Effect of pulsed radiofrequency to the suprascapular nerve (SSN) in treating frozen shoulder pain: A randomised controlled trial.

BACKGROUND: Treatment for frozen shoulder (FS) focuses on pain control and restoring movement and strength through physical therapy. We aimed to evaluate the efficacy of pulsed radiofrequency (PRF) lesioning of the suprascapular nerve for the treatment of FS pain. METHODS: Forty patients with FS were enrolled and randomly assigned into the intervention group (n = 20) that received PRF and a control group (n = 20) which received medical treatment (NSAIDs). Patients were followed-up for a total of three months. The primary outcome was the pain intensity, measured by the Numeric Pain Rating Scale (NRS). The secondary outcomes included shoulder range of motion (ROM) evaluation measured by simple shoulder test (SST); Likert-type-based patient satisfaction scale; and any adverse events (AEs) throughout the treatment period. All results were measured at baseline, at the end of one week, four weeks and 12 weeks after treatment. RESULTS: At 12 weeks post-procedure, the intervention group significantly improved their pain (NRS dropped to 2.80 ± 0.5) and there was significant improvement in range of motion (SST from 6.55% ± 2.0% to 76.50% ± 6.5) compared to control group. CONCLUSIONS: PRF lesioning of the SSN is a fast and effective modality in treating frozen shoulder pain and improving ROM for three months.

Frequency and impact of DHODH, ABCG2 and CYP2C19 SNPs on the therapeutic efficacy, tolerability and toxicity of leflunomide.

Introduction: Leflunomide is one of the commonly used drugs in treatment of rheumatoid arthritis (RA), which on administration is converted into its active metabolite teriflunomide. Aim: Our aim is to evaluate the frequencies of dihydrooroate dehydrogenase (DHODH) (rs3213422), ABCG2 (rs2231142) and CYP2C19 (rs4244285) allele distribution among patients receiving leflunomide for RA and their possible impact on leflunomide performance in disease control. Patients & methods: Patients (>18 years) who fulfilled the 2010 ACR classification criteria for RA receiving leflunomide (20 mg/day) were included in the study. Disease activity score 28 was used to assess patients disease activity. Blood samples were collected for full blood count and blood chemistry. Genomic DNA was extracted from peripheral blood. The selection of SNPs was based on the criteria of minor allele frequency among Caucasians. Results: A significant association between the therapeutic outcome of leflunomide and DHODH genotyping was observed but not with CYP2C19 and ABCG2. Importantly, there is a significant association between DHODH (rs3213422) CC genotype and the number of patients with controlled disease. Conclusion: We strongly suggest that polymorphisms in the DHODH are the major factor affecting leflunomide pharmacogenetics and therapeutic efficacy.

Constraint-Induced Movement Therapy Combined With Botulinum Toxin for Post-stroke Spasticity: A Systematic Review and Meta-Analysis.

Stroke is considered one of the main causes of adult disability and the second most serious cause of death worldwide. The combination of botulinum toxin type A (BTX) with rehabilitation techniques such as modified constraint-induced movement therapy (mCIMT) has emerged as a highly efficient intervention for stroke patients to start synchronized motor function along with spasticity reduction. The current systematic review and meta-analysis were conducted in order to evaluate the available literature about the safety and efficacy of constraint-induced movement therapy (CIMT) combined with BTX in stroke patients with upper limb spasticity. Searches were conducted on WoS (Web of Science), Ovid, EBSCO-ASC&BSC, and PubMed for identifying relevant literature published from 2000-2020. Randomized Controlled Trials (RCTs) and Quasi-experimental studies were considered for inclusion. Rayyan (systematic review tool) QCRI (Qatar Computing Research Institute) was used for independent screening of the studies by two reviewers. For risk of bias and study quality assessment, Cochrane risk of bias tool (RoB 2) and Physiotherapy Evidence Database (PEDro) scales were used. Cochrane review manager was used to carry out the meta-analyses of the included studies. The search resulted in a total of 13065 references, of which 4967 were duplicates. After the title, abstract and full-text screening, two RCTs were deemed eligible for inclusion. Both the RCTs scored 8 on PEDro and were level evidence. The studies were heterogeneous. The findings of this meta-analysis in all the three joints post-stroke spasticity assessed on modified Ashworth scale (MAS) at four weeks post-injection aren't statistically significant (elbow P-value 0.74, wrist P-value 0.57, fingers P-value 0.42), however, according to one of the included studies the therapeutic efficacy of the combination of BTX-mCIMT injection assessed at four weeks post-injection in wrist and finger flexors was promising.  The effectiveness of BTX-CIMT combination over conventional therapy (CT) for improving post-stroke spasticity still needs to be explored with long-term, multicenter rigorously designed RCTs having a good sample size. However, the BTX-CIMT combination is promising for enhancing motor function recovery and improving activities of daily living (ADLs).

