We investigated whether the intensity of cancer pain differs for malignant tumors that have spread to anterior or anterolateral/lateral portions of the vertebral body. We hypothesize that tumor spread to the anterolateral/lateral vertebral body elicits more serious pain due to increased irritation of the spinal nerve. The selection criteria were as follows: (1) advanced or metastatic solid tumor; (2) radicular pain without extremity weakness; (3) malignant lesions anteriorly, anterolaterally, or laterally located at the vertebral body either spread locoregionally or over a greater distance via metastasis based on CT scan diagnosis; and (4) patient needs to use opioids for pain relief. Severe spinal pain intensity was defined as spinal pain for which patients required either strong opioids or spinal irradiation for relief. Eighty-six patients were enrolled in the study. Bone lesions were mainly osteolytic. Thirty-nine tumors spread to the vertebral body in the anterior direction, and 47 in the anterolateral/lateral direction. Severe pain intensity related to vertebral body lesions was due to anterolateral/lateral spread, primary sites of nonurothelial carcinoma, metastatic vertebral lesions, multiple lesions within a vertebrum, and location within the cervical-thoracic spine. In conclusion, patients with tumor spread to the anterolateral/lateral portion of vertebrae bodies based on CT scan diagnosis experienced severe cancer pain. These patients needed strong opioids or palliative spinal irradiation for pain relief. Malignant tumors located laterally or anterolaterally within the vertebral body can cause pain because they involve the ventral ramus, which is the anterior division of a spinal nerve located at the anterolateral aspect of the spinal cord. It carries sensory and motor fibers to the anterolateral parts of the trunk and limbs. The ventral rami exit the anterolateral vertebral body and converge to form the nerve plexuses . Intercostal nerves also arise from the ventral rami of the thoracic spinal nerves. Radiculopathy is due to compressed or irritated nerve roots, which may cause pain, numbness, tingling, or weakness along the course of the nerve , 2. RadiIn this retrospective study, we investigated whether the intensity of cancer pain is different for malignant tumors that spread to anterior or anterolateral/lateral portions of the vertebral body based on CT scan diagnosis. We hypothesized that anterolateral/lateral tumors elicit more severe pain due to enhanced irritation of the nearby spinal nerve.We conducted a retrospective case series study using data collected from patients from the oncology wards of Chang-Gung Memorial Hospital, Taoyuan, Taiwan, between January 2010 and February 2018. A single medical oncologist specialized in urological cancer provided most of the data, and the majority of the patients had urothelial carcinomas. The patients were all hospitalized as they needed to receive systemic therapy, radiotherapy, or the management of other complications. We conducted a retrospective chart review and performed computed tomography (CT) scans for patient tumor extent and their pain management.The selection criteria included the following: (1) advanced or metastatic solid tumor; (2) radicular pain without extremity weakness; (3) malignant lesions anteriorly, anterolaterally, or laterally located at the vertebral body and either locoregionally spread or metastasized based on diagnosis using abdominal or chest CT scans; and (4) patients need to use opioids for pain relief. Radicular pain was defined as pain radiating along the dermatome of a nerve.A visual analogue scale (VAS) on a 10 cm was used to measure cancer pain intensity. The scale numbered from zero to 10, zero corresponds to no pain and 10 to maximum pain felt by patients , 6. The Analgesics were given according to the World Health Organization (WHO) ladder for cancer pain relief, with opioids and/or nonsteroidal anti-inflammatory drugs  and/or adjuvant analgesia (mainly amitriptyline) . UltraceSystemic therapy included chemotherapy, hormone therapy, or targeted therapy. Patients received palliative spinal irradiation for back pain and radicular pain in selected cases. Severe spinal pain intensity was defined as requiring either strong opioids or spinal irradiation to relieve pain. Moderate spinal pain intensity was defined as requiring Ultracet and not needing spinal irradiation to relieve pain.The parameters for evaluating the severity of spinal cancer pain intensity included tumor spread to the vertebral body , age (<65 years versus ≥ 65 years), sex, spinal location , extent of disease spread to the vertebral body , number of tumors within one vertebral body (single versus multiple), and primary site of urothelial carcinoma (yes versus no).p < 0.05 was considered statistically significant.Continuous data (presented as mean ± standard deviation) were used for the VAS for pain severity analysis, including tumor spread to the vertebral body anterolaterally/laterally and anteriorly. We used the chi-squared test to detect differences between subgroups, and n=30), bladder (n=16), and ureters (n=3). The remaining 37 patients had the following cancer site: the lung (n=10), breast (n=4), prostate (n=5), renal (n=5), gastrointestinal (n=8), head and neck (n=2), and testicular (n=3).The patients' clinical characteristics are shown in The mean VAS for pain intensity was 8.3 ± 1.3  for tumor spread to the vertebral body anterolaterally/laterally. The mean VAS for pain intensity was 4.8 ± 0.8  for tumor spread to the vertebral body anteriorly. Vertebral body lesions due to anterior spread , lateralFor back and radicular cancer pain relief, 43 patients used Ultracet alone, 20 used strong opioids, 13 of 43 patients used Ultracet groups adding palliative spinal irradiation, and 10 of 20 patients used strong opioids receiving palliative spinal irradiation. We then divided patients into those with severe pain intensity and those with moderate pain intensity based on the pain management they received, as mentioned above. Forty-three patients were grouped as experiencing severe pain intensity, and the other 43 were grouped as moderate pain intensity.p < 0.00001), urothelial versus nonurothelial carcinoma (p < 0.00001), direct locoregional spread versus distant metastases (p < 0.00001), lesion number , and lumbar-sacral versus cervical-thoracic spinal location (p=0.0004).The assessment of parameters related to pain intensity among patients with tumor spread to the vertebral body is shown in Thirty-nine patients were diagnosed with tumor spread to the anterior vertebral body. Of these patients, 37 (95%) had moderate pain intensity, 38 (97%) had tumors in the lumbar-sacral area, 28 (72%) had a primary site of urothelial carcinoma, 32 (82%) had tumors that were locoregionally spread, and 37 (95%) had single vertebral body lesions. Thirty-five (90%) patients received systemic therapy, and none among them received palliative spinal irradiation.Forty-seven patients were diagnosed with tumor spread to the anterolateral/lateral portions of the vertebral body and 41 (87%) had severe pain intensity. These patients included 13 of 14 (93%) with cervical-thoracic spine location, 31 of 37 (84%) with primary site of nonurothelial carcinoma, 30 of 37 (81%) with metastatic vertebral body lesion, and 20 of 22 (91%) with ≥2 lesions within one vertebral body. Two patients had osteoblastic and one mixed osteolytic-osteoblastic bone patterns. Twenty-three (49%) of these severe pain patients received palliative spinal irradiation and 41 (83%) received systemic therapy.Radicular pain is a type of pain radiating along the dermatome of a nerve. Radicular pain is caused by compression, inflammation, and/or injury to a spinal nerve root. Management of cancer pain is multimodal, as pain is usually a combination of inflammation and irritation. Besides opioids, physicians often prescribe NSAIDs and/or adjuvant analgesia for neuropathic pain relief –12.All were metastatic or advanced tumors. But cancer pain depends on tumor location. For pain intensity, we must emphasize that tumor location was more important than those with advanced tumor or disseminated metastases. Tumors that spread to the anterolateral/lateral portion of the vertebral body irritate spinal nerve roots more than those that spread to the anterior portion. In this study, we detected a significant difference in pain intensity between anterolateral/lateral and lateral tumor spread based on CT scans. The presence of multiple lesions within one vertebral body leads to enhanced irritation of the spinal nerve root compared to a single lesion.Pain in cancer may arise from spinal nerve root by a tumor compressing or infiltrating nearby the lesion, related to their degree and area of osteolytic site. These thoughts are important but difficult in the assessment from CT scan.Most of the patients with tumor spread to the anterior portion of the vertebral body exhibited moderate pain intensity, a lumbar-sacral location, primary site of urothelial carcinoma and locoregional spreading. Urothelial carcinoma typically spreads locoregionally and invades the vertebral body, a process that is probably linked to the development of bone metastases . Pain inConversely, most patients with anterolateral/lateral tumors that spread to the vertebral body experienced severe pain. Pain control required strong opioids or palliative spinal irradiation, in addition to systemic therapy in most cases.Other management can improve spinal cancer pain. These include effective systemic therapies such as chemotherapy, targeted therapy, or hormone therapy to let tumor response and palliative spinal surgery. Vertebroplasty and kyphoplasty are conservative treatments with high rates of spinal cancer pain relief and vertebral body stabilization.There are some limitations to the current study. First, this study is limited by its retrospective nature. Second, all subjects were in our practice and at a single referral medical center. Third, the majority of cancers were urological, as we specialize in urological cancer.Patients with tumors that spread to the anterolateral/lateral portion of the vertebral body experienced more severe pain intensity than those with tumors that spread to the anterior portion based on CT scan diagnosis. These patients required strong opioids or palliative spinal irradiation for pain relief.


