Risk factors for postoperative pain in the first three weeks after arthroscopic or open shoulder surgery.

INTRODUCTION: Shoulder surgery is a painful procedure. Adequate postoperative pain control increases patient satisfaction. The objectives of this study were to investigate postoperative pain development in shoulder surgery and to assess risk factors for high postoperative pain. HYPOTHESIS: Patients who undergo rotator cuff repair are more painful than patients who undergo different kinds of shoulder surgery. MATERIAL AND METHODS: Four hundred and sixty five patients who underwent shoulder surgery were included in this retrospective cohort study. A linear mixed model analysis was used to compare NRS (Numeric Rating Scale) for pain between different kinds of shoulder surgery in the first three weeks postoperatively. To assess risk factors for high postoperative pain odds ratios were calculated. RESULTS: Pain development in the first 3 weeks differed between procedures with rotator cuff repair being the most painful procedure. Risk factors for high postoperative pain were female sex and subacromial decompression with distal clavicle resection. DISCUSSION: Patients who undergo rotator cuff repair are indeed more painful than patients who undergo different kinds of shoulder surgery. With identifying these differences in pain development and the risk factors for high postoperative pain after shoulder surgery, we can optimize postoperative pain treatment. However, further research is needed to support these results. LEVEL OF EVIDENCE: IV, retrospective cohort study.

Comparison of Outcome After Percutaneous Mitral Valve Repair With the MitraClip in Patients With Versus Without Atrial Fibrillation.

Percutaneous mitral valve repair with the MitraClip is an established treatment for patients with mitral regurgitation (MR) who are inoperable or at high risk for surgery. Atrial Fibrillation (AF) frequently coincides with MR, but only scarce data of the influence of AF on outcome after MitraClip is available. The aim of the current study was to compare the clinical outcome after MitraClip treatment in patients with versus without atrial fibrillation. Between January 2009 and January 2016, all consecutive patients treated with a MitraClip in 5 Dutch centers were included. Outcome measures were survival, symptoms, MR grade, and stroke incidence. In total, 618 patients were treated with a MitraClip. Patients with AF were older, had higher N-terminal B-type natriuretic peptide levels, more tricuspid regurgitation, less often coronary artery disease and a better left ventricular function. Survival of patients treated with the MitraClip was similar for patients with AF (82%) and without AF (non-AF; 85%) after 1 year (p = 0.30), but significantly different after 5-year follow-up (AF 34%; non-AF 47%; p = 0.006). After 1 month, 64% of the patients with AF were in New York Heart Association class I or II, in contrast to 77% of the patients without AF (p = 0.001). The stroke incidence appeared not to be significantly different (AF 1.8%; non-AF 1.0%; p = 0.40). In conclusion, patients with AF had similar 1-year survival, MR reduction, and stroke incidence compared with non-AF patients. However, MitraClip patients with AF had reduced long-term survival and remained more symptomatic compared with those without AF.

Ultrasound guided Needling vs Radial Shockwave Therapy in calcific tendinitis of the shoulder: A prospective randomized trial.

PURPOSE: Ultrasound Needling(UN) and Radial Shockwave(RSWT) aim to dissolve deposits in Shoulder Calcific tendinitis. METHODS: RCT in 25 patients to compare short term effectiveness. Outcome measures were pain and functional outcome at 6 weeks and 1 year and decrease of deposits after 6 weeks. RESULTS: UN decreased deposit more than RSWT(P = 0.029). After 6 weeks, Constant, NRS and Oxford improved more in UN. After 1 year, there was no significant difference in NRS(p = 0.45) or Oxford(p = 0.32). CONCLUSION: Compared to RSWT, UN resulted in lower pain and faster resorption of calcifications after 6 weeks. No significant differences were found after 1 year.

Comparison of anatomic vs. straight femoral stem design in total hip replacement - femoral canal fill in vivo.

INTRODUCTION: The femoral canal fill between an anatomic and a straight prosthesis design in cementless total hip arthroplasty (THA) was compared. We hypothesised that the anatomic SPS stem has higher proximal fill and lesser distal fill than the straight stem. MATERIAL AND METHODS: The femoral canal fill was measured on 3 months routine postoperative x-rays at 5 levels of the stem in 50 consecutive patients, aged 35-83 years, who underwent 56 THA procedures by a single surgeon in this hospital. 22 patients received a straight design Ceramconcept Global stem, 34 patients received an anatomic design Symbios SPS stem. Both anteroposterior (AP) and lateral x-rays were combined to suggest a 3-D measurement. RESULTS: On the AP x-rays, the canal fill was significantly higher using the anatomic design stem at the proximal measurement levels, and was significantly higher at the distal levels using the straight stem. With the AP and lateral x-rays combined, the canal fill at the proximal levels was also significantly higher in the anatomic groups, nonsignificantly lower at the central level and significantly lower at the distal levels. DISCUSSION: In THA surgery, achieving high fill at the metaphysis of the femur and less fill at the diaphysis has been suggested to result in satisfactory outcome and high stability of the prosthesis. This study demonstrated that, compared to straight stem design, an anatomically designed stem has a significantly higher metaphyseal femoral canal fill.

