Neoadjuvant chemotherapy plus radical surgery could be a safe alternative to chemo-radiation in cervical cancer patients who are not willing to receive radiotherapy. The response to neoadjuvant chemotherapy is the main factor influencing the need for adjunctive treatments and survival. In the present paper we aim to develop a machine learning model based on cervix magnetic resonance imaging (MRI) images to stratify the single-subject risk of cervical cancer. We collected MRI images from 72 subjects. Among these subjects, 28 patients (38.9%) belonged to the “Not completely responding” class and 44 patients (61.1%) belonged to the ’Completely responding‘ class according to their response to treatment. This image set was used for the training and cross-validation of different machine learning models. A robust radiomic approach was applied, under the hypothesis that the radiomic features could be able to capture the disease heterogeneity among the two groups. Three models consisting of three ensembles of machine learning classifiers  were developed for the binary classification task of interest (“Not completely responding” vs. “Completely responding”), based on supervised learning, using response to treatment as the reference standard. The best model showed an ROC-AUC (%) of 83 (majority vote), 82.3 (mean) [79.9–84.6], an accuracy (%) of 74, 74.1 [72.1–76.1], a sensitivity (%) of 71, 73.8 [68.7–78.9], and a specificity (%) of 75, 74.2 [71–77.5]. In conclusion, our preliminary data support the adoption of a radiomic-based approach to predict the response to neoadjuvant chemotherapy.  Cervical cancer is the third most common gynecologic cancer and cause of death among gynecologic tumors in developed countries . AlthougIn early-stage disease, surgery is the mainstay of treatment, while in the locally advanced stage, chemoradiation is the most appropriate treatment. In women with locally advanced cervical cancer, guidelines suggest offering primary chemoradiation ,6, althoThe ESGO /ESTRO (European Society for Radiotherapy and Oncology)/ESP (European Society of Pathology) guidelines suggest the avoidance of tri-modality treatment in locally advanced cervical cancer . The treatment strategy should aim at avoiding the combination of radical surgery and external radiotherapy because of the significant increase in morbidity and no evident impact on overall survival (grade B). Definitive platinum-based chemoradiotherapy plus brachytherapy is the preferred treatment (grade A) . NeoadjuHowever, in parts of Europe, Asia, and South America, where access to radiotherapy is limited, neoadjuvant chemotherapy before radical hysterectomy can be an appropriate option for women with locally advanced disease. In a phase III trial, 633 women with stage IB2, IIA, or IIB squamous cervical cancer were randomly assigned to either three cycles of NACT (paclitaxel and carboplatin administered every three weeks) followed by a radical hysterectomy or standard chemoradiation. Compared with the standard chemoradiation, women receiving neoadjuvant chemotherapy followed by surgery experienced worse five-year DFS  . Five-yeHistorically, NACT followed by radical surgery has been reported as a controversial alternative in locally advanced cervical cancer. The benefit of tumor downsizing regarding prognosis has not been proven (grade C) . NCCN . The extracted data result in quantitative features describing the heterogeneity of the tumor and other intrinsic characteristics that may correlate with its biological behavior, response to treatment, and risk of recurrence.The aim of our study was to develop a radiomics signature to predict the response to NACT in locally advanced cervical cancer using MRI images at the basal evaluation. This is a retrospective analysis conducted on patients enrolled in the study protocol 143-16 approved by the Institutional Review Board (IRB) of the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano). Consecutive patients with squamous cell carcinoma, adenosquamous carcinoma, and adenocarcinoma of the cervix treated with neoadjuvant chemotherapy at the Gynaecologic Oncology Unit of the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano between 2015 and 2020 have been considered. Patients signed informed consent forms and gave their permission for data and imaging collection for research purposes.The inclusion criteria were as follows: (i) diagnosis of invasive cervical cancer; (ii) FIGO stage IB2-IIB cervical cancer at diagnosis; (iii) available basal magnetic resonance imaging. Exclusion criteria were as follows: (i) withdrawal of informed consent; (ii) lack of MRI images at baseline; (iii) neuroendocrine carcinoma. All the patients underwent MRI performed at the Fondazione IRCCS Istituto Nazionale dei Tumori at baseline as required by the study protocol and NACT was scheduled within 2 weeks.2) d1, 8, 15 q21 chemotherapy (dose-dense regimen). After 4 weeks from completion of NACT, patients were submitted to radical hysterectomy and pelvic lymphadenectomy. All the surgeries were performed at the Fondazione IRCCS Istituto Nazionale dei Tumori and all the histologic examinations were analyzed by a pathologist fully dedicated to gynecologic pathology.All the patients, according to the study protocol, were treated with 3 cycles of neoadjuvant Carboplatin (AUC5) d1 and Paclitaxel  disease on the surgical specimen. Patients achieving partial response, stable disease, and progressive disease were grouped in the “Not completely responding” cohort. Of note, patients with pathological partial response (>3 mm) were grouped in the “Not completely responding” cohort since the goal of the study is to identify the cluster of patients who would benefit most from NACT. This image set was used for the training, cross-validation, and internal testing of 3 machine learning models. More specifically, in this work, (i) the segmentation of the VOI (volume of interest) was performed manually, slice by slice, by one expert examiner, using the Trace4Research segmentation tool  and MRI T2-weighted images. (ii) The pre-processing of image intensities within the segmented VOI included resampling to isotropic voxel spacing (1.5 mm). (iii) The radiomics features computed from the segmented VOI belonged to different families: morphology, intensity-based statistics, intensity histogram, gray level co-occurrence matrix (GLCM), gray level run length matrix (GLRLM), gray level size zone matrix (GLSZM), neighborhood gray tone difference matrix (NGTDM), neighboring gray level dependence matrix (NGLDM). Their definition, computation, and nomenclature are compliant with the IBSI (Image Biomarker Standardization Initiative) guidelines . Steps fp-values were adjusted using the Bonferroni–Holm method and the significance levels were set at 0.05 (*) and 0.005 (**).Statistical analysis was conducted with embedded tools of the Trace4Research platform. To describe the distribution of each of the most relevant features in the “Not responding” and “Completely responding” classes, we calculated their medians with 95% CI and presented graphically violin and box plots for intuitive visualization and interpretation. A non-parametric univariate Wilcoxon’s rank-sum test (Mann–Whitney U test) was performed for each of the relevant radiomic predictors to verify its significance in discriminating “Not completely responding” and “Completely responding” classes. To account for multiple comparisons, the We collected MRI images from 72 patients meeting the inclusion criteria. Among those subjects, 28 patients (38.9%) belonged to the “Not completely responding” class and 44 patients (61.1%) belonged to the “Completely responding” class, according to response to treatment. The patients’ characteristics are presented in From each segmented VOI of each image considered in this study, 3738 IBSI-compliant radiomic features were computed. Of these radiomics features, five resulted as being informative and not redundant . In particular, of the five selected radiomic predictors, two were intensity-based features , two were textural features , and the last one was a deep learning-based feature (MR-T2W_DeepFeature317).p-value. Furthermore, for each model, the ROC curves for the three ensembles are plotted in p-values. Furthermore, the two most relevant radiomic predictors  also resulted as being statistically significant in discriminating the “Not completely responding” and “Completely responding” classes , according to the univariate statistical rank-sum tests. The violin plot and boxplot of the radiomic predictors are shown in For the classification task of interest (28 images from the “Not completely responding” class vs. 44 images from the “Completely responding” class), these five predictors were used for the training, cross-validation, and internal testing  of three different models of machine learning classifiers considered in this work. In the present study, we developed and internally validated a diagnostic model based on machine learning and radiomics applied to baseline MRI images that can predict the response to NACT in patients with locally advanced cervical cancer. The baseline MRI images were processed for radiomic analysis and stable, non-redundant features were combined to create, train, and internally validate different models to classify the patients into the “Completely responding” and “Not completely responding” classes.The best model developed  our results. More importantly, large prospective studies are needed to better understand the role of artificial intelligence and deep learning in this setting. At present, radiomic-based artificial intelligence seems a promising tool that might enhance the screening, early diagnosis, risk stratification, and prognostication in cancer patients. Further prospective evidence is warranted.


