Both groups received an 8-week intervention. Pain, lumbar mobility, endometriosis health profile, quality of life, depression and anxiety levels, and the patient’s perception of change were assessed before (T0) and after (T1) the intervention, as well as at a one-month follow-up (T2) and a six-month follow-up (T3). The MTG significantly improved pain intensity, powerlessness, lumbar mobility, and physical quality of life at T1 (p < 0.05). The results were maintained for pain intensity at T2 and T3. In addition, both the MTG and PG improved emotional wellbeing at T1 (p < 0.05). Neither group improved in terms of social support, self-image, and depression and anxiety levels after the intervention (p > 0.05). In conclusion, manual therapy may be an excellent complement to the gynecological treatment of endometriosis-related pelvic pain by alleviating pain and improving women’s endometriosis health profile and physical quality of life.A randomized controlled trial was carried out to assess the effectiveness of a manual therapy protocol in terms of the clinical characteristics, quality of life, and emotional condition of the women with endometriosis-related pelvic pain. Forty-one women (mean age of 36.10 (6.97) years) with pelvic pain due to endometriosis were randomly divided into (i) a manual therapy group (MTG) ( Endometriosis is a debilitating condition with features of chronic inflammation that affects 10–15% of women of reproductive age , definedTreatment for endometriosis includes hormone treatment and surgery . However, pelvic pain associated with endometriosis is often refractory to them ,8. SinceIn this context, physiotherapy can contribute to the multidisciplinary assessment and treatment of pelvic pain due to endometriosis . PhysiotThus, the aim of this study was to analyze the effectiveness of a manual therapy protocol in relation to the pelvic pain, lumbar mobility, and clinical features related to quality of life  and the emotional condition  of women who suffer from pelvic pain due to endometriosis.Participants diagnosed with endometriosis who suffered from chronic pelvic pain were recruited as a convenience sample from primary care centers in Valencia (Spain) (November to December 2021). All participants were recruited in the same way and all potential participants were provided with the same information about the study. The inclusion criteria were pre-menopausal woman between 18 and 50 years old with an endometriosis diagnosis from a gynecologist and associated pelvic pain for at least one year of evolution. The exclusion criteria were being pregnant, having rheumatic or degenerative neurological diseases, or having another injury or disease that caused pelvic pain, as well as having undergone any pelvic surgery within the previous year or receiving physical therapy treatment within the previous three months.A randomized controlled trial was carried out (NCT05418751) from January to December 2022 at a clinical center. The sample was randomly divided into two groups: (i) the manual therapy group (MTG), which received a manual therapy protocol, and (ii) the placebo group (PG), who received a hands-on placebo intervention. Evaluations were performed at four time points: (i) before the intervention (T0), (ii) after the intervention (T1) (two months after the start of treatment), (iii) at the one-month follow-up (T2), and (iv) at the six-month follow-up (T3).All participants provided written informed consent, all procedures were conducted in accordance with the ethical standards of the Declaration of Helsinki, and all protocols were approved by the Ethics Committee of the University of Valencia (num. 2063942).www.randomized.com accessed on 10 January 2022) by an external investigator who was not involved in the assessment or treatment of the participants. The participants were blinded to the treatment allocation. In addition, the outcome assessors were blinded to the study hypothesis, the intervention, and the treatment group assignment, thus avoiding researcher bias. The only researcher who was aware of treatments was the physiotherapist who performed manual therapy and placebo interventions.The randomized allocation was performed through an online randomization tool  manipulation technique: The patient was in the supine position. Manipulation was performed on a vertical axis  passing through the odontoid process of the axis. Prior to manipulation, slight cephalic decompression and small circumductions were performed. A rotation toward the side to be manipulated was performed with a cranial helical movement. This technique was applied bilaterally .Thoraco-lumbar manipulation technique: The patient was laid on the contralateral side to be treated, with the upper and lower limbs flexed leading to a complete spine rotation, focusing on the T12-L1 junction. The therapist’s caudal hand pressed on the inferior articular apophyses of T12, while their cranial hand rested on the chest of the patient. A high-velocity low-amplitude movement in forward rotation of the pelvis was then performed. This technique was applied bilaterally .Global sacroiliac manipulation technique: The patient was laid on the contralateral side to be treated. Adjustment was effected through complete spine rotation and lower limb flexion, focusing on the sacroiliac joint. The therapist’s forearm was placed on the iliac crest for manipulation along the joint. A high-velocity low-amplitude movement in a caudal to cephalic and posterior to anterior direction was performed to mobilize the sacroiliac and lumbosacral joints. This technique was applied bilaterally .Abdominal mobilization technique: The patient was in the supine position with knees flexed. The ulnar border of both hands of the therapist were placed over the lower part of the abdomen. The patient took a deep breath and, during the exhalation phase, the therapist performed a manual vibration in the cranial direction . This teBroad ligament mobilization technique: The patient was in a supine position with knees flexed. The therapist’s cranial hand was placed on the broad ligament while the other hand held the patient’s legs. An opposite movement of both hands was then performed to provoke a stretch in the abdominal region . This tePelvic diaphragm release technique: The patient was in a supine position. One hand was placed under the lumbosacral junction and the other hand on the upper surface of the pelvic area, perpendicular to the one below. A slight compression was performed for 5 min to produce a relaxation in the fascial tissue .Sphenoid technique: The patient was in the supine position. The therapist placed their fingers as follows: the first finger on the midline of the head, the second over the sphenoid (greater wing), the third on the pterion, the fourth behind the ear over the asterion, and the fifth over the occiput . The other hand was placed in the same position on the contralateral side of the head. A gentle caudal to cephalic distraction force was performed for 5 min .Fourth ventricle technique: The patient was in a supine position. The therapist’s hands were placed under the patient’s occiput with the thumb tips together. A slight compression with the thenar eminences and cephalic traction was performed for 5 min .The participants received light contact on the same points and for the same amount of time as the experimental group with no intention to treat .Neither the MTG not the PG were informed of the type of treatment they were receiving. To monitor the blinding and assess if the patients believed that the light contact that they received was normal physiotherapy, both groups were asked to guess which treatment they received at the end of the study .The demographic responses, anthropometric data, and gynecological characteristics of the participants  were collected. In order to encourage participants to provide honest responses and avoid social desirability bias, anonymity and confidentiality were ensured throughout the study.Two physiotherapists were responsible for taking baseline and post-intervention main outcome measurements. In addition, with the goal of standardizing the procedure for data collection, the researchers were trained on the assessment protocol and the use of the measurement tools.Pelvic pain intensity was assessed through the Visual Analogue Scale (VAS). It is a commonly used and validated instrument for