Nicola Portinaro

Arthroscopic Stabilization of the Shoulder in Adolescent Athletes Participating in Overhead or Contact Sports

PURPOSE To investigate the outcome of arthroscopic capsular repair for shoulder instability in an active adolescent population participating in overhead or contact sports. METHODS We identified 67 patients (aged 13 to 18 years) with post-traumatic recurrent shoulder instability for inclusion in the study from our computer database. Of these patients, 65 (96%) were available for clinical review. There were 44 male and 21 female patients, with a mean age of 16 years at the time of surgery. All patients participated in overhead or contact sports at a competitive level. Arthroscopic capsulolabral repair was performed after at least 6 months of failed nonoperative treatment. The mean follow-up was 63 months. Shoulder range of motion and functional outcomes were measured preoperatively and postoperatively with Single Assessment Numeric Evaluation (SANE), Rowe, and American Shoulder and Elbow Surgeons (ASES) scores. Furthermore, type of sport, time until surgery, and number of dislocations were analyzed from our database to find any correlation with the recurrence rate. RESULTS At final follow-up, the mean SANE score was 87.23% (range, 30% to 100%) (preoperative mean, 46.15% [range, 20% to 50%]); the mean Rowe score was 85 (range, 30 to 100) (preoperative mean, 35.9 [range, 30 to 50]); and the mean ASES score was 84.12 (range, 30 to 100) (preoperative mean, 36.92 [range, 30 to 48]). The mean forward flexion and external rotation with the arm at 90° abduction did not change from preoperative values; 81% of the patients returned to their preinjury level of sport, and the rate of failure was 21%. The recurrence rate was not related to the postoperative scores (P = .556 for SANE score, P = .753 for Rowe score, and P = .478 for ASES score), the number of preoperative episodes of instability (P = .59), or the time from the first instability episode to the time of surgery (P = .43). There was a statistically significant relation (P = .0021) between recurrence and the type of sport practiced. Recurrence rate was related to the type of sport practiced. CONCLUSIONS Arthroscopic stabilization is a reasonable surgical option even in an adolescent population performing sports activities. However, it must be emphasized to the patients and their relatives that the recurrence rate that could be expected after an arthroscopic procedure is higher than in the adult population. LEVEL OF EVIDENCE Level IV, therapeutic case series.

Prevalence of Associated Lesions in Anterior Cruciate Ligament Reconstruction Correlation With Surgical Timing and With Patient Age, Sex, and Body Mass Index

Background: Knee instability resulting from anterior cruciate ligament (ACL) rupture is an important risk factor for the onset of meniscal tears and cartilage injuries. A delay of the ligament reconstruction further increases this risk. There is currently no agreement on the right time for surgical ACL reconstruction. Purpose: To verify the correlation of time to ACL reconstruction, patient age, sex, and body mass index (BMI) with the prevalence of meniscal tears and cartilage injuries, as well as to identify the proper surgical timing to decrease the risk of developing associated injuries. Study Design: Cohort study; Level of evidence, 3. Methods: The medical records of 988 patients who underwent primary ACL reconstruction between January 2010 and May 2014 were analyzed to collect data on the prevalence of meniscal tears and cartilage injuries, surgical timing, and patient sex, age, and BMI. Logistic regression was performed to estimate the association between the prevalence of intra-articular lesions and the independent variables of surgical timing, sex, age, and BMI. Results: The risk of developing at least an associated lesion increased by an average of 0.6% for each month of delay of surgical reconstruction. The odds ratio (OR) for developing an intra-articular lesion was 1.989 (95% CI, 1.403-2.820) in those waiting more than 12 months for ACL reconstruction. A 12-month delay for the intervention nearly doubled the risk of developing a medial meniscal tear (OR, 1.806 [95% CI, 1.317-2.475]) but did not modify the risk for the lateral meniscus (OR, 1.183 [95% CI, 0.847-1.653]). Concerning cartilage lesions, the risk after a 12-month delay increased in the medial compartment (femoral condyle: OR, 2.347 [95% CI, 1.499-3.676]; tibial plateau: OR, 5.574 [95% CI, 1.911-16.258]). In the lateral femoral condyle, the risk became significant in patients who underwent surgery more than 60 months after ACL injury as compared with those treated in the first 3 months (OR, 5.949 [95% CI, 1.825-19.385]). Lateral tibial plateau lesions did not seem to increase significantly. Male sex was a risk factor for the onset of lateral meniscal tears (OR, 2.288 [95% CI, 1.596-3.280]) and medial tears (OR, 1.752 [95% CI, 1.280-2.399]). Older age (OR, 1.017 [95% CI, 1.006-1.029]) and increased BMI (OR, 1.120 [95% CI, 1.072-1.169]) were risk factors for the occurrence of at least 1 associated lesion. Conclusion: ACL reconstruction within 12 months of injury can significantly reduce the risk of meniscal tears and chondral lesions. The close association between BMI and prevalence of associated lesions suggests that attention be paid to patients with an elevated BMI when considering the timing of ACL reconstruction surgery.