Background and objectives. The efficacy of commonly prescribed analgesic and adjuvant drugs for the management of patients with radiculopathy has not been well established. Oral steroids are commonly used to treat sciatica or radiculopathy due to a herniated disk but the effect remains controversial. L-lysine aescinate showed superiority over placebo or baseline therapy with NSAIDs alone in treating sciatica, but have not been evaluated in an appropriately powered clinical trial. Materials and Methods. Randomized, double-blind clinical trial conducted in two health centers in collaboration with Uzhhorod Natioanl University in Ukraine. Adults (N = 90) with acute radicular pain and a herniated disk confirmed by MRI were eligible. Participants were randomly assigned to three groups (N = 30 in each) to receive a baseline therapy with lornoxicam (16 mg per day) and adjunctive 5-day course of IV dexamethasone  or 0,1% solution of L-lysine aescinate (5 mL and 10 mL for group 2 and 3 respectively). Primary outcomes were Visual Analogue Scale changes and the straight leg raise angle at 15th and 30th day. Results. The level of pain improvement at 15th days after initiation of therapy with dexamethasone or solution of L-lysine aescinate at doses of 5 or 10 mL was not significantly different. The lowest levels of pain were achieved in patients who received the L-lysine aescinate 10 mL, but the range of decrease in pain was slightly greater in the group administered dexamethasone. Conclusions. Among patients with acute radiculopathy due to a herniated lumbar disk a short course of IV dexamethasone or L-lysine aescinate resulted in pain improvement at 15th and 30th day. Dexamethasone may be preferable if a longer-term analgesic effect is needed. Taking into account side effects of dexamethasone, a solution of L-lysine aescinate can be used to relieve pain symptoms. Low back pain is an extremely common and important health problem worldwide ,2,3,4. ILow back-related leg pain is one of the most common variations of back pain, with about two thirds of patients presenting with it ,12,13. EWhile guidelines provide clear and consistent recommendations for the prescription of drugs for non-specific low back pain, this is not the case for sciatica or radicular pain. Drugs commonly prescribed for the management of sciatica include non-steroidal anti-inflammatory drugs, skeletal muscle relaxants, systemic corticosteroids, antidepressants, and anticonvulsants ,26,27. AComplementary and adjunctive medicine is widely applied in clinical practice. Practice routine of primary care physicians and some specialized care centers shows some support for the use of L-lysine aescinate. However, the use of this agent in patients with radiculopathies and back pain is currently not recommended in clinical guidelines. However, there are few clinical trials and a low-level of evidence due to the poor study design or small sample size. As most guidelines recommend a course of conservative care before surgery is considered, it is imperative to understand what best practice conservative care should entail ,28,29,30The available evidence does not clearly show favorable effects of analgesics, corticosteroids, antidepressants, or anticonvulsants, even compared with placebo. New strategies could be developed in expecting to improve pain management in the proportion of people with sciatica and radiculopathy. The purpose of this study was to test the effects of a IV dexamethasone or L-lysine aescinate on symptoms of acute radiculopathy and sciatica in a clinical trial.To address this issue, we performed a parallel-group, double-blind randomized clinical trial of a course of dexamethasone vs. L-lysine aescinate for patients with an acute lumbar radiculopathy associated with a herniated lumbar disk. The study was conducted among the “Vodoliy” Clinic , which collaborates with the Uzhhorod National University, and the Regional Clinical Center of Neurosurgery and Neurology  from April to July 2018. The local ethics committee approved the study protocol . The study included patients aged 18 to 75 years with a primary or recurrent episode of sciatica, lasting from one to four weeks. Sciatica or radiculopathy was defined as pain in the leg (with or without lumbar pain) spreading below the knee in the radicular pattern, with signs of root irritation (a positive straight leg test), and/or radicular neurological deficit (sensory or reflex). Additionally, the inclusion criterion was neuroimaging—MRI with the presence of protrusion of the intervertebral disc that correlate with the level of clinical manifestations.Exclusion criteria: contraindications for use of corticosteroids or L-lysine aescinate, onset of radicular pain more than two weeks prior, previous lumbar surgery, substantial or progressive motor loss, diabetes mellitus, and severe somatic pathology , systemic or epidural use of corticosteroids during the last six weeks, and pregnancy.N = 90) were randomized to three groups, comparable by the number of participants and baseline characteristics . Patients who met the criteria , for five days. Patients from the other two groups, besides the lornoxicam, received a solution of L-lysine aescinate 1 mg in 1 mL (0.1% solution) in doses of 5 mL and 10 mL per day, respectively, in the form of intravenous infusion with dilution with an isotonic solution of sodium chloride to 50 mL of total .On the first day, a magnetic resonance examination of the lumbar-sacral spine was carried out as well as a Visual Analogue Scale for pain , the measurement of the pain intensity and functional significance were tested with the Brief Pain Inventory (Short Form). The intensity of the straight leg test (a lifting test of the straightened leg) was determined with the fixation of results from 30° to 70°. In patients with clinical or visualization signs of the S1 root injury electroneuromyography was additionally performed to measure the amplitude of the H-reflex. The Brief Pain Inventory and amplitude of the H-reflex were tested as potential prognostic markers and predictors of sciatica or radiculopathy course.The results were evaluated on the fifteenth and thirtieth days of the study. On the fifteenth and thirtieth day after the start of treatment, symptom improvement was assessed using VAS and a measurement of the intensity of the straight leg test as well as repeated MRI.The control points were defined in order to determine the probability of improving the functional state of patients in the early period when the symptoms were most intense as well as in the time interval defined by the guidelines as an indication of surgical intervention in the case of ineffectiveness of conservative measures (duration of pain for 6–8 weeks).p < 0.05. The dynamics of the patient’s condition was visualized using Sankey diagrams.Statistical Analysis. The dynamic of VAS levels, the straight leg test, differences between the groups as well as the possible prediction of the course by BPI and the amplitude of the H-reflex were statistically analyzed in the software environment R version 3.4.3. Since the research design was hierarchical , and there were also factors with fixed effect  and random effect (random difference); for the analysis, the method of linear mixed regression models (mixed models) was used. For the construction of mixed regression models, an additional software package nlme 3.1-131 was used. The normal distribution of the residue of the regression model and the absence of statistical emissions were verified by inspection of a quantile–quantile normal graph. The statistical significance of the influence of factors (BPI and H-reflex) on the dynamics of pain in patients was determined by the dispersion analysis of regression models . A group of patients treated with dexamethasone was used as the reference group for comparison. It is worth noting that repeat measurements in patients are not expected to be independent of each other. The patient’s condition on the fifteenth and thirtieth day depends to a certain extent on its initial state. Therefore, in order to take into account the time communication between successive measurements of the same patient, we examined the expediency of correction of temporal autocorrelation in a mixed regression model. For this, the likelihood models of the first-order auto-recursive component were compared using the Akaike information criterion (AIC) and likelihood ratio test. Statistically significant results were considered with Baseline intensity of pain on the VAS scale was 6.9 ± 1.3 points in the first group, and exceeded similar rates in the second and third groups . The effect of this initial difference on the results of the comparison was corrected by inclusion of the absolute data obtained in each of the successive measurements into the model. The dynamics of pain reduction on the VAS scale on the fifteenth day lost statistical significance and reached p = 0.15, and only the effect on the thirtieth day retained statistical significance with p = 0.012.The mixed regression model also showed the initial difference between the groups according to the intensity of pain, and this difference in the case of the third group reached the statistical significance (p < 0.0001) and thirtieth day . On the fifteenth day, the decrease in the score of the VAS scale in both groups of L-lysine aescinate (5 mL and 10 mL) did not differ from the effect of dexamethasone . However, already on the thirtieth day in the second group, the reduction was weaker on average by 1.47 points on the scale of VAS (p = 0.0038). In the third group (compared with the first group), the decrease on the scale of VAS was weaker on average by 1.07 points (p = 0.040).Reducing the intensity of pain on the VAS scale after the course of dexamethasone is statistically significant at the fifteenth  were excluded.The significance of the straight leg test symptom for those patients who achieved a negative symptom as a result of the received pharmacotherapy was taken into account in the analysis as 90°. At the beginning of the experimental study, the mean values of the straight leg test symptom in the first group were 42.8° ± 14.2°, which was slightly less than in the second group (52.8° ± 15.6°) and the