FT-IR Analysis of Structural Changes in Ketoprofen Lysine Salt and KiOil Caused by a Pulsed Magnetic Field.

High-intensity, low-frequency magnetic fields (MFs) have been widely used in the treatment of diseases and in drug delivery, even though they could induce structural changes in pharmacological molecules. Morphological changes in ketoprofen and KiOil were investigated through Fourier-transform infrared spectroscopy (FT-IR). Unsupervised principal component analysis was carried out for data clustering. Clinical validation on 22 patients with lower back pain was managed using diamagnetic therapy plus topical ketoprofen or KiOil. The Numerical Rating Scale (NRS) and Short-Form Health Survey 36 (SF-36) were used to evaluate clinical and functional response. Ketoprofen showed clear clustering among samples exposed to MF (4000−650 cm−1), and in the narrow frequency band (1675−1475 cm−1), results evidenced structural changes which involved other excipients than ketoprofen. KiOil has evidenced structural modifications in the subcomponents of the formulation. Clinical treatment with ketoprofen showed an average NRS of 7.77 ± 2.25 before and an average NRS of 2.45 ± 2.38 after MF treatment. There was a statistically significant reduction in NRS (p = 0.003) and in SF-36 (p < 0.005). Patients treated with KiOil showed an average NRS of 7.59 ± 2.49 before treatment and an average NRS of 1.90 ± 2.26 after treatment (p < 0.005). SF-36 showed statistical significance for all items except limitations due to emotional problems. A high-intensity pulsed magnetic field is an adjunct to topical treatment in patients with localized pain, and the effect of MF does not evidence significant effects on the molecules.

Bone marrow lesions of the knee: longitudinal correlation between lesion size changes and pain before and after conservative treatment by extracorporeal shockwave therapy.

BACKGROUND: Bone marrow lesions (BMLs) of the knee have become a common finding on magnetic resonance imaging (MRI), leading to a growing interest in BML, not only for its potential role in the progression of several musculoskeletal conditions, but also for its clinical impact and treatment implications. At present, there is limited and conflicting evidence regarding whether or not pain may be correlated to BML size or not. AIM: To verify the longitudinal correlation between BML size and knee pain. DESIGN: Longitudinal. SETTING: Italian Orthopedic Institute. POPULATION: The study sample was composed of 72 patients, 27 males and 45 females, with a mean age of 55.9±10.22 years and a mean BMI of 26.1±3.7 kg/m2. All patients presented with BMLs and acute knee pain. METHODS: All 72 patients underwent a knee MRI before and 6 months after a course of high energy ESWT, in order to perform a quantitative measurement of the BML areas. KOOS (Knee Injury and Osteoarthritis Outcome Score) Pain subscale scores were obtained at the same time point. A regression analysis was performed to verify the correlation between knee BML size and KOOS pain subscale score before treatment and the correlation between the reduction of BML size and the improvement of KOOS pain score 6 months after treatment. RESULTS: A statistically significant correlation between the KOOS Pain subscale and the BML size (beta=-0.362 [CI95%: -0.019/-0.05], P=0.002) was demonstrated. The clinical score and BML area significantly improved after treatment (P<0.001). The clinical improvement was correlated to the BML size reduction (beta=0.254 [CI95%: 0.001/0.017], P=0.031). CONCLUSIONS: This study confirmed a significant correlation between the BML size and the intensity of knee pain. Furthermore, the before and after study using ESWT to treat symptomatic BMLs, revealed a correlation between size reduction of BML and KOOS pain subscale score improvement, demonstrating the utility of BML reduction as a therapeutic goal. Finally, ESWT was validated as a safe and potentially effective treatment of subchondral bone marrow lesions. CLINICAL REHABILITATION IMPACT: Our results confirm that severity of pain is correlated with BML size, and furthermore, demonstrate that increases and decreases in the amount of pain reflect growth or reduction in BML size, respectively. This information may be useful for rehabilitation and decrease the reliance on MRIs for checking the progress of bone lesions. Absence or marked reduction of pain should allow for the resumption of weight-bearing and more strenuous exercises for an adequate musculoskeletal recovery.

A novel bimodal approach for treating atrophic bone non-unions with extracorporeal shockwaves and autologous mesenchymal stem cell transplant.

We propose a novel approach for the treatment of atrophic bone non-unions via parallel applications of extracorporeal shock wave therapy (ESWT) and an autologous mesenchymal stem cell transplant. The hypothesis resides on the potentiality of shock waves (SWs) to act as a tool for manipulating the patient's mesenchymal stem cells (MSCs). In addition to the conventional physical stimulus achieved by delivering SWs at the site of non-union to stimulate the well-known trophic effects on bone tissue, a series of concomitant ESWT would be administered in tandem at a bone marrow donor site, such as the iliac crest, to precondition resident bone marrow stromal cells (BMSCs) in vivo, priming resident MSCs by enlarging and conditioning their population prior to bone marrow aspiration. The resulting sample could then be treated to further augment cell concentration and injected, under fluoroscopic control, into the non-union site through a percutaneous approach.