Postoperative pain is common but often difficult to assess, and there are many potential confounders. Over the last decades, the gender of investigator as well as participant has been found to influence pain perception in both preclinical and clinical studies. However, to our knowledge this has not been studied in various postoperative patients. Objectives of this study were to test the hypotheses that pain intensity levels early after acute or scheduled in- or out-hospital surgery are lower when evaluated by a female investigator, and higher when reported by a female patient.In this prospective observational paired crossover study, two investigators of opposite genders independently obtained individually reported pain intensity levels with a visual analogue scale in a mixed cohort of adult postoperative study patients at Skåne University Hospital in Malmö, Sweden.P = 0.006), where the male patients constituted the significant difference (P < 0.001). Pain intensity levels did not differ between female and male study patients (P = 0.210).In total, 245  study patients were included and then one female excluded. The study patients rated their intensity of postoperative pain lower when evaluated by a female than by a male investigator (Main findings of lower pain intensity reported by males to a female than to a male investigator early after surgery in this paired crossover study in mixed postoperative patients, indicate that potential impact of investigator gender on pain perception should be considered and further evaluated in clinical bedside practice.Trial registration Retrospectively registered in the ClinicalTrials.gov research database on 24th June 2019 with TRN number NCT03968497. Study patients reported significantly lower pain intensity when evaluated by a female than by a male investigator early after surgery.Male patients constituted the statistical significance of this main finding.This finding was independent of pain intensity level, but particularly pronounced at around 3 VAS units, which is the limit where patients usually start calling for pain relief.Postoperative pain intensity levels did not differ significantly between female and male study patients.This paired clinical crossover study shows for the first time, significant impact of investigator gender on pain perception in a mixed cohort of adult postoperative patients after various surgical procedures. Postoperative pain has been estimated to affect up to 80% of surgical patients , 2, and Preclinical studies have mainly been associated with lower pain sensitivity, reflected as higher pain threshold –20 or loAccording to three extensive reviews –36, the Contrarily, in a clinical context several studies suggest females to perceive more pain after surgery –47, possTo our knowledge, potential impact of gender or sex of healthcare professionals and patients on individually reported intensity levels of pain, has never been evaluated with a paired crossover study design in a postoperative clinical setting managing a diversity of surgical procedures. The term gender, based on social instead of biological characteristics according to the World Health Organization, seems more appropriate than the term sex in this context.This paired crossover study was designed to test, primarily the hypothesis that being investigated by a female healthcare professional is associated with lower levels of reported pain intensity than by a male, and secondly the hypothesis that female patients report higher levels of pain intensity, regardless of investigator gender, early after various kinds of acute or scheduled in- or out-hospital surgery in a mixed cohort of adult patients.This prospective observational crossover study, approved by the regional Human Research Ethics Review Board in Lund  and performed in accordance with the Declaration of Helsinki, was designed to evaluate potential impact of investigator and patient gender on early postoperative pain intensity in a mixed cohort of adult surgical in- and out-hospital patients managed according to local standards of care (SOC) in three post-anaesthesia care units (PACUs) at Skåne University Hospital, Malmö, Sweden.Pain intensity levels were evaluated twice in each study patient, according to a paired crossover study design, by two investigators of opposite gender. Individual order of evaluation, primarily taking clinical conditions at the PACU into consideration, were continuously coordinated by the investigators to achieve an even overall distribution of their initial evaluations. Both investigators, a 38-year-old female and a 30-year-old male, were last-year medical undergraduate students with normal body mass index (BMI), dressed in regular gender-neutral hospital staff clothing, and fully aware of main purposes of the study.Inclusion criteria were PACU care after scheduled or acute in- or out-hospital surgery, age above 18 years, cognitive and linguistic abilities to participate, and perceived postoperative pain at the time of initial evaluation. Individual physical status was classified according to the American Society of Anesthesiologists (ASA). The study participants were subjected to abdominal, urological, gynaecological, vascular or breast surgery, classified as endoscopic or minimally invasive, laparoscopic or open procedures.Written informed consent was obtained from each study patient, after oral and written study information—regarding evaluation of pain intensity levels but not potential impact of investigator or patient gender—had been provided shortly before discharge from the PACU.Based on oral information read out loudly by the investigator from a predefined protocol, each study participant was asked to assess pain intensity at rest on two occasions early after arrival in the PACU at approximately 15-min interval.The level of pain intensity was scored between ‘no’ and ‘worst imaginable’ on a horizontally held 100-mm visual analogue scale (VAS) slide ruler, blinded to the patient and subsequently handed over for the investigator to read and record the score with one decimal from the backside.Pain intensity scores at or above 4.0 VAS units, considered to indicate at least moderate pain, were to be immediately reported to PACU nurses for further clinical measures. During their PACU stay, the study patients were subjected to additional assessments of pain according to local SOC.A total number of 198 postoperative patients had been calculated to be required to statistically confirm—based on a paired crossover study design—with 95% statistical probability, and 80% statistical power, a difference of 0.2 ± 1.0 VAS units between pain intensity scores obtained by female and male investigators. To account for 20 percent estimated drop-outs, ethical approval was obtained for inclusion of 248 patients.The Wilcoxon signed rank test was used to compare VAS scores obtained by the female and male investigators, and also to evaluate potential order and carry-over effects by accordingly comparing scores obtained on the first and second study occasions.Individual differences between VAS scores obtained by the two investigators, and individual mean values of pain intensity, were plotted according to Bland–Altman. Median values of those differences were calculated within defined intervals of individual mean pain intensity and used to assess potential impact of pain intensity on individual differences between VAS scores obtained by the two investigators. The Chi-2 test was used to compare the proportions of lower pain scores obtained by the female and the male investigator, respectively. The Mann–Whitney U-test was used to compare individual mean scores between female and male study patients.Parametrical data are reported as mean ± standard deviation (SD), and non-parametrical data as median with interquartile range (IQR) in parenthesis.P) below 0.05 were considered statistically significant.Levels of probability  than corresponding levels obtained by the male [2.6 (1.4–4.1) VAS units], as also reflected in lower pain scores obtained in more patients by the female than by the male investigator . Compared with the male investigator, the female investigator obtained significantly lower pain intensity levels in males , but not in females .Of all study patients, 49% were first evaluated by the female investigator. Pain intensity levels Fig.  obtainedMild postoperative pain (< 3.5 VAS units) was reported by 66%. The Bland–Altman plot of individual differences between VAS scores obtained by the investigators, and corresponding mean pain intensity Fig. , show thP > 0.300, endoscopic or minimally invasive vs open surgery; P = 0.162, and laparoscopic vs open surgery; P > 0.300.Individual mean levels of pain intensity were median 1.9 (IQR 1.2–3.3) VAS units after endoscopic or minimally invasive, 2.9 (1.2–3.3) VAS units after laparoscopic, and 2.9 (1.2–3.3) VAS units after open surgery. None of those median pain intensities were significantly different from each other—endoscopic or minimally invasive vs laparoscopic surgery; P = 0.015) VAS scores were obtained on the first (2.6 (1.5–4.1) VAS units) than on the second (2.4 (1.2–3.8) VAS units) occasion of individual pain evaluation.Significantly higher  had been given intravenous or oral oxycontin 1 to 7 min before the first pain evaluation, and four participants  had been given intravenous or oral oxycontin eight to eighteen minutes before the second evaluation.P = 0.210) between female and male study patients [median 2.9 (IQR 1.4–3.9) vs. 2.3 (1.3–4.0) VAS units].Individual mean levels of pain intensity did not differ significantly  patients evaluated by a female investigator report lower intensity of postoperative pain regardless of pain level, have not been reported elsewhere, as far as we know. Although small, we consider these statistically significant differences to be clinically relevant, particularly since they reflect postoperative levels of pain intensity normally calling for analgesic intervention. Moreover, we found no significant difference in pain intensity levels between female and male patients after surgery.Results obtained in this paired clinical crossover study, carried out in a large cohort of adult PACU patients subjected to various kinds of in- and out-hospital surgery, conform to findings in experimentally induced nociceptive pain in females and males  or in maSimilar VAS scores of pain intensity previously obtained by emergency physicians regardless of gender, in young females subjected to pelvic examination  as well The female investigator was found to have significantly influenced pain scoring in males only. Though we also found similar influence in females, we were unable to confirm this statistically. Interestingly, this finding is in line with results of two preclinical pioneer studies within this field , 51. CurConsidering the short time between distribution of analgesics and evaluation of pain in a handful of patients together with the crossover design, we conclude that early postoperative analgesic interventions have not affected the results overall.The lack of statistical difference in pain intensity levels between female and male study patients is in agreement with findings in small retrospective  and prosThe complex relationship between pain perception and investigator gender includes both physiological and psychosocial components, and their interactions with patient and investigator . Lower pIndividual- or gender-based verbal influence of the investigators was minimized by predefined study instructions read from a protocol. To avoid interindividual variation, we involved only one study investigator of each gender, whereas previous similar clinical studies in this field –33 have Use of VAS scoring—the golden standard for clinical pain assessment—improves the precision in pain scoring and also prevents any impact of auditory memory associated with repeated verbal NRS scoring. On the other hand, since verbal scoring is often used in postoperative routine practice, the clinical relevance of slightly lower VAS scores with a female investigator can be challenged at group level. Nevertheless, these findings might still be relevant to individual patients reporting pain levels where analgesic intervention should be considered.To reduce potential bias beyond investigator gender, our investigators were equally dressed in hospital clothes, had similar body mass index and represented the same generation and level of education. In contrast to authors referring to gender attributes , 24, we Considering our paired and well-reasoned study design, our results add valuable information in the field of potential gender impact on pain perception. Our main finding is interesting, especially with reference to the majority of female health personnel. This encourages health personnel to have more focus on whether patients are pain evaluated by both female and male staff during the same session, and further on potential impact on their pain assessment. Moreover, hopefully our results will promote future studies regarding investigator gender and pain perception, and subsequently improve evaluation and treatment of acute pain conditions, which might facilitate patient recovery and return to daily life after surgery or trauma.This paired clinical crossover study shows for the first time that male patients report significantly lower pain intensity to a female than to a male investigator after various surgical procedures. This should be kept in mind when managing patients with pain in perioperative and emergency care, but further clinical evaluations, with particular reference to underlying factors, are desirable.


