Vascular calcification:When should we interfere in chronic kidney disease patients and how?

Chronic kidney disease （CKD） patients are endangered with the highest mortality rate compared to other chronic diseases. Cardiovascular events account for up to 60% of the fatalities. Cardiovascular calcifcations affect most of the CKD patients. Most of this calcification is related to disturbed renal phosphate handling. Fibroblast growth factor 23 and klotho defciency were incriminated in the pathogenesis of vascular calcification through different mechanisms including their effects on endothelium and arterial wall smooth muscle cells. In addition, deficient klotho gene expression, a constant feature of CKD, pro-motes vascular pathology and shares in progression of the CKD. The role of gut in the etio-pathogenesis of systemic infammation and vascular calcifcation is a newly discovered mechanism. This review will cover the medical history, prevalence, pathogenesis, clinical relevance, different tools used to diagnose, the ideal timing to prevent or to withhold the progression of vascular cal-cification and the different medications and medical procedures that can help to prolong the survival of CKD patients.

Advantages of Dextrose, Platelet Rich Plasma and Stem Cells over the Traditional Conventional Methods in Treatment of Sports Injuries and Joint Osteoarthritis

Osteoarthritis （OA） reflects a slowly evolving joint disease with toss and erosion of articular cartilage, osteophytes formation and weakness or laxity of the soft tissues in the synovial joints, particularly the large weight-bearing joints. The prevalence of the OA increases with age, and its radiological changes can be observed in over 50% of the retired people. Symptoms can vary from minimal to severe pain, stiffness, locking, decreased function and sometimes joint effusion. Inevitably, a wide range of potential therapies have been advocated, and not necessarily with strong supportive evidence. The Standard-of-care for treatment of pain is multidisciplinary; however, a recent systematic review reported no clear benefit of any one therapy. The Agency for Healthcare Research and Quality has called for the development of new therapies for pain management. In Interventional Regenerative Orthopedic Medicine （IROM）, Dextrose is used as a tissue proliferant for treatment of OA. It has different ways of action aiming to do tissue regeneration. Platelet Rich plasma is also used in IROM and is very promising because of delivering ＂growth-factors＂ which stimulate the local tissue progenitor cells （mesenchymal stem cells） enhancing the regeneration of the tissues. Adult Mesenchymal stem cells is the hot topic nowadays in the non-surgical joint reconstruction. The results revealed that patients treated for sports injuries and joint OA using IROM （dextrose, PRP and stem cells） showed a greater improvement regarding their sports performance as well as joint pain and function compared to those treated with traditional methods （different modalities of physiotherapy, steroids injections etc）. Moreover, athletes with sports injuries treated with steroid injections showed a deterioration in their sports performance, muscle strain, joint pain and function.

New objective scoring system to clinically assess fecal incontinence

BACKGROUND Several scoring systems are used to assess fecal incontinence(FI),among which,the most commonly used are Wexner and Vaizey’s scoring systems.However,there are significant lacunae in these scoring systems,due to which they are neither accurate nor comprehensive.AIM To develop a new scoring system for FI that is accurate,comprehensive,and easy to use.METHODS A pro forma was made in which six types of FI were included:solid,liquid,flatus,mucous,stress,and urge.The weight for each FI was determined by asking a group of patients and laypersons to give a disability score to each type of FI from 0 to 100(0-least,100-maximum disability).The disability was assessed on a modified EQ-5D+(EuroQol)description system,4D3L(4 dimensions and 3 levels)for each FI.The average score of each FI was calculated,divided by 10,and rounded off to determine the weight of each FI type.The scores for the three levels of frequency of each FI were assigned as never=0(No episode of FI ever),occasional=1(≤1 episode of FI/wk),and common=2(>1 episode of FI/wk),and was termed as frequency score.The score for each FI would be derived by multiplying the frequency score and the weight for that FI type.In the second phase of the study,a group of colorectal surgeons was asked to rank the six FI types in order of severity,and their ranking was compared with the patient and laypersons’rankings.RESULTS Fifty patients and 50 laypersons participated in the study.The weight was assigned to each FI(solid-8,liquid-8,urge-7,flatus-6,mucus-6,and stress-5),and an new scoring system was formulated.The maximum possible score was 80(total incontinence),and the least 0(no incontinence).The surgeons’ranking of FI severity did not correlate well with patients’and laypersons’rankings of FI,highlighting that surgeons and patients may perceive the severity of FI differently.CONCLUSION A new scoring system for FI was formulated,which was simple,logical,comprehensive,and easy to use,and eliminated previous shortcomings.Patients’and surgeons’perceptions of FI severity of FI did not correlate well.

