surgery depends largely on the stage of the cataract, the speed of progression, associated diseases and, most importantly, the visual acuity, to what extent it affects the ability to carry out everyday tasks. The social and economic impact of cataract surgery is significant. In the first year after surgery, it increases the economic efficiency of individuals by 1500% compared to the financial value of treatment. One study has shown a relation between visual acuity loss and cognitive decay. Cataract surgery progressively improves cognitive function .Today, the most common treatment method is phacoemulsification using ultrasound, which is characterized by a small incision, rapid recovery, anaesthesia of the globe of the eye with drops and few complications →slight [2]→moderate [3]→severe [4]→very severe pain [5]), patients reported their perceived pain during cataract surgery. There was a significant difference between the two treatments (p=0.0008), patients reporting statistically significant increases in pain during the second operation compared to the first treatment. During the first procedure, 49.1% of patients said they felt no pain at all, but this dropped to 26.4% by the second cataract surgery. Almost the same number of patients ticked the second and third levels of the scale. During the first treatment, the fourth level of pain was 5.7%, the highest level not being mentioned at all. By the second eye operation, this “strength” increased to 20.8% and 3.8% respectively . An increase in vision could be observed in all patients after both operations, which was correct, since the aim of the treatment was to regain the quality of visual acuity needed for everyday activities, with the right intervention. Thus, no patient claimed to have experienced “no or little” improvement in visual acuity. However, there was a change at the expense of the second operation. After the first cataract removal, 69.8% of patients experienced the expected results in terms of vision. After the second ophthalmic treatment, only 58.5% indicated that their need was met, where the third grade on the scale, “moderate” vision improvement, showed a numerical increase compared to the first treatment.Our survey included the patients’ knowledge of the tools and methods used in their treatment. No statistically significant difference was observed between responses to interventions (p=0.6250). In both cases, 47.2% of patients believed that their cataracts were removed using LASER, with only a small proportion, 13.2% being aware that their treatments were performed by ultrasound.Although the anaesthesia of the conjunctiva and cornea during cataract removal was exclusively by eye drops, 22.6% of patients reported anaesthesia by injection for the first operation and 15.1% for the second. We examined the subjectively perceived duration of the two treatments among patients. A statistically significant difference was found between the individually perceived duration of the two cataract removals (p=0.0013), with the second surgery being perceived as the longer one. The most commonly perceived duration of the first intervention was 10 minutes, with 43.4% of patients indicating this time range. 20 minutes showed a frequency of 35.8% and half an hour a frequency of 20.8%. No one noticed the three quarters of an hour. For the treatment of the other eye, 10 minutes fell to 30.2%, with 20 minutes being the most common (37.7%). The rate of half an hour also increased (24.5%), and three quarters of an hour was also among the responses (7.5%).Post-operative eye examinations showed that patients who underwent a second cataract removal were more likely to complain of local discomfort and disturbance. Using Wilcoxon’s measure unit, in which symptoms were assigned numerically , we found a significant difference between postoperative complaints (p=0.0099). After the first cataract removal, 65.4% of patients experienced no symptoms, and after the second treatment, this was almost halved, 37.3% of patients being asymptomatic. After the procedures, some patients had more than one type of complaint at the same time. Five patients reported two postoperative symptoms during the first operation, eight patients reported two postoperative symptoms after the second operation and one patient reported three postoperative symptoms. The most common were the feeling of a foreign body/ sandy sensation (17.3%/ 25.5%) and tearing (13.5%/ 23.5%). The burning sensation and pain in the eyes also showed an upward trend with 15.7% and 2% respectively. The pressure type perception of bulbus occurred only after the second phacoemulsification procedure.Finally, the questionnaire was used to assess which phacoemulsification treatment was more stressful for patients overall, from diagnosis to post-operative day’s inspection. Based on the responses of the subjects in our study, 58.5% found the two eye procedures equally exhausting, while 35.8% found the second procedure more difficult.11]. A similar result was reported in another study, which found a correlation between reduced blood pressure, heart rate and increased pain [10].A 2019 study found that anxiety levels were significantly higher before and during the first cataract surgery than during the second treatment (p=0.001) [11]. We found a similar result, the patients who underwent binocular cataract removal experiencing greater pain during the second procedure.There are studies in literature that compare the pain levels of bilateral cataract surgery. A 2019 meta-analysis of 8 studies concluded that the pain of first eye cataract treatment under local anaesthesia was significantly (p<0.00001) less than second eye surgery [12].A 2018 survey of patients over 55 years of age with normal cognitive function showed that there was a significant reduction in falls after cataract surgery due to a qualitative improvement in binocular visual acuity . The increase in visual acuity was also confirmed in our study. Literature suggests that this also increases the frequency of outdoor activities [13]. The difference in subjectively perceived duration of treatments showed similar results in literature. A survey of 466 patients who underwent bilateral cataract treatment concluded that the estimated time of the surgery was significantly longer during the second treatment (p=0.001) [14]. In our study, a proportional increase in exophthalmia sensitivity was observed after the second cataract surgery. A study in literature found a difference in exophthalmia sensitivity, which was significantly confirmed (p<0.05) after the two cataract surgeries, but no demonstrable difference was found for photophobia (p=0.555) [By elaborating our survey, we could state that 35.8% of patients had a more difficult time with the administrative, surgical steps of the second cataract removal. There was also evidence from literature that there was a statistically significant increase in patients’ memories of their second cataract intraoperative surgery. 