A central role for intermolecular dityrosine cross-linking of fibrinogen in high molecular weight advanced oxidation protein product (AOPP) formation.

BACKGROUND Advanced oxidation protein products (AOPPs) are dityrosine cross-linked and carbonyl-containing protein products formed by the reaction of plasma proteins with chlorinated oxidants, such as hypochlorous acid (HOCl). Most studies consider human serum albumin (HSA) as the main protein responsible for AOPP formation, although the molecular composition of AOPPs has not yet been elucidated. Here, we investigated the relative contribution of HSA and fibrinogen to generation of AOPPs. METHODS AOPP formation was explored by SDS-PAGE, under both reducing and non-reducing conditions, as well as by analytical gel filtration HPLC coupled to fluorescence detection to determine dityrosine and pentosidine formation. RESULTS Following exposure to different concentrations of HOCl, HSA resulted to be carbonylated but did not form dityrosine cross-linked high molecular weight aggregates. Differently, incubation of fibrinogen or HSA/fibrinogen mixtures with HOCl at concentrations higher than 150 μM induced the formation of pentosidine and high molecular weight (HMW)-AOPPs (>200 k Da), resulting from intermolecular dityrosine cross-linking. Dityrosine fluorescence increased in parallel with increasing HMW-AOPP formation and increasing fibrinogen concentration in HSA/fibrinogen mixtures exposed to HOCl. This conclusion is corroborated by experiments where dityrosine fluorescence was measured in HOCl-treated human plasma samples containing physiological or supra-physiological fibrinogen concentrations or selectively depleted of fibrinogen, which highlighted that fibrinogen is responsible for the highest fluorescence from dityrosine. CONCLUSIONS A central role for intermolecular dityrosine cross-linking of fibrinogen in HMW-AOPP formation is shown. GENERAL SIGNIFICANCE These results highlight that oxidized fibrinogen, instead of HSA, is the key protein for intermolecular dityrosine formation in human plasma.

Pathophysiology of tobacco smoke exposure : Recent insights from comparative and redox proteomics

First-hand and second-hand tobacco smoke are causally linked to a huge number of deaths and are responsible for a broad spectrum of pathologies such as cancer, cardiovascular, respiratory, and eye diseases as well as adverse effects on female reproductive function. Cigarette smoke is a complex mixture of thousands of different chemical species, which exert their negative effects on macromolecules and biochemical pathways, both directly and indirectly. Many compounds can act as oxidants, pro-inflammatory agents, carcinogens, or a combination of these. The redox behavior of cigarette smoke has many implications for smoke related diseases. Reactive oxygen and nitrogen species (both radicals and non-radicals), reactive carbonyl compounds, and other species may induce oxidative damage in almost all the biological macromolecules, compromising their structure and/or function. Different quantitative and redox proteomic approaches have been applied in vitro and in vivo to evaluate, respectively, changes in protein expression and specific oxidative protein modifications induced by exposure to cigarette smoke and are overviewed in this review. Many gel-based and gel-free proteomic techniques have already been used successfully to obtain clues about smoke effects on different proteins in cell cultures, animal models, and humans. The further implementation with other sensitive screening techniques could be useful to integrate the comprehension of cigarette smoke effects on human health. In particular, the redox proteomic approach may also help identify biomarkers of exposure to tobacco smoke useful for preventing these effects or potentially predictive of the onset and/or progression of smoking-induced diseases as well as potential targets for therapeutic strategies.

Red blood cells protect albumin from cigarette smoke-induced oxidation.