Human umbilical cord mesenchymal stem cells as treatment of adjuvant rheumatoid arthritis in a rat model

AIM:To investigate the effect of human umbilical cord stem cells,both mesenchymal and hematopoietic(CD34+),in the treatment of arthritis.METHODS:Mesenchymal stem cells(MSCs) and hematopoietic(CD34+) stem cells(HSC) were isolated from human umbilical cord blood obtained from the umbilical cord of healthy pregnant donors undergoing fullterm normal vaginal delivery.MSC,HSC,methotrexate(MTX) and sterile saline were injected intra-articularly into the rat hindpaw with complete freunds adjuvant(CFA) induced arthritis after the onset of disease(day 34),when arthritis had become well established(arthritis score ≥ 2).Arthritic indices were evaluated and the levels of interleukin(IL)-1,tumor necrosis factor(TNF)-α and interferon(IFN)-γ and anti-inflammatory cytokine IL-10 in serum were determined using enzyme-linked immunosorbent assay.Animals of all groups were sacrificed 34 d after beginning treatment,except positive control(PC) which was sacrificed at 10,21 and 34 d for microscopic observation of disease progression.We used hematoxylin,eosin and Masson's trichrome stains for histopathological examination of cartilage and synovium.RESULTS:The mean arthritis scores were similar in all groups at 12 and 34 d post immunization,with no statistical significant difference.Upon the injection of stem cells(hematopoietic and mesenchymal),the overall arthritis signs were significantly improved around 21 d after receiving the injection and totally disappeared at day 34 post treatment in MSC group.Mean hindpaw diameter(mm) in the MSC rats was about half that of the PC and MTX groups(P = 0.007 and P = 0.021,respectively) and 0.6 mm less than the HSC group(P = 0.047),as indicated by paw swelling.Associated with these findings,serum levels of TNF-α,IFN-γ and IL-1 decreased significantly in HSC and MSC groups compared to PC and MTX groups(P < 0.05),while the expression of IL-10 was increased.Histopathological examination with H and E stain revealed that the MTX treated group showed significant reduction of leucocytic infiltrate and hypertrophy of the synovial tissue with moderate obliteration of the joint cavity.Stem cells treated groups(both hematopoietic CD34+ and mesenchymal),showed significant reduction in leucocytic infiltrate and hypertrophy of the synovial tissue with mild obliteration of the joint cavity.With Masson's trichrome,stain sections from the PC group showed evidence of vascular edema of almost all vessels within the synovium in nearly all arthritic rats.Vacuoles were also visible in the outer vessel wall.The vessel became hemorrhagic and finally necrotic.In addition,there was extensive fibrosis completely obliterating the joint cavity.The mean color area percentage of collagen in this group was 0.324 ± 0.096,which was significantly increased when compared to the negative control group.The mean color area percentage of collagen in hematopoietic CD34+ and mesenchymal groups was 0.176 ± 0.0137 and 0.174 ± 0.0197 respectively,which showed a marked decrement compared to the PC group,denoting a mild increase in synovial tissue collagen fibers.CONCLUSION:MSC enhance the efficacy of CFAinduced arthritis treatment,most likely through the modulation of the expression of cytokines and amelioration of pathological changes in joints.

Stop chronic kidney disease progression: Time is approaching

Progression of chronic kidney disease （CKD） is inevitable. However, the last decade has witnessed tremendous achievements in this field. Today we are optimistic; the dream of withholding this progression is about to be realistic. The recent discoveries in the field of CKD management involved most of the individual diseases leading the patients to end-stage renal disease. Most of these advances involved patients suffering diabetic kidney disease, chronic glomerulonephritis, polycystic kidney disease, renal amyloidosis and chronic tubulointer-stitial disease. The chronic systemic inflammatory status and increased oxidative stress were also inve-stigated. This inflammatory status influences the anti-senescence Klotho gene expression. The role of Klotho in CKD progression together with its therapeutic value are explored. The role of gut as a major source of infam-mation, the pathogenesis of intestinal mucosal barrier damage, the role of intestinal alkaline phosphatase and the dietary and therapeutic implications add a novel therapeutic tool to delay CKD progression.

