Fibromyalgia (FM) is a disease that primarily affects women and causes pain all over the body, as well as anxiety, depression, fatigue, weight gain, a decreased quality of life, and difficulties doing daily duties. Although the cause of this disease has yet to be identified, research have been completed or are under underway with the goal of uncovering clues that can explain the disease’s symptoms and proper treatment. Our research looked into whether factors that increase inflammation in the body cause disease symptoms to worsen. Pain, lean mass, quality of life, sleep quality, muscle strength, depression, and probable factors that cause these symptoms to aggravate were assessed in the blood. Women with FM with more pain had a lower quality of life, and women with FM with lower lean mass had muscle weakness in addition to a lower quality of life. Our results recommend that initiatives be implemented to reduce inflammation, improve muscle mass and strength gain and increase the quality of life of these women.(1) The evidence points to an increase in oxygen reactive species as one of the possible causes of fibromyalgia (FM). In addition, it is plausible that an imbalance in redox markers can be associated with pain amplification and dynapenia in FM patients. The aim of our study was to investigate possible factors associated with muscle pain and lean body mass in FM patients. (2) Methods: This was a quantitative, exploratory and cross-sectional study of 47 patients with FM (53.45 + 7.32 years). We evaluated self-perceptions of muscle pain, lean body mass, body composition, quality of life, sleep quality, depression index, muscle performance and oxidative stress biomarkers. (3) Results: We observed that lower blood levels of antioxidants and poor quality of life explained 21% of the greater muscle pain. In addition, high blood levels of oxidative stress, worse muscle performance and poor quality of life explained 27% of the lower lean mass in patients with FM. (4) Conclusions: Larger amounts of lipid peroxidation and reductions in antioxidant levels, in addition to lower muscle performance and poor life quality, are possible independent contributors to greater muscle pain and lower lean body mass in FM patients. Fibromyalgia (FM) is a chronic disorder marked by widespread muscle pain lasting three months or longer, as well as other symptoms such insomnia, depression, weariness, and exhaustion; pain is reported as the main symptom of FM ,2. AccorDespite the fact that the pathophysiology of FM is unknown, mounting evidence points to mitochondrial dysfunction as one of the likely causes ,6, with The greater intensity of pain often makes it difficult to perform activities of daily living (ADL), promoting social isolation, worsening the perception of stress and generating a negative impact on the quality of life of these patients ,15. RecoFibromyalgia symptoms  are related to skeletal muscle dysfunction, and investigating muscle changes can shed light on possible explanations for mitochondrial damage. In this context, body composition components such as fat mass, lean mass and other body composition parameters become important points to be evaluated in FM . FurtherOf note, FM is often followed by a variety of clinical symptoms such as depression, unrefreshing sleep, irritable bowel syndrome, fatigue and decreased muscle strength ,22. BecaThe patients were recruited from a waiting list at the Universidade Federal dos Vales do Jequitinhonha e Mucuri’s clinical school of physiotherapy and from advertisements in the Basic Health Units and in the community of Diamantina City, Brazil. All subjects were informed about the study procedures by providing their written consent to participate in this study. The inclusion criteria were the diagnosis of FM confirmed by a rheumatologist, along with being non-smokers and non-consumers of alcohol. The existence of any inflammatory disorders, individuals in psychiatric follow-up and patients receiving oral or topical immune-suppressive drugs were all considered exclusion criteria (corticosteroids). See This is a quantitative, exploratory and cross-sectional study. This work was carried out according to the ethical principles for research involving humans (principles of the Declaration of Helsinki) and received approval from the Ethics Committee of the Universidade Federal dos Vales do Jequitinhonha e Mucuri (No. 4.510.517). All subjects were given written consent to participate in the study after being informed of the methods. The data were collected between April 2017 and June 2018.The evaluations were performed in the same order every time. Patients arrived at the laboratory at 7 a.m. after fasting for at least 8 h and without taking their medications, as they usually do in the morning. Furthermore, all patients were asked to stop taking their medications for at least 12 h before being evaluated in order to reduce the risk of acute side effects. They had been told to deliver the drugs to the lab. Following the blood collection, standardized food was served and the medicine was administered.2) was used to calculate the body mass index (BMI) [Following the blood collection, a standardized snack was served, and the medicine was administered. Personal and socio-demographic information, as well as a thorough medical history, information on drugs used and information on living habits, was initially obtained on the evaluation form. Following this, the participants went through a preparatory stage that included experimental procedures, instrument application, pain point evaluation, physical testing and anthropometric measures. The total body weight divided by height squared (kg/mex (BMI) . The assThe following 8 independent variables  were included as possible independent predictors of muscle pain or lean body mass.We used the translated and validated FIQ  for the Brazilian population to assess the impact of FM on quality of life. The FIQ is a questionnaire designed to evaluate the impact of FM on life quality through ten components separated into four sub-items: (1) physical variables ; (2) psychological disorders (well-being); (3) professional symptoms (absence from work); (4) physical symptoms . The FIQ questions are answered using the patients’ self-perceptions from the previous seven days as a reference. The final score ranges from 0 to 100, with a higher number indicating a stronger impact of FM on quality of life . AccordiThe PSQI  was used to measure the patients’ sleep quality during the previous month. The tool permits participants to be classified as ‘excellent sleepers’ or ‘poor sleepers’. There are 19 self-administered questions in the survey. The 19 questions are divided into seven categories, each with a weighting scale ranging from 0 to 3. These scores are then combined together to generate an overall score (0 to 21), with a greater score indicating poorer sleep quality. It is worth noting that a score of five or higher indicates poor sleep quality .The Beck depression inventory (BDI), which has been validated for the Brazilian population, is a 21-item self-assessment questionnaire with four response possibilities (0–3) that assesses attitudes and depressed symptoms. The cut-off points are ≤15 , 16–20 (dysphoria) and >20 (depression) .We also used 5-repetition sit-to-stand tests (5-STS and 60-STS). The patients began by sitting in a chair with arms crossed across their chests and backs against the chair. The seat was roughly 43 cm in height. The researcher stood beside the volunteer, offering directions and preventing the volunteer from falling. A digital timer was used to record the time it took to complete the 5 repetitions .g for 10 min at 20 °C and stored as plasma and erythrocyte aliquots at –80 °C. According to previously published methods, oxidative stress biomarkers were assessed by measuring plasma levels of lipid peroxidation products (thiobarbituric acid reactive substances (TBARS)) [The median cubital vein was punctured aseptically to obtain blood samples. To remove cells and debris, tubes containing EDTA were centrifuged at 3000× (TBARS)) , enzymat(TBARS))  and supe(TBARS)) ) and non(TBARS)) ). The TBThe following two dependent variables (muscle pain and lean body mass), representing the structural and functional aspects of the International Classification of Functioning, Disability and Health, were considered as dependent variables.A visual analogue scale (VAS) was used to assess self-reported muscle pain. The patients did this by placing a mark on a 10 cm horizontal line between the two ends, with 0 cm representing no pain and 10 cm representing the worst pain imaginable. Because every pain experience is subjective, the VAS is a subjective scale. This means that factors other than the present pain feeling, such as the current mood, previous experiences and expectations, could influence each pain assessment. Despite this, the VAS is a well-established method of pain assessment, with several advantages—it is simple, effective and widely used in both research and clinical practice. Furthermore, the VAS has been shown to be a reliable tool for assessing both experimental and chronic pain. VAS cut-off points for pain-intensity-related interference with functioning have been suggested for mild (<3.4), moderate (3.5–6.4) and severe pain-related interference (>6.5) .Dual-energy X-ray absorptiometry: The lean body mass was determined using a densitometer  . The appGPower software version 3.1.9.2 was used to calculate the sample size. A pilot study with ten FM patients was used to assess the sample size. We calculated 47 FM patients using all dependent variables, an effect size of 0.21 (for muscle pain), eight feasible predictors, a likelihood of error of 5% and 80% power. The Statistical Package for the Social Sciences version 22.0  and MedCalc Statistical Software version 13.1  were used to conduct statistical analyses. The Kolmogorov–Smirnov test was used to verify the data distribution. Continuous variables were displayed as the mean and standard deviation  or the median and interquartile range , depending on the distribution.p < 0.1) were included. Four assumptions were used in the linear regression analysis: linearity, residual distribution, homoscedasticity and the absence of multicollinearity. Scatter plots were used to assess the linearity of the independent variables and residuals, and a histogram was used to look at the distribution of residuals. The scatter plot confirmed the homoscedasticity, which was defined by the evenly distributed residuals in the regression line. The variance inflation factor (VIF) values below 10.0 were used to define the absence of multicollinearity. Additionally, the