Background Opioids, which have well-known adverse effects such as drowsiness paralytic ileus and respiratory depression, were mostly utilised to treat postoperative pain in the past. The increased incidence of side effects has led to a rise in interest in pain management techniques that spare opioids. Persistent abdominal pain following surgery has a major detrimental effect on patients' quality of life. While epidural analgesia is widely regarded as the gold standard to combat the pain that is present post abdominal surgeries, it is not devoid of drawbacks. The transversus abdominis plane (TAP) block has developed as a potentially effective treatment for severe abdominal pain. The TAP block acts on the neuro-fascial plane between the internal oblique and transversus abdominis muscles, which is innervated by spinal nerves from T6 to L1. Studies reveal that the addition of corticosteroids to bupivacaine in TAP blocks provides pain relief and improves the quality of life of the patient.Aims and objectives In this study, the effects of bupivacaine and corticosteroids, particularly dexamethasone and methylprednisolone, on chronic abdominal pain following surgery are examined. Assessing the quality of pain relief is the primary objective.Methodology Thirty patients who had undergone abdominal surgery and had been having persistent abdominal pain for six to eight months thereafter and had attempted unsuccessfully to treat the pain with alternative pain relief methods participated in the study. They were divided into two groups at random. Dexamethasone and bupivacaine were given to patients in Group D while methylprednisolone and bupivacaine were given to patients in Group M for ultrasonography (USG)-guided bilateral TAP blocks. At various intervals up to 12 weeks after injection, the patient's pain levels were measured using the visual analogue score (VAS), and their quality of life was assessed using the quality-of-life score.Results Patients in Group M experienced significantly less pain than those in Group D at the fourth, sixth, and 12th weeks of treatment. Furthermore, in the fourth, sixth, and 12th weeks, patients in Group M reported a superior quality of life in comparison to those in Group D.Conclusion Patients with persistent postoperative abdominal pain receiving bupivacaine and methylprednisolone in an ultrasonography-guided TAP block experience more effective and long-lasting pain relief than those who receive bupivacaine and dexamethasone. The quality of life for patients may be enhanced by using corticosteroids to optimise postoperative pain management strategies and lessen the need for opioids, as this study highlights. Historically, the cornerstone of postoperative pain management has been opioids. However, a trend in postoperative pain management towards opioid-sparing methods has occurred as a result of a greater understanding of its side effects, which include respiratory depression, paralytic ileus, and drowsiness . SpecifiThe anatomic TAP block at the Petit triangle was illustrated in 2001 by Rafi . HebbardThe most commonly used local anaesthetics in TAP block include bupivacaine, ropivacaine, and levobupivacaine. The optimal time for TAP block might be the preoperative period as it could decrease early visual analogue scale (VAS) score and opioid usage compared to the postoperative period. Numerous adjuvants have been utilised in the regional block and other peripheral nerve treatments to prolong and enhance the local anaesthetic effect ,11. VasoThe goal of this study is to increase the effectiveness of the TAP block by investigating the effects of corticosteroids, namely dexamethasone and methylprednisolone, in combination with bupivacaine. This study attempts to provide insight into these corticosteroids' potential to reduce persistent post-operative abdominal discomfort by comparing their effects. The secondary objective is to analyse the effect of these combinations on patients' quality of life and the incidence of issues associated with the block. Understanding the analgesic mechanisms of these corticosteroids, including their effects on potassium channel regulation and anti-inflammatory properties, can help optimise post-operative pain management techniques while lowering the need for opioids.Study designThis prospective, randomized experiment was to evaluate the effectiveness of dexamethasone and methylprednisolone in conjunction with bupivacaine used in bilateral TAP blocks for the treatment of persistent abdominal pain. The study was carried out at the Anaesthesiology Department of Acharya Vinoba Bhave Rural Hospital , Wardha, Maharastra, India, from December 2019 to May 2020. The Institutional Ethics Committee, Jawaharlal Nehru Medical College, Datta Meghe Institute Of Medical Sciences granted ethical clearance /IEC/Dec-2019/8597), and each participating patient provided signed informed consent.Patient selectionopenepi.com  class I and class II, aged between 18 and 60 years, who had been experiencing persistent abdominal pain for a period of six to eight months following abdominal surgery. These patients had previously attempted various forms of chronic pain management and were willing to undergo USG-guided bilateral TAP block. Exclusion criteria encompassed patients with a history of allergic reactions to local anaesthetics, diabetes mellitus, coagulopathy, and hepatic or renal dysfunction. The sample size was calculated using Group randomization and data collectionThe participants were randomly assigned to two groups (Group D and Group M) of 15 patients each by means of a computer-generated random number table. Demographic information, medical history, and medication usage details were documented for all patients. Vital parameters were recorded, and patients were positioned in the supine position in preparation for the TAP block. An anesthesiologist not involved in patient care, TAP block administration, or data collection prepared the injections for both groups.Block procedureTo locate the plane between the transversus abdominis and internal oblique muscles, the TAP block was carried out under ultrasound supervision. By using a 3.8-cm 5-10 MHz linear array probe, a single-injection TAP block was administered to each patient. Three millilitres of 1% lignocaine was locally instilled into the location prior to the block. Under ultrasound guidance, a 22-gauge spinal needle was inserted using an in-plane method into the TAP. The plane expanded and became apparent as a hypoechoic zone after the local anaesthetic solution was injected into it. Prior to injection, aspiration was done to rule out arterial puncture. The TAP block on the other side was accomplished using the same technique and medication combination. Group D participants got bilateral TAP block, each side receiving 8 mg of dexamethasone dissolved in 9 cc of 0.5% bupivacaine. Group M participants underwent bilateral TAP block, with 40 mg of injectable methylprednisolone acetate solution in 9 ml of 0.5% bupivacaine administered on each side.Outcome measuresThe primary outcome measure was pain relief, assessed using the VAS for pain at the time of the block and followed up at two, four, six, and 12 weeks post injection during in-person evaluations. The secondary outcome was the assessment of patients' quality of life using the quality-of-life score.Statistical analysisWhile percentages were used to communicate qualitative data, mean values and their related standard deviations were used to describe quantitative data. The student t-test was used to examine quantitative data, and the Chi-square test was used to evaluate qualitative data. Software from Graph Pad Prism version 6.0  and IBM SPSS Statistics for Windows, Version 20.0  were used for the statistical analysis, with a significance level of p < 0.05.Table As shown in Figure Pain can be defined as an unpleasant, emotional, complex and sensory feeling associated with injury to the tissues ,17. The Multiple theories have been postulated as the mechanism of action for the analgesia of steroids. Corticosteroids produce an analgesic effect through immunosuppressive and anti-inflammatory effects. The modulation of nuclear transcription by steroids can result in its analgesic action. Corticosteroids, through their modulation action in potassium channels of excitable cells, can increase the duration of action of local anaesthetics . Some stDexamethasone is an isomer of betamethasone and a fluorinated analogue of prednisolone. Hydrocortisone is 40 times less effective than dexamethasone . DexametSimilar to naturally occurring glucocorticoids, methylprednisolone is a synthetic corticosteroid that acts systemically and has a broad variety of physiological effects. Due to methylprednisolone's anti-inflammatory and immunosuppressive properties, it is primarily utilised in clinical settings. Among the synthetic glucocorticoids with an intermediate-acting effect are methylprednisolone and its derivatives, such as methylprednisolone sodium and methylprednisolone acetate succinate. Their main uses are as anti-inflammatory or immunosuppressive medications. Methylprednisolone has minimal mineralocorticoid activity and five times the potency of hydrocortisone (cortisol) in terms of anti-inflammatory actions . SimilarPatients in the two groups in the study were comparable in terms of weight, age, gender, and duration of pain. As shown in Figure The limitations of the study include the usage of a single dose of corticosteroid for all patients because of which the efficacy of various doses of the corticosteroid was not evaluated. Compared to dexamethasone, the administration of methylprednisolone and bupivacaine enhances the quality and longevity of analgesia of USG-guided TAP block in patients with persistent abdominal pain. In the fourth, sixth, and 12th weeks, the mean VAS among the individuals in the methylprednisolone group was considerably lower than the mean VAS in the dexamethasone group. This makes it evident that methylprednisolone, when used in conjunction with bupivacaine in TAP block, has higher analgesic efficacy than dexamethasone for at least 12 weeks. In the fourth, sixth, and 12th weeks, patients in the methylprednisolone group had better quality-of-life scores than those in the dexamethasone group.