the interpretation of pain intensity . The scaLumbar mobility was evaluated using the Schober Test, with modification. In this test, the participant stands in a neutral upright position without shoes and with their feet hip-width apart. A mark is made 5 cm below and 10 cm above the lumbosacral junction . The participant then bends forward to the maximum that they can without bending their knees, and the distance between the marks is measured, with the increase being a measure of anterior flexion. The ICC of the test is 0.77. The MCD is established at 1.8 cm .The endometriosis health profile was determined using the Endometriosis Health Profile Questionnaire (EHP-30). This questionnaire was comprised of two parts, the first being the core questionnaire, which consisted of five scales  and contained a total of 30 items. The items within the scales were summed to create a raw score and then each scale was translated into a score ranging from 0  to 100  . CronbacSelf-perceived quality of life was assessed using the SF-36 health questionnaire . It is cDepression levels were determined using the Beck Depression Index (BDI-II) . This teAnxiety levels were evaluated through the State Trait Anxiety Index (STAI) . This coThe patient’s perception of change was assessed using the Patient Global Perception of Change Scale (PGICS). In this scale, the patient reflects on their perception of the efficacy of the intervention on their limitations regarding activities, symptoms, emotions, and overall quality of life. It consists of a 7-point verbal scale, with the options “very much improved”, “much improved”, “minimally improved”, “no change”, “minimally worse”, “much worse”, and “very much worse” . It has t-test for the continuous variables and a Chi-squared test for the categorical ones. Cohen’s d was computed to analyze the effect size of the continuous variables, which was rated as either small (0.20–0.50), medium (0.50–0.80), or large (>0.80) [The statistical analyses were performed using SPSS v.24 . The inferential analyses of the data were conducted using a two-factor mixed multivariate analysis of variance (MANOVA), having a between-subjects factor “treatment group” with two categories (MTG and PG), and a within-subject factor “time measurements” with four categories  for all variables. Bonferroni correction was used for the post-hoc analyses. The assumption of homoscedasticity was determined using Levene’s test, and the sphericity using Mauchly’s test was also evaluated. A Chi-squared test was used for the categorical variables. Additionally, similarity between the groups at baseline was explored using the Student’s  (>0.80) . The eff2 = 0.25, and α error = 0.05. Since this was a study with two intervention groups and four measurement times, a minimum sample size of 12 participants per group  was generated. Considering possible dropouts, this sample was increased to 20 per group, 40 in total.For computing the sample size, the software G*Power 3.1.9.7  was used. We set a power of 80%, an effect size of fFifty participants were assessed for eligibility, of whom 41 met the inclusion criteria. Following on from this, 21 participants were randomly allocated to the MTG and 20 to the PG. All of them completed the study . There wp < 0.001; d = 1.00), T2 , and T3 . However, there were no significant differences after the placebo intervention or at the follow-up (p > 0.05). In addition, the MTG improved significantly compared to the PG at T1  and T3 .As noted in p > 0.05) or in the PG (p > 0.05), the MTG significantly showed greater lumbar mobility than the PG at T1 , T2 , and T3   .d = 1.55), control and powerlessness , emotional wellbeing , and EHP-30 total score . In addition, the changes were maintained in terms of pain at T2  and T3 , and in the EHP-30 total score at T2  and T3 . However, there were no significant differences between the time measurements for social support and self-image at T1, T2, or T3 (p > 0.05). The PG did not significantly improve any of the EHP-30 items after the intervention and at the follow-up (p > 0.05), except for emotional wellbeing at T1  and T3 . In addition, there were significant differences between the groups in terms of pain  at T1, whereas there were no significant differences between the groups for the items of control and powerlessness, emotional wellbeing, social support, self-image, and the EHP-30 total score at T1, T2, and T3 (p > 0.05).Regarding the endometriosis health profile assessed with the EHP-30 , the intp = 0.01, d = 0.72), corporal pain , general health , and physical subscale  compared to T0. However, there were no changes in the items of physical functioning, vitality, social functioning, emotional role, mental health, mental subscale, and overall quality of life (p > 0.05). In addition, these changes were not maintained at either T2 (p > 0.05) or T3 (p > 0.05). In the PG, only the mental health item was significantly increased at T2 . However, no significant changes were found at T1, T2, or T3 for the remaining items (p > 0.05). Regarding the between-groups comparisons, the MTG significantly improved the corporal pain item compared to the PG at T1 , although not at T2 (p > 0.05) or T3 (p > 0.05). For the other items, there were no significant differences between the groups at T1, T2, or T3 (p > 0.05).When the quality of life domain was analyzed  in the Mp > 0.05) , nor between the groups at T1, T2, or T3 in terms of depression, state-anxiety, trait-anxiety, and overall anxiety ( > 0.05) .2 (5) = 18.66; p = 0.002; CC = 0.56) and T3 (χ2 (5) = 14.80; p = 0.01; CC = 0.52) (p > 0.05).The MTG reported a greater perception of change than the PG at T1 (χ = 0.52) . HoweverAll the participants (100%) reported that the treatment they received was normal physiotherapy at the end of the study, regardless of the assigned group .The present study shows that a protocol based on manual therapy techniques improves pelvic pain, the endometriosis health profile, and physical quality of life. Interestingly, changes in pelvic pain were maintained after both the one- and six-month follow-ups. Furthermore, significant differences were observed in terms of pain and lumbar mobility at T1, T2, and T3 compared to the placebo intervention. However, the proposed protocol had no effect on depression and anxiety levels.Pelvic pain is one of the most common symptoms in women with endometriosis, and it often persists after medical treatment . Our resLumbar mobility and pain are closely related, as pain can limit a person’s ability to move. Furthermore, chronic fatigue and pain-catastrophizing thoughts have been related to physical limitations in the activities of daily living of women with endometriosis . AdditioRegarding the endometriosis health profile measured with the EPH-30, an improvement in control and powerlessness and in emotional wellbeing was observed. In line with these findings, a recent review concluded that pelvic physiotherapy stimulates the self-empowerment of women and supports the recovery of function that they may have lost due to pain and dysfunction . HoweverPain and associated gynecological symptoms, such as burning during urination (dysuria) and pain during sexual intercourse , have a great impact on the patients’ quality of life . After tSymptoms of depression and anxiety occur frequently in endometriosis patients and are related to chronic pain . HoweverAnother important variable that has gained attention in the field of chronic pain is the patient’s perception of change . In thisThis study had some limitations. First, since the manual therapy protocol included a variety of techniques, the improvement cannot be entirely attributed to just one of them. Second, since patients were permitted to use analgesic and anti-inflammatory medication as needed throughout the process, future studies should monitor whether this influenced the results with regard to the pain variable over time. Third, only pre-menopausal woman were included, yet women of reproductive age are those that suffer from the greatest impact . AdditioWithout waiving the limitations mentioned above, a manual therapy protocol based on soft tissue and articulatory techniques is effective at reducing pain and improving women’s quality of life but not the emotional status of women with endometriosis; hence, it may be considered a valid tool for improving pelvic pain due to endometriosis.