third group (50.6° ± 17.7°). At the same time, on the fifteenth day, the mean values of the Laseg’s symptom in the first group (65.2° ± 20.2°) were slightly lower than those in the second (64.4° ± 19.4°) and the third (60.8° ± 17.1°) groups. This difference increased even more on the thirtieth day. Additionally, on the thirtieth day after the start of the trial, the proportion of patients with a negative symptom reached 67% in the first group, 67% in the second group, and 60% in the third group .p = 0.0015) and 13.9° (p = 0.014) in the case of dosing 10 mL, than in patients receiving dexamethasone , but weaker than the positive dynamics. On the thirtieth day, the overall positive dynamics of patients receiving L-lysine aescinate was weaker by an average of 18.3° in the case of a dose of 5 mL . In general, this reduces the reliability and the value of the mixed regression model presented here.To our knowledge, this is the first trial of L-lysine aescinate in acute discogenic sciatica with a significant sample size. Additionally, it seems to be the first trial of dexamethasone not used as an emergency one-time bolus, but as a course for five days. We found a significant improvement of sciatic pain with dexamethasone and L-lysine aescinate. According to our results, the lowest levels of pain on the thirtieth day were achieved in patients who received the drug L-lysine aescinate 10 mL, but the range of decrease was slightly greater in the group of dexamethasone. This means that dexamethasone is effective for pain relief in patients with sciatica and may be preferable if a longer-term effect is needed. Taking into account the side effects of dexamethasone, a solution of L-lysine aescinate can be used to relieve pain symptoms. The effect change is insignificant with the dosage increase of L-lisine aescinate and the short-term effect is the same for both L-lysine groups in comparison with the dexamethasone group.Brief Pain Inventory values correlated with the assessment of pain by the VAS and straight leg test, which is logically explained by a common description of pain characteristics. At the beginning of treatment, every 10 points on the BPI scale was associated with a VAS increase of 0.77 points. Patients with high baseline BPI points will have better additional positive dynamics on the fifteenth day. Namely, they will observe VAS indexes on the fifteenth day below the average of 0.21 points for every 10 points of the initial BPI value (after taking into account the effect of the drug). Patients with high initial BPI demonstrate a further, and even more rapid decrease in the intensity of pain in the interval between the fifteenth and thirtieth day. If the BPI factor and a certain role in the model of the dynamics of the straight leg test are assigned, then this role is limited to the correlation of the intensity of pain on the BPI scale and degrees (the symptom is more pronounced in patients with higher BPI scores).p = 0.59. Similar results were obtained in the study of the H-reflex as a potential predictor in a mixed model with a degree of the straight leg test symptom. Therefore, the possible influence of the degree of the H-reflex on the future dynamics of the degree of the straight leg symptom under the conditions of the performed exertion has not been confirmed .The degree of the H-reflex, measured before the start of treatment, did not affect the subsequent dynamics of the patients. The significance of the H-reflex in the study is not appropriate since the statistical significance when comparing the two models with the dispersion analysis was Our results are consistent with previous studies. Over the past 40 years, no more than ten comparable studies have been published on the efficacy of systemic corticosteroids for sciatica and radicular pain ,36,37,38The above studies have certain disadvantages, in particular, some of them were not statistically significant, for example, due to the small number of patients ,33,35. OIn search of new ways and effective means of treating patients with radiculopathies, it was decided to explore the drug L-lysine aescinate. The background is based on the polymodal effect of the drug. L-lysine aescinate reduces the activity of lysosomal hydrolases, thereby inhibiting the decrease of glycosaminoglycans, which in clinical practice manifests as membrane-stabilizing and anti-exudative effects, and the inhibition of phospholipase A2 with moderate anti-inflammatory action ,41,42,43Studies of the efficacy of this agent in radiculopathies and sciatica showed superiority over placebo or “baseline therapy” ,45,46,47p = 0.0038) and 1.07 ± 0.52 scores when comparing dexamethasone with a 0.1% solution of L-lysine aescinate in a dose of 10 mL (p = 0.040).Our study used a short course of dexamethasone, which was more justified in terms of the pathophysiology of the process and clinical needs (rapid effect and favorable side effects profile). The level of pain improvement at 15 days after the initiation of therapy with 0.4% dexamethasone in 2 mL or 0.1% solution of L-lysine aescinate at doses of 5 or 10 mL was not significantly different. The difference in dynamics for 30 days was 1.47 ± 0.50 points on the VAS scale when compared to dexamethasone with 0.1% solution of L-lysine aescinate in a dose of 5 mL , the VAS was 1–2 points, the volume of movements in full. However, neuroimaging for 15 and 30 days does not indicate changes in the intensity of closure plates (type Modic II) or the size of the hernia .In our opinion, this case needs an additional comment. It is generally considered that an increase in the size of the intervertebral disk hernia is a negative predictor, but the data from numerous publications and observations indicate the opposite. Intervertebral hernia accompanied by sequestration or extrusion, without motor deficiency clinically, is more likely to by reabsorbed and “shrink”. Despite the large size, it is easier to dehydrate and reconfigure them in such a way that they do not create compressions of neuronal structures ,60.Patient M., 41, complains of moderate back pain and “striking” pain in the right leg. At the primary examination: excess body weight, neurological status without sensory, reflex, or motor deficiency. VAS: 5 points. Straight leg test right-side to 35°.MRI: On the background of degenerative-degenerative changes and protrusions, there is a L4–L5 level hernia. At the first control, extrusion of bulging and caudal migration.It is interesting that the VAS values at the first control was 0 points. In this case, the increase in size and shape changes were an element of sanogenesis: caudally displaced hernia does not compress neuronal structures .An indicative case that confirms the thesis “big hernias of the disk are most prone to regress” .Patient V., 52 years old, with back pain duration of three days. VAS: 7. The pain extends to the legs, more right, in particular, the anterior-medial parts of the thigh and legs. Hypoesthesia in the dermatome L3, straight leg test 60°. Movements exacerbate the pain.MRI: Extrusion of the intervertebral disk L2–L3 with compression of foraminal channels bilaterally. At day 30, there was a clear reduction in the size of extrusion, which was accompanied by a clinical “recovery”, a complete regression of pain .p = 0.23). Although in the 10 mL L-lisine aescinate group of L-lysine there were no cases of increase in size or caudal migration of the hernia, the difference with other groups was statistically insignificant, in particular, against the dexamethasone group, where there were three cases of deterioration of morphological characteristics. Additionally, no correlation or modifying effect of the morphometric indices of the intervertebral disc on the pain characteristics of the VAS and BPI, the degree of the straight leg test or the amplitude of the H-reflex (r = 0.16), was significant.No significant difference was found between the effect of dexamethasone or L-lysine treatment with aescinate 10.0 on the course of discopathy (This study is a comparative clinical study of the efficacy of dexamethasone and L-lysine aescinate in pharmacotherapy for back pain. The study did not contain a placebo-control, therefore, it does not allow us to judge the effectiveness of the drugs used compared to the placebo. The research design used allows us to speak only about the similarity or difference in the dynamics of the state of patients receiving different drugs.Endpoints of the study were the intensity of pain measured on the scale of VAS and the intensity of the straight leg test. Both endpoints may be subject to fluctuations as a result of the patient’s unstable approach to assessing his or her own pain, as well as due to inaccuracies in the measurement of the degree of the straight leg test symptom on the part of the physician and on the patient’s side.This article also examines the possibility of influencing the assessment of BPI and the degree of the H-reflex to the course of the disease. Both factors are closely related to the intensity of the pain or the symptom of the straight leg test, so it is not possible to correctly isolate their effects from the time-end autocorrelation of the endpoints proven in this article.Our study shows that the size of the intervertebral disk herniation, the degree of the straight leg test, Brief Pain Inventory score, and the H-reflex amplitude does not have a reliable prognostic value and does not allow for the prediction of the course of the radiculopathy, in particular, the regression of pain or need for future surgical treatment. The morphometric characteristics of the intervertebral disc according to MRI do not correlate with the intensity of pain and are not valid predictors of the clinical condition.The lowest levels of pain on the thirtieth day were achieved in patients who received the drug L-lysine aescinate 10 mL, but the decrease in pain was slightly greater in the group administered dexamethasone. Taking into account the side effects of dexamethasone, a solution of L-lysine aescinate can be used to relieve pain symptoms.The use of a solution of L-lysine aescinate in patients with sciatica and radiculopathy requires further research to more accurately determine the long-term effects and outcome.