autocorrelation of the variables was verified by the Durbin–Watson test and the values between 1.5 and 2.5 showed that there was no autocorrelation in the data. Statistical significance was set at 5%.Univariate and stepwise multivariate linear regression were used to confirm the determinants of muscle soreness and lean body mass. In each multivariate model adjusted for age, variables related with muscle pain and lean body mass in the univariate analysis  classification, the patients were overweight (28.99 ± 4.65). The FIQ had a score of 69.69 ± 12.40, indicating poor life quality, while the BDI had a score of  indicated that sleep quality was poor. The average time to complete five repeats during the 5STS (14.68 + 4.04 s) indicated that lower limb function was impaired .In our first analysis model having muscle pain as a dependent variable, we observed that the blood SOD levels were negatively associated while the FIQ score was positively associated with VAS in both univariate and multivariate analyses. In clinical terms, both variables together accounted for roughly 21% of the variation in muscle pain in FM patients . The posIn our second analysis model, we found that the TBARS level, FIQ3 score and 5STS were all adversely linked with lean body mass in both univariate and multivariate analyses, accounting for 27% of the variability in lean body mass in FM patients . A moderIn summary, our findings showed that poorer muscle performance, poor quality of life, as well as an imbalance in redox biomarkers may be independent contributing factors to increased muscle soreness and lower lean body mass in patients with FM. In this view, therapeutic efforts to balance redox biomarkers may be one of the priorities of disease management, with an emphasis on improving muscle symptoms in patients with FM, such as muscle pain and lean body mass.Notably, despite the fact that increased oxidative stress, persistent pain and fatigue are all linked to central sensitization, the mechanism behind its initiation is still unknown . Myalgia2. Similar results were previously reported [Given that mitochondrial dysfunction can cause peripheral muscle pain, weakness, fatigue and exercise intolerance , and givreported ,18,19,20reported , and FM 2 for sarcopenia [2). This conclusion is in line with earlier research revealing that patients with FM have a lower lean body mass than age-matched healthy people [The European Working Group on Sarcopenia in Older People (EWGSOP) has published a clinical definition and diagnostic criteria for sarcopenia, as well as population-based threshold values . The , as well as to poorer muscle performance and quality of life ,16. ThusThe FIQ measures the impacts of FM, including physical factors, psychological disorders, the professional situation and physical symptoms. As a result, our study revealed that sub-item 3, i.e., professional situation as measured by the number of days missed from work due to the disease’s influence on these patients’ lives, had a stronger impact on daily activities, which worsens the quality of life of FM patients . In factThe potential impacts of oxidative imbalance, poor functioning and diminished quality of life on muscle pain and lean body mass suggest that all of these parameters should be investigated in the context of FM. As a result, more research into the cause–effect correlations and prognostic factors of FM, such as mitochondrial dysfunctions, pain, disease impacts and oxidative stress in FM patients, is needed. Second, because this study focused just on women, it is important not to extrapolate too far from the findings. Finally, because blood levels of oxidative biomarkers appear to interact with age, our findings cannot be applied to other populations .The present investigation had the advantage of being conducted under controlled and uniform conditions. Furthermore, our research is groundbreaking because no previous research has looked into the possible link between oxidative stress parameters and the disease’s influence on widespread muscle pain and lean body mass in FM patients.The findings of this study were clinically relevant, demonstrating that lower muscle performance and poor life quality, as well as a reduction in superoxide dismutase levels and an imbalance favoring the degradation of lipid peroxidation byproducts, are possible independent contributors to greater widespread muscle pain and lower lean body mass in FM patients.


Photobiomodulation is a novel technique to reduce pain following different surgeries and treatments. This study aimed to investigate the effect of photobiomodulation on pain control after clinical crown lengthening procedures. Twenty patients were included and randomly assigned to two groups in this single-blind randomized clinical trial. The patients had been referred to the Periodontics Department, Tabriz Faculty of Dentistry, for crown lengthening surgery. In the laser group, diode laser therapy with a wavelength of 860 nm and a power of 100 mW was applied immediately after the surgery on the surgery day and three and seven days after the surgery. In the control group, the laser was turned off, and passive radiation was applied to the area as the test group for 30 seconds per session in non-contact mode. The pain was assessed by a visual analog scale (VAS) questionnaire on the study timelines. Data were analyzed with SPSS 20 using ANOVA and post hoc Tukey tests. Twenty patients were included in each study group, where the pain was relieved significantly over time. On the first (5.50±1.18) and seventh (1.8±0.42) days, the pain intensity was similar in the test and control groups. However, on the third day, the laser group (2.90±0.74) experienced a significantly lower pain intensity than the control group (4.0±0.67). Photobiomodulation relieved pain after clinical crown lengthening surgeries. The indications of this surgery are subgingival decay or broad decay that shortens the tooth length, fractures, and premature eruption of the anatomical tooth crown. Various techniques such as gingivectomy, undisplaced flap with/without bone surgery, apical resected flap with/without bone resection, and forced eruption with/without fiberotomy have been proposed for crown lengthening procedures. Selecting the technique depends on various factors like esthetics, crown-to-root ratio, root morphology, furcation and tooth location, and reconstruction possibility. Crown lengthening procedures have become an essential part of aesthetics, as they are widely used to enhance the esthetics and restorations in the esthetic area.The crown lengthening surgery is a technique to expose more tooth surfaces for esthetic or reconstruction purposes through lowering the gingival or bone tissue apically. A part of the patient’s pain and discomfort is associated with his mental status before the surgery and expectations. This also depends on the surgery duration, which can intensify the patient’s stress and anxiety, leading to more severe pain.Compared to bone surgeries, pure mucogingival procedures result in more pain. The technical differences between the procedures with varying exposure levels of bone connective tissue can lead to differences in postoperative pain intensities. Wide surgeries are associated with more pain than less invasive surgeries.Photobiomodulation (PBM) has been applied in dentistry for various purposes, including wound treatment, aphthous stomatitis, mucositis, nerve regeneration, postherpetic neuralgia (PHN), synovitis, arthritis, temporomandibular joint pathologies, acute abscesses, peripheral granuloma, chronic orofacial pains, and bone regeneration. The analgesic effects of PBM are due to stimulating the synthesis of androgenic endorphins like beta-endorphin, reducing cytokines, and inflammatory enzymes, pain threshold shift, morphological changes in neurons, reduced mitochondrion membrane potential, and blocking the fast axon flow, leading to the neural pathway blockage. Its inflammatory impact occurs because of the increased activity of phagocytes, number and diameter of lymphatic vessels, and decreased vessel permeability and micro-capillaries blood circulation, and decreased edemas. Concerning the importance of pain relief in crown lengthening surgery, this study investigated the impact of PBM on pain intensity after clinical crown lengthening procedures.Previous studies investigated the impact of PBM on the gingival regeneration after gingivectomy procedures, concluding that such laser therapy can enhance wound healing after gingivectomy.This single-blind clinical trial was registered in the Iranian Center of Randomized Controlled Trials with an IRCT code of 20180114038364N1 and confirmed by the Ethics Committee of Tabriz University of Medical Sciences (IR.TBZMED.REC.1398.1299). Twenty patients referring to the Department of Periodontics, Tabriz Faculty of Dentistry, for crown lengthening surgery, who met the inclusion and exclusion criteria, were selected.Patients aged 1860 with no systemic disease were randomly assigned to two groups (n=10). The flap technique was used for crown lengthening surgeries, and all the surgeries were performed by a skilled surgeon by observing all surgery principles. The patients were blinded to the intervention type.2 immediately after the surgery on the surgery day and three and seven days after surgery. For the control group, the laser was turned off, and passive irradiation was carried out on the given area. Patients in both groups were visited on the first, third, and seventh days. The laser irradiation duration was 30 seconds per session. All the laser therapy processes were carried out by meeting the laser safety guidelines.The test group was treated by the photobiomodulation with GaAlAs laser  in non-contact mode with a wavelength of 860 nm, a power of 100 mW, and an energy density of 3 J/cmThe patient’s pain status was assessed by the visual analog scale (VAS) questionnaire up to the seventh day after the surgery. Painkillers were prescribed for all the patients for one week .In this study, 20 patients were studied in two groups: control and intervention. The frequency of males and females in the laser  and control groups  was the same. In addition, the mean age in the control group was 31.2±5.4, with no significant difference from the laser group.The results showed that on the first day, pain intensity in both the control (6.2±0.79) and intervention (5.50±1.18) groups was similar. On the third day, pain intensity in the intervention group (2.90±0.74) was significantly lower than the control group (4.0±0.67). On the seventh day, the control group (2.0±0.67) experienced the same level of intensity as the laser group (1.8±0.42). Based on