Door to balloon time is a crucial factor of mortality in patients with ST-segment elevation myocardial infarction. However, the factors that contribute to failure of achieving door to balloon time ≤ 90 min in an electrocardiogram triage system remain unknown.This single-center retrospective observational study collected data from consecutive patients with ST-segment elevation myocardial infarction from April 2016 to March 2021. The primary outcome was the failure to achieve door to balloon time ≤ 90 min. A multivariate logistic regression model was performed to predict factors associated with failure to achieve door to balloon time ≤ 90 min.p = 0.02). However, there was no significant difference in sex and timing of hospital arrival between the door to balloon time ≤ 90 and > 90 min groups. Presence of chest pain and ambulance usage were significantly more frequent in patients with door to balloon time ≤ 90 min . Multivariate analysis showed that absence of chest pain  and non-ambulance usage  are predictive factors of failure to achieve door to balloon time ≤ 90 min.In total, 190 eligible patients were included. Of these, the 139 (73.2%) patients with door to balloon time ≤ 90 min were significantly younger compared to those with door to balloon time > 90 min (Patients without chest pain as the chief complaint or non-ambulance usage were significantly associated with the failure to achieve door to balloon time ≤ 90 min.The online version contains supplementary material available at 10.1186/s12245-023-00562-5. Acute coronary syndrome (ACS) is a common disease that is annually diagnosed in more than 7 million people worldwide and has a high mortality rate . ACS is Especially for STEMI, early intervention, including primary percutaneous coronary intervention (PCI), is crucial . Many guTo achieve DTBT ≤ 90 min, early diagnosis is essential. Therefore, some clinical guidelines recommend that the time from the patient's arrival at the hospital to performing an electrocardiogram (ECG)  should be ≤ 10 min if ACS is suspected , 7, 8.Some triage systems, called ECG triage systems, have proposed that ECG should be performed at the time of triage to achieve shorter DTET and DTBT and to prevent oversights , 13. TheHowever, there are limited studies regarding the factors of failure to achieve DTBT ≤ 90 min among the patients with STEMI, with the ECG triage system. Therefore, we conducted a retrospective observational study to predict the factors of failure to achieve DTBT ≤ 90 min among the patients with STEMI with the ECG triage system.This was a single-center retrospective observational study, which was conducted at the Emergency department (ED) of a 344-bed urban acute care community hospital in Japan. Annual Emergency room (ER) visits are approximately 25,000 patients including about 10,000 ambulance transportation. This hospital is a 24-h stroke/cardiovascular center with the capability of PCI. The number of ACS patients receiving emergency PCI is about 200 per year. The ECG triage system at this ED requires that ECG is performed within 5 min for all patients with chest pain or palpitations and patients over 45 years of age with epicardial pain, epigastric pain, or nausea without diarrhea and the ECG is reviewed immediately by the attending physician. This ECG triage system was launched in March, 2016 to prevent delays in intervention to a certain number of STEMI patients with the main complaint other than chest pain. Patients transported by ambulance or walk-in are triaged by trained nurses and treated according to triage priorities. Therefore, both patients receive the same medical care. However, patients transported by ambulance may be triaged according to the vital signs reported by the emergency services prior to arrival. The time to triage may therefore be affected.This study was approved by the ethics committee of the hospital and was conducted according to the ethical guidelines of the Declaration of Helsinki. The ethics committee also approved the waiver of informed consent because of retrospective nature of this study.Myocardial infarction (MI) was defined according to the Fourth Universal Definition of Myocardial Infarction . DiagnosWe obtained data including age, sex, mode of hospital arrival (ambulance usage or not), the timing of hospital arrival (on-hours or off-hours), symptoms (chief complaint), DTBT, and DTET. On-hours was defined as 9 a.m.-5 p.m. on weekdays. Chief complaint consists of chest pain, palpitations, epicardial pain, epigastric pain, nausea without diarrhea and others. In this study, door time  was defined as the time of arrival at reception for walk-in patients or the time of ambulance arrival.The primary outcome was the failure to achieve DTBT ≤ 90 min. The secondary outcome was the failure to achieve DTET ≤ 10 min. Both outcomes are defined as clinical indicator in several clinical guidelines –8. In thContinuous variables were expressed as median values with interquartile range (IQR), based on their distributions. Categorical variables were expressed as numbers and percentages. Age, sex, mode of hospital arrival, timing of hospital arrival, chief complaint were compared between the DTBT ≤ 90 min and DTBT > 90 min groups and between the DTET ≤ 10 min and DTET > 10 min group, using the Mann–Whitney U test for continuous variables based on the distributions and the Chi-square test for categorical variables when appropriate. To predict factors associated with failure to achieve DTBT ≤ 90 min and DTET ≤ 10 min, multivariate logistic regression models were constructed, adjusting for the following factors: age, sex, mode of hospital arrival, timing of hospital arrival, and chief complaint.p-values of < 0.05 were considered statistically significant.The statistical analyses were performed using R software . Two-sided Five hundred patients had ST-segment elevation on initial ECG and we excluded 310 patients; 146 were transported after diagnosis of STEMI by the previous doctor, 71 did not undergo emergency PCI, 64 were not initially treated by ER physicians, 23 had CPA (including OHCA) in ER, and 6 were transferred to other hospitals. The remaining 190 patients were eligible for this study . Chest pain and ambulance usage were significantly frequent in DTBT ≤ 90 min group than in DTBT > 90 min group . There was no significant difference in sex and the timing of hospital arrival between the DTBT ≤ 90 min and DTBT > 90 min groups. Of the 39 patients whose chief complaint was other than chest pain, 9 had dyspnea, 8 had syncope, 6 had nausea without diarrhea, 5 had difficulty moving, 4 had epigastric pain, 3 had upper limb numbness, and 4 had other symptoms.The baseline characteristics of each group are shown in Table p < 0.01, adjusted OR 3.53; 95%CI, 1.57–7.94; p < 0.01, Table The multivariate regression analysis showed absence of chest pain and non-ambulance usage were predictive factor of failure to achieve DTBT ≤ 90 min (adjusted OR 4.76; 95%CI, 2.04–11.1; p < 0.01, adjusted OR 14.5; 95%CI, 5.88–35.8; p < 0.01, Table As secondary outcomes, patients with DTET ≤ 10 min were 72.6% (138/190, Appendix Table This study showed that absence of chest pain and non-ambulance usage were predictive factors for the failure to achieve DTBT ≤ 90 min. On the other hand, off-hours presentation was not a predictive factor.The absence of chest pain as the chief complaint was associated with a significantly higher rate of failure to achieve DTBT ≤ 90 min and DTET ≤ 10 min. Consistent with our results, previous studies have reported that the absence of chest pain was an independent risk factor for delayed DTBT , 19. OurNon-ambulance usage was associated with a significantly higher rate of failure to achieve DTBT ≤ 90 min. Previous studies reported that arrival by walk-in was an independent factor for the failure to achieve DTBT ≤ 90 min similarly , 21. In In this study, off-hours presentation was not associated with the failure to achieve DTBT ≤ 90 min. This was contrary to previous studies, which reported that off-hours presentation was significantly associated with a higher rate of failure to achieve DTBT ≤ 90 min and of in-hospital mortality . Holmes In this study, the absence of chest pain was still a predictive factor for the failure to achieve DTET ≤ 10 min despite the ECG triage system included symptoms other than chest pain to the indication of ECG. The primary cause could be human factors such as individual experience and cognitive biases in the triage system. The previous study reported that more experienced ER nurses tend to perform under-triage during triage assignment . In addiThis study revealed that the factors for delayed diagnosis and treatment of STEMI patients is absence of chest pain or non-ambulance usage. The advance triage system that performs ECGs, even if patients have no chest pain or did not arrive by ambulance, could potentially prevent delays in diagnosis and treatment of STEMI. However, comprehensive testing could increase medical costs. Therefore, further research is warranted to verify the cost-effectiveness of such a system. As this research, exploratory research after the introduction of triage systems can lead to the development of a standardized Triage ECG System. The standardized triage system will be validated in a multicenter and prospective study.Our study had several potential limitations. First, our study was a retrospective observational study conducted at a single facility with urban ER-based emergencies. Generalizability may not be applicable. Second, potentially unmeasured confounders affected DTBT or DTET, such as vital signs at arrival and co-morbid conditions. Third, the accuracy of the medical records may have been hampered by vague symptom descriptions by the physicians in charge.Patients without chest pain as the chief complaint or non-ambulance usage were significantly associated with the failure to achieve DTBT ≤ 90 min and DTET ≤ 10 min.Additional file 1:Appendix Table 1. Patient characteristics according to door to ECG time.