Different studies reported the presence of oxidized (carbonylated) albumin in the extravascular pool, but not in the intravascular one of cigarette smokers. In this study we attempted to explain this apparent discrepancy exposing human serum albumin (HSA) to aqueous cigarette smoke extract (CSE). CSE induces HSA carbonylation and oxidation of the HSA Cys34 sulfhydryl group. An antioxidant action of glutathione, cysteine, and its synthetic derivative N-acetylcysteine was observed only at supra-physiological concentrations, suggesting that physiological (plasma) concentrations of glutathione and cysteine in the low micromolar range are ineffective in preventing cigarette smoke–induced oxidation of HSA. Differently, human erythrocytes resulted to be protective towards CSE-induced oxidation (carbonylation and thiol oxidation) of both HSA and total human plasma proteins.

The role of ultrasonography in the diagnosis of developmental dysplasia of the hip.

Developmental dysplasia and dislocation of the hip (DDH) have great clinical interest with a reported case incidence in developed countries of 15 to 50 per 1000 live births. Early DDH treatment is effective, and early diagnosis is the key to treatment. Late diagnosis and delayed treatment lead to a significant increase in long-term morbidity. Early diagnosis need has motivated development of screening programs. Developmental dysplasia and dislocation of the hip is related to some known risk factors: female sex, breech and other abnormal positions at birth, positive family history, joint laxity, oligohydramnios, primiparity, cesarean section associated with difficulty presentations, intrauterine growth retardation, postural foot deformities, torticollis, high birth weight, older maternal age, postmaturity, and left greater than right hip involvement. Clinical screening programs of neonates for DDH have been used for the past 60 years including clinical tests (Ortolani, Barlow, and Galeazzi) that are very specific but with only approximately 60% sensitivity. Clinical tests have not as yet demonstrated acceptable reproducibility. To aid in early detection of DDH, ultrasonographic (US) methods were developed. Graf and Harcke noted advantages of US including lack of radiation, ability to visualize nonosseous structures, noninvasive, painless, repeatability, and multiplanar examination with prognostic parameters. Progressive sophistication of US allowed development of ability to do dynamic testing for instability with progressive monitoring of resolution of instability as a treatment adjunct that is more reliable than clinical evaluation alone.8Y10,40 Graf suggested that the overall cost of US screening is balanced by the cost of later need for more complex management of late diagnosis and treatment. Subsequent introduction of newer US methods confirmed its usefulness in avoiding late diagnosis of DDH (6 months to 4 years of age). In clinically unstable hips, US confirmed instability and femoral head displacement bilaterally when only unilateral involvement and instability had been clinically diagnosed. Ultrasonographic screening compared with clinical screening has been associated with the highest number of favorable outcomes of hip normalization without surgery. The United Kingdom Collaborative Hip Trial Group recently clearly showed that US screening in association with clinical evaluation allowed reduction in splinting rates without increased risks of adverse clinical, economic, or psychosocial outcomes. It is imperative to perform a clinical examination at each routine assessment of newborns. Clinical or sonographic methods alone are susceptible to some degree of failure, but in combination, failure rate of diagnosis is markedly diminished. Several authors advocated US as an effective screening method for DDH. When performed at birth, US detected nearly all abnormal hips and no hip that was considered normal at birth was later shown to be abnormal. Although US has been demonstrated to be a useful adjunct to DDH diagnosis, there is potential risk of misuse with false-positive and false-negative results which creates lack of concordance among physicians regarding timing of US use. Literature data are divided between those who propose universal US screening of all newborns and others who recommend selective US screening using clinical screening as a base.

I.S.Mu.L.T - Rotator cuff tears guidelines

Despite the high level achieved in the field of shoulder surgery, a global consensus on rotator cuff tears management is lacking. This work is divided into two main sessions: in the first, we set questions about hot topics involved in the rotator cuff tears, from the etiopathogenesis to the surgical treatment. In the second, we answered these questions by mentioning Evidence Based Medicine. The aim of the present work is to provide easily accessible guidelines: they could be considered as recommendations for a good clinical practice developed through a process of systematic review of the literature and expert opinion, in order to improve the quality of care and rationalize the use of resources.