the Friedman test, the pain intensity decreased significantly over time in both groups .The mean use of painkillers on the first, third, and seventh days was the same in both the control and intervention groups, with no significant difference . AccordiIn this study, pain intensity in both the control and laser groups had a significantly decreasing trend until the seventh day after surgery. It was also the same on the first and seventh days for both groups. However, on the third day, the pain intensity in the laser group was significantly lower than in the control group. The number of painkillers taken was similar in both groups. On the seventh day, 80% of patients in both groups took no painkillers. pain intensity in the periodontal flap surgery on the second, third, fourth, fifth, sixth, and seventh days after surgery was lower in the laser group. Furthermore, these patients took fewer painkillers during these days, consistent with the present study since we observed significant pain relief on the third day.In a study by Heidari et al, reported that the low-level laser could be effective in pain relief by reducing the biochemical markers, oxidative stress, and edema, which itself depends on the dose (effective dose range from 0.3 to 19 J/cm2 with a mean dose of 7.5 J/cm2). Furthermore, they reported that the analgesic impact of low-level laser is higher when it is irradiated with high density in the first 72 hours after surgery, which should continue with lower doses to accelerate regeneration. Studies by Lingamaneniet al and Kohale et al revealed that laser therapy could enhance wound healing after gingivectomy. Each researcher applied a different laser (InGaAsP) and obtained the same results.In a systematic review, Bjordal et al Regarding the various stages of wound healing, photobiomodulation seems to be more effective in the fibroblastic phase of wound healing, including excessive fibroblast activity, angiogenesis, and epithelial proliferation. Effects of photobiomodulation on the fibroblast, including increased proliferation, increased growth factor secretion, and conversion into myofibroblasts, have already been observed in previous studies.Wound healing is a complicated and dynamic process with three overlapping phases. The first phase, or inflammatory phase, begins with tissue injury. The second phase, or the fibroblastic phase, includes the production of tropocollagen and collagen by fibroblasts. The final phase or remodeling lasts from months to years. In this stage, the irregular collagen fibers are removed and replaced by highly regular new fibers. reported pain relief by photobiomodulation in treating radiotherapy-induced mucositis in patients with maxillofacial cancers. Aras et al showed the impact of laser on reducing trismus and inflammation resulting from the impacted wisdom tooth surgery. Lioubavina-Hack et al presented a report on the effect of laser therapy on reducing the initial level of periodontal pathogens. Mechanisms of treatment by photobiomodulation are sophisticated, but they are necessarily dependent on the absorption of special visible red and near-to-infrared wavelengths in the photoreceptors of sub-cellular elements, particularly the electron transport chain (respiratory) in mitochondria. Photobiomodulation is a red or infrared light that stimulates the proliferation of fibroblasts through non-thermal effects. The possible mechanisms involved in pain relief are the stability of neural cell membrane, increased cell regeneration system, and increased ATP production. However, a study showed that this treatment method has no significant impact. In this regard, Heidari et al reported that laser photobiomodulation (PBM) has no impact on reducing free gingival graft (FGG). A low number of studied patients is among the reasons for differences in the results. Small size leads to the lack of reasonable certainty in the results. Age and gender are also among the variables affecting pain.Numerous studies have reported the impact of lasers on pain relief or wound regeneration. Carvalho et al2 immediately after surgery and on days 3 and 7 after surgery, as an adjunct, had limited effect on pain relief after clinical crown lengthening surgeries.Photobiomodulation (with GaAlAs laser) with a wavelength of 860 nm, a power of 100 mW, and an energy density of 3 J/cmMF and MS planned the study. Data collection was carried out by SR. Statistical analyses and interpretation of data were carried out by RCH, MGH, and SR. The manuscript was prepared by RCH and MGH and revised by MS. All the authors have read and approved the final manuscript for submission.The study protocol was approved by the Ethics Committee on Medical Research, Tabriz University of Medical Sciences.The authors declare that they have no competing interests regarding authorship and/or publication of this paper.


Introduction: The thoracic Erector Spinae Plane Block (ESPB) is an ultrasound-guided block that has gained popularity and is widely used in acute pain setups. However, data regarding its role in chronic and cancer-related pain are anecdotal. Material and Methods: The study is a retrospective analysis of patients who underwent ESPB. The cohort was divided into subgroups based on three determinants: etiology, pain type, and chronicity. Results: One hundred and ten patients were included, and genders were affected equally. The average age was 61.2 ± 16.1 years. The whole group had a statistically significant reduction in a numerical rating scale (NRS) . NRS reduction for 45 patients (41%) exceeded 50% of the pre-procedural NRS. The mean follow-up was 7.9 ± 4.6 weeks. Baseline and post-procedure NRS were comparable between all subgroups. The post-procedural NRS was significantly lower than the pre-procedural score within each group. The proportion of patients with over 50% improvement in NRS was lower for those with symptom duration above 12 months . Conclusions: Thoracic ESPB is a simple and safe technique. The results support the possible role of ESPB for chronic as well as cancer-related pain. Chronic pain is a common, complex, and distressing condition that impacts many aspects of patients’ health and quality of life. Therefore, it can place a significant burden on patients and on the broader healthcare system. The Global Burden of Disease Study of 2016 reaffirmed that the high prominence of pain and pain-related diseases is the leading cause of disability and disease burden globally [The Erector Spinae Plane Block (ESPB) belongs to a growing number of ultrasound-guided blocks that aim to deliver an analgesic solution to the soft tissue, or the interfascial plane, as opposed to the classic method of a direct nerve block. Shortly after its first description, the ESPB was adopted in clinical practice for multiple types of thoracic, abdominal, and extremity surgeries . It is rThoracic origin chronic pain represents a particular challenge as the interventional aspect requires its own special consideration. As with all neuraxial techniques, thoracic neuraxial procedures have contraindications and limitations  and other possible complications with considerable potential morbidity, including pneumothorax and neurovascular damage.Although the first description of the block was for chronic neuropathic pain, most publications are concerned with acute pain management. The current literature addressing its use for chronic and cancer-related pain is scarce and mostly anecdotal in nature ,7,8,9,10In this paper, we described the outcomes of the ESPB applied to patients at our pain institute, a regional referral center within a tertiary, university-affiliated medical center. We compared outcomes between different groups of patients based on the origin of the pain, type of pain, and symptom duration.A retrospective analysis.The study was conducted at the Pain Institute Center of the Tel Aviv Souraski Medical Center and was approved by the hospital’s ethics committee (No. 0003-20-TLV). A retrospective review was carried out on the medical records of all patients who underwent thoracic ESPB between October 2018 and August 2021.All participants provided written informed consent prior to undergoing the procedure, similar to other invasive procedures in our center. Inclusion criteria included: age of 18 years or above, diagnosis of thoracic back pain, a numerical rating scale (NRS) for pain ≥ 6, no significant motor weakness, no signs or symptoms of myelopathy, failure of other conservative treatment , and at least a one-month post-procedure follow up.Exclusion criteria: Allergy or hypersensitivity to steroid or amide local anesthetics, pregnancy, and breastfeeding.The procedure was carried out under ultrasound guidance. The patient was placed in a prone position, and the ultrasound probe was set 2.5–3 cm laterally to the spinous process at the desired thoracic vertebral level on a parasagittal plane. Normally, a high-frequency linear probe was used. In the case of obese patients, a curvilinear (2–5 MHz) probe was used. Under ultrasound guidance, a 22 G needle measuring 50 or 100 mm was then inserted in a craniocaudal direction using the in-plane technique. The injection takes place at the fascial plane, deeper into the erector spinae muscle group. The solution injected was 10 mL of 1% lidocaine with dexamethasone 10 mg for a unilateral injection and 15–20 mL of 1% lidocaine with dexamethasone 10 mg for a bilateral injection.Pre-procedural baseline demographic, clinical, and imaging data were collected. Demographic and procedural variables included: age, gender, pre-procedural NRS, and duration of symptoms at the first visit. Procedural variables included the side and level of the injection. Post-procedural variables included post-procedural NRS scores and the total number of ESPBs performed. Adverse effects were also monitored and documented. The data were collected and recorded by the pain physician in charge of the patient at the pain institute.Thoracic pain was defined as pain experienced in the thoracic area, between the T1 and T12 boundaries, and across the posterior aspect of the trunk .The main outcome measured was the change in pain intensity which was assessed using an 11-point numerical rating scale (NRS), with a range from 0 (no pain) to 10 (worst possible pain). In order to evaluate clinical significance, we used a minimal clinically important change (MCID) of 2.5  for NRS,We divided the patients into different groups based on etiology, dominant pain type, and pain chronicity. For etiology, we divided the patients into two groups: one with patients suffering from cancer-related pain and the other with patients suffering from non-cancer-related pain. Cancer-related pain was