This study aims to estimate the safety, efficacy, and median effective dose (ED50) of esketamine for preventing early postoperative pain in patients undergoing laparoscopic cholecystectomy.54 patients undergoing laparoscopic cholecystectomy were prospectively randomized into two groups (group C and group E). Different doses of esketamine were intravenously administered before the skin incision in Group E. The patients in group C received the same dose of saline at the same time. General population characteristics were recorded. The median effective dose (ED50) and 95% effective dose (ED95) were calculated using Dixon’s up-and-down method. Hemodynamic parameters were monitored, and pain intensity was assessed using a visual analog scale. We also recorded the condition of anesthesia recovery period and postoperative adverse reactions.p < 0.05). The total VAS score at resting was significantly lower in the esketamine group compared to the control group during the awakening period (p < 0.05). There was no significant difference between the two groups regarding the incidence of adverse reactions (p > 0.05).The ED50 of esketamine for preventing early postoperative pain was 0.301 mg/kg (95%CI: 0.265-0.342 mg/kg), and the ED95 was 0.379 mg/kg (95%CI: 0.340-0.618 mg/kg), calculated by probability unit regression. Heart rate (HR) was significantly lower in the esketamine group compared to the control at the skin incision (In this study, esketamine can prevent early postoperative pain effectively. The ED50 and ED95 of esketamine for controlling early postoperative pain were 0.301 mg/kg and 0.379 mg/kg, respectively.ChiCTR2200066663, 13/12/2022. Laparoscopic cholecystectomy (LC) has been the gold standard for surgical treatment of gallbladder disease because of short surgery time, good surgical vision, less trauma, less blood loss, easy recovery, and low infection rate , 2. HoweKetamine, a noncompetitive, channel-blocking NMDA-R antagonist, is considered to be highly correlated with acute early postoperative pain . The studies indicated that preemptive ketamine might reduce acute early postoperative pain, especially incisional pain and visceral pain, in patients undergoing gynecological laparoscopic surgery , 18. In In this study, we estimate the safety and efficacy of esketamine for preventing postoperative pain in patients undergoing laparoscopic cholecystectomy, and determine the median effective dose(ED50) and 95% effective dose (ED95) of esketamine by applying the up-and-down sequential allocation technology designed by Dixon and Massey.We performed a prospective, double-blind, up-down sequential allocation study to determine the ED50 of esketamine for preventing early postoperative pain. The study was conducted in agreement with the Helsinki Declaration and approved by the Ethics Committee of Affiliated Hospital of Nantong University. All participants underwent an informed consent process and signed a consent form. The study was registered in the Chinese Trial Registry . This study adhered to the CONSORT 2010 statement.2, (3) no restrictions on gender and ethnicity, (4) ASA class I and II, (5) all patients must have total comprehension. Exclusion criteria were as follows: (1) immediate extubation was not planned after surgery, (2) patients were complicated with substantial diseases of essential organs, (3) allergy to related drugs applied in the trial, (4) patients with a history of alcohol or drug abuse, (5) the patients had severe hypokalemia, ocular hypertension and intracranial hypertension, (6) participants had a history of psychiatric neurological disorders and/or taking the related medicine, (7) intraoperative changeover from laparoscopic to open cholecystectomy.The patients who were scheduled to receive laparoscopic cholecystectomy were enrolled in the study. The inclusion criteria for the studies were as follows: (1) age: ≥18 years old, (2) BMI: 18–28 kg/m66 patients requiring general anesthesia were randomized into the control group (group C) or esketamine group (group E) using a computer-generated random sequence placed in sequentially numbered opaque envelopes, which were opened before surgery. The drugs were prepared in 20-ml syringes labeled as the “study drug” and then placed into opaque envelopes before the study by an independent anesthesiologist. Another experienced anesthesiologist implemented anesthesia, and a specialized anesthesia nurse, blinded to the group allocation, performed the postoperative data collection. Patients, clinicians, and nurses were blinded to group assignment and study drugs for the duration of the trial. Incisional pain is defined as a pain restricted to incision site on abdominal wall. Visceral pain is defined as a deep, dull and hard-to-locate pain, while opioid-induced hyperalgesia (OIH) is defined as an increased sensitivity to normally painful stimuli in LC. Patients were educated to distinguish these three types of pain from our definitions.The anesthesia and surgical procedure will be consistent between the two groups. In the operating room, the patient received an intravenous fluid replacement and mask oxygen. Then, vital signs and depth of anesthesia were monitored, and baseline values were measured before anesthesia. General anesthesia was induced with midazolam 0.03-0.04 mg/kg, etomidate 0.2–0.3 mg/kg, sufentanil 0.3–0.5 μg/kg, and cisatracurium 0.15-0.2 mg/kg. After tracheal intubation, Group E received different doses of esketamine through intravenous administration, and Group C received the same quantity of saline at the same time. The anesthesia was maintained with propofol 4–6 mg/(kg·h), sevoflurane 1-1.5%, remifentanil 0.2–0.3 μg/(kg·min), and cisatracurium 0.1-0.15 mg/kg/h. Sevoflurane and cisatracurium were no longer used during skin incision suturing. Inadequate anesthesia was defined as patient movement, swallowing, lacrimation, sweating, hypertension, and tachycardia , and the bispectral index (BIS) score greater than 60. When the depth of anesthesia was considered insufficient, the propofol, remifentanil and sevoflurane infusion/intake rates were changed in steps of 1 mg/(kg·h), 0.05 μg/(kg·min) and 0.5%, respectively. BP and HR were stabilized between ± 20% of baseline. Parecoxib 40 mg was administered when pneumoperitoneum was stopped, and 0.5% ropivacaine was applied to the incision for local infiltration anesthesia.Atropine and esmolol were routinely administered to regulate Heart rate (HR), and dopamine and urapidil were used for maintaining blood pressure stability conventionally. All anesthetics were discontinued after the operation, and then the patients were transferred to the postanesthetic care unit (PACU). If the TOF ratios were 1.0, residual neuromuscular blockade was antagonized with neostigmine 0.02 mg/kg together with atropine 0.01 mg/kg, and the dosages of drugs were adjusted based on the patient’s actual conditions. The patients were extubated after surgery when they met the extubation indications.Group E received different doses of esketamine  through intravenous administration before the skin incision. The patients in group C received the same quantity of saline at the same time. The EC50 and ED95 of esketamine for the patient were determined by the up-down allocation methodology .The starting dose of esketamine was set at 0.3 mg/kg for the first participant, as determined by drug instructions. This dose is commonly used in clinical practice and many studies , 26. TheThe primary outcome measure was the ED50 and ED95 of esketamine for preventing early postoperative pain. The visual analogue scale (VAS) was used to measure the pain intensity at the time point of the awakening period  in two groups, which was an 11 cm scale from zero (no pain) to 10 (most severe pain).The secondary outcome measures were demographic data, vital signs, the condition of patients during anesthesia recovery, and postoperative adverse reactions. Demographic data were recorded, including age, gender, body mass index(BMI), ASA classification (I/II), duration of surgery, sufentanil doses, remifentanil doses, and propofol doses(intraoperative maintenance doses). Vital signs  were tabulated at the time point of T0 , T1 (skin incision), and T2 . There were also several indexes during the anesthesia recovery: awakening time , VAS score at 15 min after tracheal extubation, total VAS score(resting and cough) at 15 min after tracheal extubation, Steward score after extubation, numbers requiring rescue analgesia after extubation, numbers requiring antagonize the residual muscle relaxant, and the medication usage conditions  in PACU. The postoperative adverse reactions included nausea and vomiting (PONV), hallucinosis, dizziness, itching, nystagmus, nightmare, and postoperative respiratory depression.Steward Scale score is usually applied to assess the awakening intensity during the recovery period and mainly includes awake degree, airway patency, and limb mobility. The awake degree is divided into three categories: fully awake (2 points), response to stimulation (1 point), and no response to stimulation (0 point). Airway patency is collapsed into three categories: can cough according to the doctor’s order (2 points), can maintain airway patency without support (1 point), and respiratory tract needs support (0 point). Limb mobility is classified into three categories: limbs can do conscious activities (2 points), limbs can make unconscious activities (1 point), and no movement of limbs (0 point). The patients could be thought to be leaving the recovery room when the overall scores are greater than or equal to 4.2) or Fisher’s exact test. The ED50, ED95, and 95% confidence intervals (CIs) of esketamine were calculated using the probit method (probability unit regression) by analyzing the tallied numbers of ‘effective’ and ‘ineffective’ responses for each group based on the up-and-down allocation method.The data were processed by the software SPSS 22.0 and graphed by GraphPad Prism 9.5.1. Normally distributed continuous data were presented as mean ± standard deviation (SD) and analyzed using the Student’s t-test. Non-normally distributed continuous data were expressed as median (IQR) and analyzed using the Mann-Whitney U test. Categorical variables were expressed as frequencies (percentages) and analyzed using the Chi-square test (χp > 0.05) . No significant