Efficacy of platelet-rich plasma as conservative treatment in orthopaedics: a systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis was to evaluate the benefit of platelet-rich plasma (PRP) in non-surgical orthopaedic procedures. MATERIAL AND METHODS: We searched the Cochrane Wounds Specialized Register, CENTRAL, MEDLINE (through PUBMED), Embase, and SCOPUS. We also searched clinical trials registries for ongoing and unpublished studies and checked reference lists to identify additional studies. RESULTS: We found 36 randomised controlled trials (2,073 patients) that met our inclusion criteria. The included studies mostly had small numbers of participants (from 20 to 225). Twenty-eight studies included patients with lateral epicondylitis or plantar fasciitis. PRP was compared to local steroids injection (19 studies), saline injection (6 studies), autologous whole blood (4 studies), local anaesthetic injection (3 studies), dry needling injection (3 studies), and to other comparators (4 studies). Primary outcomes were pain and function scores, and adverse events. On average, it is unclear whether or not use of PRP compared to controls reduces pain scores and functional score at short- (up to 3 months) and medium- (4-6 months) term follow-up. The available evidence for all the comparisons was rated as very low quality due to inconsistency, imprecision, and risk of bias in most of the selected studies. There were no serious adverse events related to PRP injection or control treatments. CONCLUSIONS: The results of this meta-analysis, which documents the very marginal effectiveness of PRP compared to controls, does not support the use of PRP as conservative treatment in orthopaedics.

Pain assessment and management in haemophilia: A survey among Italian patients and specialist physicians.

INTRODUCTION: Persons with haemophilia (PWH) experience recurrent joint bleeding which leads from early synovitis to irreversible joint damage. Pain strongly affects patients' quality of life, as PWH suffer from acute pain associated with haemarthroses and chronic pain due to arthritic and degenerative complications. AIM: To investigate pain issues among PWH and their treaters in Italy. METHODS: Persons with haemophilia and specialist physicians responded to a survey focused on pain characteristics, assessment, and management by phone call and online, respectively. RESULTS: One hundred and nineteen patients (76% severe haemophilia, 61% ≥18 years) and 44 physicians were involved. Pain was reported by 61% of PWH; among those who did not experience pain, 70% were children on prophylaxis. Patients described pain as chronic (71%), acute (69%) or postoperative (8%), and rated it as severe in 65% of cases. Clinicians reported lower percentages of patients with pain (46%), classified as chronic (58%), acute (33%) or postoperative (21%), half using specific scales. Pain was systematically investigated by treaters according to 36% of patients. Paracetamol was largely the most prescribed first-line pain therapy (89%), as well the most employed analgesic by PWH (51%), who also used non-steroidal anti-inflammatory drugs (24%), cyclo-oxygenase-2 inhibitors (21%) or opioids (26%). To manage pain, 61% of clinicians stated to collaborate with other specialists. Physiotherapy was often suggested but less frequently used by PWH. CONCLUSIONS: Pain is under-recognized and unsatisfactorily addressed by haemophilia treatment centre (HTC) clinicians, with discrepant management compared to PWH responses. Education in systematic pain assessment and multidisciplinary treatment and development of management guidelines are highly needed.

Is there a standard-of-care for transfusion therapy in thalassemia?

PURPOSE OF REVIEW: Thalassemia is the most common form of inherited anemia, characterized by variable clinical phenotypes. The purpose of this review is to summarize the transfusion support in thalassemia patients and the management of transfusion-related iron overload. RECENT FINDINGS: The most recent evidence on transfusion strategy and iron chelation therapy in thalassemia arising from clinical trials as well as from recommendation guidelines are critically discussed. SUMMARY: Enhancements in the global care of thalassemia, resulting from the combination of an appropriate transfusion approach and iron chelation therapy, have produced a significant improvement in the quality of life and, finally, in the prognosis of patients affected by this inherited hematologic disorder.

Fish Intake and Venous Thromboembolism: A Systematic Literature Review.