defined as pain originating directly from a thoracic neoplastic lesion.Regarding the dominant pain type, we divided the patients again into three groups according to the pain type: nociceptive, neuropathic, and mixed pain. The neuropathic pain type was defined using strict criteria, following the current International Association for the Study of Pain (IASP) definition of “definite neuropathic pain” . In caseIn order to analyze the effect of chronicity, the cohort was divided into three groups according to the duration of symptoms: up to four months, four to twelve months, and more than twelve months.The patient clinical assessments were conducted before the procedure and at the post-procedure follow-up appointments. The pre- and post-procedural NRS were compared in the entire group and within each of the sub-groups.At the post-procedure follow-up, patients with motor neurological deficits were referred for further surgical evaluation. Patients with significant pain (NRS > 6) were offered a second thoracic ESPB. A maximum of three procedures were allowed for each patient. Patients with no significant pain (NRS < 4) at the follow-up visit, were either discharged or offered an additional second follow-up.t-test, the X2 test, and the Fisher exact test to evaluate categorical variables’ independence. ANOVA and independent t-test were used to compare NRS values between the symptom duration groups. Pre-procedure to post-Procedure NRS changes within each group were analyzed with paired t-tests. A p-value < 0.05 was considered statistically significant.The statistical analysis was performed using SPSS version 19 . Significant differences between the groups were determined using one sample One hundred and ten patients underwent the procedure, and both genders were affected equally. The average age was 61.2 ± 16.1. Sixty-one (55%) patients underwent unilateral injections, and 49 (45%) underwent bilateral injections . Seventyp-value = 0.003). Analysis of pain duration groups showed a significant difference in the distribution of the injection site   .p-value > 0.001). In fifty-eight (53%) patients, the NRS improvement exceeded the MCID, and in 45 (41%), it exceeded 50% of the pre-procedural NRS   .p-value = 0.334)  .p-value = 0.02)  .There were no major adverse effects reported. The main adverse effect was injection site soreness. Other adverse effects reported were systemic response attributed to steroid exposure, none requiring hospitalization.Thoracic spine pain is prevalent, affecting about 20% of people in their lifetime. However, research related to thoracic pain is sparse compared to lumbar and cervical spine pain .Thoracic ESPB has gained popularity since its introduction and is being widely used in acute pain setups; however, data regarding its role in chronic pain are mostly anecdotal. In this work, our purpose was to evaluate the role of ESPB in the management of chronic and cancer-related thoracic pain. We compared the outcomes based on three fundamental determinants: etiology, the dominant pain quality, and the chronicity of pain.p-value > 0.001), with 53% reporting NRS improved by more than 2.5 points, and 41% with NRS score improved by more than 50% compared to pre-procedure score. In our study, a successful, clinically meaningful procedure was defined as either a reduction in the NRS score by 2.5 or more points [Our results are consistent with those of previously published reports describing the possible benefits of ESPB ,7,8,9,10e points  or as a e points ,17, was p-value = 0.51).Cancer patients frequently suffer from a wide range of other symptoms, and the multi-factorial causes result in a ‘‘total pain experience” . As suchOf the 66 cases of non-cancer-related pain, 33 were nociceptive (50%), 28 were neuropathic (42.4%), and 5 (7.6%) were mixed pain types. The nociceptive group included pain resulting from vertebral or rib fractures, deformations including kyphosis and scoliosis, soft tissue myofascial pain , degenerThese results suggest that although the ESPB analgesic effect may differ slightly, overall, this effect is comparable between patients with pain originating from oncological and non-oncological sources and that ESPB can have a potential role in treating pain with these conditions.A second subgroup analysis, based on the dominant pain type, did not reveal significant differences in either the pre- or post-pain NRS score nor in the portion of patients who reported more than 50% improvement.p-value = 0.334). However, due to the small number of patients in this subgroup, this finding should be interpreted carefully, and conclusions should not be drawn.When the pre- and post-NRS scores were compared within the mixed pain  group, tAn analysis of the chronicity of the pain experience duration was also carried out. More than 60% of the study population experienced pain for more than a year prior to the execution of the ESPB. Given that our clinic serves as a tertiary center, often with long waiting times, such a proportion is expected. Although all three subgroups reported statistically significant NRS reduction, the largest proportion of patients with pain reduction of more than 50% was found in the patients with symptom durations of less than four months. These results support previous findings regarding the importance of early treatment and support the recommendation of early referral to a pain specialist for early intervention ,21.As mentioned above, much is yet unknown about thoracic ESPB. Not only regarding its indications and efficacy but also various technical aspects. As the procedure is a single shot, not a continuous infusion, the dosage delivered should not exceed the recommended daily dosage. We use 10 mL of 1% lidocaine with dexamethasone 10 mg for a unilateral injection and 15–20 mL of 1% lidocaine with dexamethasone 10 mg for a bilateral procedure. Corticosteroid has an established role in the management of both neuropathic and cancer pain ,23,24. TMost chronic pain patients are treated at an ambulatory outpatient clinic. This should be considered when evaluating the approach and safety aspects of such a procedure.In the immediate vicinity of the needle performing the block, there are no neuro-vascular structures at risk. To date, there have been minimal procedure-related complications reported with this block compared to the traditional thoracic neuraxial blocks ,26,27. OThe classification of the American Society of Regional Anesthesia (ASRA) for pain procedures considers musculoskeletal injections and thoracic facet medial branch block as procedures with a low risk for bleeding ,29. ReceAll patients undergoing lower thoracic ESPB are tested for motor function following the procedure to screen for any unintended motor weakness. However, we do not carry out sensory tests to evaluate the dermatomal coverage.We do not perform additional procedures before evaluating the response of the first procedure. A follow-up is routinely scheduled 6–8 weeks after the procedure. A patient that reports a substantial improvement is discharged with a set of recommendations for future maintenance by their primary care physician.This study is a single-center trial and is limited by its retrospective nature. Part of the challenge associated with retrospective analyses is the possibility that pharmaceutical changes or other manual manipulations unbeknown to the team might affect the outcomes. However, in our pain institute, we avoid the use of pharmaceutical changes following ESP in order to allow for precise estimation of the analgesic effect of the procedure for future reference in cases of additional pain management advice. Even though a substantial percentage presented an NRS improvement exceeding 50%, our results should be interpreted carefully due to the sample size of the study. Another limitation that future studies should address is the long follow-up time, as the positive effect of the block may wane over time. Furthermore, a distinction of possible spinal anatomical structures and mechanisms  is missing and should be explored on a larger scale study.In summary, thoracic pain is common and could lead to substantial disability and other negative impacts on the patient’s life and society. It was argued that thoracic pain should be considered a discrete and important clinical entity, independent of pain experienced in other areas of the spine . This stThoracic ESPB is a simple and safe technique. The results support the possible role of ESPB for chronic as well as cancer-related pain.Due to the simplicity of the ESPB, it could potentially be applied in multiple disciplines and setups, such as the emergency department and at an ambulatory practice.In the future, prospective trials should be carried out to expand our knowledge and determine the proper and safe application of this type of block.


IntroductionA dedicated relationship between total ischemic time (TIT) and clinical outcomes has been reported in ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI); however, this claim is yet to be clarified. Accordingly, this study was carried out to determine the association of TIT with in-hospital and one-year follow-up outcomes in STEMI patients undergoing primary PCI.Material and methodologyBetween December 2020 and December 2021, a total of 113 consecutive STEMI patients undergoing primary PCI were prospectively included. According to TIT, all patients were categorized into two groups: (a) shorter TIT (<180 minutes) and (b) prolonged TIT (≥180 minutes). Data regarding baseline, clinical, and angiographic characteristics, as well as in-hospital and one-year follow-up outcomes were noted among the two groups.Resultsp=0.02) at one-year follow-up.A total of 113 STEMI patients with a mean age of 69.3 ± 13.6 years were studied, and males [92 (81.4%)] were predominately affected with STEMI. A median TIT was 348 minutes. Of 113, 30 (23.0%) patients had a TIT of <180 minutes and 83 (73.5%) had a TIT of ≥180 minutes. Prolonged ischemia duration was significantly associated with composite of death, rehospitalization, and revascularization (ConclusionTIT can be considered a good quality indicator, together with door-to-balloon time and other clinical determinants, in order to improve survival in STEMI patients. Myocardial infarction (MI) has reached epidemic proportions worldwide. Mortality from MI is swiftly increasing in developing countries, especially in India. The ST-Elevation Myocardial Infarction (STEMI) Programme initiated by the National Health Mission (NHM) in Tamil Nadu endorses 3,50,000 to 4,00,000 MI deaths every year in India . PercutaStudy designDuring the period of December 2020 to December 2021, a prospective non-randomized observational study was carried out at Super Speciality Hospital, Shyam Shah Medical College, Rewa, Madhya Pradesh, India. Consecutive STEMI patients undergoing primary PCI were prospectively included. STEMI patients managed with thrombolytic therapy was the sole exclusion criterion. The study was approved by the Institutional Ethics Committee  and performed in accordance with the guidelines of the Declaration of Helsinki. Written informed consent was obtained from each of the participants.Data collectionData regarding baseline and clinical characteristics were reported. Severity of STEMI was categorized according to Killip's heart failure (HF) classification: class I, no clinical signs of HF; class II, HF with rales in half of the lung field and with S3 gallop; class III, frank acute pulmonary edema; and class IV, cardiogenic shock, hypotension, and evidence of peripheral vasoconstriction such as cyanosis, oliguria, and diaphoresis . All patDefinitions· ST-segment elevation myocardial infarction (STEMI): Angina or angina equivalent lasting for >20 minutes and ST-segment elevation of 1 mm in two contiguous leads, or new left bundle branch block, or true posterior MI with ST depression of 1 mm in two contiguous anterior leads.