Background: Tears of the gluteus medius and gluteus minimus are common causes of chronic lateral hip pain in the middle-aged population. These tears are postulated to occur after chronic degeneration of the muscle-tendon unit. The majority of these patients have a long history of peritrochanteric pain. Acute traumatic tear of the gluteus medius and gluteus minimus in otherwise asymptomatic patients is rare but can occur.Case Report: We report the case of a 78-year-old male marathon runner with acute traumatic tear of the gluteus medius and gluteus minimus. After conservative management  failed, the patient underwent operative repair. The surgery was successful, and the patient returned to his preinjury lifestyle 6 months postoperatively with no limitations.Conclusion: In most cases, chronic injuries are far more common than acute tears. Because of the nonspecific and slowly progressive symptoms, patients are often misdiagnosed with radiculopathy, osteoarthritis, or trochanteric bursitis. Patients typically present to the clinic with an insidious onset of dull pain over the lateral hip. This pain is often worse when lying on the affected side. Certain gluteal-focused movements, such as climbing stairs, may exacerbate the pain. To our knowledge, our report is only the third case of acute traumatic tear of the gluteus medius and gluteus minimus reported in the literature. Two months prior, the patient was running with his dog when he sustained a forced external rotation injury to his right lower extremity. He felt a “pop,” followed by a sudden pulling pain in his groin. The initial pain resided, but his posterior hip remained sore, and he attributed it to a possible muscle strain. He had no history of injury or symptoms related to the hip or groin.On physical examination, the patient had a nonantalgic gait. Lower extremities appeared normal with preserved range of motion. However, he reported pain with forced internal rotation and circumduction, as well as tenderness around the psoas tendon. Neurovascular examination was within normal limits. X-ray of the hip showed mild joint space narrowing and osteopenia . Right pTen months later, the patient returned to clinic with worsening of pain, especially in his lateral right hip. He stated that he completed physical therapy but had minimal relief. After therapy, he continued to run and completed a marathon. However, the pain increased to a debilitating point and forced him to quit running. On physical examination, he had preserved range of motion, with pain during hip abduction and tenderness over the right greater trochanter. Magnetic resonance imaging (MRI) of the right hip demonstrated a full-thickness tear of the right gluteus medius and gluteus minimus tendons at their greater trochanter insertion with 3.1 cm of retraction .The patient was referred to pain management for a trial of injection containing 20 mg of triamcinolone and 1.5 mL of bupivacaine to the right hip adductor and right gluteus medius and gluteus minimus tendon sheaths under fluoroscopy. However, this treatment provided minimal relief. After the failure of conservative treatment modalities, the patient elected operative repair.Arthroscopic technique was chosen. After the patient was appropriately positioned, proximal and distal anterior portals were established with fluoroscopic guidance. The trochanteric bursa was inflamed A and wasA Bledsoe brace was placed immediately. Weight bearing as tolerated was initiated immediately with the brace locked in extension for ambulation and unlocked from 0° to 90° at rest. Physical therapy was initiated 5 days postoperatively. Active abduction and strengthening were avoided for 6 weeks. At the patient's 6-week postoperative visit, he walked with no limp, the brace was discontinued, and hip strengthening was initiated. A more aggressive strengthening and home exercise program was initiated 3 months postoperatively. By the patient's 6-month postoperative visit, he was able to run 4 miles pain free. At 10.5 months postoperatively, the patient successfully completed a marathon with no pain or issues.The 3 gluteal muscles help form the muscle group known colloquially as the buttocks. From superficial to deep, these muscles are the gluteus maximus, gluteus medius, and gluteus minimus. The gluteus medius and gluteus minimus originate at the gluteal surface of the ilium and insert on the greater trochanter of the femur. Innervated by the superior gluteal nerve, the gluteus medius and gluteus minimus aid in hip abduction and internal rotation of the thigh and leg.3 Tears of the gluteus medius and gluteus minimus manifest as chronic lateral hip pain, also known as greater trochanteric pain syndrome (GTPS). In a study of more than 3,000 middle-aged adults, Segal et al estimated the prevalence of unilateral GTPS to be 15% in women and 6.6% in men, with bilateral GTPS found in 8.5% of women and 1.9% of men.5 While GTPS encompasses any etiology that causes lateral hip pain, including unequal leg lengths or iliotibial band syndrome, gluteus medius and gluteus minimus pathologies are the most common cause.6 An MRI study published in 2001 revealed that 83% of patients with lateral hip pain had findings consistent with gluteus medius pathology.7The incidence of gluteus medius and minimus tears peaks around the seventh decade of life, and tears are more common in women than in men.9 Over time, this degeneration can lead to tendinopathy and chronic lateral hip pain before ultimately tearing and retracting from the trochanteric attachment.While the exact etiology of gluteus medius and gluteus minimus tears remains unknown, one proposed cause is chronic degeneration of the muscle-tendon unit.4 In most cases, chronic injuries are far more common than acute tears. Because of the nonspecific and slowly progressive symptoms, patients are often misdiagnosed with radiculopathy, osteoarthritis, or trochanteric bursitis.12 In a French survey of 84 orthopedic surgeons, 45% were not aware that tears could occur, which may contribute to misdiagnosis.13Acute traumatic tears are rare. A literature search yielded only two reported cases.8 On physical examination, patients often have reproducible tenderness on palpation of the greater trochanter.15 Weakness in abduction may manifest as Trendelenburg gait. Trendelenburg gait has a reported sensitivity of 72.7% and specificity of 76.9% in detecting gluteus medius pathology and is the most sensitive and specific physical test for gluteus medius pathology.7 Pain during resisted hip abduction has a similar sensitivity but a lower specificity . Another test is the single leg stance in which the patient stands on the affected leg for 30 seconds. Gluteus medius tendon pathology is indicated if the patient experiences trochanteric pain.7Patients typically present to the clinic with an insidious onset of dull pain over the lateral hip. This pain is often worse when lying on the affected side. Certain gluteal-focused movements, such as climbing stairs, may exacerbate the pain.16 If x-rays are nondiagnostic and the patient continues to have refractory lateral hip pain, an MRI should be obtained. A complete tear could appear as a focal discontinuity of the tendon with retraction.17 Partial-thickness tears show a thickened tendon with increased signal intensity on T2-weighted images. Tendinosis appears as increased signal intensity on T2-weighted images with a normal-appearing tendon.18Conventional radiography of the pelvis, using a standing anteroposterior view, should be the initial imaging study. The x-ray may rule out concurrent hip osteoarthritis, osteonecrosis, or femoral neck fracture. Radiographic signs of pathology of the gluteus medius and gluteus minimus include peritendinous edema, as well as contour irregularities >2 mm in the superolateral greater trochanter. In a study by Steinert et al, the sensitivity of radiographic changes for tendon pathology was 40% and the specificity was 94%.19 Certain symptoms may predict the failure of nonoperative management. Chandrasekaran et al reported that loss of abduction and any deviation of gait pattern were predictors of failure of nonoperative management.20 Other factors such as lateral hip pain, duration of symptoms, and range of motion did not affect the likelihood that patients would require surgery. For patients who have refractory pain and/or impairment in performing the activities of daily living, operative management may be considered.15Initial management is often nonoperative. Patients should refrain from strenuous activity, and NSAIDs may be prescribed for pain. Physical therapy directed to stretch and strengthen relevant muscle groups may reduce pain and improve mobility. Last, corticosteroid and local anesthetic injections to the trochanteric area may be used.19 Measurement of satisfaction, pain scores, and return of muscle strength were comparable in both approaches; however, open techniques had a higher complication rate. Specifically, re-tears were seen in 10 of 128 patients in the open repair group vs 0 of 40 patients in the endoscopic group. Other complications such as wound infections and hematoma were also significantly higher in patients who had open repairs.Historically, tears of the gluteus medius and gluteus minimus were surgically repaired with an open transosseous approach or suture anchor repairs. Alternatively, with the growing popularity of minimally invasive surgery, an endoscopic approach may also be used to access the peri-trochanteric space. In the systematic review of repair options by Chandrasekaran et al, open and endoscopic gluteal repairs had similar patient-reported outcomes.21 Davies et al reported improvement in the mean visual pain scale in 90% of patients at 1-year follow-up, showing that the mean pain score dropped from 7 preoperatively to 2 postoperatively (P<0.05).22 Davies et al also reported that >84% of patients were satisfied with their results at 5-year follow-up, with 78% of subjects noting a subjective improvement in function.23Overall, the outcomes after operative repair are favorable regardless of surgical approach or technique. In a study by Walsh et al, only 5% of subjects had a normal walking ability before surgery, but 78% of their subjects recovered a normal gait by 6 months after surgery.Tears of the gluteus medius and minimus are common causes of lateral hip pain in middle-aged adults. These tears are believed to follow a gradual course, marked by chronic degeneration and subsequent hip pain, but acute tears are rare. Our patient, however, presented with an acute traumatic tear of the gluteus medius and gluteus minimus. He underwent operative repair and was able to return to his preinjury lifestyle 6 months postoperatively with no limitations. To our knowledge, our report is only the third case of acute traumatic tear of the gluteus medius and gluteus minimus reported in the literature.


The relationship between pain and hypertension is of great pathophysiological and clinical interest in the pain field, but the mechanism is poorly understood. This study used the postoperative patient-controlled analgesia (PCA) dose and the visual analysis scale (VAS) score to assess the relationship between pain and hypertension.  In this prospective study in a single-center hospital, 200 participants were enrolled and divided into three groups: normotensive group, hypertension without treatment group, and hypertension with treatment group. The participants scheduled for elective inhalational general anesthesia were interviewed at hospital admission. independent-samples, one-way analysis of covariance, age, and weight as covariates:P=0.021, 0.014, 0.032). No significant differences in the VAS scores and PCA dosages were observed between the male normotensive group and any one of the male hypertensive groups.  A significant difference was observed in analgesic dosage on postoperative days 1, 2, and 3 between the female normotensive group and female hypertension with treatment group ( We agree that hypertensive hypoanalgesia exists in some experimental settings. The mechanism linking postoperative pain and hypertension is far more complex than we initially believed. Therefore, more studies are required to investigate the roles that antihypertensive drugs, sex, and psychological stress play. Antihypertensive drugs may play a crucial role in mediating the relationship between pain and hypertension. Psychosocial factors were discussed but were not examined. There are few articles discussing about the relationship between hypertension and postoperative acute pain. A study on the relationship between hypertension and postoperative pain may offer clinical physicians guidance for pain management in patients with hypertension. Hypertension has long been associated with hypoalgesia . Our preerectomy . PatientThe study protocol was approved by the hospital's Institutional Review Board, and all subjects provided informed consent prior to participation. This manuscript adheres to the applicable guidelines in the Consolidated Standards of Reporting Trials.A prospective study was conducted in which potential subjects were identified through systematic review of daily admission logs. Patients (aged 20 to 75 years) scheduled for elective general anesthesia and who were willing to use morphine in postoperative pain control were interviewed at hospital admission. The sample comprised 200 participants who met the inclusion criteria.Patients were excluded if they had had liver disease, renal disease, dementia, use of chronic pain medications, conscious disturbance, secondary hypertension and myocardial infarction, cardiac bypass surgery, unstable angina, cerebrovascular events, congestive heart failure, or significant arrhythmia events in the preceding 6 months. Pregnant or breastfeeding patients were also excluded.Normotensive group (control group)Hypertension without treatment groupHypertension with treatment group, described as follows (according to the patient's daily routine treatment)Enrolled patients were divided into three groups as follows:β-blocker, a calcium channel blocker, and a diuretic.Eligible subjects were informed that they were participating in a study on essential hypertension and acute pain management. The normotensive group was defined as not having a systolic pressure over 140 mmHg or diastolic pressure over 90 mmHg more than twice between the admission and interview. Patients who revealed that they had a history of hypertension were enrolled in the essential hypertension group. Patients who did not have a history of hypertension but who had a systolic pressure of over 140 mmHg or a diastolic pressure of over 90 mmHg more than twice between admission and the interview were also placed in the essential hypertension group. Patients with hypertension were divided