Mortality after percutaneous edge-to-edge mitral valve repair: a contemporary review.

Percutaneous edge-to-edge mitral valve (MV) repair is a relatively new treatment option for mitral regurgitation (MR). After the feasibility and safety having been proved in low-surgical-risk patients, the use of this procedure has shifted more to the treatment of high-risk patients. With the absence of randomized controlled trials (RCT) for this particular subgroup, observational studies try to add evidence to the safety aspect of this procedure. These also provide short- and mid-term mortality figures. Several mortality predictors have been identified, which may help the optimal selection of patients who will benefit most from this technique. In this article we provide an overview of the literature about mortality and its predictors in patients treated with the percutaneous edge-to-edge device.

Encapsulated engineered myoblasts can cure Hurler syndrome: preclinical experiments in the mouse model.

Mucopolysaccharidosis type I (MPSI) is an autosomic recessive, lysosomal storage disorder due to the deficit of the enzyme α-L-iduronidase (IDUA). The disease accounts for a general impairment of tissue and organ functions, mainly including heart disease, corneal clouding, organomegaly, skeletal malformations and joint stiffness. Neurological deterioration affects the severe forms. Both haemopoietic stem cell transplantation and enzyme replacement therapy can be applied to the treatment of the disorder; however, they both present several limitations. Thus, the search for alternative strategies to complement the present procedures is highly desirable. A murine myoblast cell line engineered to overexpress IDUA was generated and enclosed in alginate microcapsules, which were intra-peritoneally implanted in the MPSI mouse model. Plasma and tissue enzyme activity induced by the treatment and urinary and tissue glycosaminoglycan content were monitored in the animals, progressively sacrificed up to 4 months after implantation. Significant induction of enzyme activity and reduction of glycosaminoglycan accumulation were detected in the implanted animals, complete normalization of deposits was achieved in two animals. Intra-peritoneal implantation of alginate microcapsule confirms to be a valid approach as an endogenous enzyme replacement procedure.

Genistein reduces glycosaminoglycan levels in a mouse model of mucopolysaccharidosis type II.

BACKGROUND AND PURPOSE: Mucopolysaccharidoses (MPS) are lysosomal storage disorders resulting from a deficit of specific lysosomal enzymes catalysing glycosaminoglycan (GAG) degradation. The typical pathology involves most of the organ systems, including the brain, in its severe forms. The soy isoflavone genistein has recently attracted considerable attention as it can reduce GAG synthesis in vitro. Furthermore, genistein is able to cross the blood-brain barrier in the rat. The present study was undertaken to assess the ability of genistein to reduce urinary and tissue GAG levels in vivo. EXPERIMENTAL APPROACH: We used mice with genetic deletion of iduronate-2-sulphatase (one of the GAG catabolizing enzymes) which provide a model of MPS type II. Two doses of genistein, 5 or 25 mg.kg(-1).day(-1), were given, in the diet for 10 or 20 weeks. Urinary and tissue GAG content was evaluated by biochemical and histochemical procedures. KEY RESULTS: Urinary GAG levels were reduced after 10 weeks' treatment with genistein at either 5 or 25 mg.kg(-1).day(-1). In tissue samples from liver, spleen, kidney and heart, a reduction in GAG content was observed with both dosages, after 10 weeks' treatment. Decreased GAG deposits in brain were observed after genistein treatment in some animals. CONCLUSIONS AND IMPLICATIONS: There was decreased GAG storage in the MPSII mouse model following genistein administration. Our results would support the use of this plant-derived isoflavone in a combined therapeutic protocol for treatment of MPS.

Gene therapy of Hunter syndrome: evaluation of the efficiency of muscle electro gene transfer for the production and release of recombinant iduronate-2-sulfatase (IDS).

Mucopolysaccharidosis type II (MPSII) is an inherited disorder due to a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). The disease is characterized by a considerable deposition of heparan- and dermatan-sulfate, causing a general impairment of physiological functions. Most of the therapeutic protocols proposed so far are mainly based upon enzyme replacement therapy which is very expensive. There is a requirement for an alternative approach, and to this aim, we evaluated the feasibility of muscle electro gene transfer (EGT) performed in the IDS-knockout (IDS-ko) mouse model. EGT is a highly efficient method of delivering exogenous molecules into different tissues. More recently, pre-treatment with bovine hyaluronidase has shown to further improve transfection efficiency of muscle EGT. We here show that, by applying such procedure, IDS was very efficiently produced inside the muscle. However, no induced IDS activity was measured in the IDS-ko mice plasma, in contrast to matched healthy controls. In the same samples, an anticipated and rapidly increasing immune response against the recombinant protein was observed in the IDS-ko vs control mice, although reaching the same levels at 5 weeks post-injection. Additional experiments performed on healthy mice showed a significant contribution of hyaluronidase pre-treatment in increasing the immune response.

