The treatment of first choice for lateral epicondylalgia humeri is conservative therapy. Recent findings indicate that spinal manual therapy is effective in the treatment of lateral epicondylalgia. We hypothesized that thoracic spinal mobilization in patients with epicondylalgia would have a positive short–term effect on pain and sympathetic activity.Thirty patients  with clinically diagnosed  lateral epicondylalgia were enrolled in this randomized, sample size planned, placebo-controlled, patient-blinded, monocentric trial. Pain-free grip, skin conductance and peripheral skin temperature were measured before and after the intervention. The treatment group (15 patients) received a one-time 2-min T5 costovertebral mobilization (2 Hz), and the placebo group (15 patients) received a 2-min one-time sham ultrasound therapy.p = 0.008) and skin conductance + 0.76 μS ± 0.73 (p = 0.000004) as well as a decrease in peripheral skin temperature by − 0.80 °C ± 0.35 (p < 0.0000001) within the treatment group.Mobilization at the thoracic spine resulted in significantly increased strength of pain-free grip + 4.6 kg ± 6.10 (A thoracic costovertebral T5 mobilization at a frequency of 2 Hz shows an immediate positive effect on pain-free grip and sympathetic activity in patients with lateral epicondylalgia.DRKS00013964, retrospectively registered on 2.2.2018.German clinical trial register  Lateral epicondylalgia, colloquially called tennis elbow, is a common musculoskeletal disorder within the working population between 35 and 55 years of age –3. It afThe treatment of first choice for lateral epicondylalgia is conservative therapy. Most patients will recover without surgery within 1 year after the first occurrence . A varieBialosky, et al.  proposedSo far, sympathoexcitation after SMT has been demonstrated in asymptomatic populations, as Petersen, et al.  showed aSome research indicates that there is also a sympathetic response after SMT in patient with musculoskeletal pain. There is a preliminary indication for an sympathoexcitation for patients with mechanical, unspecific neck pain –40, epicIn summary, there is evidence that SMT enforces measurable SNS activity in an asymptomatic population. Because there is little of evidence for such reactions among a symptomatic population , 43, thiWe hypothesize that a grade III spinal manual therapy directed to the ribs of T5 on the affected side with 2 Hz increases pain-free grip and excites peripheral sympathetic activity correlating with skin conductance increase and a skin temperature decrease in patients with lateral epicondylalgia humeri.The ethics commission in Salzburg/ Austria approved this research project with the official notice labelled 415-E/2158/4–2017. Written informed consent was obtained from all participants.Randomized, sample size planned, patient-blinded, placebo-controlled trial, monocentric, independent group design, intention-to-treat, trial.Patients were diagnosed and recruited at the elbow department - University Clinic of Orthopedics and Traumatology in Salzburg between May 2017 and December 2017. Women and men aged between 18 and 55 years with unilateral, acute and subacute (pain duration did not exceed 6 month) lateral epicondylalgia humeri were included. The clinical examination was carried out by an elbow expert, included following: inspection, palpation, range-of-movement, peripheral blood circulation, sensibility, motor activity, nerve bottleneck. Provocation tests for epicondylitis, one was required to be positive, were also included according to Vicenzino et al. : grippinAdditional exclusion criteria were predefined and retrieved anamnestic from patients’ case histories: bilateral elbow pain, osteoporosis, tumor diseases, history of operations on the elbow or thoracic spine, acute thoracic pain, pregnancy, oral anticoagulation, central pain medication, and biased to manual therapy. Patients were asked to avoid stimulating substances like caffeine before testing .Thirty patients  at a mean age of 45.1 ± 8.5 years met the inclusion criteria and gave written consent to participate  and labeled it. The subjects were placed with the cervical spine in neutral rotation with the arms next to the body and palms up. Fingertips and sensors were cleaned with a disinfectant containing 73.5% ethanol, and they were given sufficient time to dry before attaching the electrodes. Sensors were placed on the tip of the index and ring fingers, and the TEMP sensor was fixed to the palmar surface of the middle finger Fig. . SubjectA grade III mobilization, which is defined as a large-amplitude oscillating mobilization until the end of movement  of the rA sham ultrasound therapy (ultrasound gel and transducer with room temperature) was performed on the same segment as in the treatment group for 2 min. The setting and procedure were identical to those in the treatment group. Care was taken to ensure that no pressure was applied to the costovertebral joints in order to avoid a mechanical stimulus.PFG (in kg) was measured with a calibrated digital hand dynamometer, model KERN MAP 80K1S, Kern & Sohn GmbH, 72,336 Balingen-Frommern, Germany. Skin conductance (sampling rate: 32 SPS in microsiemens (μS)) and skin temperature (32 SPS in degree celsius (°C)) were measured with a biofeedback Nexus-4 device and BioTrace+ Software V2015B1, Mind Media B.V., 6049 CD Herten, the Netherlands.Sample size calculation: The importance of a sample size computation in this research area was pointed out by Farrokhyar, et al. . PFG wasRandomization: Based on the sample size planning, a randomization list was generated by using computer-generated random numbers and based on the random sorting method .Blinding: Patients were blinded to the allocation of the group. They did not know which group was the assumed efficient or the placebo treatment.p-value < 0.05 was considered statistically significant. All statistical analyses in this report were performed by use of NCSS [Data evaluation methods: Data consistency was checked, and data were screened for outliers and normality using quantile plots. Continuous variables were also tested for normality using the Kolmogorov-Smirnov test. Cross tabulation tables were used and analyzed with Fisher’s Exact test. After carefully testing all assumptions, a repeated measures ANOVA was done to test for group, time and interaction effects. Least significant different tests as post hoc tests were performed as one-sided as described in the sample size computation. The 95% confidence intervals for means were computed, and Whisker plots were used to illustrate the results. A  of NCSS  and STAT of NCSS .All 30 included subjects were randomized, tested and analyzed. The dropout rate was 0%. There were no immediate adverse effects or complications recorded. Long term adverse effects were not reported by the subjects themselves and not queried by the researchers as a follow-up was not planned.p = 0.77, one-sided)  Table . Generalp = 0.008, one-sided) .Within the treatment group, PFG significantly increased by 4.36 kg (95% CI: 1.8–6.92) from 17.74 kg to 22.10 kg (24.6%), which corresponds to an increase of side over time in the treatment group . There was no such change detectable in the placebo group . A significantly  greater SC was recorded for the treatment group comparing measurements at baseline and after intervention (Table The SC significantly increased by + 0.76 μS ± 0.73 (48%) from 1.58 μS at baseline to 2.34 μS after intervention on the affected side in the treatment group . There was no such change in the placebo group . No significant difference between the treatment and placebo groups was found after treatment (Table The TEMP significantly decreased by 0.80 °C ± 0.35 2.4%) from 33.94 °C to 33.14 °C on the affected side after treatment (.4% from This study investigates the short-term effects of thoracic mobilization on PFG and SNS activity in patients with lateral epicondylalgia.There are consistent findings concerning pain-free grip changes in patients with lateral epicondylalgia. Fernandez-Carnero, et al.  detectedVicenzino, et al.  recordedOther authors suspected a connection between pain at the lateral elbow and pain in the cervical or thoracic spine regarding lateral epicondylalgia as not just a localized pathology , 58. SucAccording to the improvement of peripheral outcome measures, our finding leads to the conclusion that thoracic spinal mobilization activates the body’s own descending pain inhibitory mechanisms in patients with lateral epicondylalgia. This effect goes beyond local mechanisms of pain inhibition and is widely discussed in the current literature , 25, 57.There are some limitations to this study. First, we only investigated the immediate effect after a thoracic mobilization and abstained from collecting SNS follow-up data in favor of collecting pain-free grip data as soon as possible after the intervention. We are aware that skin conductance and skin temperature are some kind of notorious for their liability and that there are also other measurement parameters like heart rate variability or salivary cortisol levels. Regardless that fact we decided for the parameters used as they are easy to access and also might be side specific . Second,The strength of our study is the planned sample size, randomization and patient blinding. Sample size calculation is important to detect differences with appropriate power . We wereThoracic costovertebral T5 mobilization at a frequency of 2 Hz has immediate unilateral positive effects recorded as an increase in pain-free grip and sympathetic activity in patients with lateral epicondylalgia. Because this is the first study on thoracic mobilization in a population with lateral epicondylalgia, there is a need for further investigation. As cervical and thoracic SMT seem effective, they are of interest, as they could have a greater impact on pain and SNS activity. Furthermore, the long-term effects of SMT techniques have to be included in future investigations.