differences in HR values were found between the two groups at the time points of T0 and T2(p > 0.05). Notably, there was a significant increase in heart rate in the control group at the time points of T1 compared to the esketamine group (p < 0.05).The mean arterial pressure (MAP) and heart rate (HR) are shown in Table p > 0.05). Compared with the control group, there was a significant decrease in the total VAS score at resting during the awakening period in the esketamine group (p < 0.05).The conditions of patients during anesthesia recovery are listed in Table p > 0.05).Postoperative adverse events as one of the outcomes are listed in Table Biliary calculus, also known as gallstone, is a crystalline solid formed from bile concentration and composition changes caused by changes in diet, hormones, medications, or rapid weight loss or weight gain . LaparosEsketamine, the S (+)-isomer of ketamine, a non-selective NMDA receptor inhibitor, possesses part of non-opioid analgesic properties and an analgesic effect twice that of racemic ketamine , 30, whiA reasonable choice of drug dosage will be necessary for decreasing the rate of adverse effects while maintaining the efficacy of the treatment. In order to determine the optimal amount of esketamine for preventing postoperative pain, four groups were divided by Yan-ling Ren and colleagues according to the different doses of esketamine, and it reported that intravenous injection of esketamine 0.4 mg/kg before anesthesia induction was a suitable dose to reduce pain sensitivity in patients undergoing thyroidectomy without increasing adverse reactions . As is wPostoperative pain after LC consists of three components: incisional pain (somatic), deep abdominal pain  and opioid-induced hyperalgesia (OIH). Incisional pain is a unique and common form of acute pain that may involve nociceptive, inflammatory, and neuropathic pain , 34. TheLocal infiltration block provides excellent analgesia for incisional pain, but unfortunately, visceral pain and opioid-induced hyperalgesia are still evident. Visceral pain is a complex, unpleasant feeling caused by trauma and inflammation that is generally described as dull, diffuse, and poorly localized, mainly transmitted by the autonomic nervous system, and is frequently accompanied by malaise and strong autonomic reflexes –38. Viscp < 0.05), suggesting esketamine could prevent early postoperative pain effectively, including visceral pain and hyperalgesia. However, there were no statistically significant differences between the two groups for the total VAS score during cough and the numbers requiring rescue analgesia during the awakening period (p > 0.05), and there are three possible explanations for these: (1) the esketamine dose too low in some patients of the Group E; (2) the sample size is too small and insufficient number of events; (3) the cough reflex exacerbate the incisional pain and visceral pain.Ketamine, which works as an NMDA antagonist, has been shown to reduce incisional pain, visceral pain and hyperalgesia , 17, 41,s esketamine, and it was significantly higher than the baseline value [Esketamine is a dissociative anesthetic with sympathomimetic and broncho-dilating properties, similar to ketamine. Recent reports found that 14/70 patients experienced treatment-emergent transient hypertension after intravenoune value , which ine value . In our Our study has some limitations. Firstly, the sample size was set according to the up-down allocation methodology rather than the sample size estimation. Secondly, the comparison of VAS scoring between the two groups had some limitations because the esketamine group used different doses. Finally, this study only examined early postoperative pain to ensure adequate analgesia during the operation, and did not evaluate long-time postoperative analgesia of esketamine.In conclusion, our study showed that the ED50 and ED95 of esketamine for preventing early postoperative pain were 0.301 mg/kg (95%CI 0.265 ~ 0.342 mg/kg) and 0.379 mg/kg (95%CI 0.340 ~ 0.618 mg/kg) respectively. Intraoperative esketamine effectively dampened intraoperative noxious stimuli and had no impact on awakening from anesthesia, with a favorable safety profile.


No correlations were found in the “negative” group or when the patient-doctor relationship was ignored. We found a significant association between subjectively assessed low back pain intensity and serum levels of total and LDL cholesterol in patients with whom the physician had a positive affinity. A positive affinity with the patients having chronic pain and the patient's trust in their physicians may ultimately mean that the patient's statement about pain is more credible, which may retroactively affect the outcome of therapy.Statistical data show that pain intensity in patients with low back pain is associated with a higher BMI, total serum cholesterol, and triacylglycerol levels. The objective of our study was to evaluate how these associations are dependent on the nature of the patient-doctor relationship. Eighty-nine patients hospitalized with chronic low-back pain  were assessed over a 3-year period. A serum lipid analysis was conducted  at admission in parallel with a subjective evaluation of pain intensity, which was assessed using a numeric rating scale. The participating physician assigned, based on their personal interaction with the patient, an attribute of affinity  towards them. Current serum lipid levels and pain intensity were correlated relative to these attributes. Pain intensity did not differ between the groups assigned positive or negative attributes of affinity. In patients belonging to the “positive” group, pain intensity correlated positively with total cholesterol ( Chronic pain is an indirectly observable phenomenon. There are no quick and accurate objective methods for evaluating its intensity. Objective electrophysiological methods, neuroimaging, and mapping the activity of the autonomic nervous system have all been used to assess acute as well as chronic pain, but they are not practical for use in everyday practice –5. In coPrevious animal and human studies have shown that both acute and chronic pain alter serum lipid levels –15. The Because blood chemistry is a routine, reproducible, and particularly easy evaluation, the goal of our work was to study the association between subjectively experienced pain and serum lipid levels in patients with chronic vertebrogenic pain but without significant obesity.A patient's assessment of their pain, in the presence of an attending physician, can be significantly influenced by their relationship with the physician. We also have the patient's motivation to be treated, which can simulate or dissimulate pain, which can be affected by their relationship with the doctor. Empathy is the ability to share the affective states of others, or the ability to understand the pain of others, and is important in the formation of a positive doctor-patient relationship . It is aWe tested the hypothesis that patients with more intensive vertebrogenic pain would have higher plasma lipid levels, especially total cholesterol, and LDL cholesterol. Additionally, we looked at how this association could be influenced by the patient-doctor relationship, also called therapeutic alliance ; an assoThis was a multiyear observational study. Over three years, 89 patients  with an M51-4 or G54.2-4 diagnosis, based on the 10th ICD-revision and chronic vertebrogenic pain were evaluated at the inpatient unit of the Department of Neurology. The vertebrogenic symptom complex includes local and referred pain and autonomic reflex dysfunction within the lumbosacral zones of the head . The paiStudy exclusion criteria included the following: dependence on tobacco, alcohol, or narcotics, hormonal therapy treatment, medical treatment for an endocrine disease, and psychiatric diagnosis. All patients were taking nonsteroidal anti-inflammatory drugs, 20 patients were taking antidepressants, and 32 patients were taking statins. All patients signed informed consent, and the study was approved by the local Ethics Committee.On the day of admission, blood samples were drawn from fasting patients. Serum lipids, i.e., total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, and triacylglycerols (TG), were measured using an automatic biochemical analyzer in a certified laboratory. In the presence of a physician, the patients assessed their pain intensity using a numeric rating scale (NRS-11) by assigning numbers 0–10 to their pain level, where 0 was a pain-free state, and 10 was the maximum imaginable pain intensity.At this same time, the attending physician assigned an attribute of affinity (or fellowship) based on their experience with the patient, where “+” means a high degree of affinity with the patient, “0” a neutral affinity, and “−” a negative affinity with the patient. The attitude towards the patient was based primarily on the subjective experience of mutual verbal and nonverbal communication.All quantitative variables are given as means and standard deviations, and qualitative variables were given as frequencies and percentages. These parameters were calculated both for all patients together and for two groups of patients, which were created according to the patient-doctor relationship. In the first group were the patients with positive affinity attribute and in the second group were the patients with negative or neutral attribute.To find the relationship between pain intensity NRS-11 and serum lipids, i.e., TC, LDL-C, HDL-C, TG, and LDL/HDL ratio, as well as between NRS-11 and age and BMI of the patients, the parametric Pearson's correlation coefficients were calculated. The required sample size for all significant correlations was calculated.t-test was used. To compare the qualitative variables, i.e., sex (M/F) and medication with statins (Yes/No) and antidepressants (Yes/No), the analysis of contingency tables was used; Pearson's chi-square test was calculated.After merging the indifferent and negative groups of patients, we obtained two groups of patients with positive and negative rapport. For the comparison of age, BMI, NRS-11, and all observed serum lipids between these two groups of patients, the parametric Student's In order to evaluate the effect of all observed variables in the assessment of the severity of chronic