63.3% could recall more events from the second treatment, compared to only 8.4% from the first intervention.Our study suggested that: • the willingness of the population to participate in general eye examinations was very low; • the level of anxiety was higher during the first operation; • patients were satisfied with the information provided on cataract treatment; • patients’ intraoperative pain feeling was higher after the second operation, which might have been associated with lower levels of anxiety;• greater improvement in subjective visual acuity after the first treatment; • patients reported the use of intraocular operative injections despite anaesthesia being given only by drops; • a high proportion of patients considered the use of LASER a surgical method. In order to improve the quantity and quality of the above conclusions, it is necessary to consult before a cataract treatment. The nursing staff, with the involvement of the attending physician, should support the patient preoperatively; sedatives and analgesics may be given to help relieve unpleasant symptoms. Enlightenment about the intervention is an important part of the preparatory step. Conflict of Interest statementThe authors state no conflict of interest. Informed Consent and Human and Animal Rights statementInformed consent has been obtained from all individuals included in this study.Authorization for the use of human subjectsEthical approval: The research related to human use complies with all the relevant national regulations, institutional policies, is in accordance with the tenets of the Helsinki Declaration, and has been approved by the review board of “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, Târgu Mureș, Romania.AcknowledgementsAll authors contributed substantially to this manuscript. The authors acknowledge the technical support from “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, Târgu Mureș, Romania with the Department of Ophthalmology. We would also like to thank all the subjects who participated in this study.Sources of FundingNo source of funding to declare.DisclosuresNone.


Postoperative pain management is an imperative issue for patients undergoing lumbar spinal fusion surgery. Delayed pain relief is associated with poor clinical outcomes. This study compared the effects of intravenously administered patient-controlled analgesia (PCA) with intravenous parecoxib, both commonly used methods for analgesic pain control after surgery.A non-randomized study was used to recruit 68 patients who were scheduled to receive lumbar spinal fusion surgery at a hospital in Taiwan from April through December of 2020. The group treated with parecoxib received an initial perioperative dose of parecoxib 40 mg during a 30-min period and then postoperative intravenous parecoxib at 40 mg per 12-h period, for 72 h. Those with PCA received morphine (0.4 mg/ml), droperidol (0.02 mg/ml), diphenhydramine (0.48 mg/ml), midazolam (0.02 mg/ml) and saline solution during the 3-day study course. Major outcomes, including visual scale pain score and Barthel index of activities of daily living, were collected via review of medical records at 4 times: 12, 24, 48 and 72 h after surgery. Comparative effects between two groups were assessed by the generalized estimating equations.p < 0.05). Notably, both effects would maintain for 72 h after surgery.After adjusting for potential confounders, the administration of parecoxib was associated with a significant decrease in pain scores and an increase in the Barthel Index, when compared with the PCA group (all This is the first trial of which the authors are aware, that supports intravenous parecoxib as significantly enhancing patient mobility, in addition to having pain control efficacy, when compared with PCA. This study could be used as a reference when instituting interventions to improve the adaptation process and clinical prognoses after lumbar spinal fusion surgery. Pain is a frequent complication following surgery, especially for those receiving lumbar spinal fusion surgery. A recent comprehensive study, covering 2,996 cases undergoing lumbar surgery, reported that low-back pain was the most frequently reported presenting clinical symptom 73%), followed by radiculopathy 18%), lower-extremity weakness (8%), and bowel/bladder symptoms (0.3%) , analgesics that are delivered immediately, upon patient demand, was utilized due to insufficient pain relief from conventional intramuscular delivery of opioids , 7. MorpAs part of a significant increase in specialized diagnostic and therapeutic methods, the selective cyclooxygenase-2 (COX-2) inhibitor, parecoxib sodium (parecoxib), has been more recently introduced. The parecoxib treatment has been mainly employed for short-term treatment of postoperative pain, and also used for the treatment of perioperative analgesia to prevent or reduce severe postoperative acute pain . CurrentBased on the findings of studies conducted thus far, the authors found that reports of the effects of use of parecoxib on pain reduction were mixed, with several studies showing significant levels of efficacy, while others reporting no substantial benefit pain relief –13. SignAn observational, non-randomized study was designed to evaluate the effects of PCA in comparison with parecoxib among post-surgery patients at a hospital in Taiwan, from April through December of 2020. Just as the participants could freely choose the approach of preemptive analgesia upon their personal willingness, we utilized the observational, non-randomized approach to avoid disrupting or altering the pattern of present care. The inclusion criteria were: (i) being at least 20 years-old at the time of recruitment; (ii) having no cognitive impairment and severe complications; (iii) being able to communicate in either Mandarin or Taiwanese, and  having u*POWER 3.1 analytical software, Franz Faul, Universitat Kiel, Germany).The sample size needed for this repeated measures research design was estimated by using Cohen's methodology , where αAll enrollees were allowed to choose between receiving either PCA or 40 mg parecoxib sodium intravenously twice a day for the following 3 days during the perioperative period. Those receiving parecoxib were initially given an intravenous bolus of 40 mg parecoxib, a parenteral COX-2-specific inhibitor, during the perioperation period. The subsequent 40 mg parecoxib was administered intravenously, at an even, computer-controlled, rate, every 12 h, throughout a period of 72 h. As to the participants of PCA group, they received the following medications: morphine (0.4 mg/ml); droperidol (0.02 mg/ml), diphenhydramine (0.48 mg/ml), midazolam (0.02 mg/ml) and saline solution, which was administered with a computerized intravenous infusion pump for 3 days. The pump intravenously infused a 3 ml bolus into patients when they pressed a button. Patients were instructed to press the button when experiencing postoperative pain. The lock-out time between each bolus injection was 5 mins. The maximum dose of PCA was limited to 50 ml every 4 h. While receiving the pain relief protocols, patients' vital signs  were monitored every 5 mins for