· Total ischemic time (TIT): Time from pain onset to establishment of infarct-related artery flow.· Cardiogenic shock: Sustained hypotension with systolic blood pressure <90 mmHg for at least 30 minutes, unresponsive to fluid administration and associated with features of tissue hypoperfusion.· Coronary flow of the infarct-related artery: It was determined visually by the operator and categorized based on TIMI grading system on a scale of 0 to 3 both before and after PCI.· Diabetes mellitus: Fasting blood sugar level of 126 mg/dL (7.0 mmol/L) or higher, HbA1c > 7, or on treatment.· Dyslipidaemia: Fasting cholesterol >200 mg/dL or on treatment.· Door-to-balloon (D2B) time: Time from first hospital arrival to the first attempt at reperfusion with any intracoronary device.· Major bleeding: The occurrence of any of the following: intracranial bleeding, intraocular bleeding, retroperitoneal bleeding, access site hemorrhage requiring surgery or a radiological or interventional procedure, hematoma ≥ 5 cm in diameter at the puncture site, reduction in hemoglobin concentration of 4g/dL without an overt source of bleeding, reduction in hemoglobin concentration of >3g/dL with an overt source of bleeding, re-operation for bleeding, or use of any blood product transfusion.· Procedural success of percutaneous coronary intervention (PCI): Achievement of vessel patency to residual stenosis < 30%.· Re-infarction: Recurrent chest pain or ischemic equivalent symptoms lasting 30 minutes, and new electrocardiogram (ECG) changes consistent with re-infarction, and the next creatine kinase myocardial band (CK-MB) or creatine kinase (CK) level measured approximately 8-12 hours after the event was at least 50% above the previous level or >3 upper limits of normal, whichever was greater.· Systemic hypertension: Systolic blood pressure of >140 mmHg and/or diastolic pressure of >90 mmHg, or on treatment.Data analysisContinuous data were explained by mean and standard deviation, and categorical variables were described as percentage and frequency. Student's t-test for independent samples was used to compare the mean between two groups, and the chi-square test or Fisher's exact test was used for comparison of categorical data. A p-value of <0.05 was taken to indicate statistical significance. Data analysis was carried out by using Statistical Package for the Social Sciences (SPSS) Version 20.0 .A total of 113 consecutive STEMI patients who underwent primary PCI were studied. The cohort was predominantly male [92 (81.4%)], with a mean age of 69.3 ± 13.6 years. Median TIT and D2B time were 348 minutes and 45 minutes, respectively. A total of 51 (45.1%) were smokers, 52 (46.0%) were hypertensives, 44 (38.9%) were diabetic, nine (8.0%) had contrast-induced nephropathy. Previous history of percutaneous transluminal coronary angioplasty (PTCA)/coronary-artery bypass grafting (CABG) was found in seven (6.2%) patients. A statistically significant differences were found for the following baseline characteristics: male gender (p=0.04), smokers (p=0.05), hypertension (p=0.03), diabetes mellitus (p=0.04), contrast-induced nephropathy (p=0.02), Killip class I (p<0.01), Killip class II (p<0.01), Killip class IV (p=0.02), pain-to-door time (p=0.02), advanced age > 75 years (p=0.02), and hours from onset to balloon < 3 hours (p<0.02). Demographic and clinical characteristics stratified according to TIT are outlined in Table Of 113 patients, 30 23.0%) had a TIT of <180 minutes and 83 (73.5%) patients had a TIT of ≥180 minutes. The angiographic and procedural parameters stratified according to TIT are presented in Table 3.0% had As depicted in Table At one-year follow-up, prolonged TIT was significantly associated with composite of death, rehospitalization, AND revascularization (p<0.03). Drugs prescribed at discharge were as follows: aspirin in 98.2% of the cases, clopidogrel in 61.9%, prasugrel in 12.4%, ticagrelor in 13.3%, single antiplatelet in 11.5%, β-blockers in 50.4%, ACE inhibitor in 35.4%, and statins in 96.5% (Table In this prospective study, we endeavored to assess the association of TIT with clinical outcomes in STEMI patients undergoing PCI and observed that the mortality rates were higher with prolonged TIT during the hospital stay and at one-year follow-up, but the values were not statistically significant. The high mortality with prolongation of ischemic time may be due to the fact that infarct size significantly affects myocardial tissue and continues to damage with each passing second of ischemic time -11. As aA recent study by Khalid et al.  advocateA number of factors that play key role in the prolongation of TIT are unawareness and patients’ failure to recognize cardiac symptoms, and unavailability of attendants, transportation, finance, and nearby facility . ReductiSeveral potential limitations of the study should be acknowledged. First, this was a single-center and non-randomized study. Second, the huge differences in baseline characteristics between patients with short TIT and those with prolonged TIT might restrict the comparability of the groups. Third, the time of onset of chest pain was recorded based on the patient or attendant's recall; therefore, we could not exclude the impact of recall bias, which may have some over or understating. Last but not least, patients were not followed up for a longer duration of time; hence, the relationship between TIT and long-term clinical outcomes remains uncertain. Further multicenter studies with large sample sizes are warranted.Findings of the current study strongly support that TIT can be a good quality measure together with D2B time and other clinical determinants in order to improve survival in STEMI patients. Hence, attempts should be made to shorten TIT in order to enhance patients’ survival.


We aimed to investigate the effect of transforaminal injection of Magnesium sulphate versus Ozone on pain intensity, functional disability and the oxidative stress biomarkers; superoxide dismutase (SOD) and Glutathione (GSH) in patients with lumbar disc prolapse.This randomized controlled trial was conducted on 135 patients having symptomatic lumbar disc prolapse, received either transforaminal injection of Magnesium sulphate with steroids, Ozone with steroids, or steroids alone. Assessment of pain severity and functional disability were done before intervention, 2 weeks, 1, 3, and 6 months after intervention. Serum SOD and GSH were measured for all included patients before and 2 weeks after intervention.P-value = 0.002, 0.005 respectively) and ozone groups , but there was no statistically significant change in SOD and GSH serum levels in control group.There was a statistically significant improvement in pain intensity and functional disability 2 weeks after intervention in the three groups, but at 1-month and 3-months after intervention, the significant improvement was in Mg sulphate and Ozone groups only. At 6-months follow up, Mg sulphate group only showed a significant improvement. There was a statistically significant increase in SOD and GSH serum levels, 2-weeks after intervention in both Magnesium sulphate  in pain intensity and functional disability. The serum levels of SOD and GSH were significantly increased at 2 weeks following both transforaminal injection of Mg sulphate and ozone. Lumbar disc prolapse is one of the most common causes of low back pain and/or radicular pain. The pathogenesis of lumbar disc related radicular pain is likely related to mechanical and/or inflammatory factors. The natural history of lumbar disc prolapse is mostly favorable, with about 80–90% of patients showing improvement within 1- 3 months . ManagemMagnesium sulfate has drawn much attention in the field of pain management, resulting in numerous publications of review articles, clinical trials, and meta-analyses . Intrave3) therapy has been emerged in the treatment of neuropathic pain, inflammatory, degenerative and herniated disc conditions , or sacroiliitis . We also excluded patients with severe lumbar disc prolapse causing lower limb weakness or sphincteric troubles, and patients with contraindications to interventions . Pregnant patients were also excluded from our study. We demonstrated in a flow diagram for the recruited patients that 195 patients were assessed for eligibility. Sixty patients were excluded . Forty-five patients in each group received allocated intervention. Nine patients in Mg sulphate group, seven patients in Ozone group, and 10 patients in control group lost to follow-up , Oswestry Disability Index (ODI), and Functional rating index (FRI).NRS is a single 11-point numeric scale for assessment of intensity of pain. It ranged from 0 to 10, where 0 indicates no pain and 10 indicates the worst pain .ODI is a questionnaire used to quantify the disability from low back pain. It includes the following items: pain intensity, the level of disability of personal care, lifting, walking, sitting, standing, sleeping, traveling, sexual and social life. Each question is scored on a scale of 0–5 with 0 representing no limitation, and 5 representing maximal limitation. The scores for all questions answered are summed, then multiplied by two to obtain the index (range 0 to 100) .FRI is a self-reported scale containing 10 items. Eight items focus on daily activities affected by back pain and 2 items focus on frequency and intensity of pain. Each item has a 5-point scale . The FRI scores ranged between 0% (no disability) and 