Three Needles Approach-A New Technique of Genicular Nerves Radiofrequency Ablation for Pain Relief in Advanced Chronic Knee Osteoarthritis: A Randomized Trial.

BACKGROUND: Ablation of the genicular nerves (GN) has emerged as a useful alternative therapeutic modality in chronic knee osteoarthritis (OA) specially for high-risk patients. However, in some cases due to the presence of other articular branches or anatomical variability, it may have a poor impact in relieving pain. Ablation of other or additional articular branches might have different outcomes. OBJECTIVES: We aimed to investigate the efficacy and safety of using 3 needles as a new technique in ablation of GN and compare it to the classic single-needle approach. STUDY DESIGN: A prospective parallel single-blind randomized study. SETTING: Department of Anesthesia and Intensive Care, Faculty of Medicine, Minia University, Egypt, and Pain Management Unit, Assiut University Hospital, Egypt.  METHODS: Fifty patients with advanced knee OA were involved in this clinical study to be treated with radiofrequency ablation of GN using either: the single-needle technique (SN group [n = 25]) or the 3-needle technique (TN group [no = 25]) and assessed for: pain with the Visual Analog Scale (VAS); knee function and disability with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); and patient satisfaction using global-perceived effect throughout 2 weeks, and 1, 3, and 6 months after the procedure. RESULTS: Significantly longer and better improvement in perceived pain (VAS), function and disability (WOMAC) with more patients' satisfaction were recorded in the TN group than the SN group at all follow-up time points without untoward events. LIMITATIONS: Short follow-up time; longer period could permit recognition of long-term outcome. CONCLUSIONS: Compared to the conventional single-needle GN ablation technique, the 3-needle  approach appears to be a promising, safe, and more effective ablation technique for patients with chronic knee OA.

Intra-Carpal Injection of Ozone versus Methylprednisolone in Carpal Tunnel Syndrome of Systemic Sclerosis Patients: A Randomized Single-Blind Clinical Trial.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most entrapment syndrome in general and is the most frequent peripheral nervous system involvement in systemic sclerosis (SSc). Local injection of steroid hydrodissection or ozone-oxygen showed favourable outcome in CTS in general. OBJECTIVES: To compare the clinical efficacy of ozone versus methylprednisolone intracarpal injection upon pain, functional status, and nerve conduction in patients with CTS due to SSc. STUDY DESIGN: A randomized single-blinded trial. SETTING: Anesthesia, pain, and rheumatology clinics in a university hospital. METHODS: Fifty CTS patients with > 3 months duration of SSc were equally randomized into either group O (injection of ozone/oxygen 25 mu-g/mL in 20 mL) or group M (methylprednisolone acetate 40mg, and 40 mg lidocaine in 20 mL). Visual analog scale (VAS) was measured pre-injection, then re-evaluated post-injection at 4 time points (1 week, 1 month, 3 months , and 6 months); Cochin Hand Function Scale (CHFS); and a median nerve electrophysiologic study was done before injection, then by the end of 3 months and 6 months. RESULTS: VAS was significantly lower in group M after 1 week (P = 0.01). Group O showed significantly lower VAS after 3 and 6 month (P < 0.001). Additionally, there was a significant decrease in the VAS during the whole study period within each group, in comparison to its baseline value. CHFS was significantly lower in the ozone group after 6 months (P < 0.001). The sixth month's sensory conduction was significantly higher in group O (P = 0.002). The motor distal latency was significantly lower in the ozone group after 3 and 6 months (P < 0.001). LIMITATIONS: Follow-up period could be furtherly extended. CONCLUSION: Both intracarpal ozone or methylprednisolone afford favorable effects upon CTS in patients with SSc. However, ozone alleviates pain much more, enhances the hand functional status, and improves median nerve conduction in study with over six months duration.