the first hour and thereafter every 4 h. Supplemental oxygen by nasal cannula was provided once the patient's oxygen saturation fell below 95%. Besides, rescue analgesia was included in the protocol once the NRS was above seven, which indicated to severe postoperative pain and inadequate pain control.Primary outcome indicators of this study comprised of levels of pain and mobility, as measured by a self-reported numerical rating scale (NRS) and the Barthel Index.p < 0.001)  to 10 (worst imaginable pain), where higher scores are associated with a more severe degree of pain. The NRS was employed due to its simplicity, reproducibility, and sensitivity to relatively small changes in pain. A literature review by Safikhani and colleagues observed that the majority of published articles recommended the NRS as the most useful response scale for the assessment of pain in adults . Additio< 0.001) .Mobility was assessed using the Barthel Index, a widely used measure of the basic activities of daily living (ADL) . The BarAdditional items addressing patients' demographic and disease characteristics were developed according to clinical experience and literature review, and were gathered by a self-reported questionnaire. These data included gender, age, educational level, job status, monthly income and certain lifestyle factors, such as seeking other alternative treatments to reduce pain, as well as use of alcohol, recorded as “non-drinker” “current drinker” or “ex-drinker.” Baseline comorbid health conditions were self-reported and identified by a review of medical records, including hypertension, diabetes, hepatitis, peptic ulcer, and heart disease. Usage of analgesic medication prior to surgery was stratified into two categories, namely, (i) if one ever used relevant medications for a period of more than 3 months, or (ii) use them for <3 months, e.g., sulindac, celecoxib or tramadol.The study protocol was approved by the Research Ethics Committee of Dalin Tzu Chi Hospital (No. B10901022-1). At the study's initiation, researchers explained the purpose of study and its procedure to all participants. Signed informed consent was obtained after the patients understood and agreed to share their information with the research team. Thereafter, the authors applied an observer-blind approach for data collection. A trained interviewer, who was not familiar with participants or with the study design, was assigned to collect all information pertaining to the outcomes and covariates. All data were obtained at four time points after surgery, namely at 12, 24, 48, and 72 h. All participants were followed from the date of enrollment until the end of the follow-up and were given the option to withdraw from the study at any time without any penalty.t-test and χ2 test as applicable. To evaluate the effect of treatment on the two groups, across the entire follow-up period, the generalized estimating equations (GEEs) procedure was utilized to assess the change pattern of NRS and Barthel Index. GEEs is a form of regression analysis which extends generalized linear models into a regression procedure with correlated observations within subjects. In a GEEs procedure, the standard errors of estimate are corrected for repeated measurement. In the present study, the baseline heterogeneity (differences existing before the intervention) between the experimental and control groups, and the maturation effects (changes in outcome variables resulting from the passage of time) were all controlled for by applying the GEEs method. All analyses were conducted using SAS statistical software, Version 9.3 together with SPSS 22.0. A p-value of <0.05 was considered statistically significant.Descriptive and inferential statistical analyses were conducted in accordance with the study aims. Descriptive parameters, including means, standard deviations and percentages, were used to describe the distributions of demographic and disease data. The baseline differences between the two groups were compared using A total of 68 patients who had lumbar spinal fusion surgery were enrolled in the study, with 36 in the PCA group and 32 in the parecoxib group. All 68 patients completed the follow-up material included in this study. Patients ranged in age from 40 to 76 years, with a mean of 60.6 years. Most patients were female (67.6%), employed (70.6%), and had low level of alcohol consumption (88.2%). The majority of patients had a monthly income of New Taiwan Dollars (NTD) ≤ 40,000 (52.9%) and reported having lower level of education . In terms of disease characteristics, most of the enrolled patients presented without comorbidities and had ever been prescribed the anesthetic medications used in this study, prior to their lumbar spinal fusion surgery (86.8%). The mean duration of pain experience prior to surgery was 2.93 years.p < 0.01)  .p < 0.01; p < 0.01). The subjects in the parecoxib group reported lower Barthel Index scores than those in the PCA group at baseline (p < 0.01)  . After cFor those with degenerative lumbar disease, lumbar spinal fusion surgery has become an increasingly common therapeutic option. A persistent challenge in a significant number of cases has been postoperative pain, leading to delay of early ambulation after surgery, thereby resulting in delayed recovery and increased risk of mortality , 5. CurrAfter adjusting for baseline differences between the two groups and for maturation effects, as determined by the GEEs model, it was observed that the perioperative administration of parecoxib was related to a higher level of postoperative daily activities, when compared to the PCA group. However, since no previous studies have been conducted comparing the impact of PCA and parecoxib, on daily activities no direct comparison of results is therefore possible. Notwithstanding, the positive effect of parecoxib use on physical activity observed in this study was consistent with findings of earlier reports, and adds to the growing body of literature on this topic , 21. It In the present study, those receiving parecoxib had a significantly greater reduction in pain score than those receiving PCA after adjusting for the baseline heterogeneity along with inherent mature effect, and this beneficial effect was maintained for 72 h after undergoing surgery, echoing the earlier study finding . SeveralIn a head-to-head comparison of the effects of parecoxib and PCA, regarding pain and daily activities, the GEEs model was used to adjust for baseline differences and temporal maturation effect, allowing for a more robust determination of the study findings. Several limitations, however, should be noted when interpreting the results. First, all participants were drawn from a single hospital in southern Taiwan, so inferences drawn from the results may not be generalizable to populations in other geographic regions. However, prior to the implementation of the study, the sample size required to ensure statistical power was calculated and the sample size used in this study may, therefore, be considered satisfactory for the data analysis