Hence, we have obtained a validation of the prototype Anspec-pro which performs equally well as the commercial device under similar conditions.Although the measurement of dielectric properties of the skin is a long-known tool for assessing the changes caused by nociception, the frequency modulated response has not been considered yet. However, for a rigorous characterization of the biological tissue during noxious stimulation, the bioimpedance needs to be analyzed over time as well as over frequency. The 3-dimensional analysis of nociception, including bioimpedance, time, and frequency changes, is provided by ANSPEC-PRO device. The objective of this observational trial is the validation of the new pain monitor, named as ANSPEC-PRO. After ethics committee approval and informed consent, 26 patients were monitored during the postoperative recovery period: 13 patients with the in-house developed prototype ANSPEC-PRO and 13 with the commercial device MEDSTORM. At every 7 min, the pain intensity was measured using the index of Anspec-pro or Medstorm and the 0–10 numeric rating scale (NRS), pre-surgery for 14 min and post-anesthesia for 140 min. Non-significant differences were reported for specificity-sensitivity analysis between ANSPEC-PRO (AUC = 0.49) and MEDSTORM (AUC = 0.52) measured indexes. A statistically significant positive linear relationship was observed between Anspec-pro index and NRS (r Pain is considered a subjective feeling  with objective roots  . Then, iIntraoperative analgesia or postoperative pain management requires to optimally be driven by an objective assessment of the patient’s status, for avoiding the complication of intraoperative awareness that continues to occur or for limiting the negative impact on postoperative hospital length of stay and costs ,5. SeverCNS [Although several commercially devices ,8,9, as CNS ,15) or tCNS ). MoreovCNS . Time-frCNS . The ratCNS ,20. The The aim of this pilot study is to validate our impedance-based methodology for postoperative pain evaluation. We primarily test the hypothesis whether the nociception measured by Anspec-pro is correlated with the standard tool . Our secondary hypothesis is that the specificity and sensitivity of Anspec-pro is similar to an existing device based on a similar approach (skin conductance measurement), namely MEDSTORM. The skin sympathetic nervous system and emotional sweating, mirrored by skin conductance response have been previously reported to assess pain in patients, post-operatively  as well As such, the focus of the study is not to perform a comparison analysis between the developed prototype and the commercial device. We need to validate Anspec-pro with an already approved device that is based on similar methodology, under the same conditions. On long term, our methodology will enable evaluation of pain by means of mathematical models which can be then included in a fully automated drug delivery for anesthesia system ,25,26,27clinicaltrials.gov . This manuscript adheres to the applicable recommendations of Strengthening the Reporting of Observational studies in Epidemiology (STROBE) statement [The prospective observational study was approved by the Ethics Committee of Ghent University Hospital (Protocol code: EC/2017/1517). The study has been registered before patient enrolment at tatement .Written informed consent was obtained from each patient during their preoperative consultation with the anesthesiologist. The course on Good Clinical Practice (GCP) has been completed by the sponsor and each technician  that were operating the devices during this clinical trial for data collection.The trial was a cohort study performed between 24 April 2018 and 22 June 2018 at Ghent University Hospital, Belgium. The patients included in the study were randomly chosen from the list of the patients that were planned to have a surgical operation under general anesthesia, considering inclusion/exclusion criteria approved through the protocol. The principal investigator evaluated the eligibility for the patient’s enrolment, informed the prospective patient about the trial, and obtained the informed consent. The patient allocation was made following simple randomization procedure to 1 of the 2 monitoring devices, using sealed opaque envelopes. On the day of surgery, the principal investigator assigned the participants by asking them to choose between 26 identical envelopes in which the Anspec-pro or the Medstorm choice was inside (13 envelopes with Anspec-pro and 13 envelopes with Medstorm). Patients were informed about the result and saw the monitor before starting the procedures.The inclusion criteria were as follows: (i) age between 18 and 75 years old, (ii) patients able to comprehend, sign and date the written informed consent document to participate in the clinical trial, (iii) patients planned for a surgical procedure under general anesthesia and expected to need a strong analgesic, type opioid, like sufentanil, during the operation and (iv) American Society of Anesthesiologists (ASA) physical status Class I–III classified by the anesthesiologist.The exclusion criteria were as follows: (i) patients having epidural analgesia infused by a pain pump, (ii) patients with chronic pain or getting medication used for chronic pain, like antiepileptics, antidepressants, opioids; (iii) participation in a clinical trial within the past 30 days; (iv) operation planned at one of the upper limbs (so that placing together the blood pressure cuff and the electrodes of the pain monitor at the same upper limb would not be possible), (v) patients staying in daily hospital or in Intensive Care Unit and (vi) pregnant women (the patient was asked before the operation). It was stated that subjects must have been withdrawn under the following circumstances: (i) at their own request, (ii) if the investigator feels it would not be in the best interest of the subject to continue, and (iii) if the subject violates conditions laid out in the consent form/information sheet or disregards instructions by the clinical investigation personal.The surgical schedule of Ghent University Hospital was assessed in order to determine subjects who met the criteria for study enrolment. During all the three phases of the study , all patients received care after local standards in all groups and the routine monitoring was made. Care providers did not make changes to the used anesthetics based on the outcomes of Medstorm or Anspec-pro devices.The study protocol consisted of two periods of pain observation: (1) preoperative: in the waiting room the patient’s pain was assessed by NRS (self-report) and also by the pain monitor for 14 min; this data was used as a baseline for the measurements after the surgery; (2) postoperative: in Post-Anesthesia Care Unit (PACU), the pain was measured like usual, thus by NRS , but also by the pain monitor, continuously for 140 min. The measurement protocol is depicted in All patients of the two study groups had a general anesthesia during surgery. The performed procedures were abdominal, gynecology, otorhinolaryngology, and urology. The general anesthesia was done like standard care and the anesthetists chose the anesthetics and analgesics during the operation. All medications were registered in the digital medical file of the patient. No changes to the study protocol were made after trial commencement.The primary outcome parameters were the postoperative pain values, namely the Index of Medstorm, the Index of Anspec-pro, and NRS. In the statistical analyses, the indexes of Medstorm or Anspec-pro were considered dependent variables predicted from NRS values.Secondary endpoints were the vital parameters and the ratings of subjective conditions .Postoperative data collection included other candidate variables considered for statistical analysis: mean heart rate (HR) and non-invasive mean arterial pressure (MAP).The subjective conditions during the study have been reported for being considered in discussions and interpretation of results: GCS score , the movement of the patient, the location of the pain monitor electrode (left/right hand), all medications including dose and time of administration , medical and surgical history of the patient. The medications were important to be documented in order to further correlate them in future analysis with time-frequency changes in the measured impedance signal.Each variable of interest has been measured and collected through the same protocol. Data were derived from four sources: (1) the nociception index from the pain monitor (Anspec-pro or Medstorm), (2) the NRS value from the patient  or from the nurse, (3) vital parameters  from the electronic medical record, (4) every real-time observation that could influence the measurements from the device’s technician or nurse.For tracking NRS, the patients were asked to quantify their level of pain on a numeric rating scale (0–10). For the patients not fully conscious, the nurses reported the NRS value assessed for the patient based on their experience.Standard care and medication were given like usual pre-, peri-, and postoperative, estimated by the experience of the nurse from recovery room or the anesthesiologist. The choice of the pain monitor was done by randomization, after the patient agreed to be part of the study.Before the operation, the index from the pain monitor (after randomized selection), the NRS and the vital parameters have been continuously monitored for 14 min. The values of these variables were registered at each 7 min . The time interval has been selected together with the clinical investigator as an optimal interval for pain assessment. Hence, the choice of 7 min is also a trade-off between the limitations given by the technology and the clinically applicable interpretation. After this step, the surgery was performed according to normal clinical procedures, while the patient’s pain was not monitored with the pain device; the perioperative medications given to the patient were noted in the personal file. After the operation, the patient stayed in the recovery room, getting the standard care from nurses. To determine the correlation between the index given by the pain monitor and the NRS value, all these parameters have been continuously monitored for 140 min. Thus, at each 7 min, the index from the pain monitor, the NRS, as well as the vital parameters were noted .The primary endpoints (pain level) were measured using the randomly assigned nociception monitoring systems and NRS.TM, ref: MD1001 , which calculates the Skin Conductance Algesimeter [One monitor was MED-STORM PAIN MONITOResimeter . The monesimeter . For thiesimeter . IncominThe other monitor was ANSPEC-PRO , a new non-invasive pain monitor evaluated for the first time in a clinical trial . It has been previously validated on awake participants with self-induced nociceptor excitation, after informed consent was given . Anspec-Both devices Medstorm and Anspec-pro are non-invasive pain monitors. Monitoring was not blinded so that the observers could see the data collected curves and note when artifacts disturbed