Functional bowel disorder (FBD) is a common gastrointestinal disease syndrome characterized by dysmotility and secretion without known organic lesions. The pathogenesis of FBD is still unclear. In recent years, with the rise of neurogastroenterology, it has initially revealed its close relationship with the “brain-gut axis.” Transcranial magnetic stimulation (TMS) is a technique for detecting and treating the nervous system, that is characterized by non-invasiveness and painlessness. TMS plays an important role in the diagnosis and treatment of diseases, and provides a new method for the treatment of FBD. In this paper, we summarized and analyzed the research progress of using TMS therapy applied to patients with irritable bowel syndrome and functional constipation by domestic and foreign scholars in recent years by means of literature search, and found that TMS therapy could improve the intestinal discomfort and accompanying mental symptoms in patients with FBD. The pat2.Rome IV: Functional Gastrointestinal Disorders, FBD includes six disorders: irritable bowel syndrome (IBS), functional constipation, functional diarrhea, bloating/abdominal distention, nonspecific functional enteropathy, and opioid-induced constipation (OIC)  , 7. Romeon (OIC) . In viewon (OIC) .3.With the publication of the Rome IV, the “brain-gut axis” is considered to be the basis of the pathophysiological changes in FBD, and there is increasing evidence to support that the evolution of functional enteropathy occurs in three stages: stage 1—gastrointestinal motility disorder; stage 2—visceral hypersensitivity; and stage 3—bidirectional brain-gut axis dysfunction , 11. The4.4.1.The stimulation methods of brain neurons are mainly divided into electrical stimulation and magnetic stimulation . The eleFunctional magnetic resonance imaging (fMRI) studies have shown that the effects of rTMS induce changes in distal brain regions, with low frequency (<1 HZ) rTMS producing inhibitory effects and high frequency (>5 HZ) rTMS producing excitatory effects . The perTMS has been studied in patients and healthy volunteers around the world for more than 25 years, and the results support the safety and reliability of TMS by evaluating its adverse effects through meta-analysis . The mos4.2.Although the Rome Committee classified FBD into 6 different subtypes, the clinical manifestations of different classifications have similar and repetitive phenomena, and may have the same pathophysiology . Constip4.2.1.Functional constipation is one of the common types of FBD. Recurrent episodes of persistent constipation have a huge impact on the physical and mental health of patients, and over time, most patients experience anxiety and depression. Chronic anxiety and depression can affect the hypothalamus, plant nerves and inhibit peripheral autonomic nerves, triggering aggravation of constipation and thus increasing the burden of treatment. TMS therapy not only improves the patient’s constipation symptoms but also significantly reduces the patient’s mental state, which is beneficial to the recovery of the disease . PatientIn the clinical efficacy observation of patients with functional constipation treated with TMS combined with electroacupuncture, Li et al.  found thTMS treatment effectively improves gastrointestinal motility, mediates emotions, and relieves symptoms by regulating the brain-gut axis, providing a safe, non-invasive, and effective treatment for the clinical treatment of functional gastrointestinal diseases. Long-term constipation will have a negative impact on the patient’s mental condition. More than half of the patients with constipation are accompanied by severe anxiety or depression. In the long term, in a state of high tension, anxiety can cause brain and intestinal axis dysfunction, which in turn aggravates the constipation condition, forming a vicious circle. TMS not only regulates the brain-gut axis disorder in patients with functional constipation but also significantly improves the patient’s anxiety and depression, which is more conducive to the treatment of constipation .4.2.2.The Rome Commission has identified abdominal pain as a necessary condition for the diagnosis of IBS, and abdominal pain is often the main cause of distress in IBS patients . AlthougIn Melchior’s experiment, it was found that while rTMS had only a slight improvement in pain threshold (VAS score decreased from 3.8 ± 2.2 to 3.0 ± 2.3), maximum tolerance and rectal compliance in IBS patients compared to healthy controls, in IBS patients with rectal hypersensitivity (pressure pain threshold ≤ for 40 mmHg), rTMS significantly increased rectal volume pain threshold and decreased pain threshold (VAS score decreased from 4.0 ± 2.4 to 3.2 ± 2.2). All patients showed a significant improvement in the sensation of abdominal pain. The failure to achieve the expected results may be related to the small sample size (only 16 patients), the different staging of rTMS, and the fact that most rTMS patients have a history of taking painkillers [painkillers can reduce rectal sensitivity ] 36). H. H36). HIBS is a chronic pain condition, and the use of active pain management and placebo therapy is not effective. Pain-relieving therapy is mostly treated with opioids, which will cause adverse reactions such as constipation over time. The placebo may have a biological analgesic response, causing adverse effects that may be more pronounced than the pain relief. TMS has been preliminarily shown to be effective for pain relief in IBS and may provide a safe, effective, and well-tolerated alternative therapy for IBS patients in the near future instead of conventional drugs see .5.As one of the common diseases of the gastrointestinal tract, the specific pathogenesis of FBD has not been clarified, which brings a heavy burden to patients physically, mentally, and economically. In recent years, with the development of neurogastroenterology, the brain-gut axis has gradually come into view and has attracted the widespread attention of researchers, and more and more studies have shown that the brain-gut axis may be the pathophysiological alteration of functional enteropathy. As a non-invasive, painless, safe, and reliable new technology, TMS can be used both for the detection of brain function and the localization of the cerebral cortex, providing new ideas for people to study the mechanism of disease occurrence and pathophysiology, and as an emerging treatment modality, providing new means for clinical treatment. In just a few decades, TMS has achieved remarkable results in clinical practice. TMS has been widely used in the treatment of psychiatric disorders and pain relief in China and abroad, but few scholars have studied its application to gastrointestinal disorders. Although only a few researchers in China and abroad have used TMS for the treatment of FBD, patients have shown significant improvement after a period of treatment with no associated adverse effects. Future research efforts on TMS for FBD on a larger scale are needed to explore the underlying mechanisms in greater depth. It is believed that with the continuous development of TMS technology and the progress of clinical medical research, TMS will be better, more closely, and more widely integrated with clinical treatment, providing more possibilities for clinical treatment plans.GL and BJ reviewed the relevant literature and wrote the manuscript. ZF designed the structure and revised the manuscript. All authors contributed to the article and approved the submitted version.This work was supported by the National Natural Science Foundation of China (81701965); Natural Science Foundation of Liaoning Province (20180550116 and 2019-MS-069).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Postherpetic neuralgia (PHN) is a severe condition that remains a challenge to treat. Spinal cord stimulation (SCS) is used in cases of insufficient efficacy of conservative treatment. However, in contrast to many other neuropathic pain syndromes, there is a huge problem in reaching long-term stable pain relief in patients with PHN using conventional tonic SCS. The objective of this article was to present a review of the current management strategies of PHN, their efficacy, and safety.  We searched for articles containing the keywords “spinal cord stimulation AND postherpetic neuralgia,” “high-frequency stimulation AND postherpetic neuralgia,” “burst stimulation AND postherpetic neuralgia” and “dorsal root ganglion stimulation AND postherpetic neuralgia” in Pubmed, Web of Science, and Scopus databases. The search was limited to human studies published in the English language. There were no publication period limitations. Bibliographies and references of selected publications on neurostimulation for PHN were further manually screened. The full text of each article was studied once the abstract was analyzed by the searching reviewer and found appropriate. The initial search yielded 115 articles. Initial screening based on abstract and title allowed us to exclude 29 articles . The full-text analysis allowed us to exclude another 74 articles  and results of PHN treatment presented with other conditions, leaving 12 articles for the final bibliography.  12 articles reporting on the treatment of 134 patients with PHN were analyzed, with a disproportionally large amount of traditional SCS treatment than that to alternative SCS: DRGS (13 patients), burst SCS (1 patient), and high-frequency SCS (2 patients). Long-term pain relief was achieved in 91 patients (67.9%). The mean VAS score improvement was 61.4% with a mean follow-up time of 12.85 months. Although the number of patients in alternative SCS studies was very limited, almost all of them showed good responses to therapy with more than 50% VAS improvement and reduction of analgesic dosage. The article contains a review analysis of 12 articles concerning the current methods of treatment for postherpetic neuralgia including conservative treatment, spinal cord stimulation, and novel neuromodulation strategies. Available information on the pathophysiology of PHN and the effect or stimulation on its course, together with a number of technical nuances concerning various types of neurostimulation are also elucidated in this article. A number of alternative invasive treatments of PHN are also discussed.  