Non-viral transfer approaches for the gene therapy of mucopolysaccharidosis type II (Hunter syndrome).

AIMS: Hunter syndrome is a rare X-linked lysosomal storage disorder caused by the deficiency of the housekeeping enzyme iduronate-2-sulphatase (IDS). Deficiency of IDS causes accumulation of undegraded dermatan and heparan-sulphate in various tissues and organs. Approaches have been proposed for the symptomatic therapy of the disease, including bone marrow transplantation and, very recently, enzyme replacement. To date, gene therapy strategies have considered mainly retroviral and adenoviral transduction of the correct cDNA. In this paper, two non-viral somatic gene therapy approaches are proposed: encapsulated heterologous cells and muscle electro-gene transfer (EGT). METHODS: Hunter primary fibroblasts were co-cultured with either cell clones over-expressing the lacking enzyme or with the same incorporated in alginate microcapsules. For EGT, plasmid vector was injected into mouse quadriceps muscle, which was then immediately electro-stimulated. RESULTS: Co-culturing Hunter primary fibroblasts with cells over-expressing IDS resulted in a three- to fourfold increase in fibroblast enzyme activity with respect to control cells. Fibroblast IDS activity was also increased after co-culture with encapsulated cells. EGT was able to transduce genes in mouse muscle, resulting in at least a tenfold increase in IDS activity 1-5 weeks after treatment. CONCLUSION: Although preliminary, results from encapsulated heterologous cell clones and muscle EGT encourage further evaluations for possible application to gene therapy for Hunter syndrome.

Mitochondrial permeability transition and release of cytochrome c induced by retinoic acids.

Retinoic acids, structurally related to vitamin A, inhibit the in vitro proliferation of different types of normal and neoplastic cells. The effects of all-trans, 9-cis, and 13-cis retinoic acids were tested on mitochondria isolated from rat liver. All the compounds were able to induce the membrane permeability transition observed as swelling and decrease in membrane potential, but 13-cis retinoic acid appeared to be the most effective. The latter was also shown to stimulate the release of cytochrome c from mitochondria, suggesting a potential target of retinoids in the induction of cell apoptosis. Interestingly, EGTA and cyclosporin A, which strongly inhibit the permeability transition induced by 13-cis retinoic acid, were without effect on the release of cytochrome c from the mitochondrial intermembrane space.

Physicochemical properties of arterial elastin and its associated glycoproteins.

Microfibrillar glycoproteins are a significant component of vascular elastic tissue, but little is known about their contribution to vascular physiology and pathology. We have investigated some physicochemical properties of the glycoproteins that may be pertinent to these roles. Because of the difficulty in isolating intact glycoproteins in a form and quantity suitable for physicochemical examination, we based our analysis on a comparison of the properties of porcine thoracic aorta and pulmonary artery extracted with GuHCl and collagenase (preparation GC) and after further treatment with dithioerythritol to remove glycoproteins (preparation GC/DTE). Amino acid analysis showed that GC/DTE had the amino acid composition of pure elastin while GC contained a higher proportion of polar amino acids, particularly in the aortic preparation. GC stained with alcian blue, particularly in the intimal region, but GC/DTE did not. GC had a higher water content and a slower viscoelastic response and the circumferential elastic modulus was approximately 50% lower (whether expressed in terms of sample weight or elastin content). Clearly, therefore, the microfibrils do not stiffen the network and may prevent the alignment of elastin fibers in the circumferential direction. Their effect on hydration may arise either because they impose mechanical constraints on the geometry of the network or because they modify the inter- and intramolecular hydrophobic or electrostatic interactions that influence the tissue organization and hydration. Molecular probe measurements of the intrafibrillar pore structure using radiolabeled and fluorescent probes showed that removal of the microfibrils caused a slight decrease in the extrafibrillar water space and a larger decrease in the intrafibrillar water space. Sucrose, a small probe molecule, was able to penetrate most of the intrafibrillar water space when microfibrils were present but was virtually excluded when they were not. Potentiometric titration and radiotracer assays of ion binding both showed that the microfibrils contribute a considerable negative charge (-9 mumoles/g wet tissue in the aortic preparation and -16 mumoles/g wet weight in the pulmonary artery) and increase calcium binding by approximately 30%.

Plant calreticulin is specifically and efficiently phosphorylated by protein kinase CK2.

Calreticulin isolated from spinach leaves has been specifically phosphorylated in vitro by protein kinase CK2 while animal calreticulin from rabbit liver is not a substrate of this kinase under the same conditions. Phosphoserine is the only phosphoamino acid detected. High affinity binding (Km = 4.4 microM) and a nearly stoichiometric incorporation of phosphate was determined. Partially purified spinach calreticulin is phosphorylated at the same site(s) by a copurifying protein kinase sharing biochemical properties very similar if not identical to those of mammalian CK2. Other plant calreticulins isolated from Liriodendron tulipifera appear to be also phosphorylated by CK2.