the registration. When the signal quality was distortional as a result of change of the integrity of the measured signal or temporary loss of connection, the event was registered as “artifact”, as were situations when the patient moved their measurement hand where the sensors were applied. In the case of Medstorm, the device’s software automatically decides if the signal quality was bad.Both nociception monitors measure bio-electrical data at the hand level, typically accounted as the appropriate location to detect the micro-fluctuations in skin electrical permeability (caused by the fill of plantar sweat glands under sympathetic control). Additionally, the post-operatory level of pain can be influenced by the level of traumatology of the surgery. Consequently, we carefully considered the type of intervention, including the part of the body concerned for the surgical procedure, as potential sources of bias. Measures were taken to reduce bias by selecting patients for enrolment that were planned for similar procedure types.Given the fact there was no comparable previous study (that includes Anspec-pro monitor), this was planned as a pilot trial.n (%), medians (interquartile ranges—IQR (range)) or mean (standard deviation—SD). Analysis of variance (ANOVA) was used for accessing the intergroup differences between the outcomes of the study.Statistical analysis was performed using Matlab Software (R2017a). Values are presented as number of patients 2). A receiver-operating characteristic (ROC) curve was built by plotting the sensitivity, or true positive rate, as a function of the false positive rate (1-specificity). The area under a ROC curve (AUC) represents the predictive ability of the test and should be at least 0.75 for good prediction. Statistical significance was accepted for p < 0.05.The relationship between two variables was described by two methods: correlation and regression analysis. The correlation analysis was performed based on the covariance as a measure of how much two random variables vary together. The values of the correlation coefficients (r) can range from −1 to 1, with −1 representing a direct, negative correlation, 0 representing no correlation, and 1 representing a direct, positive correlation. Linear regression was used to investigate if one variable can be predicted from another, by assessing the coefficient of determination  between the two groups.For statistical analysis, data from 22 patients was included. Subject demographics and characteristics are shown in p < 0.001). In addition, the vital parameters .The postoperative clinical data acquired in PACU is summarized in p = 1). No significant correlation was found between Anspec-pro index and HR  or Anspec-pro index and MAP . The correlation was statistically non-significant as well between Medstorm index and HR  or Medstorm index and MAP .The correlation analysis showed no significant relationship between the pain indexes from devices and NRS, neither in the Anspec-pro group nor in the Medstorm group  was observed between Anspec-pro index and NRS during the stay in PACU, with 15% of the variance in Anspec-pro index predicted by NRS, as seen in Medstorm= 0.12 − 0.004 × NRS, r2 = 0.004, p = 0.328), as depicted in A statistically significant positive linear relationship . Although the NRS is the golden standard nowadays to measure pain, we see that the ROC-curve for the two monitors is not conclusive, perhaps since both are sensitive to artefacts . Further adaptation of the software according to the physiological parameters, like including an NRS-guided algorithm may be an interesting next step.The results of this pilot study demonstrate that non-significant differences were reported for specificity-sensitivity analysis between ANSPEC-PRO and MEDSTORM measured indexes. Hence, we have obtained a validation of the prototype Anspec-pro which performs equally well as the commercial device under similar conditions. The AUC for Medstorm was 0.52 and for Anspec-pro it was 0.49. The correlation analysis showed no significant relationship between the pain indexes from devices and NRS, neither in the Anspec-pro group nor in the Medstorm group (with correlation coefficient r = 0.39 respectively r = −0.066). In addition, no significant correlation was found between Anspec-pro index or Medstorm index and the monitored vital parameters (HR and MAP). Even small, a statistically significant 15% of the variance in Anspec-pro index was predicted by NRS, while no statistically significant linear relationship was observed between Medstorm index and NRS , the difference is more intrinsically in the amount of data collected and post-processing. We hypothesize that the skin impedance is a dynamic system, where dynamic processes occur as a function of noxious stimulation and of opioid effects. By definition of system engineering principles of identification, characterization of a dynamic process requires a persistent excitation: in our case the multisine signal composed of sum of sinusoids in a bandlimited frequency interval. This allows to extract a transfer function of the process, i.e., a function which characterizes the dynamical processes taking place. A transfer function can never be defined by a single frequency point, as is the case with MEDSTORM. Hence, with ANSPEC-PRO, the user has more information to process, with a prospective higher degree of usefulness for clinical research. It was not our purpose to propose yet another pain monitor on the market, but rather to introduce the rationale and the means to the clinical research community for performing more in-depth analysis of the complex pain pathway monitoring process.Our study presents, however, some limitations. Factors such as postoperative cofounders  influence skin electrical properties in awake subjects. Additionally, our results may not be extrapolated to any category of patients .In conclusion, we merely wanted to verify that the proposed versatile instrumentation delivered by ANSPEC-PRO and methods used to extract information via skin impedance have meaningful clinical results. This assumption has been successfully verified as it delivers similar results to a commercial device, i.e., MEDSTORM. Through the availability of the ANPSEC-PRO instrumentation and methodology, there is a great opportunity to push-through technology and clinical state of art for pain monitoring and related research. Future research opportunities are related to the biomedical engineering domain through the analysis of the frequency response function which better characterizes the nociception dynamical process.


There were no complications associated with the balloon procedure. The present study suggests that balloon adhesiolysis for L5-S1 foramen via a contralateral interlaminar retrograde foraminal approach may be an effective alternative for patients with a high iliac crest and refractory lumbar radicular pain due to lumbar foraminal stenosis. In addition, detailed procedural aspects are described here.Several treatment modalities have been proposed for foraminal stenosis, but the treatment options remain unsatisfactory. Previous studies have shown that transforaminal balloon adhesiolysis may be effective in patients with refractory lumbar foraminal stenosis. However, in patients with a high iliac crest, balloon catheter insertion may be difficult via a conventional transforaminal approach (particularly targeting the L5–S1 foramen). It has been reported that an epidural catheter can be placed easily by a contralateral interlaminar retrograde foraminal approach. Therefore, we applied this approach to L5–S1 transforaminal balloon adhesiolysis in patients with a high iliac crest. We retrospectively analyzed data from 22 patients who underwent combined epidural adhesiolysis and balloon decompression  using the novel foraminal balloon catheter via a contralateral interlaminar retrograde foraminal approach. The pain intensity significantly decreased over the three-month period after balloon adhesiolysis ( Chronic lumbar radicular pain can adversely affect the quality of life. Transforaminal epidural steroid injection (TFESI) is one of the most common treatments for the management of chronic lumbar radicular pain, with or without low back pain (LBP), resulting from lumbar spinal stenosis, disc herniation, discogenic pain, and failed back surgery syndrome ,2,3. HowIn patients with a high iliac crest, it may be difficult to insert an epidural catheter via a conventional transforaminal approach (particularly at L5–S1), although transforaminal epidural injection of drugs is still possible. Therefore, when inserting a catheter into the L5–S1 foramen in patients with a high iliac crest, foraminal direction should be considered. Previously, Jeong et al. showed that an epidural catheter can be placed easily at the ventrocaudal aspect of the existing nerve using a contralateral interlaminar retrograde foraminal (CIRF) approach . PreviouTherefore, we applied the CIRF approach to L5–S1 transforaminal balloon adhesiolysis in patients with a high iliac crest. This study retrospectively analyzed outcomes after foraminal balloon adhesiolysis via the CIRF approach in patients who have high iliac crest with intractable lumbar radicular pain with or without LBP. In addition, we describe the detailed procedure for this alternative approach for L5–S1 foraminal balloon adhesiolysis. This retrospective study was conducted at the pain clinic at Asan Medical Center, Seoul, Republic of Korea. The necessity for informed consent was waived as only recorded data were reviewed. We reviewed the electronic medical records of patients for all necessary data that were itemized and recorded at their visits to the pain clinic. The study protocol was reviewed and approved by the Ethical Committee of Asan Medical Center , and the study was conducted in accordance with the Declaration of Helsinki.