Expression Profiling of Genes Involved in Collagen Turnover in Tendons from Cerebral Palsy Patients

Cerebral palsy (CP) is a nonprogressive central nervous system lesion clinically characterized by impairment of voluntary movement related to spasticity, time of activation, and strength of scheletal muscle. Altered muscular control may act on tendon structure and influence extracellular matrix homeostasis, in particular, collagen. The effect of spasticity on collagen turnover in CP patients’ tendons has not been described previously. We studied collagen turnover related genes in the gracilis and semitendinosus tendons of diplegic (n = 6) and quadriplegic (n = 15) patients, compared to normal subjects (n = 7). In particular, using real time RT-PCR, we analyzed the mRNA levels of the major extracellular matrix (ECM) components collagen type I (COL-I, alpha 2 chain COL1A2), the matrix metalloproteinase-1 (MMP-1) and the tissue inhibitor of MMP (TIMP-1), the enzyme responsible for collagen maturation lysyl hydroxylase 2b (LH2b), of the matricellular protein involved ECM remodelling (secreted protein acidic and rich in cysteine, SPARC), and the transforming growth factor-β1 (TGF-β1), a multipotent cytokine involved in collagen turnover. Our results show that gene expression profiles are quite different in CP samples compared to normal ones. In fact, spasticity induces relevant modifications of tendons at the molecular level, which modify their phenotypes to respond to the higher mechanical loading and increased functional demands. Interestingly, hypertonic quadriplegic subjects displayed the highest mRNA levels of COL1A2, LH2b, TGF-β1, and SPARC, suggesting that their tendons undergo higher mechanical loading stimulation.

Assessment of glutathione/glutathione disulphide ratio and S-glutathionylated proteins in human blood, solid tissues, and cultured cells

Glutathione (GSH) is the major non-protein thiol in humans and other mammals, which is present in millimolar concentrations within cells, but at much lower concentrations in the blood plasma. GSH and GSH-related enzymes act both to prevent oxidative damage and to detoxify electrophiles. Under oxidative stress, two GSH molecules become linked by a disulphide bridge to form glutathione disulphide (GSSG). Therefore, assessment of the GSH/GSSG ratio may provide an estimation of cellular redox metabolism. Current evidence resulting from studies in human blood, solid tissues, and cultured cells suggests that GSH also plays a prominent role in protein redox regulation via S -glutathionylation, i.e., the conjugation of GSH to reactive protein cysteine residues. A number of methodologies that enable quantitative analysis of GSH/GSSG ratio and S-glutathionylated proteins (PSSG), as well as identification and visualization of PSSG in tissue sections or cultured cells are currently available. Here, we have considered the main methodologies applied for GSH, GSSG and PSSG detection in biological samples. This review paper provides an up-to-date critical overview of the application of the most relevant analytical, morphological, and proteomics approaches to detect and analyse GSH, GSSG and PSSG in mammalian samples as well as discusses their current limitations.

Plasma protein thiolation index (PTI) as a biomarker of thiol-specific oxidative stress in haemodialyzed patients.

The role of oxidative stress in patients with end stage renal disease (ESRD), which occurs at significantly higher levels than in the general population, is often underestimated in clinical practice. Emerging evidence highlights the strong correlation of oxidative stress with chronic inflammation and cardiovascular disease, which are highly prevalent in most patients on maintenance haemodialysis (HD) and are a major risk factor for mortality in this population. In this study, total plasma thiols and plasma S-thiolated proteins were measured in patients with ESRD, before and after a regular HD session, and compared to age-matched healthy subjects. We found a significant decrease in the level of total plasma thiols and, conversely, a significant increase in the level of S-thiolated proteins in these patients. In most patients, post-HD plasma level of total thiols did not differ from the one in healthy subjects, whereas plasma level of S-thiolated proteins was lower in HD patients than in age-matched healthy controls. This suggests that a single HD session restores plasma thiol redox status and re-establishes the antioxidant capacity of plasma thiols. Additionally, we determined protein thiolation index (PTI), i.e., the molar ratio between the sum of all low molecular mass thiols bound to S-thiolated plasma proteins and protein free cysteinyl residues. Patients with ESRD had a significantly higher PTI compared to age-matched healthy subjects and HD was associated with a decrease in PTI to normal, or lower than normal, levels. Although this study is limited in size, our results suggest that PTI is a useful indicator of thiol-specific oxidative stress in patients with ESRD on maintenance HD. This study also emphasizes that PTI determination is a cheap and simple tool suitable for large-scale clinical studies that could be used for routine screening of thiol-specific oxidative stress.