CYP2D6 and CYP3A4 variants influence the risk and outcome of COVID-19 infection among rheumatoid arthritis patients maintained on hydroxychloroquine.

OBJECTIVES: Hydroxychloroquine (HCQ) has been used as an off label for the management of coronavirus disease (Covid-19) infection with other drugs. However, different genetic variants can affect the metabolism of HCQ leading to inter-individual differences in its efficacy. In this study, we investigated the effects of variants in CYP2D6, CYP3A4 and CYP3A5 on the risk of Covid-19 infection among patients receiving HCQ for controlling rheumatoid arthritis (RA). METHODS: A total of 60 patients were genotyped for CYP2D6*2XN, CYP2D6*4, CYP3A4*1B and CYP3A5*2. They were receiving HCQ for the treatment of RA. The patients were evaluated clinically for fever and dry cough, radiologically via chest computed tomography (CT) and immunologically via anti-Covid-19 IgG and IgM titers. RESULTS: Variants in CYP2D6 significantly affected the grade of ground glass (CYP2D6*4 AA carriers showed the higher risk for grade 3) and the risk of positive anti-Covid-19 IgM (CYP2D6*2XN CC and CYP3A4*1B AA had the lowest risk), the duration of HCQ, the use of corticosteroids or gender did not affect the Covid-19 status significantly. CONCLUSIONS: In general, the outcome of the studied patients receiving HCQ was good (no deaths, no intubation needed). CYP2D6 variants could affect the outcome of Covid-19 infection.

Possible Role of Regulatory B Cells in Different Behçet's Disease Phenotypes and Therapies: First Report from Egypt.

BACKGROUND AND AIM: The data about the role of regulatory B cells (Breg) in Behcet Disease (BD) are scarce. We aimed to evaluate the frequency of total B lymphocytes and Breg cells in different BD phenotypes and therapies attempting to unravel their function. METHODS: This cross-sectional study included 35 BD patients and 39 healthy controls (HCs). The demographic data of the study subjects were collected including age and gender. Current medications including disease-modifying anti-rheumatic drugs (DMARDs) were recorded. All patients underwent testing for baseline laboratory investigations including full blood count, liver and kidney function tests, erythrocyte sedimentation rate (ESR) by Westergren blot and C-reactive protein (CRP). Measurement of the total B lymphocytes and their subtypes B regulatory lymphocytes by flow cytometric assay. Assessment of BD activity was done using the revised Behçet's Disease Current Activity Form (BDCAF) 2006 and Behçet's Syndrome Activity Score (BSAS) 1111111111. All participants were assessed for the presence of erectile dysfunction using the International Index of Erectile Function (IIEF-5 score), and for depression using the Beck Depression Inventory. RESULTS: A dramatic drop in the number of B cells, total and regulatory, was observed in the patients compared to the HCs. Regulatory cells (Bregs) tend to be upregulated with genital ulcers or vascular disease. Bregs but not B lymphocytes were associated with BSAS and ESR. Neither the total B lymphocytes nor the Bregs correlated with CRP or the sexual function or depression scores. Of all the used medications, low-dose aspirin was seen with markedly high Bregs proportions. CONCLUSION: This study supports the role of B cells in BD pathogenesis and strongly suggests a possible role for Bregs in the resolution of different BD manifestations.

Efficacy of Genicular Nerve Radiofrequency Ablation Versus Intra-Articular Platelet Rich Plasma in Chronic Knee Osteoarthritis: A Single-Blind Randomized Clinical Trial.