pain (NRS-11), the general multivariable regression analysis was performed. We created three regression models—for all patients together and for each group of patients—with positive and negative rapport separately.In order to find whether our observed variables discriminate well enough between the two groups of patients (positive vs. negative rapport), the multivariate logistic regression model was performed. The list for predictive factors was the same as in the multivariate regression model except for the addition of NRS-11.p value less than 0.05 was considered to be statistically significant.TIBCO Statistica version 14.0 and IBM SPSS Statistics version 23 were used for statistical analysis. A p=0.92). Men had higher TG compared to women , but they did not differ in levels of TC, LDL-C, and HDL-C.The mean pain intensity was the same in men and women . The groups did not differ relative to pain intensity.Thirty-two patients (21 men and 11 women) were taking statins for lipid-lowering therapy. The statin group had lower TC and LDL-C in comparison with untreated patients  were taking antidepressants. Neither pain intensity nor lipid levels differed from patients not taking antidepressants. The lower weight and BMI in this group reflects the greater number of women in the group.Forty-three patients (18 men and 25 women) received a positive affinity attribute, thirty-six patients (18 men and 18 women) received a neutral attribute, and ten patients (3 men and 7 women) received a negative attribute. Due to the small number of subjects in the last category, these patients were merged with the neutral group, creating a group that contained 21 men and 25 women.p=0.028) and the LDL/HDL ratio which was also significantly lower in the positive affinity patients . According to the results of contingency tables analysis    in the group of positive affinity patients only. Required sample size conditions were almost fulfilled only for TC (required sample size 48) and LDL-C (required sample size 45). Neither HDL nor TG nor age and nor BMI correlated with pain intensity in any group.Analyzing the relationships between pain intensity and lipid levels in the entire sample of patients, it was shown that pain did not correlate with any particular variable. In contrast, we found a significant positive correlation between TC and pain intensity (p=0.010) , LDL-C ap=0.007) , and LDLIn order to evaluate the effect of serum lipids, age, BMI, sex, and medication with statins and antidepressants on the assessment of the severity of chronic pain, general multivariable regression analysis was performed. As the independent variable, we used all serum lipids, i.e., TC, LDL-C, HDL-C, TG, and LDL/HDL ratio, and then age, BMI, sex, and medication with statins and antidepressants; as the dependent variable, the pain intensity was used. We created three regression models—for all patients together and for each group of patients—with positive and negative rapport separately. All three models were statistically insignificant, and neither model was significant for predicting the severity of chronic pain, NRS-11.R2 are as follows: positive rapport group: R2 = 0.249, negative rapport group: R2 = 0.169, and the entire sample of patients, as the input factor, the rapport between the patient and the doctor (positive vs. negative) was added. The coefficient of determination R2 = 0.103, the only variable for which the p value is less than 0.1, was the LDL/HDL ratio (p=0.087).The values of coefficients of determination In order to find whether our observed variables discriminate well enough between the two groups of patients (positive vs. negative rapport), the multivariate logistic regression model was performed. The list for predictive factors was the same as in the multivariate regression model except for the addition of NRS-11.p=0.352, Nagelkerke R2 is only 0.146, and for the Hosmer–Lemeshow test, the p value is 0.490; the model adequately interpolated the data. The classification ability is only 59.3%. The area under the ROC curve (AUC) which determines the discrimination power of the logistic model reached the value 0.695; discrimination quality according to Tape [The results are as follows: 2LL statistics is insignificant if  to Tape  is “PoorIn our study, we found a positive correlation between the subjectively evaluated intensity of chronic vertebrogenic pain and serum total and LDL cholesterol levels in adult patients with whom the attending physician had a relationship describable as positive affinity.Experiments with animals have shown that serum lipids might reflect a nonspecific stress effect of acute and chronic pain . After aHigher serum levels of triglycerides and HDL-cholesterol were detected in the acute pain of patients with fractures and acute pancreatitis . These vIn several studies, atherogenic lipids, LDL cholesterol, and triglycerides were associated with clinical manifestations of lumbalgia (low back pain) to support the lumbar atherosclerosis hypothesis as a cause of intervertebral disc degeneration or chronic hip pain , 24. On Conversely, there is a work showing a decrease in total cholesterol in acute severe trauma. Patients with good outcomes in intensive care units showed improvement in TC levels during treatment, while a further reduction was observed in patients with infections, organ dysfunction, or death .It is also important to note that each disease has its own dynamics. During illnesses, lipid levels may change and different active substances, not only lipids, may differently affect pathological pain processes during the transition from acute to chronic pain .Compared to women, men have higher triglycerides and total cholesterol levels and lower HDL-C-levels . Also, tIn men, the total cholesterol and triacylglycerol levels correlated with the five-year probability of developing lumbar vertebrogenic algic syndrome. This relationship has not been demonstrated in women . AnotherThe role of statins in influencing pain is not yet fully clear. Attenuation of thermal hyperalgesia in an animal model of neuropathic pain, induced by partial ligation of the sciatic nerve, was independent on the statin-induced hypolipidemic effect .In our study, patients taking statins had lower TC and LDL-C in comparison with patients without this treatment. Contrary to the expectation, triglycerides in these patients were increased. This observation can be explained by statins being effective at decreasing triglyceride levels but only in hyper-triglyceridemic patients .Even though statins also exert a pleiotropic nonlipid effect, they possess anti-inflammatory properties and antioxidant and neuromodulatory effects; we did not observe any effect on pain intensity in patients treated with statins . The conSeveral studies have demonstrated frequent co-occurrences of pain and depression. Chronic pain is associated with changes in brain physiology and anatomy, and the positive impact of antidepressants might result in a reduction of these pathological processes and in the amelioration of symptoms, which can improve the quality of the life of patients , 36. TheThe most important result of our study was finding a positive correlation between the subjectively evaluated intensity of chronic vertebrogenic pain and serum total and LDL cholesterol levels in adult patients with whom the attending physician had a relationship describable as a positive affinity.Here is the distinction between affinity, which can be understood as an affirmative connection with the feelings of another person and empathy, which represents an act of understanding without the need to agree with the feelings of another . EmpathyThe positive correlation between pain and serum lipids is certainly influenced by the patient's own assessment of pain. This means that the self-assessment of pain intensity may be somewhat affected by a therapeutic relationship in which it can function as a placebo or nocebo effect. According to Fabrizio Benedetti, meeting the doctor involves many psychological responses in the patient's brain, which are responsible things such as expectations, trust, and hope. Similarly, many mechanisms are at work in a doctor's brain, such as empathy and compassion. In turn, these led to the final step of providing therapy, which regardless of its effectiveness or ineffectiveness, triggers a placebo response” .Many studies have shown that physical activity is a safe method for improving patients' physical performance and alleviating symptoms. Both high-intensity aerobic exercise and long-term low-intensity exercise were found to reduce pain, the disability rate, and psychological stress and enhance quality of life in patients with low back pain , 41. In The impact of exercise on the lipid profile is somewhat controversial; a number of data confirm the beneficial effects of the regular activity on cholesterol levels; however, significant inconsistency in the blood lipid response has been observed. The most frequently observed change was an increase in HDL-C with less frequently observed decrease in TC, LDL-C, and TG , 43.We consider the quality of the therapeutic relationship to be crucial for an objective verbal assessment of pain. Although the number of patients in our work is limited and the verification of the relationship presented in this study deserve more extensive research in relation to gender, age, and cultural habits, we consider a good therapeutic doctor-patient relationship a good starting point for more objective pain assessment.We would like to believe the research results will be similar even in selecting and assessing other patients by another therapist. Rapport is not a personality trait, and individuals experience rapport as the result of a combination of qualities that emerge from each individual during interaction . This hyIn conclusion, we found a positive correlation between subjectively evaluated chronic vertebrogenic pain intensity and serum total and LDL cholesterol levels in adult patients treated by a physician who described their relationship as having the attribute of positive affinity. This positive relationship between a physician and a patient with chronic pain, as well as the patient's confidence in the physician, may result in a more credible pain assessment by the patient, which may retroactively affect the outcome of the therapy.