Diet plays an important role in modulating the risk of arterial and venous thrombosis. Several lines of evidence attest that consumption of fish and its compounds, especially omega-3 fatty acids, may be effective to decrease the cardiovascular risk. Since the pathogenesis of arterial and venous thrombosis share some common aspects, we performed a systematic review of published clinical studies that investigated the association between fish intake and venous thrombosis. An electronic search was carried out in Medline, Scopus, and ISI Web of Science using the key words "fish" OR "seafood" AND "venous thromboembolism" OR "deep vein thrombosis" OR "pulmonary embolism", with no language or date restriction. Overall, 6 studies (5 prospective and 1 case-control) were finally identified. In only 1 small case-control study, a larger intake of total fish was found to be negatively associated with the risk of venous thromboembolism. No association was found in 4 large prospective studies, whereas a positive association was observed in the remaining. No substantial difference was also noticed between intake of fatty or lean fish. Taken together, the current epidemiological evidence does not support the existence of a significant effect of total fish consumption on the risk of venous thromboembolism.

Proteomic analysis of venous thromboembolism: an update.

Venous thromboembolism is a complex, multifactorial disorder, the pathogenesis of which typically involves a variety of inherited or acquired factors. The multifactorial etiology of this disease and the partial correlation between genotype and prothrombotic phenotype limit greatly the value of genetic analysis in assessing thrombotic risk. The integration of several new 'omics' techniques enables a multifaceted and holistic approach to the study of venous thrombotic processes and pave the way to the search and identification of novel blood biomarkers and/or effectors of thrombus formation that can also be the possible future target of new anticoagulant and thrombolytic therapies for more personalized medicine. This review provides a comprehensive overview of the latest candidate proteomic biomarkers of venous thrombosis and of the proteomics studies relevant to its pathophysiology, some of which seem to confirm the existence of a common physiopathological basis for venous thromboembolism and atherothrombosis.

Preventing postsurgical venous thromboembolism: pharmacological approaches.

The use of antithrombotic drugs for the prevention of venous thromboembolism (VTE) in patients undergoing surgery is presently based on solid principles and high-level scientific evidence. This article reviews current strategies of pharmacological thromboprophylaxis. The level of VTE risk following surgery depends on a variety of factors that the surgeon should take into account, including the type of surgery and the presence of additional risk factors, such as elderly age and cancer. In patients undergoing minor general surgery, early mobilization is sufficient as prophylaxis, whereas in those undergoing major general surgery, thromboprophylaxis with low molecular weight heparin (LMWH), low-dose unfractionated heparin, or the pentasaccharide fondaparinux is recommended. Patients undergoing major orthopedic surgery have a particularly high risk of VTE, and routine thromboprophylaxis with LMWH, fondaparinux, or a vitamin K antagonist (international normalized ratio target: 2.0 to 3.0) is the standard of care in this group of patients. Recently, two new oral anticoagulants, rivaroxaban (a factor Xa inhibitor) and dabigatran etexilate (a direct thrombin inhibitor) have been licensed to be used for thromboprophylaxis after orthopedic surgery in Europe. Mechanical methods of thromboprophylaxis (compression stockings, intermittent pneumatic compression, vena cava filters), not discussed in detail in this review, should always be considered in patients at high thrombotic risk, in association with the pharmacological strategies, or in cases of contraindications to anticoagulants, as in patients or procedures at high risk of bleeding.

Adjuvant treatments for Henoch-Schönlein purpura nephritis in children: A systematic review.

BACKGROUND: The management of Henoch-Schönlein purpura nephritis (HSPN) in childhood is controversial. Adjuvant therapies such as immunoglobulin, anticoagulants, and vitamins have been used with conventional treatments despite a lack of evidence of their efficacy. OBJECTIVE: The aim of this study was to review the scientific literature regarding adjuvant treatments administered with conventional drugs in the treatment of childhood HSPN. METHODS: Published articles were identified from the MEDLINE and EMBASE databases (1988-December 2008; key words: Henoch-Schönlein nephritis and Henoch-Schönlein purpura). The search was limited to published English-language studies on therapeutic options for HSPN in children. RESULTS: A total of 12 studies were identified and included in this review; most (n = 8) were case series or retrospective studies. Studies of conventional therapy combined with adjuvant treatment should be interpreted with caution. In particular, factor XIII administration was reported to improve kidney symptoms in 1 study. Based on the results from 9 studies, no convincing evidence on intravenous immunoglobu-lin, urokinase, or anticoagulants was identified. No substantial information was available on the benefit of antiplatelet agents or heparin in treating HSPN. Integrating treatment with vitamin E was not recommended based on the results from 1 randomized controlled trial. Fish oil was reported to be effective in 1 case series. CONCLUSIONS: Studies concerning the treatment of HSPN in children with adjuvant therapies were retrospective and recommendations were drawn from level IV evidence. One randomized controlled trial on the use of tocopherol as adjuvant treatment was identified; however, no clinical utility was reported. At present, there is no strong evidence supporting benefits with the use of adjuvant treatments.