BACKGROUND: Chronic knee osteoarthritis is a common problem with increasing of the aging population. Pulsed radiofrequency and intraarticular platelet rich plasma injection are well evidenced beneficial modalities for pain alleviation in such groups of patients. OBJECTIVE: The primary goal in this study was to compare the 2 modalities regarding pain alleviation evaluated by visual analog scale. The secondary goal focused upon the change of the Index of Severity for Osteoarthritis of the Knee by Lequesne. STUDY DESIGN: Single-blind randomized interventional clinical trial. SETTING: University hospitals. METHODS: Two hundred patients with chronic knee osteoarthritis were equally and randomly distributed into 2 groups. Group PRF received pulsed radiofrequency, whereas the group PRP received intraarticular platelet-rich plasma. The visual analog scale and index of severity of osteoarthritis were evaluated before intervention, after one week (for visual analog scale only), then after 3, 6, and 12 months. RESULTS: Visual analog scale was significantly lower in the PRF group compared to the PRP group at 6 and 12 months with P-values of 0.01 and 0.04, respectively. Regarding to the postinterventional index of severity of osteoarthritis, it was significantly lower in the PRF group than the PRP group with P-values of 0.001 at 3, 6, and 12 months follow-up. LIMITATIONS: Physical and analgesic therapy were not included in data collection, and there was no control group. CONCLUSION: Pulsed radiofrequency of the genicular nerves can be considered superior to knee intraarticular platelet-rich plasma injection for sustained pain relief and the lower severity index in patients with chronic knee osteoarthritis.

Efficacy of Hyalase Hydrodissection in the Treatment of Carpal Tunnel Syndrome: A Randomized, Double-Blind, Controlled, Clinical Trial.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy, which results from median nerve compression. A lot of nonsurgical modalities are available for the management of mild to moderate situations. Local Hyalase hydrodissection (HD) of the entrapped median nerve could offer a desirable sustained symptom alleviation. OBJECTIVES: To evaluate the clinical efficacy of Hyalase/saline solution carpal tunnel HD on pain, functional status, and nerve conduction in patients with CTS. STUDY DESIGN: A randomized, double-blinded trial. SETTING: Anesthesia, pain, and rheumatology clinics in a university hospital. METHODS: Patients: 60 patients with CTS (> 6 months' duration). INTERVENTION: patients were allocated equally into either group 1 (HD with Hyalase + 10 mL saline solution injection), or group 2 (HD with 10 mL saline solution only). MEASUREMENTS: assessment of pain using Visual Analog Scale (VAS), functional disability (FD) score, and nerve conduction studies before injection, and over 6 months after injection. Nerve conduction parameters before injection and postinjection by the end of 3 and 6 months were evaluated as well. RESULTS: Statistically significant lower postinjection values of VAS (1 ± 1.8, 2 ± 1.1, 2 ± 1.2, 2 ± 1.1) in group 1 versus (2 ± 1.2, 3 ± 1.7, 4 ± 1.5, 5 ± 2.6) in group 2 by the end of the first week, and the first, third, and sixth months, and significantly lower FD scores (15.3 ± 1.2, 13 ± 1.3, 10.2 ± 1.3, 10.2 ± 1.3) in group 1 versus (17.5 ± 1.8, 16.6 ± 2.8, 19.4 ± 3.2, 21.2 ± 2.5) in group 2 during the same time intervals. Nerve conduction study parameters have shown significantly higher velocity and lower latency in the Hyalase group than in the saline solution group by the 3 and 6 month follow-up. LIMITATION: We suggest a longer period could be reasonable. CONCLUSIONS: Carpal tunnel HD with Hyalase with saline solution is considered as an efficient technique offering a rapid onset of pain relief and functional improvements, and better median nerve conduction in patients with CTS over 6 months follow-up duration. KEY WORDS: Carpal tunnel syndrome, Hyalase, median nerve hydrodissection.

Perineural Platelet-Rich Plasma for Diabetic Neuropathic Pain, Could It Make a Difference?

