Treating soft tissue injuries can be a challenge for physicians as it can be overlooked which can lead to more problems. In recent studies, the use of Platelet Rich Plasma (PRP) has been gaining popularity for soft tissue injuries because of its benefits and minimal side effects. This study aims to evaluate the effect of PRP injection on various musculoskeletal soft tissues inflammation.This is a retrospective study of patients with soft tissue injury who underwent PRP therapy between 2015 and 2018 at an orthopaedic and traumatology hospital. The study collected demographic data including the type of soft tissue injury and Visual Analog Scale (VAS) before and after the PRP injection. Those data were statistically analysed to identify the significance of PRP.Seventy-six patients were included, predominantly female, middle aged (40-69 years old) and class one obesity. Most of the complaints (61.8%) were in the lower extremity region. Pain improvements measured with mean VAS score were observed in both acute (3.06±1.28 to 0.8±0.65) and chronic (4±1.75 to 0.97±0.62) cases. There was a significant decrease of VAS score before and after the PRP injection (p < 0.000).PRP injection is able to alleviate both acute and chronic pain in soft tissue injuries without additional analgesic. Soft tissues generally include muscles, fascia, tendon, cartilage, synovium, fibrous capsules, nerves, and ligament, nearly every element beside bones1. Surgery is a prevalent option for patients who have persistent symptoms of pain2. However, recent studies are trying to focus on anti-inflammatory regiments with greater benefits than surgery. Currently non-surgical approaches include physiotherapy, activity modification, steroid injections, and non-steroidal anti-inflammatory drugs (NSAID)3. Even though steroid injections displayed a positive outcome of pain relief, there were reports of harmful effects such as tendon degeneration and muscle atrophy4. One of the suggested natural regiments rich in anti-inflammatory agents is platelet-rich plasma (PRP)5.Soft tissue pain is frequently overlooked and may lead to debilitating conditions. This problem occurs mainly among people with high physical workload such as athletes2. The platelets and leucocytes in the PRP have the capability of releasing numerous growth factors, namely platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), epithelial growth factor (EGF), and transforming growth factor beta (TGF-β). This modality has been investigated intensively to foster healing of various musculoskeletal soft tissue diseases, especially soft tissue pain due to excessive or repetitive activities including tendinopathy and injured muscle. Although PRP injection has minor side effects to a certain degree, the advantages of not having cross reactivity and immune reaction or disease transmission risks are much more valuable. PRP can be the lead alternative for soft tissue pain therapy due to its autologous nature6.PRP is an autologous blood product which contains four to five times more platelets than the normal valueDespite positive reports regarding its efficacy, the use of PRP in specific musculoskeletal soft tissues is limited. This study aims to seek the efficacy of PRP injection on the inflammation of various musculoskeletal soft tissues as a stand-alone therapy regiment.This retrospective study has been approved by the Internal Institutional Review Board of Surabaya Orthopaedic and Traumatology Hospital. Prior to drawing blood, informed consent was obtained from each patient. Patients’ data from between January 2015 and December 2018 were extracted from medical records. The inclusion criteria for the study were adult patients who were diagnosed with musculoskeletal soft tissue inflammation, treated with PRP injection, and had their pain measured with VAS before and after the surgery. Meanwhile, patients with incomplete medical record and who had received additional analgesic after PRP injection were excluded from the study. Demographic data such as subject’s age, sex, body mass index (BMI), duration of pain, confounding disease, and site of lesion were also added. In this study, patients’ BMI were classified based on Asia-Pacific population classification as underweight (<18.5), normal (18.5 – 22.9), overweight (23 – 24.9), obese I (25 – 29.9), and obese II (> 30).Soft tissue inflammation is defined as non-infectious, non-trauma inflammation involving musculoskeletal structures other than the bone or joint. All soft tissue inflammation cases were diagnosed by orthopaedic surgeons and were grouped into upper and lower extremity based on their anatomical location. There were no limitations of the type of soft tissue inflammation. During the duration of the complaints, samples were categorised into acute pain (< 6 weeks) and chronic pain (> 6 weeks).The process of collecting PRP was conducted by the hospital laboratory. First, we collected 10 cc of the patient’s peripheral blood. Then the blood was processed and separated in a tube of Z-gel containing ACD (Adenine Citrate Dextrose) anticoagulant using high-speed centrifuge (RCF 2500 G) for 10 minutes. Three separate layers were produced: plasma, buffy coat (platelet), and red blood cells. The thick buffy coat layer, rich in platelet and growth factors, were collected and directly injected within 5 minutes to the subcutaneous tissue of the inflammation site. The bump was slowly massaged to help spread the PRP around the inflammation site. In this study, we made sure to avoid injecting tendon, ligament, as well as the vascular region in the inflammation site.VAS was measured to define pain before and after the injection. Pain was categorised based on the scale range of 0 (no pain), 1-3 (mild pain), 4-6 (moderate pain), and 7-10 (severe pain). The post-treatment pain score was measured during the patients’ following visit, ranging from 3 weeks to 3 months. Quantitative data were described in terms of mean ± standard deviation. Statistical analysis was performed with SPSS software . Paired Samples T-Test was used to determine the significant difference of VAS on pre-post PRP injection. A value of p < 0.05 indicates the result is statistically significant.A total of 134 patients were first included in this study. However, 58 samples were excluded as the patients had received additional analgesic after injection. The final total was 76 subjects. The participants were primarily female (55.3%), middle-aged (40 - 69 years), and classified as obese I (42.1%). More than half (56.6%) had confounding disease, and 59.2% were in chronic pain. The baseline characteristics of the subjects are presented in The result of VAS evaluation is displayed in 7. The degranulation also acts as chemoattractant for macrophages to take part in the healing process8. Based on previous literatures, increased platelet concentration is believed to escalate the total growth factors released, which enhance healing and the regeneration process10. The enhancement of the migratory ability leads to a better regeneration capability and slows down the natural progression of the disease. PRP works gently and will heal the microenvironment of the lesion7.PRP’s efficacy comes from the various growth factors which are released from alpha granules of activated platelets, specifically platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor-beta 1 (TGF-β1), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF), hepatocyte growth factor (HGF), and insulin-like growth factor (IGF-I)11. We found that the majority of the patients with soft tissue injuries were female (42%). Although we did not account for any correlation between gender and PRP, previous studies reported that there was not enough evidence to suggest gender plays a significant role in the outcome of PRP therapy13. The patients’ age (40 - 69 years old) reveals that the lesions were mostly found in people who were still relatively active, which might impair their daily activities and will further worsen in time13. The predominant age may also reflect the cofounding diseases found in each patient. Diabetes and hypertension are notoriously frequent in this age range. Whilst this study did not correlate cofounding diseases with pain, the improvements in VAS score implied that systemic condition did not have an effect on PRP modulation. Inflamed tendon lesions are often instigated by chronic microinjuries due to excessive repetitive stress15. Patients whose injuries were sustained from jobs with extensive movement such as manual handling of heavy loads and demanding handgrip forces, or those with repetitive movement should be considered11 for this form of therapy. Certain activities or sports such as soccer and tennis are known to be the major causes of achilles tendinitis and lateral epicondylitis16. Some soft tissue injuries are also linked to high BMI. This may be caused by a higher loading force, particularly in the lower extremity of obese patients. Obesity is associated with prolonged low-grade inflammation and impaired insulin sensitivity7. In addition, enlargement of the diameter of tendon fibre with the shortening of its modulus could weaken the fibre’s ability to resist stress and reduce its healing process capacity. This is also supported by the fact that almost 70% of our patients were overweight and obese.The characteristics of our subjects were similar to other patients in different centres4, thus the prolonged use of NSAID could be avoided. This was seen in various studies about plantar fasciitis which reported that PRP is capable of treating chronic pain18. After six months of follow-up, PRP showed a better outcome compared to corticosteroid injection in the management of elbow epicondylitis19. Conversely, there was no significant difference between PRP and corticosteroid in short to intermediate settings17. These findings were in concordance with our study where PRP has a significant value in treating both acute and chronic pain, with a considerably better result in chronic pain with a mean difference of 3.02 (±1.54).The pain relief may not be as potent as those from the use of corticosteroid or NSAID. However, PRP will stimulate the healing processSome surgeons are reluctant to prescribe PRP as a standalone treatment without additional analgesic regiment. This hesitation could be avoided by understanding the basic role and function of PRP. It is not necessary to inject the plasma directly to the tendon or ligament. Instead, the purpose of PRP injection is to enrich the surrounding inflamed locus. Our method is to inject it subcutaneously to the loose connective tissue, then gently massage the bump to disperse PRP evenly around the inflamed region. Another important element is to meticulously prepare the patient’s blood into a ready-to-use PRP that is then injected within five minutes before a clot could form.This study had limitations as well. The design of this study is retrospective which could raise some biases and confounding factors which could influence the outcome. Further studies that can focus on one type of inflammation would be beneficial. Despite the favourable outcome, we acknowledge double-blinded RCTs with large sample sizes are needed before standardising PRP as the sole treatment modality for soft tissue inflammation.Our study indicates that PRP injection can provide both short-term and long-term relief in soft tissue musculoskeletal inflammation without any additional analgesic.