Herpes zoster (HZ)‐related pain, characterized by chronic and persistent pain with a dermatomal distribution, is a relatively common complication of HZ. Pulsed radiofrequency (PRF) can effectively relieve HZ‐related pain. There is no study on the effect of the needle tip position in patients with HZ for PRF treatment. This prospective study was conducted to compare two distinct needle tip positions in PRF for HZ‐related pain.n = 36) and OP group . Quality of life and pain control were evaluated with the visual analog scale (VAS) and activities of daily living questionnaires , which were administered before therapy and at intervals of 1, 7, 30, and 90 days after therapy.Seventy‐one patients suffering from HZ‐related pain were enrolled in this study. According to the dorsal root ganglion (DRG) position and needle tip position, patients were randomly allocated to the IP group . No significant differences were found when the two groups were compared at 1 and 7 days after therapy (p > 0.05). But, the pain score was significantly lower in the IP group at 30 days  and 90 days of follow‐up . Significant differences between the two groups in terms of general activity , mood , relations with other people , sleep , and enjoyment of life  were detected after the 30‐day follow‐up. In addition, scores for the activities of daily living were significantly lower in the IP group than that in the OP group at 90 days after therapy (p < 0.05).Before therapy, the mean pain score was found to be 6.03 ± 0.45 in the IP group and 6.00 ± 0.65 in the OP group  position and needle tip position, patients were randomly allocated to the IP group (group inside of the pedicle) and OP group (group outside of the pedicle). This is the first study on two distinct needle tip positions in PRF for HZ‐related pain. In this study, it was shown that the patients in the IP group had significantly better pain relief and higher activities of daily living than that in the OP group. Kim et al.Although PRF can offer pain relief, it faces some problems. Ding et al.It has been shown that PRF can reduce HZ‐related pain, but the poor efficacy of the treatment in some patients was quite confusing. At present, studies have demonstrated that needle tip position was significantly related to treatment effects.22.1Between January 2018 and December 2019, 116 HZ patients who underwent PRF were enrolled at Wuhan No. 1 Hospital. All patients were randomized 1:1 in the study , with a two‐sided 0.05 significance level and assuming an error of 5%. According to the reduced VAS scores and the effectiveness of PRF therapy , a minimum of 35 patients per group were required.The study was conducted in accordance with the principles of the Declaration of Helsinki and the guidelines of Wuhan No. 1 Hospital. All patients were asked to sign an informed consent document. The diagnosis of HZ was based on typical manifestations such as a vesicular, painful dermatomal rash.2.2The first step in treating HZ‐related pain was antiviral therapy and drug therapy . PRF therapy was considered for HZ patients who had not responded to medical therapy.The PRF operation process was as follows. The patient was placed on the operating table in a prone position. The patient was connected to electrocardiogram monitoring, and low‐flow oxygen (2 L/min), ensuring the patient's vital signs were normal. The skin was disinfected and sterile covered. One‐percent lidocaine 3 mL was applied to the local anesthesia. Under digital subtraction angiography guidance, the needle was punctured into the target site  was used to perform the statistical analyses. Kolmogorov–Smirnov test was used to assess the normality of data distribution.t test or chi‐square test was used to compare the data between the groups. The data of VAS and activities of daily living were assessed using the Mann–Whitney U test. Graphical representations were performed by Origin software . p < 0.05 was considered statistically significant.Demographic and clinical data for patients with HZ‐related pain were described using the mean ± SD and count (percentage) to represent continuous and categorical variables, respectively. A 33.1n = 36; OP group, n = 35) were finally enrolled. Two patients in the IP group and one patient in the OP group were lost to follow‐up at 90 days after therapy. The characteristics of the included 71 patients are shown in Table p > 0.05).A total of 116 patients with HZ‐related pain were included in the study. Among them, 45 patients were excluded, and 71 patients who underwent PRF . No significant differences were found when the two groups were compared at 1 and 7 days after therapy (p > 0.05). But the pain score was significantly lower in the IP group at 30 days  and 90‐day of follow‐up  . Significant differences between the two groups in terms of general activity , mood , relations with other people , sleep , and enjoyment of life  were detected after the 30‐day follow‐up. In addition, scores for the activities of daily living were significantly lower in the IP group than that in the OP group at 90 days after therapy (p < 0.05).Figure 3.3Numbness at the site of the skin puncture occurred in two patients in the IP group and one patient in the OP group. This symptom lasted for about 1 day and disappeared without any treatment. No other adverse events or neurological complications were found in the study.4This is the first prospective study on two distinct needle tip positions in PRF for HZ‐related pain. In this study, it was shown that the patients in the IP group had significantly better pain relief and higher activities of daily living than that in the OP group.There is controversy in the treatment of HZ‐related pain with PRF. A systematic review in 2019 concluded that the evidence for most interventional procedures used to treat postherpetic neuralgia is Level 2, according to “The Oxford Levels of Evidence 2”.The mechanism of PRF for pain relief is unknown. Chen et al.p = 0.006) and 90‐day follow‐up . After the 30‐day follow‐up, scores for general activity, mood, relations with other people, sleep, and enjoyment of life were significantly lower in the IP group (p < 0.05). Unfortunately, our results differ compare with those reported by Kim and colleagues due to the following possible reasons. On one hand, it has been shown that the DRGs anatomy varies in the thoracic and lumbar spine. Shen et al.Clinically, although PRF can effectively relieve HZ‐related pain, there are still some patients with poor pain relief and the factors that influence the efficacy of PRF treatment are uncertain. At present, studies have found that needle tip position may affect the treatment efficacy. Irwin et al.There were some limitations in the study. First, the main limitation of our study was that the sample size was small and the follow‐up period was short, which may affect the reliability of this study. Second, morphine equivalent consumption may not be quantified. We could not standardize pain therapies after discharge, resulting in a potential bias of follow‐up results. Third, the pathologic anatomy of the DRG may differ in the spine. Radiologically, there were three types of the location of the DRG . In this study, we only considered foraminal and extraforaminal DRG because previous research found that the intraspinal types only occurred at the L5 level in the lumbar spine, and the incidence of the variation was 5.7%.In conclusion, the position of the needle tip had an influence on the PRF treatment in patients with HZ‐related pain. Positioning the needle tip in the area between the medial and lateral edges of adjacent pedicles offered good HZ‐related pain relief and improved quality of life.The authors have no funding and conflicts of interest to disclose.