OBJECTIVE: To evaluate the clinical effect of perineural platelet-rich plasma (PRP) injection for pain and numbness alleviation in diabetic peripheral neuropathy (DPN). STUDY DESIGN: A randomized prospective clinical trial. SETTING: Pain clinic and Rheumatology and Rehabilitation Departments, Assiut University Hospital. METHODS: Sixty adult patients with type II DM accompanied by DPN of at least six months' duration were assessed by modified Toronto Clinical Neuropathy Score (mTCNS) and randomly allocated into two groups. Group I underwent ultrasound-guided perineural PRP injection and medical treatment, and Group II received medical treatment only. Patients were followed up at months 1, 3, and 6 with regard to pain and numbness visual analog scale (VAS) and mTCNS scores. RESULTS: Significant improvement was recorded in pain and numbness VAS scale scores in group I vs group II (P ≤ 0.001 during the whole study period for both parameters); at the same time, mTCNS improved in group I in comparison with group II with P = 0.01, 0.001, and <0.001 at months 1, 3, and 6, respectively. CONCLUSIONS: Perineural PRP injection is an effective therapy for alleviation of diabetic neuropathy pain and numbness and enhancement of peripheral nerve function.

Natural Killer and Natural Killer T Cells in Juvenile Systemic Lupus Erythematosus: Relation to Disease Activity and Progression.

The contribution of innate immune cells, including natural killer (NK) and natural killer T (NKT) cells, in systemic lupus erythematosus (SLE) is still unclear. Herein, we examined the frequency of peripheral NK cells, CD56dim and CD56bright NK cells, and NKT cells in patients with juvenile SLE and their potential relations to SLE-related clinical and laboratory parameters. The study included 35 SLE children and 20 apparently healthy controls. After baseline clinical and lab work, SLE Disease Activity Index (SLEDAI-2K) and Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI) scores were assessed. The frequency of peripheral NK cells, CD56dim and CD56bright NK cells, and NKT cells was examined using flow cytometry. SLE patients showed significantly lower frequency of NK cells and NKT cells and higher frequency of CD56bright NK cells compared to controls. Disease activity, urea, and creatinine correlated negatively with NK, but positively with CD56bright NK cells. NK and NKT cells exhibited inverse correlation with the renal biopsy activity index; however, CD56bright NK cells showed direct correlations with both activity and chronicity indices. Regarding Ped-SDI, renal, neuropsychiatry disorders, and growth failure correlated inversely with NK but directly with CD56bright NK cells. NKT cell inversely correlated with renal damage and delayed puberty. In conclusion, low frequency of NK and NKT and expansion of CD56bright NK cells are marked in juvenile SLE, particularly with activity. These changes have direct effect on renal impairment and growth failure, reflecting their potential influence on disease progression.

Sympathetic skin response in patients with systemic sclerosis and rheumatoid arthritis.

BACKGROUND: Sympathetic skin response (SSR) is a technique to assess the sympathetic cholinergic pathways. Sympathetic dysfunction may participate in the development of pain, which is the major complaint in patients with systemic sclerosis (SSc) and rheumatoid arthritis (RA). OBJECTIVES: In this study, we aimed to assess the autonomic dysfunction in patients with (SSc) and (RA) using SSR as a simple neurophysiologic test. METHODS: Palmar SSR to median nerve electrical stimulation was recorded in 21 patients with SSc, 39 patients with RA, and in 60 healthy age and sex-matched control subjects. RESULTS: Palmar SSR to median nerve stimulation (of SSc patients and RA patients) shows significantly delayed latency and reduced amplitude in comparison to the control group. SSR of SSc patients has significantly delayed latency and reduced amplitude when compared to RA patients. Moreover, six SSc patients have delayed SSR in spite of the absence of manifestations of polyneuropathy. CONCLUSIONS: Patients with SSc and RA have features of autonomic dysfunction with more affection of SSc patients.

Non-invasive Oxygen-Ozone therapy in treating digital ulcers of patients with systemic sclerosis.