To assess intermittent abdominal pain in IgA vasculitis patients and its relation to demographic data, clinical manifestations and treatments.A retrospective cohort study included 322 patients with IgA vasculitis (EULAR/PRINTO/PRES criteria) seen at the Pediatric Rheumatology Unit in the last 32 years. Sixteen patients were excluded due to incomplete data in medical charts. Intermittent abdominal pain was characterized by new abdominal pain after complete resolution in the first month of disease.versus without , whereas the median of ranitidine duration was reduced in the former group .Intermittent abdominal pain was observed in 35/306 (11%) IgA vasculitis patients. The median time between first and second abdominal pain was 10 days (3–30 days). The main treatment of intermittent abdominal pain included glucocorticoid [n=26/35 (74%)] and/or ranitidine [n=22/35 (63%)]. Additional analysis showed that the frequency of intermittent purpura/petechiae  and the median of purpura/petechiae duration  were significantly higher in IgA vasculitis patients with intermittent abdominal pain compared to those without. Gastrointestinal bleeding , nephritis , glucocorticoid  and intravenous immunoglobulin use  were also significantly higher in the former group. The frequency of ranitidine use was significantly higher in IgA vasculitis patients with intermittent abdominal pain Intermittent abdominal pain occurred in nearly a tenth of IgA vasculitis patients, in the first 30 days of disease, and was associated with other severe clinical features. Therefore, this study suggests that these patients should be followed strictly with clinical and laboratorial assessment, particularly during the first month of disease course. This gastrointestinal manifestation may be associated with serious complications, as bowel intussusception or gastrointestinal bleeding.,,–versus patients without intermittent abdominal pain in the first month of IgA vasculitis were not carried out.Of note, recurrent or intermittent colicky abdominal pain in IgA vasculitis were seldom described in previous case reports or case series.Thus, the aim of the present study was to characterize intermittent colicky abdominal pain in the first month of children and adolescents with IgA vasculitis, and to assess the possible association of demographic data, clinical manifestations, laboratorial abnormalities and treatments in patients with and without this gastrointestinal manifestation.A retrospective cohort study was performed during a period of 32 years in a tertiary Pediatric Rheumatology Unit in São Paulo, Brazil. We analyzed 322 medical records. Of these, 16 were excluded due to lack of data. The remaining 306 patients fulfilled European League Against Rheumatism (EULAR), Paediatric Rheumatology International Trials Organisation (PRINTO) and Paediatric Rheumatology European Society (PRES) IgA vasculitis classification criteria.Demographic data, such as age at diagnosis in years, gender and body mass index (BMI), were evaluated.,Abdominal pain was defined as diffuse colicky abdominal pain with acute onset assessed by medical history and physical exam. Severe abdominal pain was described as the presence of at least one of the subsequent: abdominal angina ,––Intermittent purpura/petechiae were characterized as new skin lesions after total recovery of first episode, and persistent purpura/petechiae as cutaneous lesions lasting more than 30 days. The definition of arthritis was joint pain with limitation on movement or articular edema. Arthralgia was defined by articular pain without edema or limitation on motion.th percentile according to gender, age, and height on 3 or more occasions.Nephritis was defined as hematuria >5 red blood cells/high power field or presence of red blood cells in the urinary sediment and/or proteinuria >0.1g/mNeuropsychiatric involvement was characterized by the presence of at least one of the following manifestations: headache, impaired consciousness, seizures, hemiparesis and cortical blindness.Patients with IgA vasculitis were divided into two groups: with and without intermittent abdominal pain in the first month of disease course.Results were presented as median (range) or mean±standard deviation for continuous variables, and number (%) for categorical variables. Pearson’s chi-square or Fisher’s exact tests were used to compare categorical variables. Mann-Whitney test or Student’s t-test were used to compare continuous variables. For all statistical tests, a p-value less than 0.05 was considered with statistical significance.Intermittent abdominal pain in the first month of disease was observed in 35/306 (11%) of IgA vasculitis patients, and generally reported as colicky and diffuse abdominal pain. This intermittent abdominal pain was associated with new cutaneous lesions in the first month of disease in 32/35 (91%) of IgA vasculitis patients. The median time between the first and the second episode of abdominal pain was 10 days (3–30 days). The main treatment of intermittent abdominal pain included glucocorticoid [n=26/35 (74%)] and/or ranitidine [n=22/35 (63%)]. Only one IgA vasculitis patient had recurrent abdominal pain at 5 year of disease. At that moment, he reported colicky and diffuse abdominal pain, concomitantly with new cutaneous lesions and nephritis flare.versus without intermittent abdominal pain. The median of glucocorticoid therapy duration was higher in the first group . The frequency of ranitidine use was significantly higher in IgA vasculitis patients with intermittent abdominal pain versus without , whereas the median of ranitidine therapy duration was reduced in the former group   and intravenous immunoglobulin use  were also significantly higher in IgA vasculitis patients with p=0.004] .To our knowledge, this was the first study that demonstrated intermittent abdominal pain in the first month of disease as a rare manifestation of IgA vasculitis patients and was associated with skin manifestations, nephritis and severe gastrointestinal involvement. In addition, recurrent abdominal pain was rarely observed in IgA vasculitis patients.,The advantage of the present study was the selection of this population followed in a tertiary center in Latin America with predominance of complex patients.At disease onset, approximately three quarters of our IgA vasculitis patients with intermittent abdominal pain had nephritis, suggesting a severe and periodic systemic involvement of this vasculitis. Indeed, nephritis is also commonly associated with IgA vasculitis flares, as reported in a study with Finland population.Additionally, intermittent abdominal pain occurred in the first 30 days of IgA vasculitis patients. Therefore, these patients should be followed strictly with clinical and laboratorial assessment, particularly during the first month of disease course.Regarding treatment, ranitidine showed to be effective in gastrointestinal manifestations in IgA vasculitis patients, decreasing duration and severity of gastrointestinal pain and bleeding as described in a Turkish research.Of note, recently US Food and Drug Administration alerts to healthcare professionals that ranitidine contains low levels of nitrosamine impurity called N-nitrosodimethylamine (NDMA).Moreover, glucocorticoid use is indicated for severe and complicated abdominal pain in IgA vasculitis patients.The median time between the first and second episode of intermittent diffuse colicky abdominal pain was short, and the vast majority of patients associated with new cutaneous lesions, indicating that this pain etiology was probably due to disease activity. The diagnosis of abdominal pain in IgA vasculitis is usually easy and rarely requires a differential diagnosis with esophagitis, gastritis or gastric ulcer.The main limitation observed in the present study was the retrospective analysis, with potential missing data. We also did not assess the serum galactose-deficient IgA1, a well-known biomarker of IgA vasculitis associated with severe abnormalities at diagnosis.In conclusion, intermittent abdominal pain occurred in nearly a tenth of IgA vasculitis patients, in the first 30 days of disease, and was associated with other severe clinical features. Therefore, our study suggests that these patients should be followed strictly with clinical and laboratorial assessment, particularly during the first month of disease course.