IntroductionOsteoid osteomas are the most frequent true benign bone tumor in the adolescent age group and the third most prevalent benign bone tumor overall. This study was designed to assess the effectiveness of the procedure and correlate it with the analgesia offered because of the significant burden of this illness and new literature supporting the successful outcomes of image-guided percutaneous radiofrequency ablation (RFA) in osteoid osteoma.Methodology This hospital-based interventional trial was carried out in a tertiary care referral center. Forty-two patients with osteoid osteoma, ranging in age from 9 to 30, were included in the study. The patients received RFA guided by computed tomography (CT), and they were postoperatively monitored at one, two, and four weeks and three, six months, and 12 months. A numerical pain scale (NPS) was used to evaluate the patient's pain both before and after the procedure. The preoperative and postoperative results were contrasted.ResultsA total of 42 participants were enrolled in the study. Eight (19.05%) women and 34 (80.95%) men made up the group. Complete pain alleviation (NPS=0) was attained in 42.8% and 96.4% of the study group in the first and second weeks post-procedure. Almost all patients began protected weight-bearing at one week, according to their level of pain tolerance. Osteoid osteoma of the talus was a remnant lesion in one patient that required further treatment after two weeks. During the duration of the follow-up, no problems were recorded.ConclusionPercutaneous CT-guided RFA of osteoid osteoma is a safe, minimally invasive procedure and greatly reduces the duration of hospitalization. It has excellent functional outcomes and no known complications. Osteoid osteoma as a disease entity was first described by Jaffe in 1935 -4. The fOsteoid osteoma patients typically report pain at the site of the lesion, which is worst at night and is relieved by aspirin. At the site of the lesion, higher concentrations of the COX enzyme and prostaglandin are found . OsteoidThere are numerous treatment options, including surgical removal of the tumor, percutaneous CT-guided radiofrequency ablation (RFA), and medical management with non-steroidal anti-inflammatory drugs (NSAIDs). The lesion may heal in three to four years if the patient's symptoms are well-controlled with long-term medical management, but the course is unpredictable and the outcome of conservative treatments varies in the literature . An exacFollowing these various treatment modalities  for osteoid osteoma, pain is measured using a variety of tools, such as the visual analog score (VAS), the numerical pain score (NPS), etc. In the study, NPS (range 0-10) and VAS were used for pain measurement, both of which have a high correlation with other pain measurement tools ,15.A prospective interventional study was conducted at a tertiary care referral hospital in North India from February 2021 to February 2022. All newly diagnosed cases of osteoid osteoma with no prior surgical or radiological treatment were recruited in the study. Cases with recurrence and partially treated cases were excluded from the study. Ethical clearance for conducting the study was obtained from the Institutional review board and the approval number was 450/MC/EC/2021.NPS and VAS were used for comparison of the severity of pain preoperatively and postoperatively for the effectiveness of treatment. Due to the nocturnal rise in pain that is typical of osteoid osteoma, separate NPS and VAS measurements were collected during the day and at night.All patients were informed about various other modalities of treatment and detailed informed consent was taken in the local language from the patient or the parent (if the patient was below 18 years of age). Patients were followed up at one, two, and four weeks, and three, six, and 12 months, and VAS and NPS were documented on each follow-up. Before leaving the hospital, each patient underwent a physical examination to check for any issues linked to the treatment such as incision site bleeding, swelling, skin burns, neurovascular complications, and other issues.Intervention techniquePre-procedureInformed consent was obtained before the procedure. Dispersive grounding pads were applied in proper alignment, with good skin contact, and as close to the ablation site as possible, to allow the shortest current path through the patient. Regional anesthesia was administered in the form of spinal anesthesia for lesions in the lower limb and supraclavicular block was administered for lesions of the upper limb. Using a multidetector computed tomography (MDCT) scanner, the lesions were localized in thin sections Figure .ProcedureIn our research, a Covidien Cool Tip E series radiofrequency generator  was utilized. Radio-opaque markers are placed on the skin overlying the lesion Figure . For impThe relationship with adjacent neurovascular structures was assessed. A trochar and cannula were introduced into the lesion under CT guidance. The trochar was retracted and under aseptic precautions, a 14-gauge RF electrode was introduced into the osteoid osteoma nidus. The cannula should be withdrawn more than 1 cm from the electrode tip before ablation.Spot pictures were captured to verify that the electrode and cannula were in an acceptable position Figure . The tipA total of 44 patients with osteoid osteoma were received at our center. One patient had an incompletely treated lesion and one had a recurrence of the lesion after one year. Hence, both these patients were excluded from the study and a total of 42 patients were recruited. Nineteen patients (45.24%) were in the 9-15 year range, 15 patients (35.71%) were in the 16-20 year range, five patients (11.9%) were in the 21-25 year range, and three patients (7.14%) were in the 26-30 year range. The subjects ranged in age from 9 to 30, with a mean age of 16.17.Thirty-four individuals in our study were male (80.95%) while eight (19.05%) were female. The cortical region, which was affected in 38 individuals (90.48%), was the most frequently affected place in the bone, followed by intramedullary and subperiosteal involvement in two (4.76%) patients each. The proximal femur was the site of the lesion in the majority of individuals , followed by the shaft of the tibia with seven (16.67%) patients. The mean nidus size was 8.12±1.52 mm.At one week and two weeks after the treatment, we saw comprehensive pain alleviation (NPS = 0) in 42.8% and 96.4% of the study population, respectively. Preoperative mean NPS for day and night were 7.67 and 8.35, respectively, indicating that nocturnal pain is more intense. The mean NPS for day and night was 0.92 and 0.55 , respectively, on postoperative day 7 follow-up, indicating a considerable reduction in the intensity of pain and the efficacy of our treatment. Almost all patients began protective weight-bearing at one week, depending on their pain threshold.On successive follow-ups, there was total pain alleviation, and up until the last follow-up , no patient had experienced any complications following RFA. Patients have been advised to follow up every six months for the first two years and once a year after that to look for recurrence.Osteoid osteoma can be treated in several ways, including image-guided RFA, surgical excision, and MRgFUS . In patiWe noticed that the subjects ranged in age from nine to 30, with a mean age of 16.17, which was in line with previous studies in which almost 70% of patients with osteoid osteoma were under 20 years old . In our Osteoid osteoma commonly affects the cortices of the long bone's diaphysis, usually the lower limb, which was consistent with our findings . Other lLuigi De Palma et al. treated 20 patients with osteoid osteoma using the same modality and found that more than 95% of the time , the patients experienced significant pain relief . Bhavin In a study on percutaneous CT-guided drilling by Agashe et al., 23 patients - 13 men and 10 women, with a mean age of 10.03 years participated . The resA more recent method that uses radiation-free MRgFUS is being tested. The results of this study closely resemble those of ours. MRgFUS has the advantage of being a radiation-free procedure, but this procedure has the drawback of resolving osteoid osteoma in MRI less effectively than MDCT. Francesco Arrigoni et al. conducted a study on MRgFUS, using this technology to perform 32 procedures of ablation of osteoid osteoma. Of the 32 patients treated, all pain was completely relieved .There are several reported problems of image-guided RFA in the literature, including skin burn, infection, vasomotor symptoms, and hematoma ,27, but The small sample size (n=42) of our study was one of its drawbacks, as a larger sample size would have indicated better outcomes from this technique. Additionally, the short follow-up period (average follow-up period of 9.5 months) was not ideal because recurrence could happen even after a year. Cases of osteoid osteoma were not histopathologically validated in our investigation, as it was not necessary for diagnosis. Finally, we haven't performed RFA on osteoid osteomas in less common locations like the spine, ribs, or foot. The success rate at those sites was therefore not evaluated.Even though numerous procedures have been described for the treatment of osteoid osteoma, percutaneous CT-guided RFA of osteoid osteoma is very effective, has great functional outcomes, is safe and the least invasive, requires a short hospital stay, and has no known complications. Recent techniques are beginning to take off, such as radiation-free MRgFUS. The results are comparable, but long-term randomized control trials are required to prove one method is superior to the other.