100% (severe disability) .Assessment of patient’s satisfaction about the intervention was done 6 months after the interventional procedure by a psychiatrist who was blinded to the patient’s condition and the type of intervention. It was done by using the Short Assessment of Patient Satisfaction (SAPS) scale. SAPS consists of the following seven items: satisfaction with treatment, explanation of the treatment outcome, medical care, respect by the physician, participation in medical decision making, time with the physician, and satisfaction with clinic/ hospital care. Responses scales are 5-point scales. SAPS scores were interpreted as follows: 0 -10 = very dissatisfied, 11 - 18 = dissatisfied, 19 - 26 = satisfied, and 27 - 28 = very satisfied .We asked the patients to stop any medical treatment for the lumbar disc related radicular pain one week before the intervention. The selected patients were brought to the preparation room where reassurance was done. Intravenous midazolam 0.2 mg/kg was given to them, then they were placed in the prone position on fluoroscopy table and draped in a sterile manner. They were connected to a monitor  and given supplemental oxygen through a nasal cannula (3 L/min) to maintain an oxygen saturation. A 22-gauge, 3.5-inch spinal needle was used in the injection procedure. With each insertion of the spinal needle, 1 ml with 20 mg of local anesthetic lidocaine 2% was injected intradermally. Upon final needle-tip position, antero-posterior (AP) and lateral views of the fluoroscopic imaging were obtained to confirm needle positioning then the contrast was injected. AP and lateral views of the contrast spread were taken during the procedure to confirm appropriate spread into posterior epidural space.Transforaminal injection of Mg sulphate:The patients were randomly assigned into one of three groups:2.Transforaminal injection of Ozone:In this group, the patients received transforaminal epidural injection of steroids and Mg sulphate with local anesthetic .3.Transforaminal injection of steroids alone:In this group, the patients received transforaminal epidural injection of steroids  with the addition of an O2-O3 mixture, with an ozone concentration of 25 microgram /mL. We injected 3 mL of O2-O3 at transforaminal level.In this group, the patients received transforaminal epidural injection of steroids with local anesthetic (7 mg Betamethasone preceded by a test dose of 1 milliliter 2% lidocaine).After the intervention, the patients were not prescribed any medications (apart from NSAIDs for the first 3 days after injection) or specific physiotherapy regimens because they were already not responsive to them before the intervention.Oxidative stress biomarkers (superoxide dismutase (SOD) and Glutathione (GSH)) were measured for all included patients in the three groups before and 2 weeks after the interventional procedure. For this purpose, the two-site sandwich ELISA method were employed. GSH and SOD levels were determined by reading the color changes compared to the standard curve in photometry. Samples were withdrawn from patients and the collected whole blood was refrigerated at 4 c for the night, then centrifuged it for 10 min at 1000-3000 rpm. The supernatant was taken and frozen at -80 c (for 1-3 months ) for storage.Both markers SOD and GSH were measured by using double sandwich ELISA technique. The pre coated antibodies were human SOD and GSH monoclonal antibodies and the detecting antibody was biotin labeled polyclonal antibody. We added samples and biotin labeled antibody in ELISA wells then washed with TBS or PBS. We added Avidin peroxidase conjugate to the wells. We used TMB substrate for coloring after reactant thoroughly washed out by PBS or TBS. In presence of peroxidase activity TMB substrate changed into blue color. Finally, we added stop solution which changed blue color into yellow color. We measured the optical density (OD) by using ELIZA reader. The depth of the color and the testing factors in samples are positively correlated with their concentration. The standard curve was used to detect the amount of the biomarkers by plotting the average O. D for each standard against the concentration and drew a best fit curve using graph paper or statistical software analysis.Because our study was the first study to compare the therapeutic effect of transforaminal injection of Magnesium sulphate versus Ozone on the oxidative stress biomarkers in patients with lumbar disc prolapse, we calculated the sample size based on the results of a pilot study we performed before starting our study. The sample size calculation was done using G*Power version 3.1.9.7 Software. The probability of type I error (α) was 5%, effect size = 0.529, df =88, critical t= 1.66, noncentrality parameter λ= 2.51, A total sample size of 45 patients in each group was required to achieve a statistical power (1–β) 80%.IBM SPSS  Version 25 was used to analyze the data. Categorical variables such as sex and the degree of the most prolapsed disc, were expressed as numbers and percentages. Quantitative variables such as age, duration of pain, the number of prolapsed discs, NRS, ODS, FRI, SAPS, SOD and GSH were expressed as mean and standard deviation. Chi-squared test was used for comparison between Mg sulphate, Ozone, and control groups in categorical variables, whereas One-way ANOVA was used for comparison between Mg sulphate, Ozone, and control groups in quantitative variables. Paired sample t- test was used for comparison between quantitative variables before and after the interventional pain procedure. Mixed ANOVA test was used for comparing quantitative variables before and after the interventional pain procedure in Mg sulphate, Ozone, and control groups. P-value ≤0.05 was considered statistically significant. All tests were two-tailed.P-value= 0.258, 0.392 respectively)  . Whereas, after 6 months, this number was significantly higher in Mg sulphate group only in comparison to both Ozone and control groups   and ozone groups , but there was no statistically significant change in SOD and GSH serum levels in control group   in pain and functional disability in patients who received Mg sulphate in our study can be attributed to the neuroprotective and anti-inflammatory effects of Mg sulphate. The neuro-protective effect of magnesium sulfate has been one of the most challenging aspects of this drug. Magnesium was reported to plays a fundamental role in neuroplasticity. It is directly involved in the maintenance of neurological integrity and neuroprotection through reduction in glutamate release and inhibiting calcium entry into the cell via a noncompetitive blockade of NMDA receptor –24. It aIn contrast to these findings, another study revealed that infusion of Mg sulfate in patients undergoing laminectomy didn’t produce a clinically significant long-term improvement in postoperative pain severity. It showed only improvement for very short period (24 hours) .Our results revealed that transforaminal injection of ozone caused a significant improvement in the scores of NRS, ODI and FRI, at 2 weeks, 1-, and 3-months follow-up.Ozone therapy has been used in multiple studies as an additional treatment option in patients with lumbar disc prolapse. The proximal injection of the O2-O3 gas mixture to the root ganglion can normalize the levels of prostaglandins and cytokines, decrease reactive oxidant species levels, increase SOD enzyme activity, and improve the circulation around the root ganglion .In a randomized trial carried by Niu et al.(2018), the therapeutic effect of different concentrations of medical ozone on pain severity and disc retraction was investigated in patients with trauma-induced lumbar disc herniation. There was a significant disc retraction and decrease in inflammatory markers and pain severity at all groups using different ozone concentrations .Hosseini et al.(2019) performed oxygen-ozone chemonucleolysis on a large number of patients with lumbar disc herniation and registered a high success rate at all types of disc herniation and failed back surgery . Also seGallucci et al. (2007) mentioned in their study the superiority of ozone injection over steroid injection at 6-months follow-up . In contOur study revealed a significant increase in SOD and GSH serum levels, 2 weeks after intervention in both Mg sulphate and Ozone groups, but there was no statistically significant change in SOD and GSH serum levels in control group.It is well known that the development and progression of disc herniation and degeneration are closely associated with oxidative stress and reactive oxygen species (ROS). To prevent this damage, a lot of biological defense mechanisms occurs including increased antioxidant enzymes like SOD, and GSH synthesis. It was found that the activity of SOD is decreased in advanced rat lumbar inter-vertebral disc degeneration –39.4 attenuates oxidative damage and ROS generation [The beneficial effect of Mg sulphate on oxidative stress has been proven by several studies , 41. Mg neration .Ozone therapy has been also identified as a promising therapeutic intervention that have the ability to attenuate oxidative damage. Ozone administration was reported to stimulate the antioxidant system by upregulating some antioxidant enzymes such as SOD, GSH-peroxidases, transferases, and reductases .Regarding patients’ satisfaction our results revealed a significant superiority of both transforaminal injection of Mg sulphate and Ozone over steroids at 6-months follow-up.The strength of our study is that it is the first study to investigate the therapeutic effect of transforaminal injection of Magnesium sulphate versus Ozone on the clinical outcome and the oxidative stress biomarkers; SOD and GSH in patients with symptomatic lumbar disc prolapseThe main limitation of our study was that we didn’t measure the serum level of SOD and GSH at 1-, 3- and 6-months follow-up. We also didn’t do electrophysiological assessment for the included patients before and after injection. Another limitation was that we didn’t investigate the effect of transforaminal injection of either Mg sulphate or Ozone on the markers of neurodegeneration and neuroplasticity.Each of transforaminal injection of Mg sulphate and ozone results in a significant improvement in pain intensity and functional disability in patients with symptomatic lumbar disc prolapse at 2 weeks, 1-, and 3-months follow-up. Transforaminal injection of Mg sulphate causes significant long-term improvement (up to 6 months) in pain intensity and functional disability. The serum levels of the anti-oxidants; SOD and GSH were significantly increased at 2 weeks following both transforaminal injection of Mg sulphate and ozone.


