Mesenchymal stem cell implantation provides short-term clinical improvement and satisfactory cartilage restoration in patients with knee osteoarthritis but the evidence is limited: a systematic review performed by the early-osteoarthritis group of ESSKA-European knee associates section.

PURPOSE: Implantation of mesenchymal stem cells (MSCs) is a potential cell-based modality for cartilage repair. Currently, its clinical use largely surrounds focal cartilage defect repair and intra-articular injections in knee osteoarthritis. The MSCs' implantation efficacy as a treatment option for osteoarthritis remains contentious. This systematic review aims to evaluate studies that focused on MSCs implantation in patients with knee OA to provide a summary of this treatment option outcomes. METHODS: A systematic search was performed in PubMed (Medline), Scopus, Cinahl, and the Cochrane Library. Original studies investigating outcomes of MSCs implantations in patients with knee OA were included. Data on clinical outcomes using subjective scores, radiological outcomes, and second-look arthroscopy gradings were extracted. RESULTS: Nine studies were included in this review. In all included studies, clinical outcome scores revealed significantly improved functionality and better postoperative pain scores at 2-3 years follow-up. Improved cartilage volume and quality at the lesion site was observed in five studies that included a postoperative magnetic resonance imaging assessment and studies that performed second-look arthroscopy. No major complications or tumorigenesis occurred. Outcomes were consistent in both single MSCs implantation and concurrent HTO with MSCs implantation in cases with excessive varus deformity. CONCLUSION: According to the available literature, MSCs implantation in patients with mild to moderate knee osteoarthritis is safe and provides short-term clinical improvement and satisfactory cartilage restoration, either as a standalone procedure or combined with HTO in cases with axial deformity. However, the evidence is limited due to the high heterogeneity among studies and the insufficient number of studies including a control group and mid-term outcomes. LEVEL OF EVIDENCE: IV.

Intraarticular injection of microfragmented adipose tissue plus arthroscopy in isolated primary patellofemoral osteoarthritis is clinically effective and not affected by age, BMI, or stage of osteoarthritis.

PURPOSE: This study aimed to report the clinical and functional results of a series of patients with isolated primary patellofemoral osteoarthritis (PFOA) treated with intraarticular injection of microfragmented autologous adipose tissue plus knee arthroscopy. The results were also analyzed in relation to the age and body mas index (BMI) of patients, and to the stage of PFOA. METHODS: Twenty-three patients with early-to-moderate (stage 1-3 according to the Iwano classification system) PFOA who received this treatment were retrospectively analyzed, with a mean follow-up of 22.1 ± 4.2 months. Patients were assessed using the International Knee Society (IKS) knee and function and visual analog scale (VAS) scores, and relative to their capacity for climbing stairs. Differences in improvements of IKS and VAS scores in relation to age (< 60 versus ≥ 60 years), BMI (< 30 versus ≥ 30 kg/m2), and stage of PFOA (stages 1-2 versus stage 3) were finally analyzed. RESULTS: The mean IKS knee score significantly improved from 35.6 ± 14.9 points preoperatively to 61.9 ± 17.8 points at the latest follow-up, while the mean IKS function score significantly improved from 52.0 ± 14.7 points preoperatively to 82.3 ± 19.1 points at the latest follow-up. The mean VAS score significantly decreased from 8.7 ± 2.2 preoperatively to 5.2 ± 2.5 at the latest follow-up. A significant improvement in the capacity to climb stairs was found. No significant differences in improvements of IKS knee and function and VAS scores were found in relation to age, BMI, or stage of PFOA. CONCLUSION: Intraarticular injection of microfragmented autologous adipose tissue following arthroscopic debridement significantly improved overall clinical and functional scores in patients with early or moderate isolated primary PFOA at a mean follow-up of almost 2 years. Improvements were not significantly affected by age, BMI, or stage of PFOA. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Obesity increases the risk of conversion to total knee arthroplasty after unicompartimental knee arthroplasty: a meta-analysis.