undertaken. Previous studies also faced barriers to their generalizability, because of participants' restricted ethnicity, geographic location, nationality, and the nature of the medical data available, suggesting that this limitation is not unique to our study. Second, the application of an observational non-randomized study may have weakened the internal validity of the research. This is because the current study was not randomized and there may have been disparities between two groups in the surgerical procedures that were not measured to possibly affect the findings herein. Nevertheless, in this investigation, we employed the GEEs model to control for baseline differences between the two groups, and further considered the potential maturation effects; this approach differed from the priori conventional repeated measures and would likely reduce the probability of inflated type I error to some extent . FinallyAs far as the authors are aware, this is the first study to directly compare the different effects on pain and activities of daily living of the infusion of parecoxib and PCA, from a longitudinal perspective. After using the repeated measure of GEEs methodology, the results demonstrated that use of an intravenous infusion pump for parecoxib provided superior analgesic efficacy after lumbar spinal fusion surgery, when compared to PCA. As compared to use of PCA, using the parecoxib pump remarkably reduced the NRS scores throughout the 72-h study period, and patients who receive this treatment also reported higher levels of physical activity. This research provides evidence of the positive effects of Parecoxib use among those with lumbar spinal fusion surgery, particularly in terms of reducing postsurgical pain and facilitating movement.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Institutional Review Board and Ethics Committee of Buddhist Dalin Tzu Chi Hospital. The patients/participants provided their written informed consent to participate in this study.S-CC, J-CC, T-IC, and T-YT: study concept and design. S-CC, C-MC, and T-YT: acquisition of data. S-CC and T-YT: data analysis. J-CC and HH: project management. S-CC, HL, HH, T-IC, and T-YT: writing. All authors gave final approval of the version to be published and agreed to be accountable for all aspects of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Technical success, complication rate, pain evaluation using a visual analogue scale (VAS), Oswestry Disability Index (ODI) and local tumor control were examined. (3) Results: Technical success rate was 100%. No procedure-related major complications occurred. VAS score decreased from 6.8 ± 0.7 to 0.6 ± 0.6. ODI score decreased from 3.1 ± 0.7 to 1.2 ± 0.4. All patients could walk independently without neurological complication after one week from the procedure. No new bone fractures or local disease recurrence occurred during a median follow-up of 12 months. (4) Conclusions: Our results suggest that MWA and percutaneous pedicle screw fixation followed by vertebroplasty for the treatment of painful vertebral metastases is a safe and effective procedure for painful vertebral metastases with vertebral pedicle involvement, allowing pain relief and local tumor control. Vertebral metastatic disease is a very common and difficult “scenario” that causes severe morbidity in cancer patients, primarily due to the progressive onset of pain, instability, and neurologic deficit.Vertebral osteolytic metastases, in particular, cause pain and pathological fractures, with a significant reduction in quality of life and mobility. Most bone metastases have a negative impact on the patient’s short-term prognosis because bone lesions are rarely completely eradicated.Due to the poor response to conventional conservative therapies  and the frequent contraindications to surgery, interventional radiology (IR) treatment can play a critical role ,2. SeverVertebroplasty and kyphoplasty can help with bone lesion pain, but are usually not effective for mechanically unstable pathologic fractures involving the middle and posterior vertebral column. In these cases, it is necessary to perform a posterior screw fixation for structural spine stabilization.Once the patient has been selected, a pre-procedure study will be performed, and the most appropriate technique will be determined based on several factors such as the tumor’s structural features, extension, localization, and relationships with adjacent tissues. Radiofrequency, alcohol, interstitial laser, microwave, and cryoablation are all common ablative procedures ,11,12,13The purpose of the study is to evaluate the safety and efficacy of a novel combined technique of microwave ablation and CT-guided screw fixation followed by vertebroplasty (MASFVA) for the treatment of refractory painful vertebral metastases with an involved pedicle to enable synchronous local tumor debulking, pain reduction, and overall structural stabilization of the spine.This is a retrospective observational study; only existing information collected from human participants was used, and there are no identifiers linking individuals to data/samples. Institutional Review Board approval was obtained. All methods and procedures conformed to the ethical standards of the institution and the research committee, in accordance with the 2013 Declaration of Helsinki. Informed consent was obtained from all individual participants included in the study.Eleven patients  with 16 vertebral metastatic lesions  who underwent CT-guided microwave ablation and screw fixation followed by vertebroplasty (MASFVA) between January 2013 and January 2017 were included in the study. After 2017, we did not identify patients eligible for the procedure. Follow up and data collection were skipped in the period from 2019 to 2022 due to the COVID-19 pandemic. All patients had previously undergone radiation therapy in combination with chemotherapy. The clinical data of the patients included in the study are shown in The inclusion criteria were as follows: (a) presence of a lesion with evidence of histologic malignancy of vertebral metastasis that resulted in mechanical instability (infiltration of one or two pedicles), was radioresistant, adjacent to irradiation-sensitive structures and/or did not respond to chemotherapy at least 3 weeks prior to the ablation session; (b) complications associated with chemotherapy that required treatment discontinuation; (c) life expectancy greater than 2 months; and/or (e) ineligibility for surgical treatment and intractable back pain unresponsive to continuous treatment with opioids and nonsteroidal anti-inflammatory drugs (NSAIDs).The exclusion criteria were presence of primary spinal tumor, diffuse metastatic spinal disease, complete vertebral collapse (vertebra plana), extensive epidural and spinal canal infiltration , and moderate and severe neurologic deficits.The preoperative evaluation consisted of a combined oncology–radiology interventional clinical examination in the outpatient setting of interventional radiology. Pain severity was measured using the visual analog scale (VAS), which continuously rates pain on a scale of 0 to 10 to indicate pain intensity, and using the Oswestry Disability Index (ODI), with a score ranging from 0 to 5, where 0 corresponds to no difficulty or pain, while 5 corresponds to inability to perform daily activities. Both VAS score and ODI were performed in the follow-up of patients at 1 and 3 months after surgery.All patients underwent contrast-enhanced CT or MRI prior to the procedure to assess the location, size, and radiological characteristics of the lesions to proceed to intervention planning. The procedure was performed in a single vertebra in eight patients and in two vertebrae in three patients.The vertebral approach was unilateral with a single screw in four patients and bilateral with two screws in the remaining seven.A non-enhanced CT scan was performed immediately following the procedure to evaluate the results and any complications.Contrast-enhanced CT scans were acquired 3, 6 and 12 months after the procedure to perform radiological follow-up.If the patient showed persistence of pain, a complete X-ray of the spine in antero-posterior and lateral-lateral projection was also performed the day after the procedure to assess the overall biomechanical status of the spine.Drug therapy (NSAIDs and opioids) was discontinued 1 week after treatment and resumed in case of persistence or exacerbation of pain symptoms.Percutaneous bone microwave ablation (MWA) was performed under dual CT and fluoroscopic guidance to allow precise needle placement, increased operator comfort, proper visualization of fixation and local complications, and to avoid and monitor any leaks during vertebroplasty.CT acquisition data were: 5 mm collimation at 80–140 mA .The patients, in the prone position, underwent conscious sedation with continuous intravenous infusion of fentanyl citrate  and received local anesthesia including subcutaneous injection of 2% lidocaine hydrochloride. Anesthesia was planned in each case by the anesthesiologist who examined the patient prior to the procedure. Depending on the patient’s condition, the anesthesiologist could change the type of sedation (mild or deep). Pain was monitored according to vital signs.Preoperative antibiotic (a single dose of cefazolin 2 g) was administered intravenously 20–30 min before treatment.Percutaneous MWA was performed using a 2.45 GHz microwave generator  delivering energy through a 14-gauge, minichoked, water-cooled interstitial antenna (AMICA-GEN).If the metastasis was confined to the pedicle or ipsilateral half of the vertebral body, the lesion was effectively ablated using a single 14-gauge antenna.If the lesion exceeded the midline of the vertebral body, 2 MW antennas with bipedal access were placed to allow the best possible ablation of the entire lesion. The antenna length used for ablation was 20 cm in all cases.To preserve heat-sensitive anatomical structures, such as the spinal cord or nerve roots, one or more thermocouples were placed in the adjacent epidural space before starting ablative treatment.After insertion of the antenna into the lesion through a transpedicular access, the introducer was retracted to avoid interfering with microwave emissions from the active tip and to prevent overheating of the cannula during ablation, then energy delivery was initiated. During the ablation procedures, the thermocouple recorded no dangerous temperature rise (>45 °C) .n = 3), while in 85% (n = 19) two antennas were used.In 15% of the sessions, a single antenna was used  through the cannulated screw that has holes on both sides and at the tip .In patients who had very extensive destruction of the vertebral body or in cases of bilateral involvement of both pedicles, we performed treatment with the insertion of two screws in the same session.If the lesion exceeded the midline of the vertebral body, a vertebroplasty was also performed in these lesions to allow adequate vertebral cementation.In 4 cases, screws were placed in both infiltrated pedicles, while in the remaining 7 cases, only one screw was placed.After the procedure, a non-enhanced CT scan was performed, and the patients were immediately transferred to the recovery room for observation.p value less than 0.05 was considered significant. Statistical analysis was performed with OpenStat software.For the purpose of this study, continuous variables were reported as mean ± standard deviation (SD). Differences between mean VAS and ODI scores at baseline and at 1, 3, 6 and 12 months post-procedure were assessed by Student’s exact test or Fisher’s exact test, as appropriate. A In all cases, we observed the technical success of the MASFVA technique, defined as the ability to complete the procedural sequence of vertebral lesion ablation with correct screw placement without significant cement leakages. Minimal cement leakage, defined as para-vertebral, small, and asymptomatic, occurred in 3 out of 11 patients (27%), with no clinical repercussions.The overall mean duration of the percutaneous microwave ablation procedure followed by screw fixation and vertebroplasty was 63 ± 18 min.Post-procedure CT scans (without contrast enhancement) showed no major complications, such as bleeding, incorrect screw position, or cement leakage .Only 2 of the 11 patients (18%) complained of moderate pain on the postoperative day.All patients were discharged 24 h after treatment in stable condition and without complications.One week after the procedure, in clinical evaluation, all patients could walk independently and showed no signs of neurological complications. This condition persisted during the median follow up time of 1 year. Mean VAS pain assessment score on the day before treatment was 6.8 ± 0.7 .p < 0.000).One month after treatment, the median VAS pain score was 1.7 ± 1.0  with a mean reduction of 75%  compared with the baseline assessment.At the 3-month assessment, the median VAS pain score was 0.6 ± 0.6  with a mean reduction of 92% .p < 0.000).One month after treatment, the median ODI score of disability was 1.4 ± 0.4  with a mean reduction of 55%  compared with the baseline assessment  with a mean reduction of 62% (6.8 ± 0.7 vs. 0.6 ± 0.6; sessment .No infectious complications were observed during follow-up.None of the patients died from disease progression during the considered follow-up.Contrast-enhanced CT scans performed 3, 6, and 12 months after the procedure showed no local recurrence, loosening of the screws, or new fractures in the treated site.The skeleton is the third most frequent site for metastatic localization, ranking third after the lung and liver, and metastatic bone disease is the most common malignant disease of the bone.In addition, spinal metastases are the most frequently encountered spinal tumor, can affect up to 50% of cancer patients, and cause various symptoms and disability.When metastases are localized to the spine, painful or pathological fractures may be accompanied by instability and severe clinical disability when the lesion extends to the posterior spine .In the treatment of vertebral metastases there