into two groups, a treatment group and a nontreatment group, according to the use of antihypertensive agents. The treatment and choice of drugs for hypertension were oriented to international guidelines by each patient's clinician. The treatment was divided into four categories: an angiotensin-converting-enzyme inhibitor (ACEI), a General inhalation anesthesia was used and maintained using a standardized procedure by anesthesiologists. No premedication was administered to any of the patients. Before the surgery, we taught the patients how to use the PCA system and how to evaluate their own pain intensity by using the visual analogue scale . The PCA system had the following initial settings: a bolus of 1 mg of morphine at the patient's demand, 5 minutes of lockout time, and an upper limit of 20 mg of morphine. The PCA dosage setting was adjusted daily depending on the patient's pain intensity at rest. A trained research assistant obtained information on postoperative pain intensity, PCA consumption, and related side effects from the medical records.Information regarding demographic, physiologic, anesthetic, and surgical confounders was obtained using standardized questionnaires, the patients' medical records, and physical examinations. The heights and weights of the participants were obtained from patient intake sheets. The surgical sites were extracted from the operative reports approximately 1 week after admission and were classified as one of the following: (1) upper abdominal, (2) lower abdominal, (3) urologic, (4) orthopedic, and (5) others. Type and duration of anesthesia were extracted from the anesthetic record. Information regarding each patient's essential hypertension history, sex, age, presurgical weight, medical history, and postoperative course were collected. Furthermore, all nonopiate and opiate analgesic use in the initial 72 postoperative hours was recorded.P < 0.05 was considered statistically significant.Independent-samples, one-way analysis of variance (ANOVA) and Tukey's post hoc multiple comparisons were used to test for significant differences among the three groups for continuous variables such as age and body mass index (BMI) . The catP=0.021, 0.014, 0.032). A post hoc test revealed a significant difference between the normotensive group and the hypertension under medication group. Significant differences were also observed in the postoperative pain scores of the male patients in terms of the analogue scales on movement (VASM) on postoperative day 1, the analogue scales at rest (VASR) on postoperative day 1, and the VASM on postoperative day 2 among the three groups . The results of the post hoc test revealed no significant difference between the normotensive group and either of the hypertensive groups; however, a significant difference was observed in the VASM and VASR on postoperative day 1 between the hypertension with and without treatment groups.A total of 200 participants were recruited until December 2015. The first group of patients (patients without hypertension) comprised 52 subjects; the second group (patients with hypertension without treatment) comprised 82 subjects; and the third group  comprised 66 subjects. The demographics of the patients are presented in The relationship between hypertension and postoperative pain is of great pathophysiological and clinical interest in the pain field, but the mechanism is poorly understood . HyperteThis study determined that female patients with hypertension undergoing treatment required significantly more morphine than did the normotensive patients during the initial 72 hours after operation. No differences in morphine consumption and pain scores were observed between the normotensive group and either of the male hypertensive groups. An increasing number of studies have used PCA dose to evaluate acute postoperative pain . France β-blocker, a calcium channel blocker, and a diuretic. We did not have sufficient case numbers to analyze the subgroup in the patients undergoing antihypertension treatment because most of our patients received multiple descriptions; future studies are required to confirm the findings of this study.After comparing the differences in postoperative pain and sex reported in numerous studies, Zheng et al. found that age and preoperative pain were major confounders for sex-based differences in postoperative pain outcomes in a prospective database analysis. We therefore separated the data by sex for analysis. Zheng et al. confirmed that female sex is a significant predictor for postoperative pain after surgery, especially older women (aged over 50 years). We assumed that because the mean age of the female group (mean age: 55.5 years) was older and some of the women may have been menopausal, more complex hormonal effects would have been present than in the male group . BecauseAs already stated, morphine administration may suppress endogenous opiate release. We attempted to determine why women with hypertension use a larger morphine dose than normotensive women. From a psychosocial aspect, pain not only involves a central inhibitory mechanism but also an emotional element. In a review article , the autWe did not assess psychosocial stress in our patients before and after the surgeryWe did not determine whether the patients (in the hypertension with treatment group) controlled their hypertension properly using the prescriptionsThis study did not conduct a double-blinded experiment; therefore, the patients might have known they were in dosage research and cause participant biasWe did not have enough case numbers to assess the role of each type of antihypertensive drug


To establish a relationship between the Visual Analog Scale for pain (VAS) in the recovery time of epidural analgesia and the Perfusion Index (PI) values at that time and to test the possibility of using PI as an objective tool for pain assessment.th minute. Hemodinamics, VAS, and PIvalues were recorded at 5th, 10th, 30th, 60th minutes and every two hours until the birth and the 30th minute after the birth.Thirty women were included in the study. After inserting epidural catheter, the initial applicationtime of epidural analgesia was taken as 0th, 30th, 60th minutes and 2nd hour after drug administration from epidural catheter. As the pain decreased, the perfusion index increased. In 17 patients requiring additional doses, PI increased after the all medications, but a decrease was observed in the VAS values(p<0.05).HR, SAP, DAP, PI, VAS values before the procedure were different than all follow-ups (p<0.001). A negative and significant correlation was found at 10In this study, it was determined that the pain decreased with epidural analgesia, perfusion index increased and the pain level increased significantly when the perfusion index started to decrease. Labor pain is an event mechanically tiring the mother, leading stress and anxiety, and increasing oxygen demand with hyperventilation and pain is a personal and subjective experience that makes the objective measurements impossible.Many researchers have evaluated the autonomic response to pain usually by monitoring skin conductivity or heart rate.4Perfusion Index (PI) is used to measure the pulse with pulse oximeter and provides an indirect and noninvasive measurement of peripheral perfusion. In the study by Nishimura et al.,6From this point of view, it can be suggested that sympathetic tonus increase and pain caused by the elimination of the effect of epidural analgesia applied at vaginal delivery may also affect PI. The aim of this study was to establish a relationship between the VAS value at the recovery time of the epidural analgesia and the PI values at that time and to test the possibility of using PI variations as an objective tool for predicting pain onset time and assessing pain.The study was planned as an observational cohort study. The study was started after the ethics committee approval no: 03/10 of Erzincan University clinical trials ethics committee was received and informed written consents of the patients were received. ClinicalTrials.gov ID: NCT03107559.Thirty women, aged between 18-45 years, who would have spontaneous vaginal birth were included in the study. Our exclusion criterias were not prepared to participate in the procedure, under 18 years - over 45 years of age, low platelet count, infection at the puncture site, progressive neurological disease, increased intracranial pressure, presence of hypovolaemia. The cases who had received epidural catheter and had cesarean section were excluded from the study.After explaining the procedure to the patients by a gynecologist and the researcher anesthetist, perfusion index device with non-invasive pulse oximeter in addition to standard ASA monitorization (Heart Rate (HR), Systolic Arterial Pressure (SAP), Diastolic Arterial Pressure (DAP) were attached to all cases . An epidural catheter was inserted after the cervical dilatation was 3-5 cm in the vaginal examination performed by the gynecologist. We preferred to insert the epidural catheter at 3-5 cm dilatation, where the VAS value of patients was five and above. An epidural catheter was inserted between L3-L4 / L4-L5 spaces after the cervical dilatation was 4-5 cm in the vaginal examination performed by the gynecologist. After making 2 cc lidocaine  as test dose with infusion in the epidural catheter and determining that it is the right space, 10 cc 0.25 % bupivacaine  was applied through the epidural catheter. Before the procedure, HR, SAP, DAP, PI, and VAS values were recorded for each patient. The first application time of epidural analgesia was taken as 0th minute and these values were recorded at 5th, 10th, 30th, 60th minutes and every two hours until the birth. The hours when the patients started to feel pain and HR, SAP-DAP, VAS and PI values at these hours were recorded. All cases were followed up to the first 30 minutes after normal vaginal delivery. Epidural catheter was removed six hours after the birth.The primary purpose of this study was to investigate the relationship between VAS values and PI in patients who underwent epidural analgesia for vaginal delivery. And the secondary purpose of the study was to investigate the relationship between PI and HR and SAP-DAP.With this study, by examining the changes in PI, we predict that a painless birth and increased maternal satisfaction can be achieved by administering additional doses of analgesics before the patients feel any pain in the later period.By taking the paperThirty patients aged between 19-43 years were included in the study. The mean age of the patients was 26.2 ± 5.0. Their number of pregnancies ranged between one and 5 (1.6 ± 0.9) . ThirteeIt was observed that at least one measurement in terms of HR, SAP, DAP, PI, VAS, and dilatation follow-ups was different from the other measurements (p: 0.000). According to this, HR, SAP, DAP, PI, dilatation, and VAS values before the procedure were statistically different than all follow-ups after the procedure .In the data of the relationship between VAS and PI which is the main objective of our study; when all patients were taken into consideration;there was a negative but insignificant correlation between the VAS and PI before the procedure and at the 0th and 5th minutes . However, there was a negative but statistically significant correlation at the 10th, 30th, 60th minutes and 2nd hour after the drug administration from epidural catheter  .th, 30th minutes, and at 2nd hour. However, a negative but insignificant correlation was found at 4th hour, 8th hour, in the birth and in the postnatal follow-ups (p > 0.05). Seventeen out of 30 patients were found to require additional doses. When the values before and after the additional dose conducted were compared, it was observed that there was a significant difference between the VAS values before and after the drug administration (p < 0.001). There was also a significant difference in PI values before and after the drug administration (p < 0.001) (Similar condition was observed at the 10< 0.001) .When examining the correlation of perfusion index with HR, and SAP-DAP; a negative but significant correlation was determined between PI and HR before the procedure and at the 0th and 5th minutes . However, this correlation was not significant in the subsequent follow-ups. Perfusion index had no significant correlation with SAP and DAP (p > 0.05).In this study investigating the relationship between pain level and perfusion index in labor analgesia for vaginal delivery, it was determined that as the pain decreased with epidural analgesia, perfusion index increased and when the perfusion index started to decrease, the pain level increased significantly .Birth has become one of the most painful experiences known, and physical, emotional, psychological, sociological, and sometimes religious beliefs should be taken into account along with when considering treatment. Epidural analgesia is a highly effective and popular treatment for labor pain.Pain affects the endocrine system leading to increased catecholamine release resulting in vasoconstriction. A number of studies have shown that the application of painful stimuli induces the sympathetic nervous system resulting in increased heart rate,In the literature, it is possible to find some studies in which autonomic responses are evaluated by pulse oximetry.When other sympathetic system results that may affect the perfusion index were examined, a few studies are seen in the literature but they have contradictory results. Nishimura et al.,th hour to the number of patients. This is because 17 patients reached 4th and 8th hours. There is a need for studies in which all patients are followed up for the same period. The third limitation is that the anxiety level of the patients was not considered. However, fear and birth worries, pain experience, attitudes towards pain and coping mechanisms are the main factors affecting the perception of labor pain.The first one is that the sample size was small. Generalization cannot be made since follow-ups were performed only in 17 patients out of 30 patients. It is thought that more reliable results can be obtained with higher number of patients. The second one is that we attribute the lack of the correlation between VAS and PI after the 4In this study investigating the relationship between pain level and perfusion index in labor analgesia for vaginal delivery, it was determined that when the pain decreased with epidural analgesia, the perfusion index increased, and when the perfusion index started to decrease, the pain level increased significantly. According to the results of this study, it is thought that PI may be an independent parameter reflecting the perception of painful stimuli and may offer a noninvasive option to objectively assess pain perception.