®, JUVENUI, Seoul, Republic of Korea, The records of patients who underwent balloon adhesiolysis using the novel foraminal balloon catheter with guidewire  chronic (at least 3 months) L5–S1 foraminal stenosis patients aged ≥ 50 years; (2) lumbar radicular pain, with or without LBP, with an intensity ≥ 6 (out of 10) on the numerical rating scale (NRS); (3) patients unable to access the area of L5–S1 foraminal stenosis by conventional transforaminal technique because of the presence of a high iliac crest; (4) confirmed diagnosis of moderate or severe foraminal stenosis by magnetic resonance imaging (MRI) ; and (5)The exclusion criteria were as follows: (1) aged < 50 years; (2) acute pain for < 3 months; (3) could not exclude a confounding diagnosis of vascular disease or a disease of another origin; (4) signs of progressive neurological deficits or motor weakness; (5) allergies to steroids or contrast dyes; (6) uncontrollable or unstable opioid use; (7) coagulopathy; (8) systemic or injection site infection; (9) unstable medical or psychiatric condition; and (10) malignancy.All patients underwent the same ballooning procedure in the area of foraminal stenosis by the methods described below. The balloon adhesiolysis procedure was performed by two well-trained pain specialists. The foraminal balloon catheter with guidewire was the same as that used in our previous study . The intBy using caudal tilt on the fluoroscopic view, we obtained a single contour of the upper endplate of the target vertebra. The target interlaminar space was checked in an anteroposterior fluoroscopic view. To simulate the guide needle and balloon catheter pathway, a surface marker . If air remained in the balloon catheter, the radiographic image could have some air artifact, which can be mistaken for a stenotic lesion. As shown in After confirming that the needle was positioned in the ipsilateral epidural space, a 2-Fr foraminal balloon catheter containing a removable guidewire was inserted in a caudal direction. The balloon catheter was steered to the lower aspect of the pedicle into the ventral epidural space and the neural foramen with foraminal stenosis , the patients were discharged.At the first visit (baseline), all patients were taught to use an 11-point NRS (0 = no pain and 10 = worst possible pain) to assess the intensity of lumbar radicular pain with or without LBP. The patients were followed up in the outpatient department of our pain clinic at 1, 3, and 6 months after the procedure. NRS pain scores were routinely obtained on follow-up. The data, including age, sex, height, weight, underlying disease, history of previous lumbar surgery, MRI finding, dermatome of radicular pain, complication of procedure, and additional procedure during follow-up periods were collected from electronic medical records. Continuous variables are presented as means with standard deviation. Statistical analyses were conducted with repeated-measures analysis of variance using SPSS Statistics version 21 .2, respectively. In total, 12 (54.5%) patients had comorbidity or underlying disease. There were six (27.3%) patients with hypertension and five (22.7%) patients with diabetes mellitus (DM). Other diseases included hepatitis B virus liver cirrhosis, asthma, Raynaud syndrome, and coronary artery syndrome. Two (9.1%) patients had a past history of lumbar spine surgery; patient B underwent L3-5 laminectomy and discectomy, and patient H underwent L3–4 posterior lumbar interbody fusion (PLIF) surgery.In total, 22 patients underwent foraminal balloon adhesiolysis using the novel foraminal balloon catheter in areas of foraminal stenosis in our institution between May 2016 and November 2018 in accordance with the inclusion and exclusion criteria. These 22 patients were retrospectively analyzed in the present study, and the patients’ demographic characteristics are shown in p < 0.001). However, six (27.3%), six (27.3%), and four (18.2%) patients had no pain improvement (NRS < 2) at one, three, and six months after the balloon adhesiolysis procedure compared to baseline. The number of patients with minimally important (≥ 30% or ≥ two-point decrease of NRS) and significant changes (≥ 50% or ≥ four-point decrease of NRS) in pain intensity were 18 (81.8%) and 13 (59.1%) at six months, respectively.L5–S1 foraminal stenosis was found in all patients, and 17 (77.3%) patients also had lumbar central stenosis. The direction of symptoms was the left for 17 (77.3%) and right for 5 (22.7%) patients . The meaThere were no complications associated with the balloon procedure. During follow-up after balloon adhesiolysis, 7 (31.8%) patients underwent additional procedures. TFESIs were performed in four patients during the follow-up period. Two patients received medial branch blocks one month after the balloon procedure following pulsed radiofrequency (pRF) treatment to the medial branch three months after follow-up. One patient underwent TFESI one month after the balloon procedure and additional pRF to the L5 dorsal root ganglion because of continuation of symptoms .®, JUVENUI, Seoul, Korea) is commonly used for percutaneous epidural adhesiolysis via a caudal approach [Epidural adhesion can play a key role in the development of chronic lumbar radicular pain and/or LBP ,6,18, anapproach ,10,12. HPrevious studies suggested that the use of a retrograde interlaminar dorsal epidural approach with ventral epidural catheterization may be an effective approach to deliver medication to the target site ,15,20. APrevious studies suggested that, in comparison with conventional TFESI, drugs can be delivered more effectively to the target site by retrograde interlaminar ventral epidural injection, usually at the ventral aspect of the nerve root sleeve, dorsal aspect of disc herniation, or stenotic lesion ,20. MoreHowever, foraminal balloon adhesiolysis via the CIRF approach was less effective in five 22.7%) patients in this study. Patient C had no symptom improvement one month after the procedure and was additionally underwent TFESI. This might be because of DM neuropathy causing negative neuropathic symptoms. Patient H, who had previously undergone L3-4 PLIF, was not satisfied with symptom improvement and a TFESI was performed one month after follow-up; symptoms persisted at three months, and L5 pRF was conducted. Patient L did not respond at all for three months after the procedure because of DM neuropathy, and was subsequently treated with a small ketamine infusion. The symptoms of patient N also persisted, but the patient refused further interventional procedure and wanted to be treated with medication only. Patients R and S had minor symptom improvement and a medical branch block was additionally performed at one month after balloon adhesiolysis because the facet joint syndrome with axial pain became more pronounced during follow-up. After the diagnostic block confirmed co-existing facet joint syndrome, pRF of medial branch nerve was performed at the three month follow-up. These failed cases suggest that correct diagnosis and patient selection for balloon adhesiolysis is important. Indeed, previous reports have already demonstrated that factors associated with the outcome of balloon adhesiolysis for the management of chronic lumbar foraminal stenosis may be diabetes, combined LBP with lumbar radicular pain, degree of lumbar foraminal stenosis, the number of target levels, and a degenerative herniated intervertebral disc ,13,21,22.7% patieThis study had several limitations. First, this study was a retrospective study without a control group. This was not blinded, well-designed, or well-controlled. Second, two pain specialists treated all patients in this study, and some deviation of the described techniques may be present. Third, no other outcome measure tool except for pain intensity was used to assess the effectiveness of balloon adhesiolysis. Furthermore, the functional effect of the balloon adhesiolysis and medication effect were not considered in this study. Lastly, the analyzed sample size in the present study was small. This small sample size may be associated with no complications observed after the foraminal balloon adhesiolysis. More well-designed randomized controlled trials in the future will yield more reliable results about the effectiveness of this procedure.In conclusion, the present study suggests that balloon adhesiolysis via a CIRF approach may be an effective alternative option for patients with a high iliac crest and refractory radicular pain due to lumbar foraminal stenosis.


Patients with spinal fusion often have opioid tolerance and chronic pain, which makes it difficult to control postoperative pain. In this double-blind, randomized, prospective study, we assessed the safety and efficacy of intravenous low-dose ketamine for the treatment of pain in patients undergoing the lumbar spinal fusion.P < .05 was considered to be the statistically significant. The Statistical Package for the software of Social Sciences 20.0 was utilized for statistical analysis.This randomized, prospective, double-blind and placebo-controlled study was approved via the hospital institutional review committee. Patients were registered with signed written consent. All the floor nurses, recovery room and surgeons, patients, statisticians as well as research assistants were unaware of the grouping. The patients were randomly divided into ketamine group and control group by random number table. Nausea, vomiting or vomiting, the intensity of pain, adverse events, cumulative morphine consumption, as well as the amount of extra antiemetics or analgesics were evaluated at 6 hours, 12 hours, 24 hours, 36 hours, and 48 hours after the operation. For the present trial, we assumed that intravenous ketamine could improve the satisfaction of patient by reducing the total consumption of morphine equivalent and the pain scores.This study protocol was registered in Research Registry (researchregistry5896). Postoperative pain may also affect other aspects of treatment such as restriction of limbs motility or ventilation.–4The management of postoperative pain in patients with chronic pain remains a huge clinical challenge. Patients with spinal fusion often have opioid tolerance and chronic pain, which makes it difficult to control postoperative pain. Ketamine has immunosuppressive effects, antioxidant, and anti-inflammatory. The action mechanism of ketamine is related to the binding of phencyclidine site to glutamate receptors. Glutamate mediation effect determine its neuroprotective, dissociative and analgesic effects. Ketamine is now extensively utilized as a non-opioid analgesic for spinal fusion, reducing the need for opioids. Despite the ketamines benefits, the use of ketamine can present major challenges, including delirium, which appears in almost 50% of patients after the ketamine administration.Ketamine is a kind of intravenous anesthetic agent and a noncompetitive blocker for the N-methyl-D-aspartate receptors.