are many systemic clinical tools that are commonly used, and the main ones are chemotherapy, radiotherapy, hormone therapy, bisphosphonates, and analgesics .Open surgical treatment, which consists of decompressive laminectomy with long-level screw fixation and bone fusion, is indicated in cases of obvious spinal instability, clinically significant neural compression secondary to retropulsed posterior somatic wall or spinal deformity, intractable pain unresponsive to nonsurgical measures, and radiotherapy failure, but it is often of limited benefit in the management of spinal metastases due to its morbidity .Some histological forms of bone metastases, such as those arising from sarcoma, renal cell carcinoma, non-small cell lung carcinoma, and melanoma, respond less well to radiotherapy . FurtherIn a previous study, we have already evaluated as effective and safe the use of combined treatment of radiofrequency ablation with a steerable device and vertebroplasty for the management of painful bone metastases, resulting in improved patient quality of life .A systematic review of the literature conducted by Sagoo et al.  on the uIn our study, vertebroplasty has always been performed because of the intrinsic characteristics of cement both in reducing tumor, due to the cytotoxic effect from the direct exothermic reaction of cement, and in reducing pain because, together with screw fixation, it allows us to reduce pain by stabilizing fractures by acting on the interosseous sensitive fibers ,24.However, vertebroplasty usually has a limited role in mechanical support and is not effective in treating unstable spinal metastases that extend to the posterior elements, and posterior instrumentation must be inserted to stabilize the spine due to advanced cancer-related instability . GiammalThe novelty of our study concerns percutaneous screw fixation, as there are no studies in the literature regarding the combined approach of MWA and percutaneous pedicle screw fixation followed by vertebroplasty. Screw fixation is increasingly used as a minimally invasive method of fixation for the treatment of lumbar and thoracic spine disorders and is now performed percutaneously with interventional radiology techniques using cannulated screws . PercutaOur study has some limitations. It is a retrospective study, and only patients who underwent the combined MWA and pedicle screw fixation followed by vertebroplasty were included, so a comparison between the outcomes of this novel procedure and other approaches was not feasible. The small sample size and the short follow-up period did not allow the evaluation of late oncologic outcomes and quality of life.However, we believe that this is a promising new approach for the minimally invasive treatment of spine metastases combining tumor debulking, pain reduction, and increased stability of the spine.This preliminary result suggests that combined MWA and pedicle screw fixation followed by vertebroplasty is a safe and effective procedure which allows us to reduce the tumoral tissue, stabilizing the vertebral metastasis with significant pain relief and good recovery of walking capacity. This technique seems to be a promising alternative for patients with pain and unresponsive to conventional treatments that are not candidates for surgery. However, further studies with large series are required to confirm these preliminary results.


Though the incidence, characteristics, and pathogenesis of chemotherapy induced peripheral neuropathy (CIPN) by taxane based chemotherapy were extensively studied, diagnostic guidelines extent only recently.To observationally investigate whether specific tests can be used to predict and monitor CIPN severity.Fourteen female breast cancer patients receiving paclitaxel or docetaxel were evaluated using the McGill Pain Questionnaire (MPQ), National Cancer Institute Common Toxicity Criteria (NCI‐CTC) grading, clinical total neuropathy score (TNSc), quantitative sensory testing (QST) of pressure pain threshold (PPT), and numeric rating scale (NRS) scores and stocking and glove distribution testing (SGDT), at the start (T0), midst (T1), and end (T2) of their treatment and after 3 months (T3).not caused by CIPN. Pain, if present, was denominated “tingling” and “cold” in the MPQ. Median TNSc score increased from T0 (2.43) to T1 (4.71) to T2 (5.50) to T3 (5.57), as did pinprick and cold sensation disturbances in SGDT. PPT and associated NRS remained unchanged. TNSc and SGDT at T1 could not predict the NCI‐CTC grade at T3.At T3, patients scored NCI‐CTC neuropathy grade 1 (14.3%), 2 (64.3%), and 3 (14.3%) respectively. Fifty percentage scored at least grade 1 at T0, with complaints NCI‐CTC, TNSc, and stocking and glove distribution testing can be used in the early diagnosis and monitoring of CIPN, with false‐positive findings at baseline. Final NCI‐CTC grades could not be predicted. Treatment can comprise (a combination of) surgery, radiotherapy, chemotherapy, monoclonal antibody therapy, and hormone blocking therapy, depending on disease stage and specific gene expression.While a good target for antineoplastic drugs, microtubules (intracellular structures involved in movements in eukaryotic cells and in mitosis) play a role in the pathogenesis of CIPN by taxanes .Usually they are in a state of dynamic instability, a process dependent on (de)polymerization during which the ends of microtubules switch between phases of growth and shortening.Since the introduction of taxanes, the incidence, and characteristics of CIPN have been extensively described, using different scales for grading . All grade neuropathic symptoms between 0 (no symptoms) and 4 , grade 3 usually triggering chemotherapeutic agent dose correction.In this prospective and observational feasibility study we evaluate clinical tools for screening, early diagnosis and evaluation of CIPN in breast cancer, evaluating pitfalls and practicality of their application by comparing results for different tests and points in time. For broad application, tools should be easy to use, widely available and validated. Therefore, we selected questionnaires and neurological tests meeting these criteria: McGill Pain Questionnaire Dutch Language Version (MPQ‐DLV), NCI‐CTC, clinical version of the total neuropathy score (TNSc), quantitative sensory testing (QST) of the pressure pain threshold (PPT), and stocking and glove distribution testing (SGD testing).22.1For this prospective observational cohort study, patients were recruited and assessed in the Alexander Monro breast cancer institute's outpatient clinic in Bilthoven between February 2017 and October 2017.The study protocol was reviewed and approved by the regional ethics committee (CMO Regio Arnhem‐Nijmegen). Written informed consent was obtained from all patients for participation in the study and publication of anonymous data. Standard care was provided. The STROBE statement checklist for observational studies (cohort) was followed if applicable. The data that support the findings of this study are available from the corresponding author upon reasonable