Preoperative autologous blood donation in primary total knee arthroplasty: critical review of current indications.

Preoperative autologous blood donation (PABD) is a well established transfusion practice in elective orthopaedic surgery, involving immunologic and infective advantages but also involving exposure to not negligible risks, and costs as well. The aim of this study was to assess the real need for blood transfusions in primary total knee arthroplasty (TKA). Between January 2000 and July 2005, 214 patients underwent primary unilateral TKA. Altogether, 416 autologous blood units were collected, however only 47 (11.3%) were transfused. Thirty-eight patients (17.8%) received autologous blood, while 4 of them (10.5%) also received allogeneic blood. Based on the results of this study, PABD should be recommended in well selected patients undergoing TKA: older female patients with a low basal haemoglobin level.

New strategies for doping control.

Doping in sports is commonplace. The prevention of harm to the athlete, the guarantee of fair play, and a level playing field for all competitors are the basis of the current anti-doping strategies. As healthcare systems are forced to allocate increasing resources to prevent and treat the prevailing pathologies worldwide, funding for anti-doping campaigns will necessarily be restricted. Ideally, additional resources should be devoted to increasing the number of athletes tested, the panels of tests used, and the frequency of out-of-competition controls. Since doping prevention cannot be considered a priority for most healthcare systems, such an approach is unaffordable and an alternative framework should be devised, focused primarily on harm reduction rather than fair play. The identification of abnormal deviations from reference values, regardless of pathological or artificial causes, would allow the athlete to be followed and tested using conventional laboratory tests, which are affordable to governments and healthcare systems and available to clinical laboratories. Although this strategy would not detect cheating, it would safeguard athletes' health.

The management of hemophilia in elderly patients.

After the increasing rate of deaths observed during the 1980s due to human immunodeficiency virus (HIV) infection, the health-related quality of life and life expectancy of persons with hemophilia have improved, mainly due to the progresses of replacement therapy and antiviral drugs and to the improvement of the global comprehensive care provided by specialized centers. As a consequence, an increasing number of hemophiliacs have reached an older age and nowadays physicians in hemophilia centers find that they must handle age-related clinical problems never previously observed in this population. The management of elderly persons with congenital hemophilia is discussed in the first part of this review. The second part describes the general aspects of acquired hemophilia due to anti-factor VIII autoantibodies, focusing on the clinical management of elderly patients, one of the groups most frequently affected by this acquired bleeding disorder.

Therapy for children with henoch-schonlein purpura nephritis: a systematic review.

Although severe kidney involvement in children with Henoch-Shonlein purpura (HSP) is rarer than that in adults, morbidity should not be underevaluated and follow-up is mandatory. Some drugs are introduced as well-defined treatment options, others can be promising therapeutic alternatives. Therapy of HSP nephritis in children can range from simply steroids to combined immunosuppressant treatments. The prophylactic treatment for renal complication of patients with HSP has been sometimes suggested, but with conflicting results and ultimately not clearly proven. The treatment of overt HSP nephritis includes steroids and other immunosuppressant drugs. Methylprednisolone pulse therapy and prednisone per os are tested drugs. These steroids could be used in combination with other immunosuppressant drugs, such as cyclosporin A and cyclophosphamide. Unfortunately, of these two drugs, only cyclophosphamide is demonstrated as effective in a recent randomized controlled trial. However, since there are insufficient data and unstructured study designs, ACE-I, azathioprine, mycophenolate mofetil, and urokinase need to be more tested in childhood HSP nephritis. In addition to drugs, other techniques are used to treat the severe form of nephritis. Of these, in a multicenter study, plasmapheresis demonstrated efficacy in delaying the progression of kidney disease. However, no convincing studies have been made to date concerning either intravenous immunoglobulin, factor XIII administration, antioxidant vitamin E, and fish oil to treat HSP nephritis.

Blood doping by cobalt. Should we measure cobalt in athletes?