PURPOSE: The aim of this meta-analysis was to to determine the influence of obesity on patient outcome and implant survivorship after primary unicompartmental knee arthroplasty (UKA). METHODS: A PRISMA systematic review was conducted by searching the Medline (PubMed), EMBASE, and Cochrane electronic databases to identify clinical studies investigating the effect of obesity on outcomes after UKA. Data were collected on aspecifically designed extraction form. Methodological quality was assessed using the Methodological Index for Nonrandomized Studies score. Quantitative meta-analysis was carried out using RevMan 5.4 software. RESULTS: A total of 17 studies were included; 43,845 primary UKA patients were classified by their BMI: on-obese (BMI 25 to < 30 kg/m2); obese (BMI 30 to < 35 kg/m2); severely obese (BMI > 35 kg/m2). Pooled analysis showed no statistically significant difference in Knee Society Score (KSS) pain in the obese (n.s.) and the severely obese (n.s.) group compared to the non-obese group, while the KSS function score was lower in the severely obese (P = 0.0002) compared to the obese (P = 0.06) and the non-obese group. Postoperative Oxford Knee Score (OKS) was lower in the obese group (P = 0.01) but not in the severely obese group (P = 0.16). Postoperative Range of Motion (ROM) was comparable in the obese and non-obese group (P = 0.16). Implant survival at 10 years follow-up was significantly lower in the obese (82.5-95.3%; P < 0.0001) and the severely obese group (87.5-93.8%; P < 0.0001) thanthe non-obese group (83.6-98.6%). CONCLUSION: Obesity and severe obesity were associated with significantly higher revision and lower implant survival rates. Obesity did not influence clinical and most functional outcomes after UKA, whereas KSS function score was significantly lower only for the severely obese patient group. LEVEL OF EVIDENCE: III, meta-analysis.

Femoral component malrotation is not correlated with poor clinical outcomes after total knee arthroplasty.

PURPOSE: Proper rotational alignment of the femoral component is critical for a successful total knee arthroplasty (TKA). The aim of this systematic review was to analyse the available literature to examine the effect of the TKA femoral component malrotation on clinical outcomes and assess a cut-off value for femoral rotation leading to revision surgery. METHODS: A detailed and systematic search from 1996 to 2019 of the PUBMED, Medline, Cochrane Reviews and Google Scholar databases had been performed using the keyword terms "total knee arthroplasty OR replacement" AND "femoral alignment OR malalignment OR femoral rotation OR malrotation" AND "clinical outcome". We used the methodological index for non-randomized studies (MINORS) to identify scientifically sound articles in a reproducible format. RESULTS: Eleven articles met inclusion criteria. A total of 896 arthroplasties were included in this review; 409 were unexplained painful TKA patients, while 487 were painless TKA patients. The mean age of patients was 67.5 (± 2.1) years. The mean post-operative follow-up delay was 46.8 (± 32.2) months. The mean of MINORS score was 21 points indicating good methodological quality in the included studies. CONCLUSIONS: The present review confirms that the malrotation of the femoral component in TKA does not correlate automatically to poor clinical and functional outcome. The clinical relevance of this study was that, to improve accuracy in femoral component rotation, surgeons should consider the anatomical variability of femur in each knee and perform additional measurements pre- and intra-operatively. Taking a more accurate approach will shed light on unanswered questions in unhappy TKA. LEVEL OF EVIDENCE: III.

Humeral shaft non-union in the elderly: Results with cortical graft plus stem cells.