Spinal cord stimulation is an established treatment option for patients with pharmacologically resistant PHN. High-frequency stimulation, burst stimulation, and dorsal root ganglion stimulation are promising options in the management of PHN due to the absence of paresthesias which can be painful for patients with PHN. But more research is still required to recommend the widespread use of these new methods. Herpes zoster is a viral infection caused by human alphaherpesvirus 3, also known as varicella-zoster virus (VZV), the same virus that causes chickenpox in children. After the acute phase of inflammation, the virus reaches the sensory nervous system and remains latent in trigeminal or dorsal root ganglions for a long period of time. Reactivation of the VZV happens with advancing age or immunosuppression and leads to the development of acute herpes zoster. Pain in affected regions can remain even after the rash resolves. This condition is known as postherpetic neuralgia (PHN) . PHN is Antiviral medications , peroral glucocorticosteroids (GCS), and epidural injections of GCS are used to treat acute herpes zoster. However, treating acute disease does not prevent the development of postherpetic neuralgia . VaccinaWhen conservative treatment is ineffective, physicians can try glucocorticoid nerve blocks and pulsed radiofrequency (PRF) of the dorsal root ganglion (DRG). Kotani et al. compared the efficacy of intrathecal administration of methylprednisolone in combination with Marcaine vs. Marcaine injection alone. A 70% reduction in diclofenac use was noted in the group of patients who had been treated with methylprednisolone [The analgesic effect of radiofrequency denervation of dorsal root ganglion on the thoracic level persists for approximately 6 months. Yingwei et al. demonstrated an improvement in patients' quality of life and a reduction in tramadol intake in their study . When thWe searched for articles containing the keywords “spinal cord stimulation AND postherpetic neuralgia,” “high-frequency stimulation AND postherpetic neuralgia,” “burst stimulation AND postherpetic neuralgia,” and “dorsal root ganglion stimulation AND postherpetic neuralgia” in Pubmed, Web of Science, and Scopus databases. The search was limited to human studies published in the English language. There were no publication period limitations. Bibliographies and references of selected publications on neurostimulation for PHN were further manually screened. The full text of each article was studied once the abstract was analyzed by the searching reviewer and found appropriate. The initial search yielded 115 articles. Initial screening based on abstract and title allowed us to exclude 29 articles . The full-text analysis allowed us to exclude another 74 articles  and results of PHN treatment presented with other conditions, leaving 12 articles for the final bibliography see .Implantation of the system for chronic neurostimulation may be recommended for patients resistant to pharmacological and minimally invasive therapies. There is a series of studies describing the efficacy of peripheral nerve field stimulation (PFNS) and peripheral nerve stimulation (PNS) in regions of pain , 11, how12 articles reporting on the treatment of 134 patients with PHN were analyzed, with a disproportionally large amount of traditional SCS treatment than that to alternative SCS: DRGS (13 patients), burst SCS (1 patient), and high-frequency SCS (2 patients). Long-term pain relief was achieved in 91 patients . The mean VAS score improvement was 61, 4% with a mean follow-up time of 12.85 months. Although the number of patients in alternative SCS studies was very limited, almost all of them showed good responses to therapy with more than 50% VAS improvement and reduction of analgesic dosage. Considering the severity of pain associated with PHN (with an average VAS score of 8 to 9), large randomized-controlled trials comparing alternative and traditional modes of SCS are required, with a substantial amount of PHN patients enrolled.Devices for conventional (tonic) spinal cord stimulation can generate impulses with a frequency range of 2–1200 Hz. The level of electrode implantation is determined by the region of pain, which is usually the same as a dermatome affected by the virus. Pain is also usually accompanied by severe allodynia and discoloration.There is no need to place an electrode on the level of pain when using HF stimulation or burst stimulation; in these cases, we implant electrodes above the region of pain to overlap pathways of pain signals to higher levels of the nervous system .Contraindications for performing SCS include diffuse pain that is difficult to localize; severe somatic comorbidities; intractable drug addiction, suicidal attempts in the past, and severe mental disorders .Electrodes are placed under fluoroscopic guidance . Implantμs and pulse frequency of 30–100 Hz is chosen for tonic stimulation. The amplitude is selected for each patient individually based on the comfort level of paresthesias [The pulse width of 100–500 sthesias . Due to sthesias . HoweverSeveral studies are describing immediate alleviation of the pain associated with subacute herpes zoster (about 2 months after the onset of the disease) in patients after the SCS trial that has lasted between 7 and 10 days and 2, 5 months. The patients continued to experience pain reduction after 1-year postprocedure. A series of studies demonstrated a complete pain reduction for 1–46 hours during the trial. Some patients with implanted SCS systems had a complete reduction of pain for 2–6 months, others for 3–66 months , and in SCS was also considered a treatment option for acute PHN. Harke et al. described 4 patients who suffered from intolerable acute pain for 1, 8 months. Trial percutaneous electrodes were implanted which lead to immediate pain relief. The baseline VAS score almost immediately reduced from 9, 0 to 1, 0. There was no recurrence of pain syndrome for 13–39 weeks . The intConventional spinal cord stimulation generates electrical impulses with a frequency lower than 1200 Hz. The goal of stimulation is to mask patients' feeling of pain by covering the region of pain with paresthesias. Paresthesias are determined as sensations produced by stimulation and perceived as tingling, goosebumps, or vibration. HF10 stimulation uses a frequency of 10000 Hz and differs from tonic SCS by controlling pain without paresthesias . HF10 stμsec at 500 Hz frequency with a total duration of each burst of 1 msec. The frequency of the bursts is 40 Hz. Passive repolarization happens between the bursts and lasts for about 5 msec. [Burst stimulation is a type of stimulation in which impulses are delivered in series of 5, with each impulse lasting 100  5 msec. , 25, 32. 5 msec. , 25. Bur 5 msec. –35. Besi 5 msec. . We foun 5 msec. .Aβ-, Aδ-, and C-fibers when applying low frequencies. Generating action potential at very low frequencies, DRGS enables the blocking of pain stimuli through the activation of opioid receptors without engaging of GABA system [Studies show that DRGS plays a key role in the management of nociceptive as well as neuropathic pain. The method is especially useful for the treatment of the pain in cases when conventional spinal cord stimulation is not effective enough, primarily due to the difficulties in getting paresthesias in strictly limited areas such as the groin area, the outer side of the foot, or specific intercostal space . One of A system . MoreoveA system . Kim et A system . This stA system , 40.A clinical case of an 80-year-old man with 15 years duration of pain in the left side of the head and neck in the area of the C2 dermatome was described by Lynch et al. The patient has permanent severe pain with no response to multimodal therapy including tramadol 50 mg 2 times per day, pregabalin 75 mg 3 times per day, hydrocodone-acetaminophen 5/500 3 days per day, and facet joint block. The patient was referred to implantation of the lead for the test stimulation. After the surgery, the level of pain decreased by 50% and the patient stopped taking analgesic drugs. A reduction of 20% was noted in 6 months postoperatively and the patient still did not need any medications .Hunter et al. in the study of DRGS for various etiologies described 4 patients with PHN whose mean reduction of pain was 81, 2% assessed by NRS and a successful trial rate was 75% . HoweverHerpes zoster and postherpetic neuralgia associated with it are common diseases that severely impact the quality of life and cause the progression of disability in elderly people. Treatment of PHN is usually a challenge since it is often unresponsive to traditional management options. Vaccination against herpes zoster infection can decrease the risks of having an infection and the severity of its clinical presentation. Spinal cord stimulation has been used for over 50 years for the treatment of pain syndrome. The effective analgesic effect of SCS has been proven by numerous studies. Neurostimulation is especially relevant for patients with severe comorbidities. Considering high efficacy, minimal invasiveness of neurostimulation, and ability to control analgesic effect postprocedure, it can be applied as one of the first steps in the management of neurogenic pain syndromes. However, physicians should strictly follow inclusion criteria, indications, and contraindications for the treatment to avoid negative results in the postoperative period. Novel stimulation strategies such as burst stimulation and high-frequency stimulation could be a possible solution to the treatment of severe cases of PHN due to their ability to provide pain relief without unpleasant paresthesias. Lately, dorsal root ganglion stimulation becomes a popular method of PHN management. DRGS of specific ganglions does not cause paresthesias in the regions that are not affected by pain, which is especially important for patients with allodynia as a symptom of PHN. Despite some promising results demonstrating a significant decrease in pain intensity after DRGS, there were also conflicting reports on its efficacy. Controlled trials with larger cohorts are needed to conclude the efficiency of different types of stimulation.