Circulating Levels of Hypoxia-regulating MicroRNAs in Systemic Lupus Erythematosus Patients with Hemolytic Anemia

Objective MicroRNAs are fine regulators for gene expression during the post-transcriptional stage in many autoimmune diseases.HypoxamiRs(miR-210 and miR-21)play an important role in hypoxia and in inflammation-associated hypoxia.Systemic lupus erythematosus(SLE)is a chronic systemic autoimmune disease that would potentiate many pathological complications,including hemolytic anemia.This study aimed to investigate the role of hypoxamiRs in SLE/hemolytic anemia patients.Methods This work was designed to analyze the circulating levels of↱the miR-210 and miR-21 expressions and hypoxia-inducible factor-1α(HIF-α)in SLE/hemolytic anemia patients.SLE activity was evaluated for all patients by SLE Disease Activity Index(SLEDAI).Clinical manifestations/complications and serological/hematological investigations were reported.HIF-αconcentration was assayed by ELISA and expression of miR-21 and miR-210 was analyzed by qRT-PCR.Results The results indicated that the fold change of the miR-210/miR-21 expressions in plasma was significantly elevated in SLE/hemolytic anemia patients.A strong positive correlation between the miR-210 and miR-21 expression levels was also recorded.Among the associated-disease complications,hypertension,arthritis,oral ulcers,and serositis were associated with a high circulating miR-210 expression,while the occurrence of renal disorders was associated with the increased miR-21 expression.Furthermore,the HIF-αlevel was remarkably elevated in SLE/hemolytic anemia patients.A high positive correlation was recorded between the HIF-αconcentration and miR-210/miR-21 expression levels.The occurrence of oral ulcers,arthritis,and hypertension was associated with the increased HIF-αconcentration.On the other hand,SLEDAI and white blood cell count were positively correlated with miR-21/miR-210.The erythrocyte sedimentation rate was positively correlated with miR-21.Conclusion The dysregulation of the circulating miR-210/miR-210/HIF-1αlevels in SLE/hemolytic anemia patients advocated that the hypoxia pathway might have an essential role in the pathogenesis and complications of these diseases.

Spinal accessory neuropathy in patients with chronic neck pain

AIM: To assess the presence of spinal accessory neuropathy in patients with chronic neck pain.METHODS: Patients with pain either regional or focal in the neck or shoulders for at least 6 mo(chronic neck pain) were recruited randomly from the Rheumatology and Rehabilitation Outpatient Clinic at the Faculty of Medicine-Suez Canal University. Two groups were compared: 30 patients with chronic neck pain with mean age(36.97 ± 12.45 years) and 10 apparently healthy controls. Trapezius muscle examination including inspection and range of motion both active and passive was performed. A full clinical neurological examination was carried out to exclude peripheral neuropathy and motor neuron disease. According to the subject's type of work, cases were categorized into labor-intensive and non-labor intensive tasks. A nerve conduction study(NCS) was performed on spinal accessory nerves at both sides for all patients and controls. Parameters including latencies and amplitudes of compound motor action potential(CMAP) were compared with the chronicity of neck pain using the neck disability score. This cross sectional study was carried in the Rheumatology and Rehabilitation Department, at Suez Canal University Hospital, Ismailia, Egypt.RESULTS: Physical examination revealed that 80% of cases had spinal trapezius muscle spasm. Restricted neck motion was present in 16.6% of cases. No one suffered from muscle wasting or weakness. Pain was bilateral in 18 patients(60%), localized to the right side in six patients(20%) and localized to the left side in six patients(20%). The causes of neck pain in the patients studied were nonspecific, due to physical stresses, cervical spondylosis and mild cervical disc herniation. Mean disease duration in patients with labor-intensive tasks was(3.9 ± 2.1 years), which was longer than that in patients with non-labor intensive tasks(3.1 ± 1.9 years); however, this difference was statistically insignificant. Spinal accessory NCSs were performed while subjects were in sitting positions and relaxed with naturally suspended arms to minimize muscular movement. The results of electrophysiological studies revealed that mean right and left latencies of the spinal accessory nerve were 2.96 ± 0.69 ms, 2.98 ± 0.61 ms in the patient group and 2.44 ± 0.38 ms, 2.33 ± 0.36 ms in control group respectively. These differences were statistically significant with P = 0.028 and 0.006 respectively. Spinal accessory NCS showed normal CMAP amplitude in both patients and controls. Comparing the results of the neck disability index(NDI) to different characteristics in patients with chronic neck pain, showed that patients with labor-intensive work had a higher NDI score mean(34.7 ± 9.5) compared to those with non-labor-intensive work, with significant statistical difference(P = 0.011). In addition, mean NDI scores were higher in males, and patients aged over 40 years and this difference was statistically significant(P = 0.007 and P = 0.009 respectively). Correlation studies between right and left spinal accessory nerve latencies and disability percent calculated using the NDI revealed a positive correlation. Moreover, there was a positive correlation between age and disability percent.CONCLUSION: This study demonstrates electrophysiological evidence of demyelination in a significant proportion of patients with chronic cervical pain.