Background and aimsCannabinoids are increasingly used for medicinal purposes, including neuropathy. Gastroparesis is a neuromuscular disorder and neuropathy plays a large role in its pathogenesis. It is thus reasonable that cannabinoids can serve a beneficial role in the management of gastroparesis. Our study evaluates the effect of cannabinoids on gastroparesis symptoms.MethodsTwenty-four (n=24) patients with gastroparesis and refractory symptoms were selected from a single gastroenterology practice associated with a tertiary care medical center. The ‘Gastroparesis Cardinal Symptom Index' (GCSI) and an analog scale rating abdominal pain were applied to prospectively assess the effect of cannabinoids, in the form of dronabinol and medical cannabis, on refractory gastroparesis symptoms. Patients completed a GCSI form and rated their abdominal pain, before and after treatment. There was a minimum of 60 days of cannabinoid use between reporting intervals. Total composite GCSI symptom scores, GCSI symptom subset scores, and abdominal pain scores were calculated before and after treatment.ResultsA significant improvement in the GCSI total symptom composite score was seen with either cannabinoid treatment . Patients prescribed marijuana experienced a statistically significant improvement in every GCSI symptom subgroup. Significant improvement in abdominal pain score was also seen with either cannabinoid treatment .ConclusionsCannabinoids dramatically improve the symptoms of gastroparesis. Furthermore, an improvement in abdominal pain with cannabinoids represents a breakthrough for gastroparesis-associated abdominal pain treatment, for which there are currently no validated therapies. Gastroparesis is a chronic neuromuscular disorder that results in delayed gastric emptying in the absence of mechanical obstruction . The conThe socioeconomic impact and detrimental effect on the quality of life resulting from gastroparesis is significant and is increasing in recent years. Over 10% of patients reported being disabled due to their condition, while many other gastroparetics report missing significant work days and income -6. HospiThe pathophysiology resulting in gastroparesis symptoms is not fully understood, although neuropathy likely plays a large role in its pathogenesis. The impairment of normal phasic motor activity in the distal stomach produces the clinical manifestations related to delayed gastric emptying. The frequency and direction of the phasic motor activity is regulated by the gastric slow wave, a rhythmic electrical oscillation, which is generated by the interstitial cells of Cajal in the proximal gastric body - this area thus is known as the "pacemaker" zone of the stomach . TreatmeCannabinoids, primarily delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are becoming increasingly studied and used for medicinal purposes. Dronabinol, a synthetic THC analog, is used for nausea, vomiting, and anorexia in human immunodeficiency virus (HIV) and cancer though it has been used for symptom management in other conditions -14. MediThe effects of cannabinoids on gastroparesis symptoms were prospectively assessed in 24 patients. Patients were selected based on refractory symptoms from a single gastroenterology practice associated with a tertiary care medical center. Patients included in the study first required a confirmed diagnosis of gastroparesis via a nuclear gastric emptying study that displayed delayed gastric emptying, and esophagogastroduodenoscopies (EGD) that ruled out mechanical obstruction. Only patients with symptoms that were refractory to standard therapies for gastroparesis were included , endoscopic therapy (e.g. botulinum toxin injections), and some patients had implantable gastric stimulators and/or surgical pyloroplasty).Patients were prescribed either dronabinol, medical cannabis, or both, for symptom management. Those who received both treatments had them prescribed sequentially (dronabinol then marijuana) if dronabinol did not adequately relieve symptoms. Marijuana was prescribed as needed at varying THC:CBD ratios (at the discretion of the cannabis dispensary) and taken via vaporized inhalation or sublingual drops. The dosage of dronabinol ranged from 2-10 mg twice daily to four times daily. Patients completed a GCSI form, a validated symptom index for gastroparesis, before and after treatment  for each group, we utilized a paired-sample t-test and reported 95% confidence intervals for mean score differences. We used an unpaired t-test to analyze the differences in treatment outcomes between the study groups. We reported two-sided p-values and a p-value less than 0.05 was considered statistically significant. All statistical analyses were performed using the SPSS Statistical software v25.0 .Baseline characteristics were collected for all 24 patients in the study  Table .Table Paired sample T-tests were performed and a statistically significant improvement in the abdominal pain score was also seen in patients who received either cannabinoid treatment. When analyzed individually, both marijuana and dronabinol showed a statistically significant improvement in abdominal pain scores as well (p<0.05) Figure .To compare marijuana and dronabinol, pre- and post-treatment GCSI and abdominal pain scores were analyzed and unpaired sample T-tests were performed. Marijuana was superior to dronabinol in improving all symptoms, with statistical significance seen in the abdominal pain score and the total symptom composite score  (p<0.05) Figure .There are only a small number of available treatments targeted for gastroparesis, and many of the treatment options are limited by side-effect profiles, restricted recommended treatment duration, and unsubstantiated efficacy data.Prokinetics are often used because they target the underlying pathophysiology of the disease process, although symptom severity does not necessarily correlate with gastric emptying times ,16. Of tPain control is important in gastroparesis since up to 90% of gastroparetics report abdominal pain . NeuromoEndoscopic and surgical interventions are not well-studied in gastroparesis and data regarding effectiveness are scarce and often conflicting . Given tCannabinoids represent a new treatment in this difficult-to-treat, burdensome condition with minimal data-supported treatment options. By extrapolating from the indications for treatment with dronabinol and by utilizing the newly approved indications for medical cannabis in New York, cannabinoids clearly can benefit patients suffering from gastroparesis symptoms.We demonstrated that cannabinoids dramatically, and significantly, improve all symptoms of gastroparesis. Furthermore, abdominal pain was significantly improved with cannabinoids. This role in pain management represents a breakthrough for gastroparesis-associated abdominal pain treatment, for which there are currently no validated therapies.When both cannabinoid treatments are analyzed individually, both therapies resulted in an improvement in the GCSI composite symptom score, all GCSI symptom subset scores, and abdominal pain scores, though ‘bloating/distention’ with dronabinol treatment did not reach a statistical significance. When compared directly, marijuana was superior in improving overall symptoms, though this seems mainly driven by significant superiority in improving abdominal pain.Our study represents one of the first studies analyzing cannabinoids for the treatment of refractory gastroparesis symptoms . TherapiLimitations of this study include the small sample size due to the study design and the lack of a placebo-controlled or blinded methodology, though this would be difficult for marijuana studies. Also, the length of treatment prior to reassessing symptoms varied between patients, as it is unclear how long it would take to reach a therapeutic benefit from cannabinoid treatment. Furthermore, there was no standardized concentration of THC and CBD in the marijuana prescribed. At this point in New York, the THC:CBD ratios are variable. A trial-and-error process ensues, where the patient may adjust the THC:CBD ratio until maximal symptom relief and minimal side effects are achieved. It appears that THC was required to benefit the patients, but no definitive THC:CBD ratios can be recommended at this time.In conclusion, cannabinoids dramatically improve refractory gastroparesis symptoms, including abdominal pain. Marijuana may be superior to dronabinol in improving these symptoms, though both cannabinoids seem to be promising as novel therapeutic options in gastroparesis. Further studies should be conducted to confirm the efficacy of cannabinoids in refractory gastroparesis, and focus should be applied to optimal THC:CBD dosing, long-term efficacy, and sustainability of symptom improvement, as well as the side-effects of chronic cannabinoid use.