To describe success and failure (S&F) after lumbar spine surgery in terms equally understandable across the entire health ecosystem.Back and leg pain and disability were prospectively recorded before and up to 12 months after the procedure. Satisfaction was recorded using a Likert scale. Initially, patients were classified as satisfied or unsatisfied. Optimal satisfaction/unsatisfaction cutoff values for disability and pain were estimated with ROC curves. Satisfied and unsatisfied groups underwent a second subdivision into four subcategories: success , incomplete success , incomplete failure , and failure .A total of 486 consecutive patients were recruited from 2019–2021. The mean values of preoperative PROMs were ODI 42.2 (+ 16.4), NPRS back 6.6 (+ 2.6) and NPRS leg 6.2 points (+ 2.9). Of the total, 80.7% were classified as satisfied, and 19.3% were classified as unsatisfactory. The optimal disability and pain cutoff values for satisfaction/unsatisfaction  defined a subdivision: 59.6% were classified as success, 20.4% as incomplete success, 7.1% as incomplete failure and 12.4% as failure. The descriptions of each group were translated to the following: success—all patients were satisfied and presented no or only mild to tolerable pain and no or borderline disability; incomplete success – all patients were satisfied despite levels of pain and/or disability worse than ideal for success; incomplete failure – all patients were not satisfied despite levels of pain and/or disability better than expected for failure; failure – all patients were unsatisfied and presented moderate to severe pain and disability.It is possible to report S&F after surgery for DDL with precise and meaningful operational definitions focused on the experience of the patient. The surgical treatment of degenerative disk disease of the lumbar spine (DDL) is characterized by the heterogeneity of indications, techniques and results . At the The problem in contemporary medicine is that the concept of S&F has never been precisely defined –6. HowevThis scenario offers an opportunity for the utilization of an operational definition. Operational definitions may not be perfect, but they allow an honest and predictable interaction among everybody involved in a process. A good operational definition must balance precision  and communicability . The a priori hypothesis of this study is that an operational definition of S&F after lumbar spine surgery that attends to these requirements may be formulated by the combination of satisfaction, pain, and disability measures.This study was performed at Hospital Moinhos de Vento (HMV), a private institution with 485 beds and limited medical staff. HMV has a clinical database for many diseases following the ICHOM criteria .Cases of DDL, such as lumbar disk herniation, lumbar stenosis, degenerative spondylolisthesis and back pain due to disk degeneration treated surgically from May 2019 to February 2021 and followed up to 12 months are included in the database. Patient-reported outcome measures (PROMs) and data relative to the number of levels and surgical technique were also registered.The study was approved by the Ethics Committee of the Moinhos de Vento Hospital , and only participants providing a completed informed consent form participated. Data from medical records and PROMs were collected after informed consent was obtained from the participants. All methods in the study were performed in accordance with relevant institutional and national guidelines.PROMs questionnaires were administered by trained interviewers from the hospital`s value management office pre- and postprocedure (telephone and/or electronic forms), and satisfaction was measured using a Likert scale  at four Functional disability related to the lumbar spine was reported by the Oswestry Disability Index (ODI) . Back anCategorical variables were summarized using absolute frequencies and percentages, while continuous variables were analyzed using means, standard deviations, medians and interquartile ranges. To compare proportions, the chi-squared test and Fisher’s exact test were used when appropriate, and the Mann–Whitney U test was used to compare continuous variables.Analyses were stratified into pre- and postoperative periods. Subsequently, the postoperative group was divided into satisfied and unsatisfied groups, and comparisons between groups were performed. Furthermore, the postoperative group was also divided into success, incomplete success, incomplete failure and failure, and comparisons between group pairs were developed.p value < 0.05.The optimal cutoff values of disability and pain were estimated by the receiver operating characteristic (ROC) curve by minimizing the Euclidean distance between the curve and the point (0.1) in the ROC space. The ROC curve of pain was built considering the highest value between NPRS back and NPRS leg. Areas under the curve (AUCs) and respective 95% confidence intervals (95% CIs) were also estimated. Sensitivity (Sen), specificity (Spe) and correct classification rate were also calculated for both measures. All analyses were performed using R software, version 4.0.3. Statistical significance was defined as a During the study period, 486 patients underwent surgery, but 80 16.4%) of the initial cohort did not respond to follow-up. After exclusion, the clinical cohort included 406 patients. Responders and nonresponders had similar background information (Table 6.4% of tp < 0.01). The reduction in the percentage of patients unable to work due to back pain (22.6% to 19.40% p = 0.26) was not significant.Global pre- and postoperative outcomes are presented in Table The outcomes of satisfied (80.7%) and unsatisfied 19.3%) patients are presented in Table % patientThe sensitivity (Sen) and specificity (Spe) of the values of disability and pain used to discriminate between satisfied and unsatisfied patients were studied with ROC curves Fig. , showingThe data show that approximately 75.0% of satisfied patients presented pain ≤ 5, and 75.0% of unsatisfied patients presented pain ≥ 6 points. At the same time, ~ 75.0% of satisfied patients presented an ODI ≤ 27, and ~ 75.0% of unsatisfied patients presented an ODI ≥ 28 points.Success (59.6%)—satisfied with pain and disability levels concordant ;Incomplete success (20.4%)—satisfied with pain and disability levels nonconcordant (NPRS ≥ 6 AND/OR ODI ≥ 28);Incomplete failure (7.1%)—unsatisfied with pain and disability levels nonconcordant (NPRS ≤ 5 AND/OR ODI ≤ 27);Failure (12.4%)—unsatisfied with pain and disability levels concordant (NPRS ≥ 6 AND ODI ≥ 28).The satisfied and unsatisfied groups were further subdivided based on concordance or nonconcordance with the discrimination cutoff values:The PROMs values of the four categories are presented in Table We measured satisfaction, pain, and disability in a cohort of 406 patients who underwent surgery for DDL. Based on the combination of PROMs, we created four outcome categories in the following terms: success (59.6%)—satisfied with pain and disability levels concordant ; incomplete success (20.4%)—satisfied with pain and disability levels nonconcordant (NPRS ≥ 6 AND/OR ODI ≥ 28); incomplete failure (7.1%)—unsatisfied with pain and disability levels nonconcordant (NPRS ≤ 5 AND/OR ODI ≤ 27); and failure (12.4%)—unsatisfied with pain and disability levels concordant (NPRS ≥ 6 AND ODI ≥ 28).The clinical profile of success  is comparable with the normal healthy population, that is, pain in the range of “no pain”  and ODI It is intuitive that there is not a sharp limit between S&F. Intermediary categories were then created for satisfied patients with pain and disability worse than expected (incomplete success) and for unsatisfied patients with pain and disability better than expected (incomplete failure).Our S&F model is based on satisfaction, disability, and pain, with satisfaction as the main criterion. The choice of satisfaction as the primary anchor may be debated. Some authors demonstrate that there is a discrepancy between satisfaction and PROMs , while oWe then chose ODI and NPRS  as complFor the method of this study, we adopted the final raw score of pain and disability as outcomes. Many authors base their studies on preoperative-to-postoperative variation as well as on MCID –24. PrevAnother peculiarity of our study was to assess pain considering the highest value between back and leg pain. We assume that the patient’s suffering is better assessed in this manner. Other authors have previously done the same .The translation of numerical values into simple and meaningful terms is the aim of our study. It is not exactly a “result” because it was not originally extracted from our data. A summary of the available literature will be presented in this section to support our rationale.Satisfaction was linked to back/leg pain ≤ 5 in our cohort as well as in previous similar studies , 27. PaiZelman and coworkers  studied In Japan , the meaIn the short term, the pertinent literature determines the existence of a borderline zone between the ODI values of disabled and nondisabled patients, ranging from 21 to 31 points. In our cohort, an ODI ≤ 27 points were linked to satisfaction, and this value lies within this borderline zone. Therefore, patients with an ODI ≤ 27 points can be described as individuals with no disability or borderline disability.Success– All patients are satisfied, and present no or only mild to tolerable pain and no or only borderline disability.Incomplete success – All patients are satisfied despite levels of pain and/or disability worse than ideal for success.Incomplete failure – All patients are not satisfied despite levels of pain and/or disability better than expected for failure.Failure – All patients are unsatisfied, and all present moderate to severe pain and disability.Our results support the description of four operational definitions:The precise concept (or diagnostic criteria) of S&F after low back surgery has never been and will probably never be defined –6. NonetA process of shared decision based on concepts such as “33.0% improvement in ODI” or “to reach MCID in leg pain” is almost impossible. This difficulty is more visible in people with low literacy but can happen in more educated people . AccordiWe emphasized the importance of our operational definitions for communication among all stakeholders of spine surgery. However, there is one specific scenario where this type of definition reaches its most relevant moment: this is the preoperative discussion between patient and doctor concerning the indication of surgery . Patientscience of practice [. With this approach, it was already demonstrated, for example, that return to work [This study was based on a single institution, so our results need to be replicated and tested to obtain better validation. Our cohort included different diseases , surgical techniques, approaches, and surgeons in one single group. This is in line with a recent tendency of the surgical literature, the so-called practice , 37. Wit to work , improve to work .Other criticisms can be made on the lack of attention to relevant clinical aspects such as the relatively short follow-up in patients who underwent fusion and the influence of educational level or previous surgery on the results. The objective of this study, however, is not to describe the rates of success and failure (which truly may depend on timing or many other variables) but rather to describe a manner (simple and communicable) of reporting the basic endpoints of success and failure. The rates of S&F may change, but the way they are described may not.Finally, there is the problem of reducing all possible outcomes into only 4 categories. The complexity of degenerative disc disease and the heterogeneity of treatments and results deserve a very granular subdivision of possible outcomes. Such a “perfect” definition, on the other hand, would be cumbersome during the process of decision-making. It must be recognized that the broader aim of developing a completely truthful and sophisticated definition of S&F has not proven feasible in the context of lumbar spine surgery. The more complex and sophisticated the definition, the more difficult it is to be understood and communicated, and vice versa. This tradeoff is inevitable. It is the opinion of the authors that the simplicity and communicability of our operational definitions were obtained without compromising precision.It is possible to report S&F after surgery for DDL with operational definitions based on satisfaction, disability, and pain that are precise, simple, and meaningful to all people involved in the process. Our operational definitions of success, incomplete success, incomplete failure, and failure may improve the process of shared decisions focused on the experience of the patient.