request.2.2Of 21 screened women, we included 16 female patients diagnosed with of breast cancer scheduled for treatment with taxane based chemotherapy, aged 18 years or older. Patients with a history of chronic pain, pre‐existing neuropathy, a history with risk factors for polyneuropathy  or not able or willing to give informed consent, were excluded.2.2.1Fourteen out of sixteen included subjects were interviewed and neurologically assessed four times during chemotherapy cycle: at the start (T0), midst (T1), and end (T2) and after 3 months (T3). At baseline, age, ethnicity, medical history, height, weight, current medication, tumor characteristics, and treatment characteristics were recorded. At each assessment point patients filled out the MPQ‐DLV, the NCI‐CTC grade and TNSc were determined, and QST of PPT and SGD testing took place. A NCI‐CTC grade of CIPN at T3 was considered the final outcome of severity. For the further tests, their predictive value at earlier stages for the NCI‐CTC grade at T3, and thus long‐term severity, was investigated.2.2.2The Indication for Common Toxicity Criteria Grading of Peripheral Neuropathy Questionnaire (ICPNQ) was used to determine the severity of CIPN on the NCI‐CTC scale, grading 1 (sensory changes or pain), 2 (any autonomic symptoms or subjective motor weakness), 3 (symptoms lead to ADL impairment), or 4 (ADL dependency).2.2.3The McGill pain questionnaire consists of 20 groups of words, each containing three to four adjectives used to describe pain sensations, of which patients choose a maximum of 1 per group. The adjectives can be categorized in one of three dimensions of pain: sensory, affective, or evaluative dimensions. These descriptions form the core of the MPQ, although the questionnaire also contains questions about the influence of the pain on quality of life (QoL), visual‐analogue scale (VAS) for pain intensity, and questions about location and course of the pain. To obtain insight in pain characteristics (if present), only the list descriptive words from the MPQ‐DLV, was used.2.2.4The TNS has been validated against other oncological grading scales for peripheral neurotoxicity . The shortened TNSc, used in this study, includes evaluation of sensory symptoms, motor symptoms, autonomic symptoms, pinprick sensibility, vibration sensibility, strength, tendon reflexes, scoring 0–4 on 7 items. It has a positive correlation with the NCI‐CTC grading system and an even higher sensitivity to CIPN changes.Severity of sensory, motor, and autonomic symptoms were evaluated by asking patients for localization of symptoms, extent of limitation and number of symptoms, respectively. Pinprick sensibility was tested in the upper and lower extremities. Vibration sense was tested by placing a vibrating tuning fork  on bony prominences of the upper  and lower extremities , bilaterally. If vibration sense in the most distal testing point was not disturbed, more proximal points were not tested and assumed to be normal .2.2.5Patients with neuropathic pain often develop mechanical hyperalgesia.2.2.6Sensory CIPN symptoms in patients treated with taxanes often emerge in a stocking and glove pattern.2.3n) and mean ± SD/median–interquartile range (range) for averages. Non‐continuous changes in NCI‐CTC, TNSc, and NRS were assessed with the Friedman test and χ2. Mean PPT and maximum NRS were used for each anatomical site at any point in time, and the length of the affected area  for SGD testing and further analyzed using one‐way analysis of variance in normal distribution  and sphericity . For prediction of NCI‐CTC grade at T3, ordinal regression analysis was used. p values <.05 in two‐tailed tests of significance, are considered significant.Statistical analyses were performed using IBM SPSS Statistics 22 for Windows. Descriptive statistics were used to describe patient characteristics and to report the results of the MPQ, NCI‐CTC grades and SGD testing, resulting in number of cases  and then a second analysis to compare the outcomes of the patients tested at T3 with their previous outcomes (within subject comparison).3.1n = 7) or 2 (n = 2) at T0. Complaints of sweating (n = 3) were reported to be related to previous treatment with Doxorubicin and Cyclophosphamide (n = 2) and/or were present only locally after breast‐ and axilla surgery (n = 2). The scoring of urinary disfunctions , sensory changes  and positional dizziness related to low blood pressure and/ or low hemoglobin levels (n = 1) were all unrelated to (CI)PN.CIPN grade distribution at each measuring time are shown in Figure At T1 two of the patients suffered of grade 1 neuropathy, 10 patients of grade 2 neuropathy, and the remaining two patients had no neuropathy symptoms. Grade 2 neuropathy was mainly caused by autonomic symptoms as bladder dysfunction, palpitations, increased sweating and subjective weakness. Next to autonomic symptoms, patients mentioned the following sensory symptoms: dull feeling, tingling, and pain in upper and lower extremities.n = 10). One patients with grade 3 suffered from bladder dysfunction, constipation, and increased sweating and a dull feeling and pain in extremities, impairing ADL.At T2 all patients experienced (substantively comparable) symptoms, of which the majority a grade 2 neuropathy  in some patients. Remarkably, the one patient with no neuropathy at T3 still had grade 2 neuropathy at T2. In all other patients no recovery was seen, their complaints either remained stable or worsened.χ2(2) = 17.105, p < .001). Post‐hoc analysis with the Wilcoxon signed‐rank test showed a significant difference from T0 (Mdn = 0.00) to T1 (Mdn = 2.00) , from T0 to T2 (Mdn = 2.00)  and from T0 to T3 (Mdn = 2.00) , but not between T1, T2, and T3 (p > .05).For NCI‐CTC there is a significant difference when comparing scores at T0 and T3 (3.2χ2(2) = 15.148, p = .001), as well as when comparing T0–T3 outcomes in the already tested subjects (χ2(3) = 19.324, p < .0005). Mean TNSc score ± SD (range) was 2.43 ± 1.09 (1–4), 4.71 ± 2.27 (1–8), 5.50 ± 2.68 (2–12), and 5.57 ± 2.53 (2–10) for T0, T1, T2, and T3 respectively.TNSc score was statistically significantly different at the various time points when comparing the outcomes at T0–T2 of the complete study population , T2 , and T3 , but not between T1, T2, and T3 (p > .05). Since the TNSc showed a significant difference when comparing T0 to T1, but there were no significant differences in TNSc between T1, T2, and T3, we used ordinal regression to test whether the TNSc score at T1 (as early as possible) could be related to NCI‐CTC‐scores at T3.Post hoc analysis with the Wilcoxon signed‐rank test revealed statistically significant differences in TNSc score between T0 and T1 (3.3p = .017) for all 56 measurements. Graphical representation of the different measurements (14 patients at 4 time points) in Table The correlation between NCI‐CTC grade and TNSc score was 31.8% (3.4At T0 three patients indicated to experience pain: two described it as “tingling” (left hand and right foot respectively) and one as “pulling” (left hand). At T1 again