Anti-TNF-αtreatment in Behcet's disease with cerebral vasculitis:a case report

A 27 year-old male patient was diagnosed with Behcet＇s disease cortex）, （TNF） which resulted in reduced visual acuity and field of vision. This alpha blocker therapy on Behcet＇s cerebral vasculitis （BD） case and posterior visual pathway demonstrates the effect of tum affection （visual or necrosis factor

New Erra with Auto-Haemotherapy

The active researchers, till now, did not find a curative treatment for many diseases threatening lives of the patients. Proper management and treatment for those patients can give them longer and healthier lives. Over the years, auto-haemotherapy has been used to treat illnesses and diseases such as： arterial circulatory disorders, autoimmune diseases as rheumatoid arthritis, gout, bronchitis, allergies, ache vulgaris, skin eczema, leg ulcers, chronic sinusitis, skin lesions, HIV infection, HCV, Lyme disease, connective tissue diseases, fibromyalgia, asthma, history of heart attack and fungal infections. It helps in cessation of smoking, treatment of drug and alcohol addiction, decreasing the appetite, losing weight in obese patients and speeding up the recovery after a long period of illness. It has also been used in combination with conventional cancer treatment. Auto-haemotherapy is a simple technique where the blood is drawn from a vein and re-injected into a muscle. The blood in the muscle works as a foreign body that will be rejected by the reticulo-endothelial system. It stimulates the immune system and the bone marrow to increase the production of macrophages which are the body＇s cleaners. The macrophages cleanse everything, they eliminate bacteria, viruses, cancerous cells called neoplastic cells, this is a spring cleaning, and they even eliminate fibrin which is a clotted blood. Auto-haemotherapy is a very powerful technique with a low cost. It requires a syringe and a physician who knows how to withdraw blood from a vein and straight away does an intra-muscular injection with this blood under aseptic condition which increases and stimulates the immune system. Minor auto-haemotherapy technique was applied to 176 patients suffering from different diseases such as： Type I diabetes mellitus, bronchial asthma, chronic sinusitis, allergic conjunctivitis, allergic rhinitis, skin problems （vesicles, eczema, ulcer）, finger nail problem （infection, paronychia）, acne vulgaris, gastro-intestinal tract problem, lactose intolerance, connective tissue disease, AFS （adrenal fatigue syndrome）~ myasthenia gravis, fibromyalgia, gout, generalized osteoarthritis, joint osteoarthritis, low back pain with MODIC changes Type 1 on MRI （with or without spinal canal stenosis）, auto-immune diseases （ankylosing spondylitis, rheumatoid arthritis）, and infectious vaginal discharge. Also it has been applied to patients in order to stop smoking, and to other patients in order to lose weight. Results showed that the patients suffering from the previous different diseases improved significantly after being treated with auto-haemotherapy. In addition, the heavy smokers were able to decrease dramatically the number of cigarettes they were smoking, and the obese patients were able to lose their weight and they had less appetite.

Anti-CD-20 Therapy in Refractory Adult Still’s Disease

Adult Still’s disease is a relatively rare form of rheumatoid arthritis with systemic inflammatory features. The prevalence is around 1.5 cases per 100,000 - 1000,000. In the current case we display a 30-year-old male patient with refractory adult still’s disease who suffered recurrent attacks of fever 39.5°C, arthritis in proximal interphalangeal joints (PIPs), wrists, tempromandibular joints (TMJs), knees and ankles, stitching chest pain, dyspnea, erythematous rash over the trunk, sore throat, weight loss (15 Kilograms in 4 months). The patients’ disease remained uncontrolled despite of synthetic disease modifying anti-rheumatic drugs and repeated intramuscular corticosteroid injections. Laboratory workup revealed erythrocyte sedimentation rate (ESR) of 95, C-reactive protein (CRP) of 100 mg/L, hemoglobin 10.5 gm%, leukocytosis 12,000/microlitre, mild elevation of liver function tests and dyslipidemia. Serology revealed negative rheumatoid factor, anti-nuclear antibody titre of 1:80, elevated serum ferritin 4000 micrograms/litre. The patient was started on rituximab (375 mg/m2), prednisolone 20 mg/day and selective Cox-2 inhibitor. Follow up for over three months following the completion of his pulse therapy, revealed no relapse of fever or fatigue, with morning stiffness of 5 - 10 minutes, VAS of 3, DAS28 of 3.8, HAQDI of 0.62, ESR 23, CRP 4.9, Hb 12.5 gm%, leucocytic count 9000/microlitre, the dose of prednisolone was successfully reduced to a dose of 5 mg/day orally. Conclusion: Anti-CD20 therapy successfully controlled systemic and articular refractory disease with sustained efficacy over a follow up period of up to 24 weeks.