Introduction Neuropathic pain commonly causes high levels of pain that impairs multiple facets of the lives of patients. Multiple first-line treatments such as physical therapy and pharmacological intervention exist. Treatment refractory to these interventions may be considered for spinal cord stimulation (SCS). However, modest rates of meaningful relief leave room for improvement. Dorsal root ganglion stimulation (DRGS) has been touted to be a viable alternative solution to SCS with more specific targets and, consequently, fewer side effects. Thus, DRGS has been accepted as a better alternative to spinal cord stimulation. In contrast, we report a series of DRGS patients who had lower rates of meaningful pain relief than what was reported in the literature.MethodsWe present a series of 11 patients who underwent both DRGS trial and subsequent permanent implantation with negative outcomes  in 55% of patients. Patient records were searched for comorbidities that could potentially affect the DRGS implant . Once delineated, the predictive value of each comorbidity for negative outcomes was estimated.ResultsEighteen patients had a successful DRGS trial which was defined as a ≥ 50% pain reduction as well as increased ability to perform daily activities. Seven patients elected not to proceed with the permanent DRGS. Of the 11 remaining patients that had the permanent DRGS, four patients reported being completely pain-free ≥ one month following implantation, one reported a significant increase in pain improvement at four months post-operation, and six patients reported pain that was ≥ 50% of their pre-surgical pain 4-12 months following implantation. ConclusionIn our case series, we observed a discrepancy between DRGS trial outcomes and outcomes following permanent implantation. We found that a stronger correlation may exist between worse outcomes and smoking. Older age, the presence of diabetes, and cancer had more modest associations. These comorbidities may have value as tests for predicting negative outcomes of permanent DRGS implantation. Additionally, we hypothesized that this could also be due to the presence of psychological factors which obscure the true result of the DRGS trial. Thus, we suggest that DRGS be prescribed with caution in these patient populations, and use comorbidities to test for the likelihood of negative outcomes. Limitations of this study are those that are intrinsic to a retrospective case series. Neuropathic pain, especially when chronic, can significantly impact the day-to-day activities of patients as they experience high levels of pain which affect their mental health, mood, work performance, etc. In the US, the prevalence of neuropathic pain is about 7%-15% among the general population with differences in age, gender, and race. Further, ~1.5% of these patients have neuropathic pain that is refractory to the current protocol of treatment [Spinal cord stimulation (SCS), which involves inserting electrodes into the dorsal epidural space, is widely accepted as a second or third-line treatment for neuropathic pain . In 2019DRGS specifically stimulates the dorsal root ganglion (DRG) and its associated dermatome without affecting other tracts in the dorsal columns as in SCS. DRGS was suggested to be a more effective form of treatment for CRPS by Deer et al. , produciBetween September 2018 and June 2020 DRGS trial was performed on 18 patients for neuropathic pain in multiple areas  or CRPS. Charts were reviewed retrospectively and ≥ 50% reduction of pain was used as an outcome measure for the DRGS trial. If trial results were positive, permanent implantation of the DRGS was indicated. Patients with permanent DRGS were separated by positive and negative pain outcomes, defined by whether the patients reported a ≥ 50% reduction of pain, then listed with their co-morbidities to determine potential predictors of negative outcomes.Inclusion criteriaPatients that had neuropathic pain located in the low back and below, i.e. the low back, pelvis, buttocks, thighs, and calves which were refractory to more conservative treatments and SCS trial as well as a successful DRGS trial were candidates for permanent DRGS.Eighteen patients had successful DRGS trials. Success was defined as a ≥ 50% pain reduction, as well as an increased ability to perform daily activities. Of the 18 patients, seven patients elected to not proceed with permanent DRGS. Thus, this study reviews the outcomes of the remaining 11 patients Tables . The paiIn Germany, DRGS was previously reported by Morgalla et al. to be very effective for pain in the leg (76% improvement) and back (44% improvement) at one year. However, we report that DRGS had more modest results with only 45% reporting ≥ 50% reduction in pain and worsening pain in some of those without relief. We suggest that smoking more so than age, diabetes, and cancer may account for the discrepancy in pain relief. Morgalla et al. reported that the average age of their patients was around 56.8 years old. We found our average patient age to be around 64.27 years old. However, Morgalla et al. did not report co-morbidities of their patients in their study, thus we used national rates to compare [It is important to note that diabetes can also lead to peripheral neuropathy. This might lead to a potential confounding variable as painful diabetic peripheral neuropathy (PDPN) is due to different pathophysiology than the neuropathic back pain evaluated in this study. PDPN is thought to be pain arising as a direct consequence of abnormalities in the peripheral somatosensory system in people with diabetes. These abnormalities are ascribed to symmetrical, length-dependent sensorimotor polyneuropathy attributable to metabolic and microvessel alterations as a result of chronic hyperglycemia exposure . SimilarTaking a more whole-person approach, we speculate that psychological factors involved with pain may play a role in false-positive DRGS trials leading to failed DRGS implantation. It has been well documented that psychological factors such as previous anxiety or depression influence the presence and magnitude of chronic pain . Stress-Areas of future studyAreas of further study include larger prospective studies of patients with permanent DRGS implants as well as comparison and analysis of the comorbidities between patients with positive and negative outcomes. Further, multivariate regression with a larger cohort would more substantially determine the independent impact of each comorbidity on negative outcomes of DRGS. Additionally, a study detailing why patients that respond positively to the DRGS trial suffer from negative outcomes following permanent DRGS may also be appropriate. Other areas of study include pathophysiologies of how comorbidities such as diabetes mellitus, smoking, cancer, and age interact with the DRGS implant. Literature concerning DRGS and its interactions with diabetic patients is already underway but seems limited to mostly animal models and case reports . ChapmanLimitationsLimitations of this study are mostly those that are intrinsic to a retrospective case series. These consist of a small sample size which limits the value of any correlation that was drawn. Due to its retrospective nature, the results of this study depend greatly on the accuracy as well as acceptability of the medical records.In our case series, we found that there was a discrepancy between DRGS trial outcomes and outcomes following permanent implantation. We found that a correlation may exist between worse outcomes and smoking. Older age, the presence of diabetes, and cancer had more modest associations. These comorbidities may have value as tests for predicting negative outcomes of permanent DRGS implantation. Additionally, we hypothesized that this could also be due to the presence of psychological factors which obscure the true result of the DRGS trial. Thus, we suggest that DRGS be prescribed with caution in these patient populations, and use comorbidities to test for the likelihood of negative outcomes.


To observe the effect of warm acupuncture combined with meloxicam and comprehensive nursing on pain improvement and joint function in patients with knee osteoarthritis.  Eighty-one patients with KOA were randomly divided into control group (CG), traditional Chinese medicine group (TCMG), and combined group (JG). The CG was treated with meloxicam. The TCMG received warm acupuncture treatment. The JG was treated with meloxicam combined with warm acupuncture. Three groups were given comprehensive nursing intervention, and the course of treatment was 4 weeks. Knee function was assessed by knee pain, activity, stability, walking ability, and ability to walk up and down stairs. Improvement time of clinical symptoms of patients was assessed from knee pain, swelling, and movement limitation. Pain mediators (prostaglandin E2 (PGE2), substance P (SP), dopamine (DA), 5-hydroxytryptamine (5-HT)) were detected by enzyme-linked immunosorbent assay (ELISA). Oxidative stress indicators (superoxide dismutase (SOD) and malondialdehyde (MDA)) of the enrolled patients were detected by water-soluble tetrazolium-1 (WST-1) and the thiobarbituric acid (TBA) method. The clinical efficacy was assessed by the visual analog scale (VAS) score.  After treatment, the pain scores of the three groups decreased, and the scores of mobility, stability, walking ability, and the ability to walk up and down stairs increased. Compared with the CG and the TCMG, the JG had a greater range of changes in pain, mobility, stability, walking ability, and ability to walk up and down stairs after treatment. After 7 d, 14 d, and 28 d treatment, PGE2, SP, DA, 5-HT, and MDA in the three groups were decreased compared with before treatment, and the decrease in the JG was more obvious than that in the CG and the TCMG. SOD levels in the three groups were increased, and the increase in the JG was more obvious than that in the CG and the TCMG. The total effective rate of the JG (96.30%) was significantly different from that of the CG (77.78%) and the TCMG (81.48%). The improvement time of knee pain, swelling, and movement limitation in the JG was shorter than that in the CG and the TCMG, and the difference in the improvement time of movement limitation in the TCMG was statistically significant.  Warm acupuncture combined with meloxicam and comprehensive nursing can effectively improve knee swelling and pain in patients with KOA, and the mechanism may be related to reducing the content of inflammatory mediators. Knee osteoarthritis (KOA) is a common chronic degenerative bone and joint disease in clinic . Its cliMeloxicam is the main treatment of osteoarthritis that can improve the early symptoms of patients . HoweverP > 0.05)  with 27 cases, Chinese medicine group (TCMG) with 27 cases, and combined group (JG) with 27 cases. All patients met the diagnostic criteria for KOA. There was no significant difference in general clinical data between the three groups ( > 0.05) .  Inclusion criteria are as follows: (1) comply with the relevant standards of knee osteoarthritis in guidelines for the diagnosis and treatment of osteoarthritis ; (2) pat  Exclusion criteria are as follows: (1) allergic; (2) asthma; (3) with mental illness; (4) patients with severe heart failure; (5) digestive ulcer; (6) combined with bone tumor and bone tuberculosis.Patients in 3 groups were treated with symptomatic treatment before medication, such as prohibiting outdoor exercise, ensuring adequate rest, regular diet, good life management, correcting bad habits, and keeping warm.The CG was treated with meloxicam , once a day, with warm water after meals, 0.75 mg once. Patients with strong pain can be increased to 1.5 mg.The TCM group carried out warm acupuncture treatment : choose Patients in 3 groups were given comprehensive nursing during treatment . (1) HeaThe three groups were compared for knee pain, activity, stability, walking ability, ability to walk up and down stairs, and improvement time of knee pain, swelling, limited activity, and other symptoms.The clinical efficacy was evaluated by the VAS score . (1) SigSuperoxide dismutase (SOD) was detected by water-soluble tetrazolium-1 (WST-1), and malondialdehyde (MDA) was detected by the thiobarbituric acid (TBA) method. The kits were purchased from Emjet Technology Co., LTD.In each group, 2 mL venous blood was extracted on an empty stomach in the morning before and after treatment and centrifuged at 4 000 r/min for 10 min. Supernatant was extracted and stored at −80°C for one-time detection after sample collection. The contents of prostaglandin E2 (PGE2), substance P (SP), dopamine (DA), and 5-hydroxytryptamine (5-HT) in serum were detected by enzyme-linked immunosorbent assay (ELISA) in strict accordance with instructions.T test was used to test differences between groups, and count data were measured by the χ2 test. P < 0.05 means the difference is statistically significant.SPSS22.0 statistical analysis software was used to analyze the obtained data. All measurement data were represented by Before treatment, there were no statistically significant differences in pain, mobility, stability, walking ability, and ability to walk up and down stairs among the three groups . After tThere was no significant difference in pain mediators among the three groups on 0 day of treatment . After 7The total effective rate of CG was 77.78% . The totThe improvement time of knee pain, swelling, and activity limitation in the JG was shorter than that in the CG and the TCMG ; the impAfter treatment, there was no significant difference in SOD and MDA levels among the three groups . After 7Knee osteoarthritis (KOA) is a common clinical degenerative disease of bone and joint, which can lead to joint deformity or even disability if not treated in time . MeloxicIn TCM, KOA belongs to the category of “knee paralysis” and “bone paralysis” . The onsThe comprehensive nursing in this study is comprehensive and covers a wide range, including health education, psychological guidance, dietary guidance, and functional exercise guidance. Health education in comprehensive nursing can explain disease-related knowledge to patients and strengthen their disease cognition so that they actively cooperate with treatment and nursing work. Psychological guidance can alleviate patients' negative emotions and make them establish confidence in treatment. Dietary guidance can promote patients to develop good eating habits and avoid improper diet that affects the effect of disease control. Functional exercise guidance can promote patients to carry out scientific rehabilitation training, which is beneficial to recover their knee function as soon as possible.Oxidative stress plays an important role in the occurrence and development of KOA. Under normal circumstances, the generating and eliminate of oxygen-free radicals in the body are in a state of balance, and free radicals produced by oxygen metabolism can be cleared in time, and in patients with KOA, oxygen--free radicals generated will increase, excess oxygen-free radical has inhibitory effect on cartilage cell proliferation, can result in cartilage cell aging, and death and thus accelerating the degradation of cartilage matrix, eventually resulting in damage of cartilage , 21. MDAWarm acupuncture combined with meloxicam and comprehensive nursing has a clear effect on the treatment of KOA, could improve the clinical symptoms of patients, play a good analgesic effect, and promote patients to recover as soon as possible.