BACKGROUND: Blood doping is commonplace in competitive athletes who seek to enhance their aerobic performances through illicit techniques. PRESENTATION OF THE HYPOTHESIS: Cobalt, a naturally-occurring element with properties similar to those of iron and nickel, induces a marked and stable polycythemic response through a more efficient transcription of the erythropoietin gene. TESTING THE HYPOTHESIS: Although little information is available so far on cobalt metabolism, reference value ranges or supplementation in athletes, there is emerging evidence that cobalt is used as a supplement and increased serum concentrations are occasionally observed in athletes. Therefore, given the athlete's connatural inclination to experiment with innovative, unfair and potentially unhealthy doping techniques, cobalt administration might soon become the most suited complement or surrogate for erythropoiesis-stimulating substances. Nevertheless, cobalt administration is not free from unsafe consequences, which involve toxic effects on heart, liver, kidney, thyroid and cancer promotion. IMPLICATIONS OF THE HYPOTHESIS: Cobalt is easily purchasable, inexpensive and not currently comprehended within the World Anti-Doping Agency prohibited list. Moreover, available techniques for measuring whole blood, serum, plasma or urinary cobalt involve analytic approaches which are currently not practical for antidoping laboratories. Thus more research on cobalt metabolism in athletes is compelling, along with implementation of effective strategies to unmask this potentially deleterious doping practice.

Serum ferritin as a marker of potential biochemical iron overload in athletes.

OBJECTIVES: Beyond hematological manipulation, iron supplementation therapy is commonplace in athletes to counterbalance physiological or pathologic anemia and to prevent physiologic dysfunction. However, misuse of iron therapy, occasionally resulting in iron overload, is not free from metabolic risks. DESIGN: We planned to measure baseline serum ferritin concentration in sedentary individual and athletes. SETTING: The Institute of Clinical Biochemistry of the Verona University. PARTICIPANTS Serum ferritin was measured in 60 male healthy sedentary controls, 80 amateur road cyclists, 42 male professional cross-country skiers, and 88 professional male road cyclists. ASSESSMENT OF RISK FACTORS: The biochemical iron overload was ascertained by measuring baseline serum ferritin concentration as a reliable approach that mirrors the total body iron content. MAIN OUTCOME MEASUREMENTS: The concentration of serum ferritin in healthy controls was 112 +/- 78 ng/mL, whereas that of amateur cyclists, professional skiers, and professional cyclists was 127 +/- 76 ng/mL (P = 0.185), 183 +/- 130 ng/mL (P = 0.001), and 332 +/- 218 ng/mL (P < 0.001), respectively. RESULTS: Both categories of professional athletes showed significantly increased concentrations of serum ferritin, whereas the concentration of amateur cyclists was comparable to that of healthy sedentary controls. CONCLUSIONS: Professional endurance athletes have serum ferritin concentrations that are 2-fold to 3-fold higher than those of matched sedentary individuals and amateur athletes, exceeding the threshold for the diagnosis of biochemical iron overload and unveiling potential metabolic risks.

Recent acquisitions in the management of iron overload.

Chronically transfused patients develop iron overload, which leads to organ damage and ultimately to death. The introduction of the iron-chelating agent desferrioxamine mesylate dramatically improved the life expectancy of these patients. However, the very demanding nature of this treatment (subcutaneous, continuous infusion via a battery-operated portable pump) has been the motivation for attempts to develop alternative forms of treatment that would facilitate the patients' compliance. In this review, we describe the most important advances in iron-chelation therapy.

Iron-chelation therapy: an update.

Chronically transfused patients develop iron overload that leads to organ damage and ultimately to death. The introduction of the iron-chelating agent, desferrioxamine mesylate, dramatically improved the life expectancy of these patients. However, the very demanding nature of this treatment (subcutaneous continuous infusion via a battery-operated portable pump) has been the motivation for attempts to develop alternative forms of treatment that would facilitate the patients' compliance. In this review, we describe the most important advances in iron-chelating therapy. In particular, we analyze a new method of administering desferrioxamine mesylate (twice daily subcutaneous bolus injections) and a novel, orally active iron chelator (ICL670A). We also present a meta-analysis of the largest trials on the oral iron chelator deferiprone and the results of combined therapy (deferiprone and desferrioxamine).

[Clinical use of erythropoietin]. / Impiego clinico dell'eritropoietina.

The introduction of recombinant human erythropoietin (RHuEPO) has dramatically changed the therapeutic approach to the anemia of chronic renal failure. Clinical studies have also demonstrated that RHuEPO is effectiveness in various non-uremic conditions, such as anemia associated with onco-hematological disorders, prematurity, HIV infection and to reduce the exposure to allogeneic blood in surgical patients. In this review, we briefly analyze the main clinical applications of RHuEPO, with particular attention to the potential complications deriving from its use.