three patients had pain; the two patients with the “tingling” feeling still among them, although one now described the pain as “cold.” The patient with the “pulling” pain at T0 had no pain at T1. One patient had new onset of pain in the feet, described as “mild” and “pricking.” At T2 seven patients reported pain, mainly described as “tingling” and “tight.” At T3 5 out of the 11 patients still had pain, predominantly described as “tingling” and “cold.”3.5For all measurements in one specific subject PPT could not be found, because it was above maximum pressure. This patient was excluded from further analysis of PPT and NRS. Analysis with non‐parametric Friedman testing in the presence of multiple outliers, presented median PPT and NRS scores at the different measuring points and times, showed none of the QST measurements of PPT (at any measuring point and measuring time), as well as NRS‐scores, showed significant changes over time. Graphic presentation of these results are presented in Table 3.6Paresthesia usually starts at the most distal nerve endings (fingers and toes) and progresses proximally.χ2 = 9.14; p < .05) and lower extremities  and cold sensation in upper  and lower extremities  at T0, T1, and T2 for the complete study population. Results of post‐hoc Wilcoxon signed‐rank testing are presented in Table Friedman testing in the presence of multiple outliers and abnormal distribution, presented significant differences in outcomes for pinprick in upper χ2 = 9.1; p < .054This study shows that NCI‐CTC grading (as determined with ICPNQ) and TNSc were both able to find significant differences compared to baseline from T1 onwards. Thus with NCI‐CTC and TNSc early signs of CIPN can be identified. However, both scoring systems were unable to detect differences between T1, T2, and T3. So either there were no actual changes in CIPN severity after T1, or the tests were not sensitive enough to track subtle changes. Only recently, guidelines are published addressing the (early) diagnosis and evaluation of CIPN, partially due to difficulties interpreting scores in the presence of co‐morbidity, differences between scores .Additionally, nine patients showed signs of neuropathy according to NCI‐CTC at baseline, although pre‐existent neuropathy had been excluded. These patients scored “autonomic” symptoms related to co‐morbidity or earlier treatments in the absence of typical primary symptoms of CIPN, such as sensory disturbances. Therefore, the NCI‐CTC‐grading of CIPN using ICPNQ is not specific enough as a baseline denominator. In accordance to this, Beijers et al. showed that the sensory and motor subscales of the ICPNQ had adequate internal consistency, but the autonomic subscale did not.The use of TNS(c) with neurological examination, can offer a solution in this motor symptoms misinterpretation. As mentioned, TNS and TNSc are more sensitive for CIPN changes than NCI‐CTC, as it incorporates objective and subjective measures.QST measurements of PPT at the trapezius muscle, rectus femoris muscle, thenar eminence, and abductor hallucis muscle could not find significant changes between measuring points. Pain sensitivity for mechanical stimuli (blunt pressure) did not change. However, some caution regarding the reproducibility of a handheld pressure algometer is in place, considering that pressure must be applied at the exact same spot in all patients and at all points in time. Lacourt et al. found that first‐measurement should be excluded as they yield higher thresholds compared to following measurements,SGD testing proved useful in the diagnosis of CIPN, as it was capable to detect significant differences compared to baseline and between other time points. It could therefore be used to monitor CIPN progress. Pinprick sensation disturbances became apparent from T1 onwards, while cold sensation disturbances started later at T2. This may be explained by the fact that the perception of pinprick pain is related to activity in A‐fiber nociceptors, while cooling the skin activates not only A‐fibers ánd C‐fibers.In analysis of the subgroup of patients that also received carboplatin treatment, emerging complaints of CIPN did not occur significantly more than in other subjects. In analysis of the subgroup that also received carboplatin treatment, emerging complaints of CIPN did not occur significantly more than in the other subjects. They were therefore included in the further analysis regarding the use of diagnostic tools. Theoretically however, they could influence the different scores, by the mechanisms and specific complaints to which they cause CIPN.Despite the small study population, this study addresses the possibilities as well as the pitfalls of different tests used in the (early) recognition and the monitoring of the progression of CIPN related complaints. For women with breast cancer receiving taxane based chemotherapy, NCI‐CTC and TNSc scales, as well as the “stocking and gloves” distribution of pinprick and cold testing abnormalities, but not (threshold) pinprick testing and associated NRS scores, are useful for determining the progression of CIPN symptoms. However, confounders influence (from baseline onwards) the definitive score. Mainly the scoring of autonomic and motor symptoms cause false positive scoring in relation to complaints caused by CIPN. These important pitfalls should be addressed when using these tests in clinical practice or research, and prevents proper guidelines to be developed for the (early) diagnosis and monitoring of CIPN. Review of the current literature, in combination with Delphi‐assessments, are useful for the formulation of an algorithm and current approach. For future research, the application to other chemotherapeutic agents, patients, and tumors and the possibility for prediction, should be addressed.In conclusion, this feasibility study shows that diagnostic tools should be used for the diagnosis of CIPN. A definitive approach cannot be formulated, due to the influence of confounders and lack of research addressing different cancer and chemotherapy types in relation to the wide variety of available tools.The authors have stated explicitly that there are no conflicts of interest in connection with this article.Frank van Haren: Conceptualization ; formal analysis ; supervision ; visualization ; writing – original draft ; writing – review and editing . Sandra van den Heuvel: Conceptualization ; data curation ; formal analysis ; writing – original draft ; writing – review and editing . Mandy Ligtenberg: Data curation ; writing – original draft . Kris Vissers: Conceptualization ; supervision ; writing – review and editing . Monique Steegers: Conceptualization ; supervision ; writing – review and editing .This study was performed in line with the principles of the Declaration of Helsinki. The study protocol was reviewed and approved by the regional ethics committee (CMO Regio Arnhem‐Nijmegen). In execution and publication of this study, the STROBE statement checklist for observational studies (cohort) was followed if applicable (included as such in Section