Background: Neuropathy is the most prevalent broad-spectrum microvascular complication of diabetes. The present study aims to evaluate the effect of empagliflozin with vitamin D supplementation on diabetic peripheral neuropathy.Methods: A prospective, randomized, controlled study was conducted for six months including 150 type 2 diabetic patients, divided into three groups (n=50/group): Group 1, patients on oral hypoglycemic agents; Group 2, patients on empagliflozin and Group 3, patients on empagliflozin with vitamin D. Biochemical parameters were estimated for outcome measurements and patients’ neuropathic pain was analysed using Douleur Neuropathique 4 Questions, Neuropathic Pain Symptom Inventory and Ipswich Touch the toes test questionnaire. Data were analysed using a one-way analysis of variance.p<0.05). A remarkable decrease (by 17.4%) from baseline in the HbA1C level was observed after six months of treatment only in Group 3, whereas in other groups (1 and 2), there was a non-significant decrease in HbA1C levels when compared to baseline. Moreover, a significant improvement in neuropathic condition was seen only in Group 3.Results: Diabetic neuropathy in males was more prevalent (more than 50%) as compared to females in all three groups, with an average age of 50±6 years, along with a diabetic history of 15±4.5 years and a glycated hemoglobin A1C (HbA1C) level of >10%. The mean value of serum vitamin D level significantly increased by 64.7% (19±5 to 54±8 ng/mL; Conclusion: The results indicated that empagliflozin with vitamin D supplementation significantly controlled or reduced HbA1C and improved diabetic neuropathic symptoms in patients. It is suggested that this combination can be considered as the primary therapeutic approach for neuropathic complications in diabetic patients. Diabetes mellitus (DM) is the largest global epidemic of the 21st century and is associated with various complications classified as microvascular and macrovascular . AccordiPre-clinical studies have demonstrated the association between low levels of neurotrophins (nerve growth factors [NGF]) with vitamin D deficiency . NeurotrThe present study was a cross-sectional, observational, open-label randomized controlled study of six-month duration, which evaluated the therapeutic effect of a new class of anti-diabetic drug, i.e. SGLT2i with vitamin D on diabetic neuropathic pain in type 2 DM patients (diabetic neuropathy as a primary complication). Patients from the Department of Medicine (outpatient and inpatient) in a tertiary care hospital were selected and analysed by three different neuropathic pain assessment scales, i.e. Douleur Neuropathique 4 Questions (DN-4), Neuropathic Pain Symptom Inventory (NPSI), and Ipswich Touch the toes test (ITTT) between September 2020 and August 2021 (including patient recruitment time). The institutional ethics committee (IEC) approval was obtained (MMDU/MMIMSR/IEC/1565) prior to conducting the study. Written informed consent was signed by all the patients for participation in the study.Study designp<0.05 was considered statistically significant. During the study, the drugs were prescribed as per guidelines, and patients were instructed not to change their medicines, diet, and lifestyle without the physician’s advice, throughout the study period.The sample size was calculated based on the data obtained from previous studies using Power and Precision software . A total of 150 patients 41-60 years of age were identified according to inclusion and exclusion criteria and were divided into three groups (n=50/group) by simple randomization as Group 1, patients on oral hypoglycemic agents; Group 2, patients on EMPA 25 mg once daily and Group 3, patients on EMPA 25 mg once daily with vitamin D . The data were normally distributed according to the Kolmogorov-Smirnov normality test. The parametric data were analysed using paired Student's t-test followed by Dunnett's test; 2 were excluded from the study.Inclusion criteria were as follows: patients (aged 40-60 years) having type 2 DM for at least 10 years, taking one or two oral hypoglycemic agents regularly, with glycated hemoglobin A1C (HbA1C) >10%, low vitamin D levels (≤20 ng/mL), never on SGLT2i before inclusion in the study and having a DN-4 score more than 4. Patients with other types of diabetes, current or previous use of vitamin D or multivitamins, pregnant women, patients with chronic kidney disease stage 5, diabetic ketoacidosis, liver cirrhosis, hypothyroidism/hyperthyroidism, osteoporosis, patients already taking neuropathic drugs, anti-epileptics and patients with a body mass index more than 30 kg/mThe DN-4 questionnaire was used as a diagnostic tool to identify and assess polyneuropathy in diabetic patients; this questionnaire consists of two parts, i.e. interview of patients and examination of patients (which further comprises 10 items). Initial seven items were related to the patient’s personal complaints including sensational variations and pain; however, the last three items were linked with the physical examination. For comparison and analysis, the scoring system was based on “Yes” and “No” scored as 1 and 0 for each answer, respectively. The score of the questionnaire was in the range 0-10, where 0 was the minimum and 10 the maximum score. If a patient had a DN-4 score of less than 4, then the pain was unlikely to be neuropathic pain, but if the score was more than 4, then the pain was likely to be neuropathic pain .To assess and characterize the nature of neuropathic pain, a self-rated questionnaire, NPSI, was taken into consideration that included 12 items grouped into five domains including superficial burning pain (Q1), deep pressing pain (Q2-Q3), paroxysmal pain (Q5-Q6), evoked pain (Q8-Q10) and paresthesia/dysesthesia (Q11-Q12). These items were rated on an 11-point numeric rating scale from 0 to 10 where 0 corresponds to “no symptom” and 10 signifies “worst symptom imaginable.” Moreover, this questionnaire consisted of two temporal items (Q4 and Q7) to assess the number of pain paroxysms and pain duration  where Q4 was assessed as 1 = “permanently,” 2 = “between 8 and 12 hours,” 3 = “between 4 and 7 hours,” 4 = “between 1 and 3 hours,” 5 = “less than 1 hour”, referred in the past 24 hours, and Q7 was assessed as 1 = “more than 20 hours,” 2 = “between 11 and 20 hours,” 3 = “between 6 and 10 hours,” 4 = “between 1 and 5 hours,” 5 = “no pain attack” [To assess the sensitivity in the feet, a quick and easy ITTT was used based on a non-throbbing feather-like soft touch for one to two seconds to each adjacent foot toe, i.e. the sensitivity was checked for adjacent six toes of both the feet of the patient. If the touch was not felt, it was recorded as “N” and if the touch was felt, it was recorded as “Y”. If a patient felt touch in all six or five out of the adjacent six toes (both feet), then his/her sensation was considered normal and if the patient did not feel when touched at two or more out of the adjacent six toes, then he/she was considered likely to have reduced sensation and might be at risk of a diabetic foot ulcer .Along with above-mentioned non-invasive tests, all other routine biochemical tests like liver function test (LFT), renal function test (RFT), HbA1C and serum vitamin D level tests were performed on all enrolled patients on the day of enrollment (day 1) and at the end of the study (after six months). All information related to patient demographics, medical history and response to the above questionnaires was recorded in the case report form.2. All the patients had type 2 DM for more than 10 years. The patients were recruited from inpatient (14±2%) and outpatient (86±4%) wards for all three groups. There was no statistical difference found in demographic data of type 2 DM patients in all three groups ; the majority of patients affected from diabetes were males (more than 50%) as compared to females in all three groups. The mean age of patients was 50±6.2 years and the body mass index (BMI) range of patients was 26-30 (27.7±2.1) kg/mDrug-prescribing patterns in recruited patients were studied and analysed on the basis of symptoms and existing co-morbid conditions. The major categories of drugs prescribed were oral hypoglycemic agents  along with anti-hypertensive, anti-platelets, statins, and antibiotics.p<0.05) after giving vitamin D supplementation for six months. The serum vitamin D level significantly (p<0.05) increased by 64.7% (18.91±5.3 to 53.71±7.8 ng/mL) in Group 3 after giving vitamin D supplementation for six months. Moreover, HbA1C levels remarkably decreased from 13.09±2.0% to 10.80±2.8% only in Group 3 after six months of supplementation with respect to baseline parameters. Table All the parameters under investigation such as bilirubin direct, bilirubin total, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), urea, creatinine, uric acid, sodium, and potassium levels were found in the normal range among all three groups. The mean baseline serum vitamin D levels in all the three groups of type 2 DM patients at the time of inclusion were 17.78±5.3, 18±4.1, and 18.91±5.3 ng/mL, respectively. But the levels of vitamin D were significantly increased to 53.71±7.8 ng/mL in Group 3 (Patients were included on the basis of the DN-4 score (those with a score of more than 4 were considered to have the pain of neuropathic origin). Patients were asked to define their pain in seven domains: burning, painful cold, electric shock, tingling, feeling of pins and needles, numbness, and itching. Results of our study showed that initially, the percentage of patients experiencing the seven domains as per the DN-4 questionnaire was higher in all three groups: burning, >52.7%; painful cold, >37.5%; electric shock, >72.1%; tingling, >83.2%; feeling of pins and needles, >63.69%; numbness, >62.3%; and itching, >43.1%. After receiving treatment as per study methodology, there was a maximum change in the percentage of patients only in Group 3: burning, 47.97%; painful cold, 44.37%; electric shock, 51.80%; tingling, 51.39%; feeling of pins and needles, 51.14%; numbness, 52.45%; and itching, 41.08%  decrease in all the parameters of neuropathic pain and patients showed significant improvement in the percentage score: burning sensation (47.33%), squeezing sensation (41.44%), pressure (36.95%), spontaneous pain in past 24 hours (52.17%), electric shock (53.33%), stabbing sensation (43.61%), number of panic attacks (45.29%), pain increased by brushing (42.19%), pain increased by pressure (53.47%), pain increased by cold (35.88%), feeling of pins and needles (41.22%) and tingling (40.86%). Figure The assessment of the nature of neuropathic pain was done by the NPSI questionnaire. Results of the NPSI score showed that at the time of recruitment in the study, the domain score range in all the three groups varied: burning sensation (5.7% to 6%), squeezing sensation (4.3% to 4.5%), pressure (4.4% to 4.7%), spontaneous pain in the past 24 hours (2.2% to 2.4%), electric shock (4.5% to 4.8%), stabbing sensation (4.5% to 4.7%), number of panic attacks (3.3% to 3.4%), pain increased by brushing (3.8% to 4.1%), pain increased by pressure (4.2% to 4.6%), pain increased by cold (3.1% to 3.4%), feeling of pins and needles (5.4% to 5.7%) and tingling (5.5% to 5.9%). However, after giving treatment for six months, the percentage score decreased in Groups 1 and 2, but was non-significant. On the other hand, in Group 3, there was a significant  was high as compared to patients with 5th, 4th, 3rd, 2nd and 1st degree impairment in all the three groups. Moreover, there was no patient with normal feet sensations in all three groups. The results after treatment with EMPA along with vitamin D  showed a remarkable reduction in all the degrees of impairment and patients experienced an improvement in sensitivity along with prevention of foot ulcers on follow-up. All the patients (100%) recovered from 1st degree impairment and had normal feet sensation after receiving EMPA with vitamin D. Furthermore, the percentage of patients with 6th, 5th, 4th, 3rd and 2nd degree showed an impairment improvement by 69.23%, 62.50%, 55.55%, 46% and 44.44%, respectively. Figure 2 for the overweight category were at an increased risk of developing diabetes-related complications [An epidemic of diabetes in Asians is expected to rise over the next several years with India projected to have the largest diabetic population by 2030 . The malications . Our BMIications .p<0.05) improvement in neuropathic pain symptoms such as burning, painful cold, electric shock, tingling, feeling of pins and needles, numbness with itching, and also improvement in the degree of neuropathic impairment of feet.A major problem in the treatment of DM is neuropathic pain. For ages, biguanides such as metformin have been the first choice of drug for DM either as monotherapy or as a combination of biguanides with sulphonylureas and other neurotonic medicines for the treatment of neuropathic complications, although sensory profiles are heterogeneous in neuropathic pain disorders, and subgroups of patients respond differently to treatments . A new cIn contrast, previous studies have shown that when diabetics are treated with metformin for a prolonged duration at higher doses, it decreases serum cobalamin, and increases levels of methylmalonic acid and homocysteine, thus becoming the leading cause of severe peripheral diabetic neuropathy . This poIn summary, we determined whether EMPA in combination with vitamin D exerted a therapeutic effect beyond glycemic control on neuropathic complications in DM. The combination ameliorated neuropathy as well as systemic oxidative stress while exerting minimal to absent side effects. To our knowledge, our study is one of the first to present data that supports the use of EMPA in combination with vitamin D in the reduction of diabetic neuropathy while improving patients' quality of life. In the future, it can potentially be used as a first-line treatment in diabetic neuropathic patients. This study also supports the view that the concept of combination therapies can pave the path towards more individualized, patient-specific treatments.


Root canal therapy linked to pulpal diseases or trauma is common in modern dental care. The 2% Lidocaine which is considered as the gold standard has some drawbacks in pulpal anaesthesia. Ropivacaine has beneficial anaesthetic effects on pulpal anaesthesia.Therefore, it is of interest to compare and evaluate the pulpal aesthetic effect using 0.5% Ropivacaine and 2% Lidocaine in symptomatic irreversible pulpitis. A double blinded randomized controlled clinical trial consisting of 110 lower molar and premolar toothwith irreversible pulpitis cases for root canal therapy were selected and randomly divided into 2 groups. Group A: 2% lidocaine with epinephrine and Group B: 0.5% ropivacaine. The pulp sensibility tests with heat test, cold test and electric pulp test were completed.The preoperative pain score was measured with Visual Analogue Scale (VAS) pain scale. The classical inferior alveolar nerve block (IANB) technique was administered to all patients by a single operator. Subjects were asked for lip numbness and presence or absenceof lip numbness. Postoperative pain scores were recorded during access opening and on placing files in the canal. There is no statistical difference between the groups during pre operative conditions. The mean pain scores within group A and group B is recorded.The difference was found to be statistically significant with p value ≤ 0.05. Significant difference between the mean values after and before the treatment is observed. However, there is no statistical significance between the mean pain scores between the accessand pulp. The 0.5% Ropivacaine and 2% Lidocaine with epinephrine does not have any significant difference during access opening. However, 0.5% Ropivacaine groups were effective while placing the file in the canal. Thus, 0.5% Ropivacaine showed better results eventhough it was not statistically significant for further consideration in this context. Pulpal inflammation may or may not be associated with toothache, which will be recognized as acute and chronic pulpitis based on the duration of the condition. The localized increase in tissue fluid pressure associated with acute inflammation usually resultsin toothache. Clinically, it can be divided into reversible and irreversible pulpitis. The treatment for reversible pulpitis will be with pulp protecting agents and for irreversible pulpitis is preferably root canal treatment. Local anesthesia is an effectivemethod of pain control since 1884, which is used to initiate root canal procedure. Lidocaine is a short acting (vasodilator), where 2% Lidocaine is commonly used in dentistry. To increase the depth and duration of anesthesia, epinephrine was added to Lidocaine.Nonetheless, in 1964 epinephrine containing local anesthetic solution was contraindicated in hyperthyroidism and significant cardiovascular diseases . As well, adding vasoconstrictor reduces the pHof the solution (acidic), rendering the injections uncomfortable to the patients. Hence, search for a long‑acting local anesthetic agent continues for effective pain control for treatment of irreversible pulpitis . StudiesA prospective, single centre, Double Blinded Randomized Controlled Clinical Trial is designed.Approval for the project was obtained from the Institutional Review Board and Ethical Board of Saveetha Institute of Medical and Technical Sciences, Chennai, India [SRB Reference No.SRB/SDMDS10/19/ENDO/01].Based on study done by E.Shadmehr et al, 2016, efficacy of Lidocaine with epinephrine or clonidine for inferior alveolar nerve block technique in patients with irreversible pulpitis and T.F.Krzeminski et al. 2011, efficacy of Ropivacaine and Articaine withepinephrine for infiltration anesthesia, sample size estimation was calculated using a nMaster software version 2.0 by applying the details in the sample size determination formula, where H0: P1 = P2 and H1: P1 ≠ P2. p1= proportion in the first group,p2=proportion in the second group, α= significance level and 1-b = power.The samples were included in the study according to the following inclusion criteria: Subjects with the age group above 18 years, teeth with irreversible pulpitis, only lower posterior teeth (molars and premolars) and Pre operative pain score more than orequal to VAS score 4. And the subjects were excluded from the study if they have any of the following: Teeth with periapical lesions, periodontally compromised teeth, teeth with non- carious lesions and subjects suffering from any systemic conditions.The volunteer patients fitting the inclusion criteria described above were included in the study. The study participants for the study were recruited from the pool of patients in the Department of Conservative Dentistry and Endodontics at our Institution.The patients were informed about the procedure and informed consent was taken from all patients included in the study.Sequence Generation:Randomization was done well in advance by a third person that was not related to the study. Randomization was done using block randomization procedure, assigned to Group A- 2% Lidocaine with epinephrine (n=55) to Group B- 0.5% Ropivacaine (n=55).SNOSE  method was implemented for allocation concealment, which concealed the sequence until interventions were assigned. A piece of paper containing randomized group number was sealed in the dark coloredenvelope containing respective serial number over it prepared by a third person. The group is mentioned clearly and sealed in the envelope. Patients were assigned their study numbers as they sequentially entered the study. The envelope was opened once theintervention was assigned. Based on the group assigned in the paper, respective treatment was carried out.Patients and the clinician were unaware of the type of treatment group and they were blinded. But the evaluator knew about the type of group. Hence, it is a double-blinded study. Patients were divided into two groups as Group A - 2% Lidocaine with epinephrineand Group B - 0.5% Ropivacaine.Prior to the treatment, a careful medical and dental history was taken. Preoperative data for each patient was recorded in the predesigned patient's chart, which includes age, sex and tooth number. The treatment and the study design were explained to thequalifying patients and informed consent was obtained from the voluntary patients who were willing to participate in the study. The confirmatory tests were done to the selected tooth by keeping the contra lateral tooth as control. Heat test, cold test andelectric pulp testing (EPT) were done to confirm the diagnosis of symptomatic irreversible pulpitis. All selected teeth were randomly divided into two groups with 55 each (N=110) depending on the type of local anesthetic agent used. Randomization of the localanesthesia used was done by an envelope draw method for all the selected teeth, present either in different patients or in the same patient. Pre operative pain score was recorded for the selected tooth using visual analogue scale (VAS). Depending on the typeof local anesthesia, the teeth were treated as follows:2% Lidocaine with epinephrine  loaded in a 26 gauge needle unlock syringe were administered by an inferior alveolar nerve block (IANB) on the quadrant of the selected tooth.0.5% Ropivacaine  loaded in a 26 gauge needle unlock syringe were administered by inferior alveolar nerve block (IANB) on the quadrant of selected tooth.After administering the local anaesthesia, the presence or absence of lip numbness were noted and heat test, cold test and EPT test were done. After that the tooth was isolated with a rubber dam. Access opening of the tooth was done using endo access bur andEndo Z bur (Dentsply Sirona). The pain score during access opening was recorded using Visual analogue pain scale (VAS). After gaining access to the pulp chamber, the hand files such as K file of # 10 and 15 were placed in the canals in order to take workinglength and to clean and shape the canals. The pain score during placing the files were also noted