Patients admitted to the intensive care unit (ICU) are vulnerable to severe pain as a result of tissue injury due to serious illnesses, inflammation, major surgeries, body positioning, medical devices, and traumatic injuries. The management of pain in the critically ill population is emerging as a standard of care in the intensive care unit (ICU).Although, Schulz-Stübner S. et al. in their work underlined that 95% of physicians and 81% of nurses believed the patient had adequate analgesia . In partDespite being a frequent symptom in the ICU and despite numerous improvements, pain is underdiagnosed, especially in sedated and intubated patients. Inconsistencies in pain assessment result, therefore, in suboptimal pain management .Inadequate pain control can lead to detrimental effects on several organ systems in critically ill patients; effects on the respiratory system such as hypoventilation, decreased ability to cough, atelectasis, pneumonia, or on the cardiovascular system such as tachycardia, or increased myocardial oxygen demand .The consequences of inadequate pain control can include sleep deprivation or agitation. Pain assessment in the critically ill patient may be impaired by sedation because the administration of sedatives may mask some manifestations of pain, and the excessive use of some analgesics may result in over-sedation. So, it is essential to discriminate between the two components, especially adopting a careful assessment of pain during the execution of “sedation holidays,” with an eventual preference for multimodal strategies .Furthermore, pain control in surgical and trauma patients is a major issue. In these patients, a valid chest wall expansion, effective coughing, mobilization, and positioning are the conditions for a rapid weaning from mechanical ventilation, and they are all dependent on adequate analgesia .In postoperative patients, suboptimal pain control can also cause prolonged ileus, nausea, and vomiting, with a major risk of aspiration, then a delay in the healing of wounds, and the risk of infection with increased cytokine production , 9.Recent reports have also suggested that, over the long term, a significant number of patients with pain and discomfort during mechanical ventilation are at higher risk of developing post-traumatic stress disorder , 11.Adequate postoperative and post-trauma pain management is crucial for the achievement of effective rehabilitation. All of these potentially modifiable, destructive sequelae of surgery and injuries can severely limit a patient’s return to a normal life.Therefore, it is vital that physicians and nurses closely caring for these issues, and adopt an optimal pain management strategy that includes a reduction in noxious stimuli, adequate analgesia, and the promotion of education regarding sedation and analgesia to the ICU staff.For decades, opioids have been the pillar of acute pain management. Historically, opioids  were the gold standard for managing moderate to severe pain .Opioid-related adverse drug events are common in hospitalized patients. The most frequent are nausea and vomiting (> 55%), and pruritus (> 33%) .Even short-term use of potent opioid compounds for acute pain can produce clinically significant hyperalgesia .A recent study by Chu et al.  suggesteAside from the numerous and common side effects associated with opioids, the latest evidence details the possibility of an increased risk of metastasis associated with opioids use during anesthesia, although there is no uniformity on this topic in the current literature , 17. In Opioid-free anesthesia can improve post-operative outcomes in several surgical settings without evidence of adverse effects on patient safety and pain management .Evidence has demonstrated that multimodal analgesia can enhance pain relief, and results in fewer adverse reactions than therapy provided through use of a single medication or modality  .As part of efforts to facilitate a patient’s return to normal function, enhanced recovery after surgery (ERAS) protocols have been widely implemented, first for elective colorectal surgery and now for other types of surgery, including emergency laparotomy. Two major components of ERAS pathways include setting of patient expectations prior to surgery and opioid minimization through use of multimodal and regional anesthetia strategies .Extrapolating from lessons learned from enhanced recovery after surgery protocols, surgical intensivists are increasingly utilizing multimodal pain regimens (MMPRs) in critically ill surgical patients recovering from major surgical procedures and injuries .Multimodal analgesia allows for a decrease in opioid use when combined with nonopioids in relieving pain .This strategy ensures a more focused and patient-centered plan of care.Based upon this premise and numerous evidence-based clinical trials, the American Pain Society (APS) and the American Society of Anesthesiologists (ASA) pointed out multimodal analgesia for pain management .The time of opioids as the pillar of acute pain management in the surgical ICU has begun to be supplemented by other options.Locoregional ultrasound-guided anaesthesia procedures enhanced the reliability of nerve block practice. Such improvements are also extremely useful as an aid or alternative to general anaesthesia in frail patients with reduced cardiorespiratory reserve or those taking chronic therapies with impact on haemostasis . Ultrasound-guided interfascial blocks of the thoracic and abdominal wall are safe and relatively easy to perform .For pain treatment in thoracic surgery and in thoracic trauma, the blocks more commonly used are the thoracic paravertebral (TPV) block and the erector spine plane (ESP) block, in addition to thoracic epidural analgesia .Since the 1980s, the interest in, and impact of, thoracic paravertebral blocks in reducing post-operative pain for several thoracic surgical procedures have grown. By incorporating enhanced recovery after surgery (ERAS) protocols into their clinical practices, there has been a reduction in narcotic drugs, and also an improvement in complication rates and a decrease in length of stay . NowadayAs concerns abdominal surgery, epidural analgesia has long been recognized as the gold-standard technique for analgesia after abdominal surgery . HoweverFrom operating rooms, peripheral blocks have begun to spread in the ICUs both for pain control in the post-surgical setting as well as in patients with several conditions.In 2020–2021 the high risk of exposure associated with airway instrumentation during SARS-Cov2 infection led to increased focus on regional anesthesia as an alternative to intubation and general anesthesia. Several papers emphasized that ultrasound-guided regional blocks are safer for medical personnel and patients in the era of Covid 19 .In the past 20 years, in accordance with the growing interest and widespread diffusion of LRA in the critical patient, selected reviews have explored the topic , 36.Ongoing and continuing focus on the topic has led researchers to investigate the possible role of LRA and multimodal analgesia in the neurocritical patient as well .Therefore, this case study aimed to evaluate the improvement of pain management in our intensive care unit considering the change in organization and the increasing contribution of anesthesiological skills.We retrospectively analyzed anonymized and aggregated data on all in-patients admitted to the ICUs of Maurizio Bufalini Hospital at Cesena, from January 1 2015 to December 31 2021.The types of loco-regional anesthesia we considered in this study are those practiced in our intensive care unit. Those include a neuraxial approach , peripheral nerve blocks, and nerve blocks with a perineural catheter.Our study population is, therefore, represented by all patients during their ICU stay. We searched for patients who had received one of these types of analgesia, and we analyzed data on pathology at admission date (like trauma and surgery—both elective and emergency), on the type of treatment given .The ICU where the analysis was performed serves as a Hub center for trauma, neurosurgical, and neuroradiological conditions. The number of beds historically was 18, which increased to 23 from March 2020 , 39.In the years prior to the study period, the study hospital had two different intensive care units staffed by two different departments. The merger of the two departments was started in 2014, but the medical staff of the two intensive care units continued largely to be distinct. The head of the Anesthesia and Intensive Care Department changed in March 2016, and gradually the teams  moved toward integration, expanding the number of physicians with expertise in different subspecialties. Specifically, since 2017, physicians with distinctive anesthesiologist skills have started to shift in the ICU. The unifying process was fully completed during 2019.As can be observed in Fig. The total number of patients who received at least one loco-regional analgesia treatment increased from 36 in 2015 to 94 in 2021, with a maximum of 106 in 2018.The first peripheral nerve block was performed in 2017, and the first perineural catheter was placed in 2020; the annual number of these procedures quickly rose to 10 in 2021.The number of admissions and the case mix of surgical and trauma patients did not increase over the observed period to justify the increase in the application of loco-regional anesthesia techniques (see Table In a multicenter study conducted between August 2011 and May 2012, Jabudensen et al. reported the utilization of epidural anesthesia in 6.38 percent of patients admitted to the ICU .In the ICU under study, the percentage of patients submitted to locoregional analgesia techniques rose from 4.78 in 2015 to 8.90 in 2021. Furthermore, two completely new procedures for the setting were introduced, namely the peripheral nerve block and the perineural catheter.We found a remarkable increase in the use of loco-regional anesthesia techniques during the period 2015–2021. The absolute numbers may seem low, but it is the trend that is important.Comparing different case mixes can be misleading. Even knowing some characteristics of the population, for example, not all trauma and post-surgical patients can benefit from LRA techniques. However, it seems possible that LRA techniques were slightly underutilized before the integration of the different intensivist and anesthesiologist teams.The increasing use of loco-regional anesthesia techniques in our ICU is likely due to both the world-wide spreading of the echo-guided approach and the changes in team composition.Boosting the skills of the intensivist team certainly helped to gradually undermine the paradigm by which ICU analgesia should coincide solely with intravenous opioid analgesia.Obviously, our experience does not answer the complex issues of the suitability or otherwise of having hyper-specialized teams. However, human resource governance and the impact of different organizing models on the volume of services provided, and health outcomes, is an absolute priority for healthcare management.Assessing the impact on clinical outcomes of loco-regional analgesia techniques and quantifying the relationships between the resources employed and the volume of health care benefits delivered is not an aim of this case study.Such aims would require well-designed studies with sizable amounts of data to explore; this paper is also meant to be a call for research on these issues.Nonetheless, we would highlight that having progressively integrated the different teams has contributed to the spread of loco-regional analgesia techniques in the ICU.Furthermore, it should be kept in mind that in Italy the course of study provides the same postgraduate medical school specialization for intensive care and for anesthesia .In conclusion, we believe that focus on pain care deserves a pivotal role in the treatment of critically ill patients, and that pain management should be recorded in the medical record, and should lead to pain-control strategies. The steady increase in attention to pain issues, in addition to being crucial from a pathophysiological and clinical point of view, is part of an overall process of humanizing intensive care.