Although ablations are performed with conscious sedation or general anesthesia, microwave ablations can be painful post procedure. Newer analgesic modalities, including regional blocks, have promoted the proliferation of less invasive anesthesia care for ablative procedures. This study evaluates whether bilateral paravertebral blocks reduce the need for additional analgesics in comparison to unilateral blocks in microwave ablations. In this retrospective study, individuals undergoing microwave ablation who underwent unilateral versus bilateral nerve blocks at a single institution from 2017 to 2019 were compared. Categorical variables were analyzed using Pearson’s chi-squared tests. Comparisons of means were completed using multiple T-tests corrected using the Holm-Sidak method with  Furthermore, intraoperatively, pain management is of the utmost importance. Intraoperative pain can induce physiologic responses, such as shock or bradycardia, which can lead to early termination of the procedure, decrease the intensity of the ablation intraoperatively, and even lead to profound post-operative morbidity6. Analgesics, including opioids, are frequently prescribed to alleviate these symptoms, but given concerns of dependence on such agents, other forms of periprocedural pain control have been implemented. Options that have been utilized in non-OR anesthesia (NORA) settings to decrease pain associated with thermal ablations include, but are not limited to, anti-inflammatories, such as NSAIDs and dexamethasone, mixed opioid agonist/antagonists, such as tramadol, and peripheral nerve blocks7. In addition to aiding the technical success of a procedure, providing adequate analgesia has demonstrated lower pain scores, increased intraprocedural patient cooperation, decreased readmission rates, and decreased post-procedural pain medication requirements9.Percutaneous thermal ablations have become mainstays in oncologic therapy. However, despite their minimally invasive nature, up to 33% of patients undergoing radiofrequency (RFA) and microwave (MWA) ablations experience significant post-procedural pain as a sequela of post-ablation syndromeWhile the efficacy of these agents in producing a variety of different downstream positive effects is clear, these elements largely have not been evaluated against each other for liver ablations. The present study specifically investigates regional peripheral nerve blocks and whether a unilateral or bilateral paravertebral block is more effective in decreasing post-procedural opioid requirements, utilization of general anesthesia, and decreasing rates of admission to the hospital.This study was approved by the Massachusetts General Brigham Institutional Review Board, completed with a waiver of consent, and HIPAA-compliant. All methods were performed in accordance with the relevant guidelines and regulations, including the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort studies. A retrospective study was performed analyzing all patients who underwent liver MWA from January 2017 to December 2019 at a single institution. A total of 112 procedures among 106 patients were performed during this period. Among the procedures performed, 28 underwent ultrasound-guided unilateral thoracic paravertebral blocks (TPVB), and 84 underwent bilateral blocks. A 10-point Visual analogue scale (VAS) score was used to quantify patient pain levels at baseline as well as at post-procedural intervals . Data primarily focused on analyzing the reduction of admissions and post-procedural morphine milligram equivalents (MME) with regards to unilateral vs. bilateral blocks. At this institution, the department cycled from no paravertebral blocks to bilateral as an effort to reduce pain. This study explores this transition.Selection criteria for performing unilateral versus bilateral blocks was based on anesthesia preference built on lateralization of the tumor. Tumors in liver segment VII generally were considered for unilateral blocks, whereas tumors in segment II, IVa, and most of VIII were given bilateral blocks see Fig. , though Prior to performing the block placement, the risks, benefits, and alternatives to paravertebral block administration were discussed with each patient, and informed consent was obtained. The patient was placed in prone position and prepared using sterile technique, and the ultrasound machine was positioned appropriately in transverse plane between the T7 and T8 vertebrae. The needle was inserted in-plane from lateral to medial, aiming for the thoracic paravertebral space located at the junction of the pleura and the acoustic shadow underneath the transverse process, as depicted in Fig. The same procedure was performed on the opposite side for patients receiving bilateral blocks.Prior to MWA, patients were given a subset of acetaminophen, celecoxib, tramadol, lidocaine, and/or gabapentin, which was decided by the proceduralist based on physician comfort and preference. Intraoperatively, patients received systemic analgesia in the form of dexamethasone, fentanyl, and/or hydromorphone. Following the procedure, patients were offered multi-modal analgesia that generally constituted of acetaminophen, opiates, and ketorolac if renal clearance permitted. Patients received instructions and counseling on use of pain medications prior to discharge. Pre-, intra- and post-operative pain management regimens are summarized in Supplementary Table A total of 106 patients undergoing 112 liver MWA procedures were included in the analysis. Categorical variables were analyzed with Pearson’s chi-square tests, and continuous variables were performed using unpaired t-tests. A Holm-Sidak correction with α = 0.05 was applied to account for multiple comparisons. Multivariate logistic and linear regressions were used to identify risk factors associated with increased rate of admission and usage of MME, respectively. All statistical tests were done on Prism 7 , and descriptive statistics were utilized for basic comparison. All analyses were done at the per procedure level. Procedures were stratified according to age, gender, location of tumor, and primary tumor type. VAS was utilized for comparison with respect to pre- and post-procedural pain. Post-operative pain control, use of general anesthesia, and hospital admission rates were compared between patients who underwent unilateral vs. bilateral paravertebral block placement.Material was presented at the 2021 Society for Interventional Radiology Annual Scientific Meeting.A total of 112 procedures among 106 patients were analyzed in this study. There were 28 unilateral block placements among 28 unique patients and 84 bilateral block placements among 78 patients. Several individuals underwent more than MWA procedure due to the development of multiple lesions over time. One individual in this study had residual metastatic disease left requiring additional MWA therapy and thus an additional paravertebral block placement. There were no statistically significant differences between age, gender, body mass index, ASA score, mode of anesthesia, pre-procedure labs, primary tumor type, procedure characteristics, pre- and post-procedural pain scoring, intra-operative and post-operative analgesics, and ablation size as measured in Watt-hours between unilateral block and bilateral block groups. Patients in the unilateral group were more likely to receive gabapentin pre-procedure  but less likely to receive a lidocaine patch . As expected, there was an increase in local injectate dosage among patients who received bilateral blocks compared to those who received a unilateral block. For example, among patients who received bupivacaine 0.5%, those in the unilateral block group received on average 24 mL compared to 40.38 mL in the bilateral block group (p = 2.3e−08). Similarly, patients who received ropivacaine 0.5% received 16.25 mL in the unilateral group compared to 37.44 mL in the bilateral group (p = 1.6e−04). Overall patient and procedure characteristics are summarized in Supplementary Table Patients who received a bilateral block had a lower admission rate compared to those with only a unilateral block . This was a statistically significant difference (p = 0.003) as determined by multiple logistic regression Table . Among tThose patients who underwent bilateral nerve blocks fared the best when it came to decreased utilization of post-procedural morphine equivalents, with an average utilization of 3.70 ± 7.44 MME. By comparison, those who underwent unilateral nerve block had an average MME usage of 5.56 ± 8.22 units, raising concern that those patients who underwent unilateral nerve blocks exhibited a greater need for pain control. This difference was not significant as determined by multiple linear regression , reflecting the institution’s practice in switching from placing unilateral paravertebral blocks to bilateral over the course of the study period.Finally, there was a statistically significant decrease in the proportion of unilateral blocks performed over time with a concomitant rise in the proportion of bilateral blocks , including admissions for post-procedural pain , compared to unilateral paravertebral blocks. Furthermore, there was a clinically significant lower burden of opioids required in patients who underwent bilateral nerve blocks as demonstrated by the decreased MME utilization . The lack of statistical significance is likely due to lack of power, as well as a relatively wide standard deviation in starting opioid needs, which may reduce the apparent efficacy of total MME even if pain itself is improved.10.In this study, patients in the unilateral and bilateral block groups also received multimodal analgesia pre-procedure, intra-operatively, and post-operatively. There was a statistically significant difference in pre-procedure gabapentin and lidocaine patch usage across the two groups. Patients in the bilateral block group were more likely to use lidocaine patch  and less likely to require gabapentin . This finding suggests that patients who receive bilateral paravertebral blocks rather than unilateral may require fewer systemic agents to treat neuropathic pain in favor of local agents, thereby reducing likelihood of developing adverse drug reactions11. Microwave ablation of hepatic lesions following these blocks resulted in minimal pain, and post-procedurally, patients reported minimal pain within the first 24 h and required few analgesics.The utility of paravertebral blocks in reducing patient pain is well documented in the literature. Thoracic paravertebral blocks (TPVB), for instance, have been shown to be well tolerated and provide symptomatic relief of pain13. However, although numerous studies have discussed the benefits of TPVB, consideration of utilization of general anesthesia often arises and may be appropriate in certain scenarios. A general consideration of the strengths and weaknesses of general anesthesia (GA) in the setting of PRFA of hepatocellular carcinoma (HCC) has been previously reported14. In their study, advantages included an overall decreased number of sessions to accomplish complete tumor ablation, as well as decreased hospitalization, reduced systolic pressure, and reduced hepatic blood flow, thus increasing tumor ablation diameter. Disadvantages of GA included increased risk of myocardial infarction, malignant hyperthermia, stroke, the limitations of requiring necessary equipment, and pre-procedural risk stratification14. In the appropriate clinical scenario, these and other considerations should be made.A considerable amount of literature continues to reiterate the benefits and superiority of TPVB for percutaneous radiofrequency tumor ablation (PRFA)15. Afferent fibers arising from the liver parenchyma have demonstrated partial crossing to the contralateral side at the thoracic level, which may explain why bilateral blocks provide better anesthesia coverage16. Major limitations in unilateral blocks have been described, including “failure to achieve total visceral anesthesia” due to lack of proper involvement of both the parasympathetic and contralateral sympathetic nerve fibers17. Thus, despite their less invasive and time-saving elements, unilateral blocks fall short in their ability to adequately treat and prevent patient pain. However, the relatively more invasive aspect cannot be overlooked: a balance must be struck in this regard, and the clinician must use their gestalt to determine the most appropriate option in each individual case. This fine balance of achieving proper sedation and analgesia while maintaining appropriate blood pressures and minimizing patient pain is, of course, a critical topic in interventional radiology that continues to be explored20.This study demonstrated that bilateral paravertebral blocks were preferred over unilateral. While the precise innervation of the hepatic parenchyma is not well understood, perception of pain is thought to be mediated by a complex network of both visceral and somatic afferent fibers, with postoperative pain usually having a dominant somatic componentLimitations of this study include both its retrospective nature and a limited number of cases overall. Of the 112 procedures analyzed in this study, only 28 were unilateral block placements. This discrepancy between the number of recipients who received a bilateral block compared to those that received a unilateral block reduces the power of the study. Therefore, findings that were not statistically significant, such as the decreased MME among patients receiving bilateral blocks, may still be clinically significant. However, although the results of the study favor the use of bilateral paravertebral blocks, each case must be considered individually, and the interventionist must adapt to a variety of situations in which local anesthesia may be preferred over regional or general anesthesia. Further inquiry with a larger sample size in a prospective study design is necessary to elucidate and bolster the findings in this report.By the merits of this study, bilateral paravertebral blocks were superior to unilateral paravertebral blocks in reducing rates of hospital admission for liver microwave ablation and usage of systemic agents to treat neuropathic pain. Of note, reducing post-procedural MME reduced the admission rate for pain.Supplementary Table 1.Supplementary Video 1.