–15 Nevertheless, ketamine has not yet been authorized via the Food and Drug Administration to decrease the demands for opioids. Thus, the safety and effectiveness of low-doses ketamine in the spinal fusion need to be further investigated. In this double-blind, randomized, prospective study, we assessed the safety and efficacy of intravenous low-dose ketamine for the treatment of pain in patients undergoing the lumbar spinal fusion. Although ketamine is administered by different routes, the side effects can be better controlled by intravenous administration because of its lower half-life. We assumed that intravenous ketamine could improve the satisfaction of patient by reducing the total consumption of morphine equivalent and the pain scores.The clinical researches have indicated decreased opioid demands after operation and improved the pain control in patients with opioid tolerance with intra-operative injection of ketamine.22.1This randomized, prospective, double-blind and placebo-controlled study was approved via the institutional review committee of Handan Central Hospital (HBHD70442). Prior to registration, this trial has been registered with the Research Registry (researchregistry5896). Patients were registered with signed written consent. All the floor nurses, recovery room and surgeons, patients, statisticians as well as research assistants were unaware of the grouping. Only the nurses in operating room were not blinded.A prospective study were conducted in patients aged from 16 to 75 years and ASA physical condition 1 to 3 years who planned to undergo the elective lumbar fusion under the condition of general anesthesia. Exclusion criteria included poor control of hypertension, serious pulmonary or cardiac disease, severe renal or hepatic insufficiency, and elevated intraocular pressure, pregnancy, with the history of mental disorders, inability to operate patient-controlled analgesia pump, understand numerical pain scale, and speak Chinese, known allergies to hydromorphone or ketamine.2.2The patients were randomly divided into ketamine group and control group by random number table. And group assignment was assigned in opaque envelopes with sequential numbers. On the operation day, a nurse who was not involved in the evaluation or management of the patient opened the envelope and then prepared the ketamine or an equivalent amount of the normal saline as assigned. Before the end of this research, the assignments of group are not made public to researchers or patients Fig. .2.3Each patient was given a standard protocol of general anesthesia. All the patients were induced by intravenous Target Controlled Infusion (TCI) 5 ng/ml of remifentanil and intravenous TCI 4 μg/ml of Propofol as well as intravenous 1 mg/kg of Rocuronium for the convenience of tracheal intubation. During the surgery, TCI 2–8 ng/ml of remifentanil and TCI 2.5–4 μg/ml of Propofol were utilized to maintain anesthesia, and the value of Bispectral Index was maintained at 40 to 60. Both the 2 groups were given 20 mg/kg of tranexamic acid intravenously before skin incision and after induction. If necessary, intravenous Rocuronium and the muscle relaxant were given throughout this procedure. The mean patient arterial pressure was kept above 60 mm Hg. The patient was kept at a normal temperature with 36 to 37°C core temperature. In the whole operation process, we utilized the water bath coaxial fluid and blood warming device and forced air warming device. All the cases were treated with the system of cell salvage autologous blood recovery.2.4In the patients of Group A, blind test solution  was administered intravenously after orotracheal intubation and prior to skin incision for more than 2 minutes. After the initial administration, the minimum value of 3 μg/kg ketamine was maintained, this continues until patient recovered from the anesthesia. Afterward, the infusion rate decreased to 1.5 μg/kg.min and it kept for 2 days. Patients in Group B were received the same amount of normal saline.2.5Nausea, vomiting or vomiting, the intensity of pain, adverse events, cumulative morphine consumption, as well as the amount of extra antiemetics or analgesics were evaluated at 6 hours, 12 hours, 24 hours, 36 hours, and 48 hours after the operation. Patients needed to score their most severe rest pain and nausea at each time point. Pain during movement was evaluated when the patient tried to lift both legs in a supine position. Nausea was an unpleasant feeling related to the awareness of urge to vomit; and the vomiting represents the forced removal of the gastric contents from mouth. We recorded the absence/existence of the nausea and the number of vomiting episodes (over 10 ml).2.6The pre-study data of our department revealed that the average morphine consumption of patients with spinal fusion from 0 to 24 hours after the operation was 36 mg and standard deviation was 24. With the type 1 5% of error (α) and 80% of power (1 - β), the calculations of sample size indicated that each group of 60 patients needed to determine a reduction of 30% in the morphine consumption. Considering the uncertainty in our calculation of standard deviation and dropouts, we decided to include 150 subjects (75 in each group).2.72) test and crosstabs were utilized to detect the relationship between categorical variables. And P < .05 was considered to be the statistically significant.In this present study, the Statistical Package for the software of Social Sciences (SPSS) 20.0 was utilized for statistical analysis. The continuous variables were expressed with the form of error or mean ± standard deviation. And the continuous variables was evaluated with Kolmogorov-Smirnov normality test. Group comparisons on the variables that showed normal distribution were performed using one-way analysis of variance. The Mann-Whitney U analysis of variance was utilized for the discrete numerical variables that did not display the normal distribution. The chi-square (χ3Ketamine is commonly used in spine surgery as a nonopioid analgesic, decreasing opioid requirements. The beneficial and adverse effects of ketamine are dose-related, but optimal dosing of ketamine remains undetermined. In this double-blind, randomized, prospective study, we assessed the safety and efficacy of intravenous low-dose ketamine for the treatment of pain in patients undergoing the lumbar spinal fusion. We assumed that intravenous ketamine could improve the satisfaction of patient by reducing the total consumption of morphine equivalent and the pain scores.Conceptualization: Yongxue Chen.Data curation: Hua Wang, Long Ma.Formal analysis: Hua Wang, Long Ma.Funding acquisition: Yongxue Chen.Investigation: Hua Wang, Long Ma.Methodology: Yongxue Chen.Resources: Yongxue Chen.Software: Yongxue Chen.Supervision: Yongxue Chen.Validation: Long Ma.Visualization: Long Ma.Writing – original draft: Hua Wang.Writing – review & editing: Yongxue Chen.


Pain during colonoscopy is a critical quality indicator and often a limiting factor for unsedated colonoscopy. This study aimed to identify factors associated with pain during colonoscopy and establish a model for predicting a painful colonoscopy.Patients aged 18 to 80 who underwent unsedated colonoscopy were prospectively enrolled in 2 tertiary endoscopic centers in China. The primary outcome was the rate of painful colonoscopy and then we identify high-risk factors associated with painful colonoscopy. A prediction model with an intubation discomfort score (IDS) was developed and validated.2 , constipation , and anticipating moderate or severe pain  were identified as independent predictive factors for painful colonoscopy and used to develop the IDS . Patients with IDS ≥1 had increased insertion time [9.32(6.2–13.7)] minutes vs 6.87(5.1–10.4) minutes, P = .038) and decreased cecal intubation rate . Abdominal compression  and position change  were more frequently required in the group of patients with IDS ≥1. These results were externally validated in a validation cohort.Totally 607 patients participated in this study, including 345 in the training cohort and 262 in the validation cohort. Body mass index (BMI) of <18.5 kg/mThe intubation discomfort score developed in this study was useful for predicting pain during colonoscopy, with IDS ≥1 indicating painful colonoscopy. Thus, sedated colonoscopy is recommended. However, several drawbacks of sedated colonoscopy have been reported, such as sedation-related complications, post-procedure activity restrictions, longer recovery time, requirement of an escort, and increased cost.,6 These factors were positively associated with the unwillingness of patients to undergo colonoscopy. Hence, unsedated colonoscopy is gaining interest and has been recently advocated by several researchers.–10Currently, colonoscopy is the standard method for the management of colorectal disease. Screening colonoscopy decreases the incidence and mortality of colorectal cancer by detection and treatment of precancerous lesions and early cancer. Thus, routine administration of sedative or analgesic agents to all patients was considered unnecessary. However, unsedated colonoscopy is considered an option for some but not for all patients. If we could identify patients who are at a high risk of experiencing pain during colonoscopy at the preoperative stage, targeted administration of sedatives or special techniques could be recommended.Previous studies have reported that 74% of patients felt no pain or only mild discomfort during unsedated colonoscopy.Here, we prospectively collected the data of patients undergoing colonoscopy with an aim to investigate the possible risk factors associated with painful colonoscopy using a stepwise multivariate regression model. Furthermore, we developed a novel point score to predict whether patients were at a high risk of a painful colonoscopy so that another appropriate method of colonoscopy or the aid of special techniques can be recommended to facilitate the completion of the procedure.22.1This prospective study was conducted at 2 tertiary centers in China. The patients of the training cohort were enrolled from the Xijing Hospital of Digestive Diseases; those of the validation cohort were enrolled from the Shaanxi Second People's Hospital. The study protocol were approved by the ethics committee of Xijing Hospital and Shaanxi Second People's Hospital. Written informed consent was obtained from all patients.Consecutive patients aged 18 to 80 years old who willing to undergo unsedated colonoscopy were enrolled in this study. Exclusion criteria included the following: no bowel preparation or colon cleansing by enema only; no need to reach the cecum; prior finding of severe colon stenosis or obstructing tumor; history of colectomy, unstable hemodynamics; pregnant or breastfeeding women; and inability to provide informed consent. Both training and validation cohorts were enrolled with the same inclusion and exclusion criteria. This study was registered with ClinicalTrials.gov (NCT03540173).2.2All patients were prescribed polyethylene glycol electrolyte powder  for bowel preparation according to the preference of the treating physician. The patients were asked to drink the first 2 L of PEG4000e between 19:00 and 20:00 on the night before the colonoscopy within 2 hours. Subsequently, on the day of the examination and 5 hours before the procedure, the patients were asked to consume the remaining 2 L. Patients were encouraged to drink more clear liquids after purgatives for adequate hydration before colonoscopy. In addition, they were instructed to have a regular meal for lunch and only liquid diet for dinner on the day before the operation. This preparation method has been previously reported with an acceptable cleansing rate.All colonoscopies were performed between 08:00 and 13:00 by 4 experienced colonoscopists. Before the start of the study, all the colonoscopists had performed >3000 colonoscopies independently. A high-resolution adult video colonoscope  was used for every procedure.2.3 surgery, and comorbidities). Anxiety status was evaluated using the hospital anxiety and depression (HAD) scale. Abdominal pain during the examination was evaluated by a previously validated 4-point verbal rating scale , and moderate or severe pain during the procedure was assumed to indicate “painful colonoscopy;” the degree of pain was recorded in all patients with complete and incomplete