ObjectiveThe medical evidence supporting the efficacy of selective dorsal rhizotomy (SDR) on children with spastic diplegia is strong. However, the outcome of SDR on adults with spastic diplegia remains undetermined. The aim is to study the effectiveness and morbidities of SDR performed on adults for the treatment of spastic diplegia. MethodsPatients who received SDR in adulthood for the treatment of spastic diplegia were surveyed. The survey questionnaire addressed the living situation, education level, employment, health outcomes, postoperative changes of symptoms, changes in ambulatory function, adverse effects of SDR and orthopedic surgery after SDR. ResultsThe study included 64 adults, who received SDR for spastic diplegia. The age at the time of surgery was between 18 and 50 years. The age at the time of the survey was between 20 and 52 years. The follow-up period ranged from one to 28 years. The study participants reported post-SDR improvements of the quality of walking in 91%, standing in 81%, sitting in 57%, balance while walking 75%, ability to exercise in 88%, endurance in 77%, and recreational sports in 43%. Muscle and joint pain present before surgery improved in 64% after surgery. Concerning the level of ambulatory function, all patients who walked independently in all environments maintained the same level of ambulatory function. Eighteen percent of the patients who walked independently in some environments improved to the independent walking in all environments. All patients who walked with an assistive device before SDR maintained the assistive walking after SDR. Concerning adverse effects of SDR, 50% (32 of 64 patients) developed numbness in the various parts of the legs. Two patients reported a complete loss of sensation in parts of the legs, and one patient reported numbness and constant pain in the bilateral lower extremities. Ten patients (16%) reported recurrent spasticity after SDR, and three patients (5%) reported ankle clonus, which is an objective sign of spasticity. Tendon lengthening surgery after SDR was needed in 27% and hip and knee surgery in 2% and 6%, respectively. ConclusionsThe great majority of our 64 patients, who received adulthood SDR for spastic diplegia, improved the quality of ambulation and abated signs of early aging. Numbness and diminished sensation in the lower extremity was the most common adverse effect of the adulthood SDR. Selective dorsal rhizotomy (SDR) performed in children with spastic diplegia provides the sustained benefits into adulthood , 2. HoweThe Institutional Review Board of Washington University School of Medicine approved this retrospective quality of life survey . We obtained consent from patients directly or from guardians. The subjects of this study were adults (age > 18 years) with cerebral palsy who received SDR as adults between 1989 and 2018 at St. Louis Children’s Hospital. Patients received SDR using the surgical technique previously reported , 7. ApprThe survey was constructed with questions on demographic information, living situation, employment status, quality of life, the perception of health, motor and ambulatory functions, braces/orthotics, side effects of SDR, post-SDR treatment, and pain issues. Demographic information included the date of birth, living situation, highest education level, and current work status. Questions about bladder function, numbness, and loss of sensation were asked to assess the side effects of SDR. We asked participants who indicated numbness or loss of sensation in the lower limbs to further indicate if daily activities were hindered due to the loss of sensation. Participants were also inquired about back pain issues, scoliosis, and orthopedic interventions post-SDR.The Diener Satisfaction with Life Scale (SWLS) was used to assess the quality of life and subjective well-being by rating five statements on a scale of one (strongly disagree) to seven (strongly agree). Summary scores on the Diener SWLS are interpreted as follows: 31-35 - extremely satisfied with life, 26-30 - very satisfied, 21-25 - slightly satisfied, 20 - neutral, 15-19 - slightly dissatisfied, 10-14 - very dissatisfied, and 5-9 - extremely dissatisfied. Reliability of this scale has been reported to be greater than 0.80 [A five-point scale from poor to excellent was utilized to evaluate the perception of one’s personal health, as seen in Question 1 of the SF-36 health survey . Yes/no The ambulatory function was assessed by asking patients to indicate their level of function before and after SDR on a three-level classification system. Level I includes patients who can walk on their own without using walking aids, go up and down the stairs without needing to hold the handrail, walk wherever they want to go, and run and jump although their speed, balance, and coordination may be slightly limited. Patients at level II can walk on their own without using walking aids, but need to hold onto the handrail when going up and down the stairs and often find it difficult to walk on uneven surfaces, slopes, or in crowds. Lastly, level III includes patients who can stand on their own, only walk using a walking aid, find it difficult to climb stairs or walk on uneven surfaces, and may use a wheelchair when traveling for long distances or in crowds.Experiences with pain were gauged by asking participants to report back pain and the severity of pain on the Numeric Pain Rating Scale (NPRS). The NPRS is a 0-10 scale with 0 indicating no pain and 10 being the worst pain imaginable. We asked for the location of the pain and any interventions they received to alleviate pain, such as care from a physician, medications, surgical treatment, physical therapy, and injection treatment for back pain.Study CohortThe number of patients who received selective dorsal rhizotomy during adulthood totals to be 139 patients. Their most up-to-date contact information was gathered from the Center for Cerebral Palsy Spasticity at St. Louis Children’s Hospital’s databases. Due to outdated contact information, 21 patients could not be reached. Out of the remaining 118 potential participants, three patients declined the study, and 81 responses were collected. From the collected responses, 17 responses were omitted because either the post-SDR follow-up period was less than one year or the patients were not diagnosed with spastic diplegia. Ultimately, the total number of patient responses used in the study totals to be 64, which represents 54% of potential participants who met the study criteria.Demographics of Study CohortOf the 64 patients who received SDR for spastic diplegia, the age at the time of surgery was between 18.1 and 50.0 years (mean age: 31.6 ± 9.1 years). The postoperative follow-up period ranges from 1.0 and 28.2 years (mean duration: 6.6 ± 5.5 years). Age at follow-up varied from 20.2 to 52.3 years (mean age: 38.1 ± 9.0 years). Male participants made up 58% of the study population , 6% as fair, and 2% as poor. Most participants were classified in the slightly satisfied bracket of the Diener SWLS, with the mean overall score being 24.1 ± 7.4 Table .Preoperative Symptoms and Postoperative ImprovementBefore SDR, 83% of all patients experienced decreased endurance, 88% deterioration of walking, 81% muscle and joint pain, 87% deterioration of balance while walking, 92% decreased ability to stretch, and 91% feeling of increased spasticity in legs. SDR alleviated decreased endurance in 77% of the group, deterioration of walking in 86%, muscle and joint pain in 64%, deterioration of balance while walking in 78%, decreased the ability to stretch in 88%, and feeling of increased spasticity in legs in 85%.  of the group, which decreased to 3% (two patients) after SDR. Out of the eight patients who experienced urinary incontinence before SDR, seven patients did not report incontinence post-SDR. One patient had continuing urinary incontinence, while one patient developed incontinence after SDR. Upon review of clinic notes for the patient who developed urinary incontinence after SDR, it was found that no significant urinary control problems were indicated after SDR. Some patients with cerebral palsy can suffer from neurogenic bladder and incontinence even without SDR . The incNumbness in lower extremities was reported in 50%, out of which 22% of the patients experienced numbness affecting daily activities. The most common locations that patients experienced numbness at were the outer parts of the calves and feet. Complete loss of sensation in small areas of the legs was noted in 5% of all patients, which was most frequently experienced below the knee and the posterior parts of the thigh.Back pain was reported in 56% (36 patients) of the patient cohort. Out of the 36 patient experiencing back pain, 13 patients had continuing back pain from pre-SDR. Seven patients had back pain prior to SDR, which disappeared after the surgery. Six patients reported back pain during the post-SDR follow-up visit. Ten patients had no reported back pain before and after SDR, but developed back pain over a longer period of time after SDR. Because back pain was not reported at the post-SDR follow-up visit, it cannot be determined with certainty whether the pain in the back is a result of SDR. On the Numeric Pain Rating Scale of 0 - 10 with 0 representing no pain and 10 being worst pain imaginable, mean back pain score was 4.4 ± 2.2. Location of pain was most frequently identified to be the lower back (77% of patients with pain) and middle back (16%). Most patients received physical therapy for back pain (58%) and medications (33%). More invasive treatments for back pain, such as surgical treatment or injections, were not pursued by many patients, with percentages remaining at 6% and 17% respectively , Achilles tendon lengthening (37%), adductor lengthening (5%), and calf muscles lengthening (11%) Table .The present study shows strong evidence that the reduction of spasticity with SDR in adults with spastic diplegia likely reverses or halts deteriorating ambulation. Until now, when the adults were losing the ability to walk due to persistent spasticity, no treatment was deemed available that can prevent the late onset of functional loss. Our clinical experience of treating adults with SDR up to 50 years of age allowed us to learn more about the negative effects of persistent CP spasticity in adults. As they age, the adults develop increasingly tight muscles, tendons, and joints; sitting, standing and walking become increasingly limited; endurance can decrease in a short time frame; muscle and joint pain increases; they often lose the ability to walk before 50 years of age. The late functional decline in adults with spastic cerebral palsy has been recognized in the clinical arena , 4. The The main goal of SDR on adults is a reversal or cessation of the declining ambulatory and other motor functions. In our patients, the great majority improved the ambulatory function after SDR. The quality of independent walking improved in 91% of study participants. Those who were independent ambulators before surgery maintained the independent ambulation after surgery. Also, the ability to exercise improved in 88% of participants. In contrast, sitting ability did not improve in 43%. We assume the floor sitting failed to improve in the group. Another goal of SDR on adults is relief of muscle and joint pain. Eighty-one percent of participants had body pain before surgery. It is significant that 36% of them persisted with body pain with no improvement. Some study participants describe electric shock pain, pins and needle pain, nerve pain, radiating pain, and spasms that were not present before SDR. One female participant who underwent SDR at 48 years of age developed constant severe pain in the entire lower extremities. The pain is not relieved by medication, and the cause of the pain is unclear. Future patients should be informed of the possible new pain after SDR. Also, the pain outcome should be a factor in the selection of adults for SDR. Patients who have generalized or localized pain that is resistant to pain medication may not benefit from SDR. The persistent pain would have a dominating impact on the overall quality of life, even after spasticity is reduced. Adulthood SDR had more negative outcomes than childhood SDR , 2. The Ten survey participants (16%) felt persistent spasticity or a return of spasticity. Three participants (5%) reported ankle clonus. One participant described a gradual return of spasticity approximately one year after surgery. She had no clonus. She underwent the baclofen pump placement and bilateral knee replacements. Reasons for other participants to feel persistent or a return of spasticity include spasticity in the quadriceps because of a catch during a fast stretch, muscle imbalance between quadriceps and hamstrings, only returned in the left Achilles tendon, and spasms in the legs. Whether spasticity can return to only one muscle is unclear. It should be noted that the reported spasticity in the ten adults was not verified by neurological examination. In some of the patients, the tight muscles may have been mistaken for spasticity. In conclusion, the present study shows that SDR on adults can benefit patients with spastic diplegia up to 50 years of age. However, adulthood SDR may be associated with adverse outcomes, i.e., numbness, and failure to reduce spasticity and body pain. The adverse outcomes were more common in patients over 40 years of age.