Extracorporeal Shock Wave Therapy Is Effective in the Treatment of Bone Marrow Edema of the Medial Compartment of the Knee: A Comparative Study.

OBJECTIVE: To test the hypothesis that shock wave therapy can produce a statistically significant improvement in symptoms and imaging features of the knee bone marrow edema syndrome (BMES) within 6 months of treatment. SUBJECTS AND METHODS: Eighty-six consecutive patients suffering from BMES of the medial compartment of the knee were prescribed a course of high-energy extracorporeal shock wave therapy (ESWT) and clinically followed up at 3 and 6 months and finally from 14 to approximately 18 months after treatment. Thirty-one patients were unable to undergo ESWT but returned for the 6-month and final follow-up; these were referred to as the conservative (control) group, while the other 55 patients constituted the ESWT group. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Visual Analog Scale (VAS) score of each patient were calculated at every follow-up. The BME area was assessed using magnetic resonance imaging before treatment and at the 6-month follow-up. RESULTS: Statistically significant improvements were observed in clinical scores and in the BME area for both the ESWT and the control group (p < 0.05). The improvements in the ESWT group were statistically better in all parameters compared with the control group: the ESWT group had a reduction in the BME area of 86% versus 41% in the control group, the VAS pain score improved by 88% in the ESWT group versus 42% in the control group, and the WOMAC score improved by 65% in the ESWT group versus 22% in the control group. Clinical scores were significantly better for patients with medial tibial lesions in the ESWT group. CONCLUSION: In this study, ESWT reduced pain and the BME area in the knee, with significant clinical improvement noticed 3 months after treatment.

Mesenchymal stem cells as therapeutic target of biophysical stimulation for the treatment of musculoskeletal disorders.

BACKGROUND: Musculoskeletal disorders are regarded as a major cause of worldwide morbidity and disability, and they result in huge costs for national health care systems. Traditional therapies frequently turned out to be poorly effective in treating bone, cartilage, and tendon disorders or joint degeneration. As a consequence, the development of novel biological therapies that can treat more effectively these conditions should be the highest priority in regenerative medicine. Mesenchymal stem cells (MSCs) represent one of the most promising tools in musculoskeletal tissue regenerative medicine, thanks to their proliferation and differentiation potential and their immunomodulatory and trophic ability. Indeed, MSC-based approaches have been proposed for the treatment of almost all orthopedic conditions, starting from different cell sources, alone or in combination with scaffolds and growth factors, and in one-step or two-step procedures. While all these approaches would require cell harvesting and transplantation, the possibility to stimulate the endogenous MSCs to enhance their tissue homeostasis activity represents a less-invasive and cost-effective therapeutic strategy. Nowadays, the role of tissue-specific resident stem cells as possible therapeutic target in degenerative pathologies is underinvestigated. Biophysical stimulations, and in particular extracorporeal shock waves treatment and pulsed electromagnetic fields, are able to induce proliferation and support differentiation of MSCs from different origins and affect their paracrine production of growth factors and cytokines. SHORT CONCLUSIONS: The present review reports the attempts to exploit the resident stem cell potential in musculoskeletal pathologies, highlighting the role of MSCs as therapeutic target of currently applied biophysical treatments.

Soft-focused extracorporeal shock waves increase the expression of tendon-specific markers and the release of anti-inflammatory cytokines in an adherent culture model of primary human tendon cells.

Focused extracorporeal shock waves have been found to upregulate the expression of collagen and to initiate cell proliferation in healthy tenocytes and to positively affect the metabolism of tendons, promoting the healing process. Recently, soft-focused extracorporeal shock waves have also been found to have a significant effect on tissue regeneration. However, very few in vitro reports have dealt with the application of this type of shock wave to cells, and in particular, no previous studies have investigated the response of tendon cells to this impulse. We devised an original model to investigate the in vitro effects of soft-focused shock waves on a heterogeneous population of human resident tendon cells in adherent monolayer culture. Our results indicate that soft-focused extracorporeal shock wave treatment (0.17 mJ/mm(2)) is able to induce positive modulation of cell viability, proliferation and tendon-specific marker expression, as well as release of anti-inflammatory cytokines. This could prefigure a new rationale for routine employment of soft-focused shock waves to treat the failed healing status that distinguishes tendinopathies.

Effectiveness of extracorporeal shock wave therapy in bone marrow edema syndrome of the hip.