colonoscopy. The patients were also asked to grade their anticipated pain and normal abdominal pain using the same 4-point verbal rating scale before the examination. All data were collected by 1 investigator (WLM) who did not participate in the data analysis.The following variables were systematically collected: demographic data ; indication for colonoscopy ; and medical history ,2.4 In the current study, events per variable were set as 27 according to our previous experience. The number of possible predictors were 11 in this study. Thus, about 300 patients may be sufficient to produce significant power to identify risk factors associated with pain. To compensate the possible drop-out, 330 patients were planned to be enrolled in the training cohort.Sample size calculation was performed by maximum likelihood estimation based on logistic regression as described previously.t test or one-way ANOVA was used comparing normal distributed continuous variables. To assess the factors associated with painful colonoscopy, a multivariate logistic regression analysis was performed using the variables with P values <.1 in the univariate analysis. The cutoff values of the quantitative variables and IDS were determined by receiver operator characteristics (ROC) analysis.The training cohort was used to determine the factors influencing pain during colonoscopy and to develop the IDS, and the validation cohort was used to verify the IDS. Categorical variables were described as percentages. Continuous variables were described as means ± standard deviation (SD) or medium (range). Chi-Squared test was used comparing categorical variables when appropriate. Student P < .05 was considered statistically significant. Analyses were mainly performed with SPSS version 19.0 . Subgroup analyses were performed with Stata 12.0 .All tests of significance were two-tailed, and 33.1A total of 1220 patients undergoing unsedated colonoscopy from March 2018 to October 2018 were prospectively enrolled in this study , of which 613 were excluded . Finally, 345 patients from the Xijing Hospital of Digestive Diseases and 262 patients form Shaanxi Second People's Hospital were included in this study  +1 × C  +1 × E .In the training cohort, we evaluated the influence of patient-related factors on pain during colonoscopy. Univariate logistic regression analysis indicated that age, marital status, BMI, constipation, and expectation of pain before colonoscopy may influence the degree of pain during the examination. After multivariate logistic regression analysis, only low BMI , constipation , and anticipation of moderate or severe pain  had a significant influence on painful colonoscopy  and high-risk (IDS ≥ 1) groups by ROC curve analysis. The area under the ROC curve of the IDS for the prediction of painful colonoscopy was 0.66 (95% CI 0.59–0.72) and 0.61 (95% CI 0.53–0.69) in the training and validation cohorts, respectively Fig. . PatientIn order to investigate whether IDS score is still useful after excluding the patients undergoing diagnostic colonoscopy, we did a sensitivity analysis to investigate in both training and validation cohort, the rates of painful colonoscopy significantly elevated when IDS increased from 0 to 3 (Supplementary Table 1). Similarly, patients with IDS ≥ 1 had higher rate of painful colonoscopy, longer insertion time, and more frequent requirement of abdominal compression and position change (Supplementary Table 2). All of these results indicated that IDS score is also useful for patients undergoing screening or surveillance colonoscopy.P = .338; 0 (0–3) vs 0 (0–4) in validation cohort, P = .709). HAD scores was not found to be correlated or associated with the pain score in this study (Supplementary Table 3).We also compared the HAD scores between patients undergoing diagnostic and screening/surveillance colonoscopy. There were no significant difference between the 2 groups [0 (0–4) vs 0 (0–3)] in training cohort, 4,12However, approximately 20% of patients experience pain during intubation, which may in turn prevent patients from participating in screening colonoscopy; thus, identifying patients who are more likely to experience pain is essential before colonoscopy. In this study, we found that low BMI (<18.5 kg/m2), constipation, and anticipation of a painful procedure are independent factors associated with painful colonoscopy, and we also showed that the insertion time was significantly longer in high-risk patients; these results are consistent with those of a previous study. Moreover, in our study, we developed a simple scoring system (IDS ≥ 1 for high-risk patients) to identify those who are likely to be at high risk of experiencing pain during colonoscopy, which could in turn help in choosing or recommending for painless colonoscopy and other special examination methods.Unsedated colonoscopy has some advantages, and nearly 80% of the patients could undergo unsedated colonoscopy with mild or no pain. However, BMI alone is not a suitable representative of abdominal or visceral fat. Thus, further studies should evaluate waist or hip circumference as a predictor of painful colonoscopy. Moreover, we also found that anticipation of pain among patients is correlated with painful colonoscopy, which was also reported previously. While constipation as a factor has not been mentioned in previous research, patients with irritable bowel syndrome have been reported to experience more pain;,19 some patients in our study had irritable bowel syndrome. Furthermore, several studies have demonstrated that nervousness or anxiety before the examination contributes to a painful colonoscopy. However, in our study, the HAD scale had no correlation with painful colonoscopy, which could be because the HAD scale is a tool to evaluate normal anxiety level and thus may not reflect the level of anxiety regarding the procedure. In addition, some researchers believed that a history of abdominal or pelvic surgery could lead to a more difficult and painful colonoscopy.,21 By contrast, such observation was not noted in approximately 60% of the patients who had a previous surgery, which could be attributed to the minimally invasive surgery they underwent. Female sex and younger age were considered risk factors for painful colonoscopy.,23 Although no statistically significant correlation between these 2 factors and painful colonoscopy in our study was observed, we found that women and younger patients tend to experience more discomfort.In slender patients, angulation of the sigmoid colon may be sharper and may require constant straightening, which contributes to painful colonoscopy. Our study used BMI as an indicator of obesity and found that a low BMI is associated with painful colonoscopy; this result is consistent with that in a previously published research.,25 This technique can be tried in unsedated patients with IDS > 1. Secondly, CO2 insufflation, the use of small-caliber endoscopes or cap-assisted colonoscopy may be helpful to alleviate pain. Lastly, sedation can ensure patients painless during the whole procedure.We established a simple and easy scoring system to classify patients into high- and low-risk groups, which could in turn aid in the selection of the most appropriate method for colonoscopy. Patients with low-risk scores had significantly shorter insertion time and less abdominal compression and position change. This phenomenon suggested that the procedure of intubation seemed to be easier in patients with less pain. For patients at low risk (IDS < 1), unsedated colonoscopy may be suitable. For patients at high risk of experience pain (IDS ≥ 1), there are several methods which could be useful for preventing or reducing pain. Firstly, it has been reported water exchange method instead of air insufflation can reduce pain during intubation in several high-quality studies.The strength of this study is its design. First, the relevant data of non-anesthetic colonoscopy were collected prospectively, and the pain prediction model was established by evaluating the factors affecting the degree of pain during colonoscopy in the experimental group. A validation group was set up to validate the result of the experimental group. Second, the scoring system developed was simple to it use facilitate among clinical workers. Lastly, the multicenter design of the study makes the results more generalizable.Nevertheless, this study has some limitations. Firstly, the experience of endoscopists may significantly affect the pain associated with the procedure and the willingness of patients to repeat the examination. In the present study, all colonoscopies were performed by experienced endoscopists who had performed >3000 colonoscopies independently. The findings based on the performance of experienced endoscopists may not be generalized to the procedures performed by trainees or inexperienced endoscopists. Secondly, although the sensitivity of IDS score was suboptimal, negative predictive value was more than 80% in both training and validation cohorts, which meant most of patients with IDS < 1 (without any high-risk factors) would be suitable for unsedated colonoscopy. In previous studies, there was not better prediction model to predict painful colonoscopy. The efficiency of the model may be further improved by collecting more patient-related parameters or enrolling more patients in further clinical trials. Thirdly, the current study only enrolled unseated patients, the number of these patients is limited since most of patients underwent sedated colonoscopy in clinical practice. The number of unsedated patients included in this study seems relatively little. Some risk factors associated with pain may be missed due to the small sample size and patients willing to undergo unsedated colonoscopy were enrolled in this study would result in underestimation of the real risk of painful colonoscopy in the whole population, which could be further investigated in larger studies with involvement of more endoscopic centers. Last but not least, psychotropic or narcotic drugs can increase the pain threshold during colonoscopy. Only less than 3% of patients in this study took TCA or narcotics. No significant differences were found between patients taking TCA or narcotics and those not taking. However, the effects of TCA or narcotics on painful feeling during colonoscopy deserves further investigation in larger studies.2), constipation, and anticipation of pain are associated with painful colonoscopy, and we developed a novel, objective, noninvasive, and conveniently applicable scoring system to predict painful colonoscopy in the preoperative stage.In summary, a low BMI (<18 kg/mYanglin Pan, Xuegang Guo participated in the design of the study; Limei Wang, Shaowei Yao, Qin Tao participated in the data collection and the design of the study; Xiaoyu Kang, Hui Luo participated in the analysis and manuscript preparation; Limei Wang, Hui Jia, Hui Luo participated in the data analyses and wrote the manuscript; Linhui Zhang, Xiangping Wang give critical revision of the manuscript for important intellectual content.