using Visual analogue pain scale (VAS).Statistical analysis was performed using a statistical software program Windows, Version 21 (SPSS). The Normality tests Kolmogorov-Smirnov and Shapiro-Wilks tests results reveal that all variables follow Normal distribution. Therefore, a parametric testis applied to analyze the data. Data was entered in Microsoft excel spreadsheet and analyzed using SPSS software (version 21). For the test, a p value of < 0.05 is to be considered statistically significant. Chi Square test were used to assess the descriptivestatistics, Independent t test were used to assess the mean difference between the treatment groups. One-way ANOVA were used to assess the significant differences in the pain scores within the treatment groups. Tukeys post hoc test were used to assess themultiple group comparison within the groups.A total of 110 teeth of patients were included in this clinical trial. Data analysis was done with the 110 teeth. Table 1 (see PDF) depicts the lip numbness present or absent after administering the anesthesia in both the groups. Table 2 (see PDF) depicts thepre-operative pain between the groups. The difference was not found to be significant statistically . Table 3 (see PDF) depicts the mean post-operative pain (access) between the groups. The difference was not found to be significant statistically. Table 4 (see PDF) depicts the mean post-operative pain (pulp) between the groups. The difference was not found to be significant statistically . Table 5 (see PDF) depicts the mean pain scores within group A and group B. Thedifference was found to be significant statistically . Table 6(see PDF) depicts multiple comparisons of mean pain scores preoperatively and postoperatively. There is a statistically significant difference between the mean values pre operativepain and postoperative pain after administering local anesthesia during access and when placing file (pulp). However, there is a no statistically significant difference between the mean values postoperative pain after administering local anesthesia during accessand when placing file (pulp). Table 7 (see PDF) depicts multiple comparisons of mean pain scores preoperatively and postoperatively. There is a statistically significant difference between the mean values pre operative pain and postoperative pain after administeringlocal anesthesia during access and when placing file (pulp) . However, there is a no statistically significant difference between the mean values postoperative pain after administering local anesthesia during access and when placing file (pulp).This prospective double blinded randomized clinical trial compared the pulpal anesthetic effect using 2% Lidocaine with epinephrine and 0.5% Ropivacaine by inferior alveolar nerve block technique in patients with symptomatic irreversible pulpitis. The onsetof anesthesia is an important issue for anesthesia success evaluation. The onset of anesthesia in inferior alveolar nerve block and infiltration injection are different and the later technique provides quicker anesthesia .The pulWe show that the 2% Lidocaine with epinephrine group had 90.9 % of lip numbness and 0.5% Ropivacaine had 94.5% of lip numbness after anesthesia. The 0.5% Ropivacaine and 2% Lidocaine with epinephrine does not have any significant difference during accessopening. However, 0.5% Ropivacaine was effective during access opening. The 0.5% Ropivacaine and 2% Lidocaine with epinephrine does not have any significant difference while placing file in the canal. However, 0.5% Ropivacaine groups were effective while placingfiles in the canal. The 0.5% Ropivacaine showed better results even though it is not statistically significant. Hence, it can also be used as a local anesthesia in cases with symptomatic irreversible pulpitis.


Patients with persistent complex limb pain represent a substantial diagnostic challenge. Physical exam, and tests such as nerve conduction, are often normal even though the patient suffers from severe pain. In 2015, we initiated a team-based approach to evaluate such patients. The approach included physicians from several specialties  combined with the use of advanced imaging with Magnetic Resonance Neurography (MRN). This preliminary case series discusses MRN findings identified in patients with previously difficult-to-diagnose peripheral limb pain and describes how this combination of approaches influenced our diagnosis and treatment plans. We extracted demographics, patient characteristics, presenting features, diagnostic tests performed, treatments provided, referral diagnosis and the diagnosis after interdisciplinary team evaluation from patient charts. We evaluated MRN and electrodiagnostic studies (EDX) ability to identify injured nerves. We compared abnormal findings from these diagnostics to patient reported outcome after ultrasound-guided nerve block. A total of 58 patients, 17 males and 41 females, were identified. The majority of patients presented with lower extremity pain (75%) and had prior surgery (43%). The most commonly identified abnormality on MRN was nerve signal alteration on fluid sensitive sequences, followed by caliber change and impingement. Comparing the outcome of diagnostic nerve blocks with abnormal nerve findings on MRN or EDX, we found that MRN had a sensitivity of 67% and specificity of 100% while for EDX it was 45 and 0%, respectively. After interdisciplinary discussion and imaging review, a more specific diagnosis was produced in 78% of evaluated cases opening up additional treatment pathways such as nerve-targeted surgery, which was performed in 36% cases. This descriptive case series demonstrates that a majority of patients evaluated by our team for complex limb pain were women with lower extremity pain resulting from surgery. In addition, an interdisciplinary team evaluation and the use of the moderately sensitive but highly specific MRN imaging modality resulted in a change in diagnosis for a majority of patients with complex limb pain. Future studies investigating patient outcomes after diagnosis change are currently underway based on the findings of this preliminary study. One third of adults in the United States currently suffer from chronic pain at a huge cost to society . PersistChallenges in diagnosis and treatment are not unique to the field of pain management. Other fields utilize interdisciplinary teams and advanced diagnostics to focus the diagnosis and guide the treatment plan in the care of complex patients . For exaA key tool utilized by this interdisciplinary pain team was advanced magnetic resonance imaging (MRI) of the peripheral nerves. Magnetic resonance neurography (MRN) –11, a suIn this preliminary case series, we report on 58 patients who were treated by our interdisciplinary pain team during a 3-year period. Our aim was to share our experience with this novel team approach, discuss MRN findings identified in patients with previously difficult-to-diagnose peripheral limb pain and describe how this combination of approaches influenced our diagnosis and treatment plans.We conducted a single-center retrospective case series to understand the impact of an interdisciplinary team approach on the diagnosis and treatment of patients with refractory limb pain. All data were collected in accordance with the ethical standards of the Institutional Review Board at Stanford University School of Medicine. Extraction of data from patient charts was approved as a chart review protocol; consequently, no patient consent was required for inclusion in the study.All patients included in the study had upper or lower extremity limb pain and were referred to Stanford Hospital & Clinics Pain Management Clinic for evaluation between January 1, 2015 and November 1, 2018. Patients were included if they received evaluation by MRN and were discussed at our bimonthly, interdisciplinary care team meeting (see below).The interdisciplinary team was established in 2015 to discuss complex cases where a diagnosis was not clear using standard approaches . The team consisted of anesthesiologists subspecialized in Pain Medicine , peripheral nerve surgeons collaborating from plastic surgery and neurosurgery , musculoskeletal radiologists  and an MRI physicist (DY). We also benefited from the expertise of physical therapists and pain psychologists from the Stanford Pain Medicine Clinic who attended meetings when able, but also independently evaluated a majority of our patients (see section Results). During the team meeting, the pain medicine specialist or surgeon would describe the history focusing on the relevant pain description, current and past medications, and pertinent physical exam such as distribution of sensory and motor changes. Results from other diagnostics such as electromyography/nerve conduction studies , ultrasound-guided blocks, and any other treatments were reviewed. Next, the radiologist would review and describe the results of MRN. This was followed by a discussion of the patient's case to generate a consensus diagnosis and multimodal treatment plan. Following the meeting, any subsequent diagnostic tests were ordered and the agreed upon treatment plan was communicated to the patient.Multiple MR sequences of different imaging planes and contrast were employed for evaluating peripheral nerves. Patients were scanned in the Discovery MR 750 3T MRI scanners . The adopted MR pulse sequences and their sequence parameters are briefly summarized in Medical records were reviewed retrospectively. Information collected included: demographics , age at symptom onset, duration of symptoms, limb affected, reported initiating event, referral diagnosis , diagnosis after team evaluation, diagnostics performed , and treatments initiated .Demographic data are presented as mean ± SD or percentages, as indicated in the results and tables. Nerve abnormalities identified by MRN review were classified into the following types: signal alteration, caliber change, impingement/focal deviation/fat obliteration, mass or mass-like lesion, and direct trauma/disruption.Nerve abnormalities between MRN and EDX were compared. Out of the 26 patients who had EDX and MRN, there were 3 different scenarios we observed: (1) Patients came with EDX already performed and we added MRN for additional diagnostic information (6/26 patients), (2) We ordered MRN and EDX simultaneously (15/26 patients), (3) We felt we needed more diagnostic information after discussion of MRN findings and therefore ordered EDX (5/26 patients). The sensitivity and specificity of MRN and EDX in detecting nerve involvement in the pain syndrome was determined using the outcome of a diagnostic nerve block as the gold standard. This is based on the fact that local anesthetic blockade inhibits all conduction of a given peripheral nerve from reaching the central nervous system and results in regional anesthesia limited to the dermatome innervated by that nerve. Consequently, an improvement in pain with nerve block would suggest at least some contribution of that nerve to the patients' pain condition. For calculation of sensitivity