To compare the International Prostate Symptom Score (IPSS) and novel Visual Prostate Symptom Score (VPSS) in patients with lower urinary tract symptoms (LUTS), to correlate scores with uroflowmetry and prostate volume and assess patient perceptions regarding pain prior to, and after prostate biopsy.Patients with LUTS who had an indication for transrectal ultrasound (TRUS) biopsy were included. Patients completed the IPSS-, VPSS- and prostate biopsy pain assessment questionnaires. Assessment included uroflowmetry, post- void residual volume and prostate volume (measured with TRUS).One hundred men were included. There were statistically significant correlations between the VPSS score and IPSS score (correlation coefficient (r) = 0.802); VPSS and Qmax (r = −0.311); VPSS and. Qave (r = −0.344); prostate volume with VPSS (r = 0.194) and Qmax (r = −0.260). The VPSS was quicker to complete than the IPSS (mean 100 vs. 165 seconds). The mean anticipated pain score before biopsy was 2.8 (range 0-6), and after biopsy (experienced pain) it was 1.8 (range 0-5). The pain during biopsy was less than expected in 67% of patients.In men with LUTS scheduled to undergo prostate biopsy, the VPSS score correlated positively with the IPSS score. Men with limited education take less time to complete the VPSS. Patient's perception of expected pain or discomfort during TRUS-guided prostate biopsy was significantly higher than the pain actually experienced during biopsy. Men with lower education level had significantly higher expectation of pain prior to biopsy, but similar pain during biopsy. The International Prostate Symptom Score (IPSS) is used to assess lower urinary tract symptoms (LUTS) in men with bladder outflow obstruction (BOO), which is most often due to benign prostatic hyperplasia (BPH), prostate cancer or urethral stricture –3. The IAdam E. Groeneveld, a urologist who has worked for many years in African countries, developed a simplified assessment of the force of the urinary stream. Using this concept, we developed a Visual Prostate Symptom Score (VPSS) which also assesses urinary frequency during the day and night, and the patient's overall quality of life   guided prostate biopsy is the gold standard in diagnosing prostate carcinoma . AlthougAlthough several studies have been performed to document pain during- and after transrectal prostate biopsy using different numbers of biopsy cores and different forms of local anesthetic or analgesia, to our knowledge no prospective study has been performed to assess patient perceptions and expectations of transrectal prostate biopsy prior to and after the procedure.After obtaining institutional ethics committee approval, men that presented with LUTS and who had an indication to undergo TRUS-guided prostate biopsy were included.All were given both the IPSS, and subsequently, the VPSS questionnaire to complete and it was noted whether the patient completed the questionnaire on his own or whether he asked for assistance. In addition, the time taken (in seconds) to complete the questionnaire was also noted. Information on the patient's level of education, literacy, occupation and income were documented. Peak (Qmax), and average (Qave) urinary flow rates, voided volume, and ultrasound-measured postvoid residual urine volume were obtained for each patient.The equipment necessary for the TRUS-guided prostate biopsy was shown to each patient and following this, the patient was asked to complete the TRUS-guided prostate biopsy assessment questionnaire , with a An ultrasound machine with a transrectal intracorporeal probe was used for the ultrasound biopsy guidance. A semi-automatic spring coil device with an 18-gauge needle was used to obtain 8 core biopsies in all patients. TRUS was also used to calculate the prostate volume. Lubricating jelly containing lignocaine was inserted rectally in all patients before TRUS was initiated. The procedure was performed by four different providers.Statistical analysis was performed using GraphPadInstat® software, with Student's t-test for parametric variables, Mann-Whitney test for nonparametric data, Fisher's exact test for contingency tables and Spearman's rank test for correlation analysis. A two-tailed P-value < 0.05 was accepted as statistically significant.In the period May 2010 to October 2013 a total of 100 men were evaluated . The patient's years of formal schooling were as follows: 1-7 years in 31 patients and 8-12 years in 66 patients, four had a tertiary education and three had no formal schooling.There was a statistically significant positive correlation between the total VPSS score and total IPSS score and also between the prostate volume measured by TRUS and by digital rectal examination (DRE) . The VPSIn the group of education grade ≤ 7, only 17.6% could complete the IPSS without assistance, whereas 38.2% could complete the VPSS without assistance. This difference was not statistically significant for the education grade ≥ 10.The mean duration of procedure for prostate biopsy was 5.7 minutes (range 2-12 min). The mean time between inserting lignocaine jelly to inserting TRUS probe was 3.6 mins (2-5 min). The mean pain score before biopsy (anticipated pain) was higher than after biopsy (experienced pain). The mean pain score before biopsy was 2.8 (range 0-6) and mean pain score after biopsy was 1.8 (range 0-5). The pain during biopsy was less than expected in 67% of patients, with the score 1 point less in 33%, 2 points less in 17%, and ≥ 3 points less in 17%. In 23% of patients the anticipated pain-and experienced pain scores were the same and in 10% of patients the experienced pain score was higher than the anticipated pain score. In the group of patients with < 7 years compared to the group with > 8 years of schooling, the mean pain score before the biopsy was significantly higher, but after the biopsy there was no significant difference. The mean pain score before biopsy for patients with < 7 years was 3.5 (range 1-6) and after biopsy was 1.6 (range 0-4). Whereas with patients > 8 years of schooling the mean score before biopsy was 2.7 (range 0-5) and then 1.8 (range 0-5) after biopsy.The mean prostate volume estimation on DRE was 41.4 cc (25-100) and on TRUS 47.3 cc (12-148). The histological diagnoses of the prostate biopsies were as follows: adenocarcinoma in 50 patients, BPH or normal prostatic tissue in 40 and prostatitis in 10. Patients with benign rectal exam vs. malignant rectal exam had the following pain assessment scores: Mean score before biopsy 2.8 vs. 3.0 and after biopsy 1.8 vs. 1.6 (not significant). Patients with < 50 cc TRUS prostate volumes versus > 50 cc prostate volumes had the following scores: Mean score before biopsy 2.8 vs. 2.9 and after biopsy 1.8 vs. 1.7 (not significant).A sixth grade reading level is considered necessary to understand the questions asked in the IPSS . This woThe VPSS has not been disseminated to, or studied at other institutions. Further multi-institutional investigation and investigation on patients with other racial or ethnic backgrounds could be considered.TRUS-guided prostate biopsy is a common procedure, performed on an outpatient basis, to diagnose prostate cancer. Important  questions that remain unanswered, are whether patient's perceptions of pain or discomfort during TRUS-guided prostate biopsy, as well as after the procedure, warrant that the procedure be performed under general- rather than local- or no anesthesia, and also whether these perceptions of pain and discomfort relating to the diagnostic procedure may present a barrier to the early detection of prostate cancer. There are conflicting opinions regarding the question of intrarectal lidocaine (lignocaine) gel being more effective than lubricating jelly only , 18 in dThe reason for using a TRUS-guided prostate biopsy assessment questionnaire with score ranging from 0-6  and not Previous investigations have shown that even when anesthesia-free, TRUS-guided prostate biopsy was considered to be only mildly uncomfortable for most patients, 19% judged that it should be accompanied by some type of anesthesia and 6% of patients judged that the procedure was so uncomfortable that it should have been performed under general anesthesia  about the procedure beforehand and that this may have ensured more realistic expectations of pain to be experienced during the procedure.Showing the biopsy equipment to the patients prior to them completing the score questionnaire may have altered the pre-biopsy scores-this is a possible limitation of the study method.Another possible limitation of the study is that the procedure was performed by four different providers. Some providers might have had more experience with TRUS-guided biopsy and performed a more rapid, and possibly less uncomfortable, procedure which could lead to different results.In men with LUTS scheduled to undergo prostate biopsy, there was a statistically significant positive correlation between the total VPSS- and total IPSS scores. In men with a limited level of education, the VPSS took significantly less time to complete than the IPSS.Patient's perception of expected pain or discomfort during TRUS- guided prostate biopsy was significantly higher than the pain actually experienced during biopsy. Men with lower education levels had significantly higher expectation of pain prior to biopsy, but reported similar mean pain score during biopsy when compared to men with higher education level. There was no significant difference in pain experienced by patients with malignant prostates compared to benign prostates or with larger- compared to smaller prostates.