Acute abdomen is a common disease in the emergency department (ED) and usually results in huge medical expenditure. To relieve abdominal pain effectively and reduce bed occupancy rate in emergency rooms, electroacupuncture is a practical method in the treatment of abdominal pain.Five hundred patients will be randomly and evenly divided into experimental and control groups. Both groups should have their basic information taken and their bilateral acupuncture points ( Hegu (LI 4), Neiguan (PC6), Zusanli (ST 36), Shangjuxu (ST37), Xiajuxu (ST39), Taichong (LR3), and Taibai (SP3)) will be intervened by electroacupuncture or vaccaria Seeds, in this clinical study. Electroacupuncture has been introduced to this experiment as an auxiliary technique. The experimental group will receive real electroacupuncture, but the control group will receive a placebo electroacupuncture in which transcutaneous electrical nerve stimulation will not be turned on. After the intervention, we will evaluate the difference in abdominal pain, the length of stay at the emergent observation ward, and the proportion of revisits with abdominal pain.In Taiwan, medical expenditure is increasing annually because of the higher bed occupancy caused by acute abdominal pain in the hospital. We expect that the combined treatment of electroacupuncture and modern medical treatment will not only reduce bed occupancy and the length of ED stay but also effectively decrease the rate of readmission and revisits by 72 h. By means of electroacupuncture, the spiraling cost of health care can eventually be reduced.NCT03199495. Registered on 27 June 2017.ClinicalTrials.gov identifier:  In the USA, about 5 million patients have suffered from abdominal pain and visited the ED. These accounted for around 5–10% of all emergency patients . In 2014nal pain . Around nal pain . Therefoet al. found that the cost of medical care for the returning ED visits is higher than for the initial ED visits and that the cost of medical care for other hospital ED visits are higher than for the original ED visit [The definition of ileus is that partial or complete intestine is obstructed. Hence, the intraluminal contents cannot be excreted , 5. SympED visit .Compared with Western medicine, traditional Chinese medicine is considered a complementary medicine. Acupuncture is a safe therapy with low risk of adverse side effects in clinical practice . It has Electroacupuncture therapy is an auxiliary technique for acupuncture. Stimulating acupuncture points with pulse current through an electroacupuncture apparatus can increase gastric emptying and reduce the period of ileus after abdominal or laparoscopic surgery. Furthermore, side effects after the operation were reduced. For example, functional constipation could be alleviated efficiently , 19.To the best of our knowledge, electroacupuncture has not been applied to the treatment of acute abdominal pain in EDs. In this study, we will collaborate with an ED in order to investigate whether electroacupuncture can alleviate acute abdominal pain effectively and reduce the length of stay in the emergency observation area. We expect that the combination of traditional Chinese medicine and Western medication can provide efficient treatment for patients and save medical resources.This is a prospective randomized controlled clinical trial with a two-arm, parallel-group design Fig. . Data anWe expect to recruit 500 patients and allocate them randomly to an experiment group or a control group. Patients who come to the Changhua Christian Hospital ED with acute abdominal pain will be evaluated by the attending physicians. The patients are in urgent conditions such as unstable vital signs and must stay in the hospital for further examination will be excluded by ED physicians. The consultation sheet will be issued after seeking the patients’ agreement.age of 20 to 90 years, either gender;the chief complaint consists of gastrointestinal symptoms, such as nausea, vomiting, diarrhea, bloating, and constipation;diagnosis with International Classification of Diseases 10th revision (ICD-10) code K00-K94: Diseases of the digestive system.Participants meeting all of the following criteria are included:patients are not likely to follow the instructions of the trial or cannot communicate reliably with the investigator;cardiac diseases, such as arrhythmia, or equipped with cardiac pacemaker, deep brain stimulator, or other electronic implants;abnormal vital signs;serious injuries;physical symptoms of a neurological problem;the situation of ileus needs surgery;pregnancy status;mental disabilities or unconsciousness.Participants meeting one or more of the following criteria are excluded:This study will be conducted in the ED at Changhua Christian Hospital. All of the traditional Chinese medicine doctors in this research have more than 10 years of acupuncture experience.n = 26 and 28, respectively) was calculated. With these parameters, a sample size of 208 subjects in each group was needed to have 80% power and 5% level of significance by independent t test. With a predicted attrition rate of 10%, the minimum number of subjects required at baseline was calculated to be 229 per group. Patients meet the inclusion criteria will be randomly assigned by computer in a 1:1 ratio, and the results of this random assignment will be sequentially numbered into each sealed opaque envelope containing a card labelled ‘electroacupuncture’  or ‘placebo electroacupuncture’ (control group). Whenever a patient participates in the study, a sealed opaque envelope will be opened by a doctor.The sample size calculation was based on the results of our previous pilot study by using the statistical software G*Power 3.1.9.2. The minimum sample size for estimating the difference in the mean change of visual analog scale (VAS) at 15 min between the experimental and control groups with an effect size of 0.275  and VAS of the patients.Patients in the experimental group will receive electroacupuncture with electrostimulation by using a Ching Ming electroacupuncture device. Disposable, sterilized acupuncture needles  will be inserted to a depth of 15–35 mm. Needles are inserted correctly and are manually stimulated until the “De Qi” sensation is elicited. Among the seven acupunctural points mentioned above, only Hegu (LI 4), Neiguan (PC6), Zusanli (ST 36), and Taichong (LR3) with electrical stimulation are conducted. The frequency of electrical stimulation is 2 Hz, and the intensities of the stimulation are below 9.8 mA for 15 min . Once itSham electroacupuncture is delivered by Vaccaria seeds which are categorized as spherical, smooth, and hard. Patients in the sham acupuncture group receive sham electroacupuncture by using Vaccaria seeds which are secured onto the same acupuncture points as the experimental group and then covered by patches of transcutaneous electrical nerve stimulation with the power off. The control variable in this study is carried out with the electrical stimulation off. After 15 min, the investigators will remove Vaccaria seeds and patches of transcutaneous electrical nerve stimulation.During the study, all participants will receive Western conventional therapy simultaneously, and the researchers are responsible for recording all of the data and for the safety of patients. If any hemorrhages, bruises, or swelling occur after pulling out needles, the doctor will directly make provisions for the patients. For example, putting ice packs on the bruised area can be useful for absorbing bruises. After treatment, all of the patients should be followed up by a phone interview within 3 days.Abdominal pain is registered and evaluated by the BPI and VAS. The BPI is used to assess the severity of pain and the impact of pain on daily functions. The VAS is graded from 0 (no pain) to 10 (severe pain). Patients are evaluated at three time points in this study: before intervention (VAS-1), after intervention (VAS-2), and 3 days after the intervention (VAS-3).The duration of staying in ED after electroacupuncture treatmentThe number of unplanned ED revisits within 72 hours.The secondary outcome measurements are the following:The research assistant will keep tracking the direction (conditions) of post-treatment participants. Any personal information will remain confidential in a safe. Only the principal investigators can get the assessment Fig. .Fig. 2St test, and categorical variables between the two groups are compared by using the chi-squared test or Fisher’s exact test. A paired t test is used to determine whether the mean difference between post-treatment and pre-treatment VAS and BPI levels is zero. To estimate the effect of electroacupuncture treatment and adjust for the possible inter-correlations of data collected from the same patient and other covariates, we will use a generalized estimating equation to fit a linear regression model that yields robust standard errors estimated in the model.All data will be analyzed by using IBM SPSS Statistics for Windows, version 22.0 . Continuous variables between the two groups are compared by using the Student’s Each group of patients will be randomly assigned by computer in a 1:1 ratio. The medical information will be documented and stored separately from personally identifiable data. Independent personnel will record data on the paper version of a case report form and input the data to the computer database. The medical information and the group allocation will not be visible to third parties. All data will be stored in the database and inspected by a person who is not involved in this study. The doctors and statistician will not have access to these data until patient evaluations are completed. If subjects withdraw from the study, no further data will be collected from them. Data already obtained will be used only in analysis of this study. Once we complete the study, we will delete the data from the database.In Taiwan, medical expenses caused by return visits have been increasing gradually year by year , 21–23. Acute abdomen pain is one of the most frequent causes of admission to EDs. In the past, in Changhua Christian Hospital, we observed that most patients with acute abdomen pain were between about 20 and 90 years of age. Therefore, we will include patients up to the age of 90 years.The BPI and VAS are tools of pain assessment. Because the BPI is indirectly derived from the scores of the questionnaire items, we use the VAS to estimate the minimum sample size for this study.According to past studies , 19, theIn general, if not placed on the ears, Vaccaria seeds could not show any therapeutic function. Therefore, we do not place the seeds on ears instead of the acupuncture points on the body. Because they are small, the seeds cannot give efficient simulations to the patient. In addition, we do not press the seeds to increase unnecessary simulations. As a result, Vaccaria seeds give the patients psychological therapy only. We expect that Vaccaria seeds constitute a good candidate for the control group. We anticipate that electroacupuncture can alleviate acute abdominal pain efficiently, shorten the period of stay in the ED, reduce return visits, and achieve a medical cost reduction.Recruitment began on April 17, 2017 and was completed by April 16, 2018.