and specificity, if a patient reported decreased pain after local anesthesia block of a detected abnormal nerve this was classified as a true positive. If a patient reported no change in pain after local block of a nerve without detected abnormalities this was classified as a true negative.Furthermore, the sensitivity of MRI was compared to that of EDX using the one-sided McNemar's test with significance of 5% and the odds ratio. To evaluate the impact of our team approach on diagnosis, the referral diagnosis was compared with the diagnosis after our interdisciplinary team meeting including discussion of MRN results.A total of 17 male and 41 female patients met our inclusion criteria. The interdisciplinary pain team evaluated these patients between January 1, 2015 and November 1, 2018 . PatientAfter initial evaluation, all patients 100%,  underwenMRN scans revealed nerve abnormalities in 71% of patients including signal alteration (60%), caliber change (26%), impingement (22%), mass or mass-like lesion (7%), and direct trauma/disruption (2%) in nerves that were consistent with the patients presenting regional symptoms . ImportaSince 43% of patients identified surgery as the initiating event for their pain condition, implying that surgery itself could trigger complex limb pain, we were particularly interested in understanding the MRN findings of the subgroup of patients who underwent Nerve Team recommended surgery as a treatment for their pain (see below). Of the patients who underwent surgery , MRN finp-value from one-sided McNemar's test was 0.07 and the odds ratio was 3.0.Twenty-six patients underwent EDX in addition to MRN, however, there was agreement on the exact abnormal nerve(s) between MRN and EDX in only 6 patients . In 18 oOverall, the referral diagnoses before interdisciplinary team evaluation tended to be less specific such as: complex regional pain syndrome not otherwise specified (NOS), neuropathy without specified nerve involved, and regional diagnoses such as “limb pain” or “joint pain.” Ultimately, we changed the diagnosis in 45 out of 58 patients, 78% of cases . In the Multimodal treatment plans were instituted in all patients . MedicatOur results suggest that an interdisciplinary team evaluation combined with the moderately sensitive, but highly specific, MRN imaging modality can change diagnosis for a majority of complex patients with limb pain. Future studies focused on outcomes after diagnosis change would further strengthen our findings and are currently underway at our institution.p = 0.07). Moreover, the odds ratio of 3.0 supports the potential for MRN to improve sensitivity in diagnosis, however, the magnitude of this effect requires further study.In our results, MRN identified more abnormal nerves than EDX, which led to higher sensitivity to detect nerve damage that correlated with pain. The higher sensitivity of MRN may stem from the improved spatial localization of small nerves. EDX measurements are acquired through local volume conduction of electric signal between manually placed electrode and target nerves . This prIt has been previously described that MRN in isolation is subject to both false positives and false negatives . One appOur retrospective analysis demonstrated that team management combined with MRN refined diagnosis in 78% of cases. We are not the first to report that MRN can solidify diagnosis in complex cases of neuropathic limb pain. Chhabra et al. , demonstOne unique aspect of limb pain is the diagnosis of CRPS . CRPS isThere are several limitations to the current study. We have shown that our approach frequently results in a change in diagnosis, however, whether this improves outcomes remains an open question for further study. Given the retrospective nature of this work and the diversity of patients we cared for over a 3-year time period, finding consistent, reportable outcomes that could then be correlated back to the change in diagnosis was not possible. Additionally, such correlations would be subject to many confounding variables that we did not feel it would be useful. Instead, based on the current findings, we are designing a prospective study to evaluate whether interdisciplinary team management with MRN changes patient-reported outcome measures which will be an important next step to clarify the benefit of our approach to patients , 26. AddCombining novel imaging techniques with interdisciplinary team meetings is an important approach to help care for patients with refractory, difficult-to-diagnose pain syndromes. Such an approach may help uncover the underlying etiology of complex pain cases and contribute to new and more directed management plans. We hypothesize that such targeted and mechanism-specific treatments will ultimately result in better outcomes which we are now positioned to evaluate.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Institutional Review Board at Stanford University School of Medicine. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.EJ, DY, and VT performed chart review and wrote the manuscript. EJ, DY, AL, and VT performed analyses. SB and AL read all the imaging studies. All authors contributed to patient care, case review, manuscript editing, and approved the final submission.DY, SB, and AL have received research support from GE Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To evaluate variables affecting the need for analgesia after ultrasound-guided percutaneous liver biopsy performed on an outpatient basis.This was a retrospective analysis of 1,042 liver biopsies performed between 2012 and 2018. The data collected included the age and sex of the patient, as well as self-reported pain in the recovery room, the pain treatment used, the indication for the biopsy, and the lobe punctured. As per the protocol of our institution, physicians would re-evaluate patients with mild pain , prescribe analgesics for those with moderate pain , and prescribe opioids for those with severe pain .p < 0.05). The need for analgesia did not differ in relation to patient age, the lobe punctured, or the indication for biopsy (nodular or diffuse disease). The analgesic most commonly used was dipyrone (in 75.9%), followed by paracetamol alone (16.4%) and their combination with opioids (7.6%).The main indications for biopsy were related to diffuse disease (in 89.9%), including the follow-up of hepatitis C (in 47.0%) and suspicion of nonalcoholic steatohepatitis (in 38.0%). Pain requiring analgesia occurred in 8.0% of procedures. Of the 485 female patients, 51 (10.5%) needed analgesia, compared with 33 (5.9%) of the 557 male patients (Ultrasound-guided percutaneous liver biopsy is safe and well tolerated. Postprocedural pain does not correlate with the lobe punctured, patient age, or the indication for biopsy and appears to affect more women than men. Despite the development of new techniques for cirrhosis staging, such as elastography, liver biopsy continues to be the classical gold-standard technique,5-7. For focal lesions or masses, a tissue core obtained through biopsy for histological analysis provides optimal conditions for further tissue processing, such as a more refined immunohistochemical analysis,9. The current methods for obtaining liver tissue samples are percutaneous, transjugular, endoscopic and laparoscopic biopsy,10-12. Among the percutaneous methods, the most widely used are sheathed (Tru-Cut) needle biopsy, suction (Menghini) needle biopsy, and, less commonly, fine-needle aspiration biopsy,13,14.Liver biopsy plays an important role in the evaluation of liver disease. Direct tissue examination is key for the confirmation and grading of chronic hepatitis, allowing fibrosis to be staged, as well as allowing associated diseases and alternative diagnoses to be excluded,14. Although a variety of imaging guidance methods can be used, the most popular methods are ultrasound and computed tomography (CT), the former, as depicted in ,15. Ultrasound is the preferred technique because of its wide availability, ease of use, and flexibility of scanning planes, as well as because it does not expose patients to ionizing radiation. In most patients, the liver is easily accessible through ultrasound. It is also a real-time technique, allowing the needle path to be visualized at all times during the procedure,16,17.The use of imaging guidance has improved the accuracy of percutaneous procedures and decreased complication rates. An additional variation is the use of a guidance device attached to the transducer, to secure the needle and guide it in a predetermined direction. However, those devices are costly, and, once the needle has been secured to the device, the angles and approaches are static, no repositioning being possible-21. In most cases, punctures are performed with a free-hand technique, allowing virtually infinite planes and approach angles, as well as allowing changes in those during the procedure.During ultrasound-guided puncture, the needle is usually inserted by using an in-plane approach, in order to visualize the entirety of the needle, including its tip. The in-plane approach is preferable to an out-of-plane approach, in which the needle is observed in cross-section, the disadvantage being that the needle is crossed only once by the ultrasound beam, which can lead to misinterpretations of the needle tip position,15,22,23. For diffuse liver diseases and multilobar nodular diseases, such as metastases, the laterality of the specimen collection is at the discretion of the operator. Right lobe biopsy, through an intercostal approach, is preferred by most of the operators. On the other hand, most radiologists prefer a left lobe subxiphoid route. It has been hypothesized that a right liver path would result in more postprocedural pain because it passes through diaphragmatic and intercostal muscle fibers.Complications after ultrasound-guided percutaneous liver biopsy are rare, the most common being pain , followed by, at a much lower incidence, hematoma, pneumothorax, and hemobilia. In real-life settings, most liver biopsies continue to be performed under local anesthesia,15,23.Although postprocedural patient comfort is a key objective when percutaneous liver biopsy is performed on an outpatient basis, the approach to using prophylactic pain medication in biopsies in general is controversial. In most cases, premedication is withheld, despite evidence that preprocedural sedation and analgesia has beneficial effects on patient anxiety and post-biopsy pain. The VAS pain score is derived from subjective self-report measurement of symptoms, translated from a handwritten mark placed at one point along a 10-cm line. The line represents a continuum from the absence of pain, on the left (at 0 cm), to the “worst possible pain” on the right (at 10 cm). The marks are translated in centimeters for record and can be tracked for pain evolution or comparison between patients.To standardize the evaluation of pain provoked by interventional procedures, a visual analog scale (VAS) is commonly used in order to provide a subjective assessment of pain by the