Anesthesiologists ranked pain as #1. Surprisingly, patients ranked emesis #1, gagging on the endotracheal tube #2, and nausea #3. Patients ranked pain as a distant #4 outcome to avoid! Since anesthesiologists, as well as Post Anesthesia Care Unit (PACU) Registered Nurses, are laser focused on pain, why do patients rank emesis well ahead of pain?In 1999, Macario, et al. published two scientifically validated surveys, one for anesthesiologists and a separate one for patients . Both gr#1 and #3 are the reason we group those experiences as postoperative nausea and vomiting (PONV). When patients sign a surgical consent, they are giving their surgeons permission violate their integument with a sharp scalpel or a trocar. Pain is the natural expectation of integument violation. Asking PACU patients a closed end question like, ‘Are you having pain?’ plays into their pre-surgical expectation.Violation of the integument is a common experience often accompanied with pain. Emesis is not usually associated with a cut in the integument. Patients’ outcomes ™) instead of additional opioids. To the occidental anesthesiologist, Asian patients appear more stoic. These patients more commonly view pain as a natural part of life and are less apt to complain.High anxiety patient populations like Eastern European derived (Ashkenazi) Jewish, Hispanic and Arabic ones have heightened expectations of surgical pain. Pain complaints are likely from culturally acquired expectations rather than from their somatic experience. In PACU, these patients may benefit from acetaminophen 1,000 mg plus diphenhydramine 50 mg therapy, either intravenously or orally , a 0.6% PONV rate without antiemetics was published . This 0.The long held anesthesia syllogism is ‘Surgery is painful, opioids are pain killers, therefore, all surgery requires the (judicious) use of opioids.’ Opioid Free Anesthesia or why it’s never easy to go against long established practice . Trying opioid free, cosmetic surgery outpatients, not a single pain or PONV admission despite all patients having had commercial insurance to cover such an eventuality [not ask PACU patients if they have pain, a both objective and subjective phenomenon. It is probable that to drawing patient’s attention to pain could increase pain related complaints and possibly pain medication requirement, including opioid administration. The institution of pain as a vital sign and publications implying improved postoperative courses with pain reduction could have driven clinicians to be obsessed with trying to eliminate pain by asking patients if they had pain. Subsequent administration of opioids could result in more PONV. The overuse of postoperative opioid use has led to addiction and a modified immune system [Pain and PONV remain the two most common causes for unexpected admission after outpatient surgery. Over a two decades in more than 4,000 ntuality . Some ofe system ,11.


One of the most severe side effects of photoimmunotherapy (PIT) for head and neck cancer is pain. As there are presently no detailed reports on pain and pain management in PIT, we conducted a retrospective case series study. We conducted a retrospective study of five patients who had received PIT at the National Cancer Center Hospital East between January 2021 and June 2022 using medical chart data. All patients experienced pain, evidenced by an increased numerical rating scale (NRS) after PIT, regardless of the illumination method. The daily change in mean NRS rating shows that the pain was highest on the day of PIT, with ratings of 6.8 and 7.8 for the frontal and cylindrical diffuser methods, respectively; it dropped the following day quickly. Four of the five patients received fentanyl injections for postoperative pain management beginning on postoperative day (POD) 0. All patients who underwent therapy using a cylindrical diffuser required postoperative pain management with opioid drugs. Pain after PIT tended to be most intense immediately after or one hour after illumination and declined the following day, suggesting the need to have a pain relief plan in place in advance. Over 90% of head and neck cancers are squamous cell carcinomas (HNSCCs), and locally advanced HNSCC has a poor prognosis with a reported five-year survival rate of <50% ,2. The rPhotoimmunotherapy (PIT) is a treatment in which cancer cells are selectively destroyed by injection of cetuximab sarotalocan sodium  antibody cetuximab, and a light-activated dye (IRDye700DX: IR700)), followed by non-thermal red light (690 nm) illumination of the tumor site using a frontal or cylindrical diffuser 20–28 h later. It is expected that irradiation with 690 nm laser light will activate the dye and induce a rapid cytotoxic reaction only on cells to which the complex has bound. Since light-induced activation and antigen-antibody binding are required for induction of the apoptotic effect, it is expected to selectively destroy only cancer cells while minimizing damage to the normal tissue surrounding the tumor cells. The mechanism of action of this therapy is that the activation of antibody complexes causes physical stress on the cell membrane, resulting in an increase in transmembrane water, which ultimately leads to cell rupture and necrosis. This reaction is considered to occur in a short period of time, as short as one minute after laser irradiation. It has also been suggested that the rapid release of immunogenic signals from cancer cells induces immature dendritic cells to mature and trigger a host immune response against the tumor, but this has not been clinically confirmed at this time.As tumor illumination methods, cylindrical diffusers placed in needle catheters are used to treat interstitial tumors, while frontal diffusers are used to treat superficial tumors.  The non-Cetuximab was selected for this treatment because 80–90% of HNSCC patients express EGFR ,8,9,10. One of the most severe side effects of PIT is pain. In the Japanese phase I trial, 100% of the patients reported pain at the application site, and pain of Grade 3 or above was common, being observed in 33.3% of patients. Therefore, pain management must be provided when PIT is used in medical practice . UnfortuWe conducted a retrospective study of HNSCC patients who had received PIT at the National Cancer Center Hospital East between January 2021 and June 2022 using medical chart data. In this period, a total of six patients received PIT in the National Cancer Center Hospital East. However, one patient was excluded from the study because she was advanced in age and cognitively impaired, which made it difficult to assess pain correctly, and nurses could not evaluate her pain correctly, either. The five patients consisted of two men and three women. All patients had an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of <1 and were able to communicate their pain status articulately and without any issues. The median age was 60 years. Two patients had buccal mucosa cancer, two had oropharyngeal cancer, and one had nasopharyngeal cancer. Additionally, three of the five eligible patients received PIT more than once. Of these patients, one patient received a first PIT at another hospital, and one patient received the first PIT as part of a Phase I clinical trial, so the first data for these two patients were excluded from the analysis. Hence, we evaluated a total of nine PIT sessions, which received PIT at the National Cancer Hospital East as daily clinical practice, and the number of times PIT was performed in each of the five cases: once, twice, and three times in two, two, and one patient, respectively. Regarding the illumination technique, two patients received treatment via frontal diffuser only, one via cylindrical diffuser only, and the remaining two via both techniques .Postoperative pain management may be difficult for a surgeon alone, and consultation with a palliative care specialist is recommended if postoperative pain management is inadequate or pain symptoms are severe . AdditioThis case series study was based on a daily clinical practice in which a nurse periodically asked the patient to rate their pain after receiving PIT, using the NRS, which comprises ten pain levels, with the 10th level denoting maximum pain; this information was recorded in the patient’s medical record. Pain after PIT was frequently assessed in all patients and recorded in the electrical medical records because it was recognized as an important symptom incurred by PIT.Descriptive statistics were used to analyze the means, medians, and frequencies. All calculations were performed using Microsoft Excel 2021 .This case report was approved according to its compliance with the Ethical Guidelines for Life Sciences and Medical Research Involving Human Subjects and was subjected to the ethical review procedures of the National Cancer Center. Compliance with the relevant guidelines was also ensured while performing research involving the participants during the original studies. Ethical approval for this study was obtained from the National Cancer Center Institutional Review Board (Research Project No. 2021-262). The Institutional Review Board asserted that informed consent to the study was not required due to its retrospective chart review design.All patients experienced pain evidenced by increased NRS after PIT regardless of the illumination method. Patients 1, 3, and 4 reached the maximum NRS rating of 10 one hour after illumination. In Patient 4, for whom a frontal diffuser was used, NRS was mild (2–3) six hours after illumination, whereas in Patients 1 and 3, for whom a cylindrical diffuser was used, the pain persisted with NRS ratings of 6–9 six hours after illumination. The daily change in mean NRS rating shows that pain was highest on the day of PIT, with ratings of 6.8 and 7.8 for the frontal and cylindrical diffuser methods, respectively; it dropped the following day quickly. The NRS decreased slightly until the postoperative day (POD) 3. However, patients for whom the cylindrical diffuser method was used subsequently showed an increase in NRS at POD 4. This increase in NRS is not significantly different from the NRS of POD 1-3 and is similar to that before hospitalization  Table 2Table 2.Four of the five patients received fentanyl injections for postoperative pain management beginning on POD 0. All patients who underwent therapy using a cylindrical diffuser required postoperative pain management with opioid drugs, but for one of the two patients who underwent therapy using a frontal diffuser, opioid pain management was deemed unnecessary and was thus not performed. In Patients 1 and 3, for whom a cylindrical diffuser was used, the maximum opioid dose required  and the mean NRS (4–7.5) tended to be higher than in patients for whom a frontal diffuser was used. In both cases, the required opioid dose dropped from POD 2 onward and reached a dose comparable to the dose prior to treatment on POD 4  Table 3Table 3.No increase in body temperature or C-reactive protein (CRP) was observed in the frontal diffuser patients after PIT, but a slight increase in body temperature was noted in the cylindrical diffuser patients on POD 0 and POD 1. On POD 4, body temperature had returned to baseline, but CRP elevation was observed .To our knowledge, this is the first case series study on pain and pain management after PIT. All patients experienced pain after PIT, which is consistent with the results of a phase I clinical trial in Japan . Even thNRS tended to be lower upon treatment with a frontal diffuser compared to that with a cylindrical diffuser. In general surgery, the pain has been reported to be mild in less invasive cases . CylindrThe required opioid dose had returned to baseline by POD 4, demonstrating that postoperative pain is a manageable symptom. NRS decreased slightly to POD 3 for both frontal and cylindrical diffusers.However, the NRS increased again at POD 4 in the cylindrical diffuser. This increase in the NRS for POD 4 was similar to the baseline and may have been a patient-reported bias, as opioid use was also decreasing. Additionally, while NRS tended to be lower for treatment with a frontal diffuser than with a cylindrical diffuser, opioid pain management was still necessary, suggesting that opioid pain management is essential for PIT. However, it is important to monitor the pain status and management continuously, as there have been reports of pain continuing for more than 4 weeks after administering PIT . From thPIT has been reported to induce necrosis of the tumor site shortly after the illumination ,16. In tThis study has two limitations. First, the pain symptoms and management could not be clarified due to the small sample size. Second, as the study is retrospective, the missing data values or reproducibility of the NRS could not be compensated for during the analysis. Since data were collected from medical records, missing data could not be evaluated. In addition, because the NRS assesses only the intensity of pain, it was difficult to identify the nature of the pain. Furthermore, the NRS is based on the patient’s subjective assessment, making it impossible to achieve reproducibility. Nevertheless, the NRS is commonly used in clinical practice to assess pain intensity, and in this study, pain management could be assessed by analyzing the variability of the NRS after PIT. More data needs to be collected to clarify the results of this study in more detail, and prospective data collection should be considered in the future.In conclusion, although the pain accompanying PIT varies according to the method used, it develops early and can be successfully controlled using opioid analgesics with quick results. Thus, the importance of preemptively establishing a pain management plan was demonstrated. Going forward, it is necessary to further verify fluctuations in pain status and accompanying analgesic treatments through prospective clinical trials in order to establish postoperative pain management protocols for PIT.