BACKGROUND: Digital ulcers (DUs) in Systemic sclerosis (SSc) result from recurrent Raynaud's phenomenon (RP) and microtrauma with high impact on quality of life. Medical use of ozone (triatomic oxygen) was initiated in the 19th century. Ozone has multiple therapeutic effects in wound healing due to the property of releasing nascent oxygen, which has been shown to stimulate antioxidant enzymes. We aimed to assess the effects of ozone therapy on the healing of scleroderma DUs and determine levels of expression of vascular endothelial growth factor (VEGF), and endothelin-1 type A receptor (ETAR) autoantibodies in the wounds after treatment. SUBJECTS AND METHODS: Fifty SSc female patients with DUs, were randomized into ozone group (I) (n=25) treated by calcium channel blockers plus oxygen-ozone treatment and control group (II) (n=25) treated by calcium channel blockers only. Ozone group received noninvasive oxygen-ozone treatments for 30 minutes per day for 20 days using the ozone generator device. Therapeutic effects were graded into 4 levels according to Zhang and other researchers. The wounds sizes were measured at baseline and day 20, respectively. Expressions of VEGF and ETAR autoantibodies proteins were determined by immune-histochemical examination. RESULTS: Demographics and clinical characteristics of the 2 groups showed no significant differences. At day 20, the effective healing rate was significantly higher in group (I) than in group (II), where it represented 96% (24/25) in ozone group versus 44% (11/25) in control group, and (𝑃 = 0.007). After treatment, the wound sizes in both groups were significantly smaller than before treatment. In group (I), the wound size reduction was significantly more than in group (II) (0.75 ± 0.30 versus 2.44 ± 0.80 mm), (𝑃 = 0.00). At day 20, VEGF was significantly higher in ozone group (I), than in control group (II), (83.96±9.68) versus (67.92±6.55), (𝑃 = 0.00) while, ETAR was significantly lower in ozone group (I), than in control group (II), (3.14±1.12 versus 4.59±1.24), (𝑃 = 0.00). CONCLUSION: Ozone therapy may be beneficial tool in the treatment of DUs in SSc patients, where it promotes the wound healing through a potential induction of VEGF and down-regulation of ETAR at sites of the ulcers.

Implication of Two Different Doses of Intradiscal Ozone-Oxygen Injection upon the Pain Alleviation in Patients with Low Back Pain: A Randomized, Single-Blind Study.

BACKGROUND: Low back pain (LBP) is mostly induced by disc herniation (DH) or degeneration and has a burden upon social activity and economical aspects of life. An abundance of medical and surgical interventions have evolved to resolve this problem, but one of the newly introduced techniques, which is the minimally invasive, low cost ozone-oxygen mixture (O3-O2) intradiscal injection, offers a rapid onset amelioration of symptoms with a sustained duration of pain relief. OBJECTIVE: We aim to evaluate the quality of pain alleviation using 2 different doses of intradiscal injections of O3-O2 mixture. STUDY DESIGN: A prospectively randomized, single-blind study. SETTING: Pain clinic, anesthesia, intensive care, and pain department in Assiut University Hospitals. METHODS: Sixty patients with symptomatizing single lumbar DH were subjected to O3-O2 intradiscal injection and randomly allocated into one of 2 groups; group A: received 10 mL, 40 µg/mL of O3-O2 and group B: received 10 mL, 30 µg/mL of O3-O2. Pain score and functional ability of the patients using the visual analog scale (VAS) and Oswestry Disability Index (ODI) were evaluated after 1, 6, and 12 months and compared to the basal values. Patient satisfaction and reduction of DH were evaluated after the sixth month. RESULTS: There were no significant differences between the 2 groups regarding the clinical outcome; however both the ODI and VAS evaluations showed highly significant improvement (decreased) (P < 0.01) after injection and during the entire follow-up period. There were highly significant negative correlations between the DH reduction percentage and both the VAS and ODI scores after 6 months in both of the groups. LIMITATIONS: This study was limited by a small sample size; it was also an active control trial, which may explain the insignificant difference in between the groups, in addition to being a single-blind trial. CONCLUSION: Intradiscal injection of O3-O2 mixture is a very valuable maneuver in the reduction of DH size and improvement of pain quality, with either ozone concentrations of 40 µg/mL or 30 µg/mL. KEY WORDS: Low back pain, ozone, disc herniation.