patientGiven the low incidence of adverse effects, a large number of patients are needed in order to achieve adequate statistical power. The objective of this study was to evaluate differences in the need for analgesia after ultrasound-guided percutaneous liver biopsy performed on an outpatient basis in unsedated patients, analyzing variations regarding age, sex, laterality of the specimen collection, and indication for the biopsy (nodular vs. diffuse disease).This was a retrospective cross-sectional study involving the analysis of data related to outpatient liver biopsies performed at our institution between 2012 and 2018. Data were retrieved from the procedure database of the institution, which includes data on clinical indication, puncture laterality (right vs. left lobe), number of liver punctures, needle size and throw, picture archiving and communication system image registration of biopsy tract, and clinical data relevant to the postprocedural observation period. The inclusion criteria were being ≥ 18 years of age; having been referred to our tertiary care center for outpatient liver biopsy because of nodular or diffuse disease; having received no sedation or intravenous anesthesia during the procedure; having been submitted to a single liver puncture with an 18G Tru-Cut needle with a 2.0-cm throw; and a single fragment having been retracted during the biopsy. The procedures were performed by four different radiologists with at least three years of experience in interventional procedures and were analyzed by one dedicated pathologist with 11 years of experience in 2012. Repeat procedures performed in the same patient on different dates were considered new events. The study was approved by the local research ethics committee (Reference no. 2.308.943). Because of the retrospective nature of the study, the requirement for written informed consent was waived.3, and an activated partial thromboplastin time < 1.5 times greater than normal, in the last four weeks. Patients were instructed to fast for 6 h before the procedure, which was scheduled in the next available half-hour time slot, from 7:00 a.m. to 3:00 p.m. Before each procedure, the performing physician informed the patient of the risks, benefits, and success rates associated with the procedures. Baseline vital signs  were assessed by the staff nurse.The biopsy prescription written by the treating physician, consisting of a brief medical history and a statement regarding the indication, was analyzed by one of the staff radiologists. Administrative personnel contacted the patient by telephone to check for recent coagulation studies and complete blood count, as well as to provide the patient with instructions regarding preparation. Strict coagulation parameters were followed, which means that we scheduled only patients who were not under anticoagulant therapy or that were able to withhold anticoagulation, with an international normalized ratio ≤ 1.5, a platelet count > 50,000 cells/mmAll procedures were performed under real-time guidance with the same ultrasound system  with 1.9-6.0 MHz convex array transducers , under local anesthesia from the skin to the liver capsule with 10 mL of 1% lidocaine, and involved the use of 18G core biopsy needles with a 2.0-cm throw-either automatic  or semi-automatic . For patients with diffuse diseases such as steatosis and cirrhosis, the liver lobe to be targeted was determined by the physician. For patients with multifocal lesions, the most accessible lesion with adequate parenchymal layering was targeted. For patients with solitary lesions, the laterality was naturally determined by that of the lesion side. In right lobe punctures, the standard approach was intercostal, whereas a subxiphoid approach was used for left lobe procedures. We selected only those procedures in which the liver capsule was punctured only once and no coaxial system was used.For the first 3 h in the recovery room, patients who had undergone a left lobe puncture were required to remain in the supine position, whereas those who had undergone a right lobe puncture were required to remain in the right lateral decubitus. For the next hour, all of the patients were sitting. Routine evaluations in the recovery room were performed by a nurse immediately after the procedure, as well as at 15 min, 30 min, 45 min, 1 h, 2 h, 3 h, and 4 h after the procedure, unless a complication was detected. In each evaluation, patients were questioned about pain (yes or no). If they answered yes, a radiologist was called for a more detailed evaluation, in which pain was graded with a visual analog scale. Physicians would reassure and re-evaluate patients with mild pain (1-3 on the VAS), prescribe analgesics for those with moderate pain (4-6 on the VAS), and prescribe opioids for those with severe pain (7-10 on the VAS). The analgesics used were either dipyrone (1 g) or acetaminophen (750 mg). When opioids were required in order to manage the pain, morphine was prescribed, at a dose of 4 mg (for patients < 70 years of age) or 2 mg (for patients ≥ 70 years of age). At the end of the 4-h observation period, patients with no complications were discharged and those with pain or any complication were held for further observation. If a patient reported persistent or increasing pain after analgesia, if the physical examination revealed signs of intra-abdominal bleeding , or if there were changes in the vital signs suggestive of acute bleeding , CT angiography would be promptly performed and analyzed by the radiologist, who would prescribe the appropriate treatment.p < 0.05 were considered statistically significant. All statistical analyses were performed using the Predictive Analytics Software package, v. 18.0 .Data are presented as mean ± standard deviation or as absolute and relative frequencies. We used the chi-square test to quantify associations between variables. Values of p < 0.05).Between 2012 and 2018, a total of 1,589 liver biopsies were performed at our institution . Of thosp < 0.05). The need for analgesia did not differ by patient age or in relation to the indication for biopsy (nodular vs. diffuse disease). The analgesic most commonly used was dipyrone (in 75.9%), followed by paracetamol alone (in 16.4%) and either in combination with an opioid (in 7.6%).During recovery room follow-up, 8% of the patients reported pain strong enough to require supplementary analgesia (> 3 on the VAS). Analgesia was required by 7.7% of the patients who had undergone a right lobe puncture and by 8.9% of those who had undergone a left lobe puncture, no statistical difference being found between the two groups. Of the 485 female patients, 51 (10.5%) reported pain requiring analgesia, compared with 33 (5.9%) of the 557 male patients , CT, magnetic resonance imaging, and ultrasound,12,27-31.Despite the recent development of noninvasive methods for liver evaluation, liver biopsy continues to be the classical gold standard and an essential tool in the investigation and histological follow-up of liver diseases. A series of different material sampling techniques can be used, including fine needle aspiration, the Menghini technique, and core biopsy, the last being the preferred method. Using needles of at least 18G precludes the need for more experienced pathologists. Augmenting diagnostic accuracy by retrieving more tissue specimens with larger bore needles comes at the cost of increasing the risk of complications,32,33. The pathologists at our institution consider the use of 18G needles the best option for striking a balance between diagnostic accuracy and the risk of complications.Because of its wide availability, low cost, real-time imaging, and versatility of planes of approach, together with the fact that it does not expose patients to ionizing radiation, ultrasound is currently the most widely used method,3,11,12, might be explained by the fact that we excluded procedures in which there was more than one capsular puncture or more than one tissue specimen was retrieved and included only procedures in which an 18G needle was employed. In addition, the study population was composed of patients considered normal within strict coagulation parameters. Although a major complication was a rare outcome in this study, we recommend that liver biopsies be performed in tertiary care centers, where such complications can be managed and treated promptly.In the present study, the complication rate was particularly low, there having been just one major complication, defined as grade 3 in the Cardiovascular and Interventional Radiological Society of Europe Classification System for Complications, among the more than 1,000 cases evaluated. The low rate of complications, in comparison with that reported in other studies,34. At our institution, cooperative outpatient biopsies are performed using local anesthesia that consists of 10 mL of 1% lidocaine, without epinephrine, as is the case at most of health care facilities offering this kind of procedure.There has been debate regarding the need for periprocedural sedation and routine intravenous anesthesia during liver biopsies, although some institution use it on a routine basisIn the present study, laterality did not prove to be an issue to be considered regarding post-biopsy pain. The need for analgesia was similar in the right and left lobe puncture groups, even after adjustment for all relevant variables. In addition, the need for analgesia was more common among the female patients than among the male patients. That might be because women have a different response to pain, have a different relationship with their body, or simply feel more comfortable expressing a need for analgesia to the nurses at our institution, the majority of whom were female.None of the patients in our sample sought treatment for pain or complications after the 4-h observation period, indicating that it is a sufficient postprocedural observation period for liver biopsies. The one patient who developed a complication presented with increasing pain, within the first 30 min after the puncture, that did not respond to dipyrone or morphine. The complication was promptly diagnosed by CT angiography as an expanding hematoma and was treated by selective embolization.Despite its significant statistical power, our study has limitations. One such limitation is the retrospective nature of the study. The fact that we included only outpatients, who are, in theory, more fit than are inpatients, might constitute a selection bias. In addition, to homogenize the sample, we did not include procedures with more than one capsular puncture, which could have increased the complication rate significantly.In conclusion, ultrasound-guided percutaneous liver biopsy is a procedure that is safe and well tolerated. The most common complication is pain, which seems to be intrinsically related to the procedure itself, not correlating with the laterality of specimen collection, patient age, or the type of disease (nodular vs. diffuse). An observation period of 4 h appears to be sufficient to detect virtually all complications.