Monitoring osteoporosis therapy:Can FRAX help assessing success or failure in achieving treatment goals?

AIM: To assess:(1) Whether the World Health Organization fracture risk assessment tool(FRAX) can be used for monitoring osteoporosis patients receiving treatment as well as its clinical implications; and(2) The relation between fracture incidence and post-treatment FRAX.METHODS: Five hundred and seventy-nine osteoporotic women known to be adherent to the prescribed osteoporosis medication, had dual-energy X-ray absorptiometry scan and fracture probability calculated at baseline, 2 and 5-year of osteoporosis treatment. Those patients who responded to treatment and did not sustain a new low trauma fracture during the first 2 years, continued their treatment and were re-assessed 3-year later. The patient subgroup who did not achieve an improvement in their bone mineral density(BMD)or sustain any fracture within the first 2-year, had their osteoporosis treatment changed. Outcome measures included BMD and FRAX assessment calculated 3-year after commencing new osteoporosis treatment. RESULTS: There was a significant negative correlation between 10-year probability of major osteoporotic and hip fractures and BMD at the total proximal femur at 2-year of treatment(R =-0.449 and-0.479 respectively), and at 5-year(R =-0.489 and-0.594 respectively). At both 2 years and 5 years of treatment, the 10-year fracture probability showed significant correlation with the incidence of fracture(P < 0.01). On comparing fracture probability, there was a significant difference(P < 0.05) between the responders and non-responders to osteoporosis treatment.CONCLUSION: In women currently or previously treated for osteoporosis, the FRAX tool can be used to predict fracture probability. Osteoporosis treatment does not annul prediction of fractures. FRAX tool may be of value in guiding clinicians towards the need for continuation or withdrawal of treatment.

Management of Musculoskeletal Pain

Musculoskeletal pain is a distressing, unpleasant feeling and an emotional experience associated with actual or potential tissue damage. Prolotherapy is an injection therapy designed to stimulate tissue healing. Lyftogt PIT （perineural injection therapy） treats the neurogenic inflammation. Therefore it stops the pain and promotes the release of NGFs （nerve growth factors） which are important for tissue regeneration. Vitamin D3 receptors are ubiquitous in tissue distribution, which opens the possibility for unforeseen biological functions of vitamin D endocrine system. Dextrose is the most commonly used tissue proliferant in prolotherapy. It has different ways of action aiming to stimulate the tissue regeneration. Platelet Rich Plasma is also used in the IROM （interventional regenerative orthopedic medicine）, and it is very powerful because it delivers ＂growth-factors＂ which stimulate the local tissue progenitor cells （adult mesenchymal stem cells） enhancing the regeneration of the tissues. Adult Mesenchymal stem cell is the hot topic nowadays in the non-surgical field of pain management. In this paper, 250 patients suffering from chronic pain and dysfunction of different body joints （knee, hip and elbow）, were treated with one or two injection therapy techniques, to evaluate the patient improvement regarding the pain and function. The effect of adding an intra-articular injection of vitamin D to the above techniques was also evaluated regarding the joint pain and function improvement. Some of the patients were treated with Platelet Rich Plasma and others were treated with Bone Marrow Stem cells. The results of the 250 patients were compared with those obtained from 30 matching control patients, having same conditions and were treated with physiotherapy, Conclusions show that the therapeutic benefit from combining the two techniques, Lyflogt Perineural Injection Therapy and Prolotherapy, is better than using only one of them regarding the pain and function for the different body joints. Adding an intra-articular injection of vitamin D to the treatment of some patients gave a better result than those treated with dextrose only. However, using the Platelet Rich Plasma and the Stem cells instead of dextrose gave the best results ever regarding the pain and function of the musculoskeletal system.