Effective non-opioid pain management is of great clinical importance. The objective of this pilot study was to evaluate the effectiveness of multimodal mechanical stimulation therapy on low back pain.2. Ten patients used a contained motor chassis attached to a thermoconductive single-curve metal plate. The next 10 patients' device had motors attached directly to a multidimensionally curved plate.11 female and 9 male patients aged 22–74 years  receiving physical rehabilitation for acute (12) or chronic (8) low back pain chose heat (9) or ice (11) to accompany a 20-minute session of mechanical stimulation (M-Stim) therapy  The M-Stim was delivered in 12 possible repeating “therapy cycle” patterns by three vibration motors  with amplitudes between 0.1–0.3 m/sp = 0.0112), while the second reduced pain from 4.8 ± 2.0 cm to 3.2 ± 1.9 cm . Initial pain was greater with acute injury  and for patients older than 40 (5.44 vs. 4.52), but pain reduction was proportional for chronic and younger patients. There was no significant difference between plate configurations.Mean pain on a 10 cm Visual Analog Scale (VAS) with the first motor/plate configuration went from 4.9 ± 2.3 cm to 2.5 ± 2.1 cm (57% decrease, A Phase I clinical pilot investigation on a multi-motor multi-modal device was promising for drug free pain relief. Results suggested pain relief independent of thermal modality, patient age, or pain chronicity. Future research should investigate pain reduction over time for acute and chronic pain.https://ClinicalTrials.gov, identifier: NCT04494841. OpioidsHeat, ice, acupressure, myofascial trigger point massage, whole body vibration, low frequency focal vibration, and high frequency vibration with and without ice all reduce low back pain –7. Recenvia central pain modulation (cold) and reduction of spasm and central sensitization (heat). The objective in the current pilot was to demonstrate 50% pain reduction for patients with acute or chronic low back pain after 20 min of use, and to observe patterns to optimize for a full randomized controlled trial of mechanical stimulation vs. electrical stimulation. Ongoing follow-up studies of acute and chronic low back pain control for catastrophizing, Pain Interference, Pain Intensity, and Depression.This pilot project sought to evaluate an external mechanical stimulation (M-Stim) gate control-based pain relief device consisting of multiple vibration motors in an array on a thermally conducting metal plate configured to be in direct contact with the low back. In addition to the neuromodulatory M-Stim, patients could choose heat or cold to elicit local and central pain relief 2.2.1.In this prospective, single-blinded pilot study patients were recruited at a physical therapy and rehabilitation center in an office complex outside a large inner city metropolitan area. Acute and chronic low back pain patients seeking care were identified by their clinician and offered the opportunity to participate in a study on a new low back pain device prior to initiation of physical rehabilitation interventions for the day. Study personnel verified eligibility and completed informed consent. Inclusion criteria included age 18–90, a self-report of pain greater than 4 on a 0–10 self-report numeric pain rating scale, and the capacity to understand the relevant risks and potential benefits of the study. Exclusion criteria included radicular pain reflecting a potentially mechanical etiology, BMI greater than 30 (for whom the prototype device would not fit), sensitivity to cold or vibration ; diabetic neuropathy, new neurologic deficits, or skin lesions to the low back area. Patients were informed that they would be giving feedback on design and usability of a pain relief device but they were blinded to the pain reduction hypothesis.2.2.After informed consent, study personnel gave enrolled patients a choice of heat, ice pack, or no thermal intervention. A frozen solid ice pack  with 4–22 g sections or a microwaved single chamber 150 g clay pack were inserted behind the metal plate, and the device was attached to the patient over a single layer of thin clothing. Patients were instructed how to toggle between 12 different vibration frequency patterns, with five different intensity settings for each pattern. Patients then rated their pain using a 10 cm 0–10 Visual Analog Scale and chose the mechanical stimulation pattern they preferred. Patients then began completing demographic information and medical history while the device was in operation, but they could change the stimulation pattern at any time. After at least 20 min, the device was stopped, and patients recorded a post-treatment pain score. Patients also gave human factors feedback on usability, mechanical stimulation pattern preference, comfort, suggested improvements, whether they would recommend the device, pain relief on a 1–7 Likert scale ranging from “No relief” to “Complete relief”, and design parameters.Ten patients used a contained motor chassis attached to a flat thermoconductive single-curve metal plate . After aa priori power analysis was performed. Statistical analysis was conducted within Excel (Version 2210 Build 16.0 2021 Microsoft Corp). Mean and standard deviations are reported for age (<40 years and ≥40 years), cold/hot treatment preference, sex, device plate configuration, and pain chronicity. Pain scores in cm on VAS were reported with standard deviations and t-test p-values.For the pilot study, no 3.p = .0112), while the second motor/plate configuration reduced pain from 4.8 ± 2.0 cm to 3.2 ± 1.9 cm , however this difference between plate configurations was not found to be statistically significant (p = 0.1094). Initial pain was greater with acute injury  and for patients older than 40 (5.44 vs. 4.52), but pain reduction was proportional for chronic and younger patients. Average pain reduction in both groups was 5.3 on a 7-point Likert scale.During two non-consecutive weeks  11 females and 9 males aged 22–74 years  receiving physical rehabilitation for acute (12) or chronic (8) low back pain were enrolled . Mean pap < 0.0014), and for all subgroups except males (p = .056). Initial reported pain was significantly greater for patients with acute  than chronic pain , but pain reduction was similar amongst all subgroups  by five patients. Eight of ten patients in the second cohort kept a diary of their use of device over a week. Findings included: Pain change on a (1–7) Likert scale continued to improve for all but one who had complete relief after the first session). All eight patients used the device at home, 1 of 4 also used the device at work, 1 of 4 in the car, half used it at home, and half reported use in bed. No preference for vibration therapy pattern was noted and no side effects or adverse events were reported.4.This pilot project evaluated an intervention integrating local and central pain interventions including mechanical stimulation, heat, cold, and patient control over intensities and modalities. Initial results demonstrated significant overall pain reduction, with greater initial pain reported by patients with acute pain. Anecdotal and diary results for eight patients suggested that pain relief continued to improve over a week's duration.The underlying rationale for mechanical stimulation in multiple frequencies is based on new discoveries related to gate control. In 1965, Melzack and Wall hypothesized that stimulation of sensation mechanoreceptors “shut the gate” on pain transmission, an inhibitory mechanism known as “Gate Control” . A web oIn 2017, Hollins et al. reported that Pacinian corpuscles were responsible for 90% of gate control pain relief . This fiIn addition to activating gate control theory-based pain relief, studies suggest vibration may also benefit low back pain through musculoskeletal mechanisms over time. By improving proprioception and improving muscle strength and size through high frequency vibration , pain frIn our study, we adapted the size of Lundeberg's plate, but used the frequencies found effective for gate control. While frequency is often reported in focal mechanical stimulation research, amplitude depends on how the motors are mounted, measured, and attached to the body, and is rarely reported. The change between our first and last configuration changed two parameters that may have affected amplitude differently. While mounting the motors directly to the plate should have increased the transmission of force, the curvature on the edges of the second plate configuration likely reduces the free movement of the plate, dampening the amplitude. In bench testing, removing the rim, but not the ergonomic configuration of the plate, improved transmission of the vibration to the skin.5.Preliminary data from this pilot of a multimodal thermomechanical low back device showed significant pain relief that persisted or improved with continued use. Interesting findings for future investigations included approximately four-hour reported pain relief in the five patients asked to report duration, and similar pain reduction across groups despite idiosyncratic use of frequency patterns and thermal choices. Phase 2 studies will incorporate an active control, and will use a primary outcome measure of opioid use or initiation in patients who have not had spine surgery, with pain as a secondary outcome. Additionally Phase 2 studies will include measures of catastrophizing, depression, and pain interference with three month follow up for acute use, and six month follow-up for chronic patients.Our pilot findings suggest a that patient-controlled device that incorporates vibration, heat, and cold might potentially provide a drug-free pain management solution for low back pain. We observed that while acute pain was greater than chronic pain, both responded consistently to the intervention. Given the prevalence and severity of pain combined with our opioid epidemic, these preliminary findings are promising and support future randomized controlled trials.