There is no gold standard for treatment of bone marrow edema syndrome of the hip (BMESH). Usually, treatment is conservative, owing to the favorable and self limiting prognosis. In musculoskeletal disorders, the effectiveness of extracorporeal shock wave therapy (ESWT) has been widely recognized and recent research supports its use in the treatment of the first stages of avascular osteonecrosis of the proximal femur and in other conditions where bone marrow edema is present. On this basis, we performed a prospective study to evaluate the effectiveness of ESWT in normalizing the symptoms and imaging features of BMESH. Twenty consecutive symptomatic patients underwent two treatments of high-energy ESWT and were followed-up at 2, 3 and 6 months, with a final clinical follow-up at mean 15.52 ± 1.91 months. Patients underwent magnetic resonance imaging of the hip and were evaluated according to the Harris hip score. The mean improvement in HHS over the course of the study was of 58.5 ± 14.9 points (p < 0.0001), and the mean edema area reduced from 981.9 ± 453.2 mm(2) pre-treatment to 107.8 ± 248.1 mm(2) at 6 months. ESWT seems to be a powerful, non-pharmacological tool that produces rapid pain relief and functional improvement and aids the normalization of the vascular and metabolic impairments which characterize BMESH.

Extracorporeal shock wave therapy in musculoskeletal disorders: a review.

Regenerative therapy is one of the most challenging and intriguing branches of modern medicine. Basic research has demonstrated the effectiveness of extracorporeal shockwaves (ESWT) in stimulating biological activities that involve intra-cell and cell-matrix interactions. These interactions are at the basis of the current clinical applications, and open the horizons to new applications in tissue regeneration. It is also feasible that shock waves could be used to treat various orthopaedic pathologies, removing the need for surgery. However, suitable translational studies need to be performed before ESWT can become a valid alternative to surgery.

Extracorporeal shock wave therapy in pillar pain after carpal tunnel release: a preliminary study.

"Pillar pain" is a relatively frequent complication after surgical release of the median nerve at the wrist. Its etiology still remains unknown although several studies highlight a neurogenic inflammation as a possible cause. Pillar pain treatment usually includes rest, bracing and physiotherapy, although a significant number of patients still complain of painful symptoms two or even three years after surgery. The aim of this study was to investigate the efficacy of low-energy, flux density-focused extracorporeal shock wave therapy (ESWT) in the treatment of pillar pain. We treated 40 consecutive patients with ESWT who had pillar pain for at least six months after carpal tunnel release surgery, and to our knowledge, this is the first study that describes the use of ESWT for treating this condition. Our results show that in all of the treated patients, there was a marked improvement: the mean visual analogue scale (VAS) score decreased from 6.18 (±1.02) to 0.44 (±0.63) 120 d after treatment, and redness and swelling of the surgical scar had also decreased significantly.

Effectiveness of ESWT in the treatment of Kienböck's disease.

Kienböck's disease is a rare, painful disorder of the wrist that can seriously restrict the quality of life of patients who have the disease. Although a century has passed since the pathology was identified, its etiology is still uncertain, with mechanical, traumatic, vascular, and systemic factors all being advocated. Likewise, there is no consensus regarding treatment, and no approach-either conservative or surgical-has been demonstrated to yield significantly better outcomes. Extracorporeal shock wave treatment (ESWT) has been effective in stimulating fracture healing, and it has been adopted as a therapy to restore vascular supply in those bone conditions characterized by vascular impairment. We report our experience in treating 22 patients with Kienböck's disease at various stages with high-energy shock waves. Our results indicate that ESWT has a positive effect on pain and functional impairment of the wrist, and may delay surgical treatment. Further studies are necessary to understand the full potential of this therapeutic tool.

Safety and reliability of the drug tolerance test: our experience in 739 patients.

BACKGROUND: Drug tolerance tests (DTTs) are commonly used to find a safe therapeutic alternative for patients with previous type B adverse drug reactions (ADRs), but few studies on safety and reliability are available. METHODS: We retrospectively studied 739 subjects with previous ADRs who underwent DTTs; 12 months after the test, use of the tested drug(s) and occurrence of ADRs were investigated in 260 of them. RESULTS: ADRs to antibiotics and nonsteroidal anti-inflammatory drugs were the main reasons for which DTTs were requested. 925 DTTs were performed in the 739 patients, with 97 ADRs. Twelve months after the test, 125/260 patients interviewed had used the tested drug(s): 118 of them experienced no ADR, 4 experienced 'true' ADRs, and 3 reported predictable/unclear reactions. CONCLUSION: Our data show that DTTs are safe and reliable at 1 year, but patients and general practitioners do not trust them. It is strongly advisable to have better information on methods, benefits, risks and reliability of DTTs.