Treatment strategies for nipple injury are mainly based on aetiology. However, some damaged nipples do not heal after the aetiology was corrected. This study retrospectively analyses the effect of debridement for treating chronic injury of lactating nipples. The medical records on nipple injury management in the authors’ department from December 2015 to January 2020 were retrospectively analysed. A total of 167 patients were enrolled and grouped based on the presence or absence of nipple debridement. The difference in the healing effect, pain relief rate and recurrence rate of nipple injury between the two groups after 1 week was examined. The cure rate of nipple injury in the intervention group (54.3%) was significantly higher than in the control group (26.7%). In addition, the complete pain relief rate in the intervention group (48.1%) was significantly higher than in the control group (23.3%). However, the recurrence rates between the two groups (36.4% (16/44) vs. 34.8% (8/23)) had no statistically significant differences. For patients with no improvement after correction of the aetiology of the in the nipple damage, debridement can improve the healing environment of nipple breakage and thus relieve nipple pain. The pain caused by nipple injury not only brings unpleasant sensations but also subjectively shortens the breastfeeding time2. Moreover, it may increase the mental stress of nursing mothers by affecting their mood, sleep and general daily activities, thus influencing milk secretion and objectively shortening the breastfeeding time 5. Improper or untimely treatment may induce milk deposition and mastitis6.The incidence of nipple injury is 58% to 62.9%7. Consequently, there is currently no high-quality research on their treatment8. Therefore, the evidence-based basis for the treatment of nipple injuries is insufficient.The type and severity of nipple injuries are affected by subjective factors. There is no uniform consesus on the definition, classification and evaluation methods for nipple injuries9. Currently, the clinical problem is that some nipple injuries are unresolved after removal of the cause. To evaluate the symptomatic treatment of nipple injuries, Vieira et al.10 analysed 496 studies on the promotion of nipple injury healing, including the use of lanolin, the combination of lanolin and nipple shields, breast milk, hydrogels, polyethylene film dressings, sprays and distilled water containing chlorhexidine and alcohol. However, these results are uncertain due to the sample size.The principle of nipple injury treatment is etiological and symptomatic treatment. Active management including early detection and treatment would help mothers recover within 2 weeksIn this study, the authors retrospectively selected patients with nipple injury who had no remission after correcting the aetiology and analysed the difference in the treatment effect between patients who had nipple debridement and those without any treatment.The medical records of all lactating patients with nipple injuries at the Breast Disease Prevention and Treatment Centre of the Haidian Maternal and Child Health Hospital from December 2015 to January 2020 were collected and analysed. (1) Patients with nipple injuries within 4 months after delivery who presented with white matter keratinisation and necrotic tissue in the nipple, (2) patients with repeated nipple pain, milk deposition, or mastitis in the corresponding area, (3) those whose nipple injuries remained for more than two weeks after the aetiology was corrected, (4) those who have no acute mastitis symptoms such as fever and (5) those whose follow-up period reached 1 month and their information was complete were included in the study. However, (1) patients whose babies showed short lingual frenula or abnormal structures of the palate, (2) those who have nipple infections, (3) those who have flat or concave nipples, (4) those with nipple vasospasmand (5) those who have uncorrected poor breastfeeding methods were excluded.All patients were divided into the intervention and control groups according to whether nipple debridement was indicated or not.The following data were retrieved for all patients with nipple injury: demographics, medical history, treatment method, treatment outcomes including the status of nipple breakage after treatment, degree of nipple pain, recurrence and nipple image data.The healing effect of debridement on nipple injuries was evaluated according to the change in the diameter of the damaged area after treatment. The results were then categorised into the following: cured, improvement(reduction of the diameter)and ineffective(the diameter did not reduce or the diameter increased).The degree of pain relief was evaluated based on the patients’ pretreatment pain status. The results were categorised into the following: complete remission (pain disappeared), partial remission (pain was relieved) and no remission (no change in pain or pain increased).To evaluate the recurrence, in patients who were cured, a recurrent lesion in the same site of the same nipple within 1 month was considered a relapse.This case series was approved by the medical ethics committee of the Haidian Maternal and Child Health Hospital and informed consent for study participation was taken. In addition, all methods were conducted according to the relevant guidelines and regulations.In the intervention group, the patients underwent nipple debridement. The operation procedure was as follows: the nipple was disinfected by iodophor and anaesthetised by 1% lidocaine. The nipple lesion was completely debrided with ophthalmic scissors to remove the keratinised necrotic tissues until fresh nipple tissue is visible. Nipple debridement is all about the direction and depth to allow the patients to continue to exclusively breastfeed with good sucking after compression and hemostasis .Table2 = 13.451;P = 0.001)  patients who were cured, 1923.5%) patients who improved, 18 (22.2%) patients in whom the treatment was ineffective. In the control group consisted of 86 patients, 23(26.7%) patients were cured, 29(33.7%) patients improved, 34(39.5%) patients were in whom the treatment was ineffective   patients obtained complete pain relief, 25(30.9%) patients got partial remission and 17(21.0%) patients had no remission. In the control group, 20(23.3%) patients obtained complete remission, 28(32.6%) patients got partial remission and 38(44.2%) patients had no remission  (Table All cured patients were followed up by telephone 1 month after the treatment. There were 1636.4%) recurrences in the intervention group and 8(34.8%) recurrences in the control group (χ% recurre11, and the necrotic tissue in the wound prevented angiogenesis, granulation tissue formation, epidermal regeneration and normal extracellular matrix formation, thus forming a physical barrier for re-epithelialisation, preventing local drugs from directly contacting the wound and affecting the curative effect14. Anghel et al. considered that adequate debridement of necrotic tissues is the core of promoting wound healing 15 and a basic step to promote chronic wound healing 1. In this study, for patients with no improvement after etiological treatment, nipple debridement was used to remove necrotic tissues. The patients who underwent debridement had significantly better therapeutic outcomes than those untreated with medicine or surgery, suggesting that nipple debridement plays an important role in promoting the healing of chronic nipple injuries. Debridement not only clears the wound but also promotes the growth of fresh epithelial cells, thus speeding the healing process.After the nipple was damaged, its movement during lactation prevents the creation of a new nipple surface, that is, the chronic wound healing process increased the risk of local infectionIn this study, pain relief in the intervention group was significantly better than in the control group. It was shown that nipple debridement can also create favourable conditions for nerve repair, reducing nipple pain. This allows mothers to assess the effect of modifying their breastfeeding methods, to reduce the potential of further injury to the nipple, and to determine and practice methods to achieve and maintain exclusive breastfeeding.9.This study has several limitations. First, the retrospective design of this study may have resulted in case selection bias. Second, there was a timing difference between the two groups: nipple debridement in th intervention group was performed starting in the middle of 2017 and the control group was actively observed from 2015 to 2020. Third, there was no strict matching of the causes, and no aetiology was classified and analysed. Fourth, the authors did not compare the frequency and degree of recurrence between the two groups. Last, in this study, the authors defined chronic injury of the lactating nipples as those without relief for more than two weeks after the aetiology was corrected, depending only on the results of subjective individual studies, which need to be discussed furtherIn conclusion, this study revealed that nipple debridement on lactating nipples with chronic injury can create good conditions for wound healing, especially for patients with obvious pain and repeated milk deposition. Note that nipple debridement is minimally invasive. It is necessary to minimise damage to normal tissues while removing necrotic tissues to avoid the wound area from increasing and the damage from deepening, thus affecting the function of the mammary duct.