INTRODUCTION: Humeral shaft is a common site of fracture non-union. Biology and bone quality represent some of the problems that the orthopaedic surgeon has to face up in the elderly. The goals of treatment of humeral shaft non-union are the achievement of mechanical stability and creation of a favourable biologic environment. Bone graft and stem cells are some of the augmentation techniques available to reach these goals. PURPOSE: Evaluation of the outcomes of humeral shaft non-union in elderly population treated with cortical allograft and stem cells. MATERIAL AND METHODS: A cohort of 21 patients with humeral shaft non-union was reviewed. Inclusion criteria were patients aged more than 65 years, with a diagnosis of humeral shaft non-union treated with cortical allograft and stem cells. Primary endpoints were 'bone healing' and 'time-to-union'. Secondary endpoints were shoulder and elbow function and patients' quality of life with Oxford Shoulder Score (OSS), Constant score and EuroQol-5D (EQ-5D). RESULTS: 6 patients met the inclusion criteria. In 5 of them, the cortical allograft was opposite to a plate, whereas in the other one a "Sandwich" technique was chosen because of large osteolysis. 'Bone healing' occurred in all patients after a mean of 3.3 months (range 2-5). In all but two patients, the elbow range of motion was in almost normal range (15-130). The mean OSS was 35.8 (+/- 6.4), whereas the mean Constant was 53.3 (+/- 2.2). The mean EQ-5D index was 0.451 (+/- 0.21). DISCUSSION: Bone healing occurred in all patients, with a time-to-union comparable or even better compared with other series. The use of cortical bone graft provide both stability and biological benefit, whereas stem cells improve the non-union environmental biology. Functional outcomes were lower than other series and patients' quality of life was similar to Italian elderly women. CONCLUSION: The use cortical allograft with stem cells is a viable strategy to treat humeral shaft non-union in the elderly.

Management of the First Patellar Dislocation: A Narrative Review.

First patellar dislocation is a common injury of the knee, involving often adolescents and the active population. The consequences of the first episode can be various and potentially disabling. Among these, acute patellar dislocation can often result in recurrent patellar instability. Recurrent patellar instability is certainly multifactorial but depends primarily on the injury of the medial patellofemoral ligament (MPFL), the major soft-tissue stabilizer of the patella. Some classifications are extremely useful in establishing the diagnosis and therapy in patellofemoral disease, in particular in terms of instability. Among those, Henri Dejour and WARPS (weak atraumatic risky anatomy pain and subluxation)/STAID (strong traumatic anatomy normal instability and dislocation) classifications are certainly the most frequently used. There is no clear agreement on the management of the first patellar dislocation. A conservative approach seems to be the first choice in most of cases, but the presence of patellar displacement or osteochondral fractures makes surgery mandatory at the beginning. In addition, there is no clear consensus on which surgical strategy should be used to approach first dislocation, in relation to the possible variation in location of the MPFL injury, and to the eventual presence of preexisting predisposing factors for patellar instability. MPFL reconstruction may theoretically be more reliable than repair, while there is no clear evidence available that osseous abnormality should be addressed after the first episode of patellar dislocation. A narrative review was conducted to report the etiology, the diagnosis and all the possible treatment options of the first patellar dislocation. Modern classifications of the patellofemoral instability were also presented.

Preliminary results of autologous adipose-derived stem cells in early knee osteoarthritis: identification of a subpopulation with greater response.

PURPOSE: The purpose of this study was to report the clinical and functional results of a series of patients with early knee osteoarthritis (KOA) treated with the intra-articular injection of autologous adipose-derived stem cells (aASCs) plus arthroscopic debridement. The hypothesis was that protocol would significantly improve the clinical and functional outcomes in patients with early KOA. METHODS: Fifty-two patients with early KOA, who received arthroscopic debridement followed by percutaneous injection of aASCs, were enrolled into the study and retrospectively analyzed with an average follow-up of 15.3 (range, 6 to 24) months. Patients were assessed through the IKS knee and function scores and VAS pain scale. RESULTS: The mean IKS knee score improved from 37.4 (range, 14 to 79) points pre-operatively to 62.6 (range, 27 to 95) points at the latest follow-up (p < < 0.01). The mean IKS function score improved from 57.2 (range, 25 to 100) points pre-operatively to 83.0 (range, 35 to 100) points at the latest follow-up (p < < 0.01). The mean VAS score decreased from 8.5 (range, 3 to 10) pre-operatively to 5.1 (range, 0 to 8) at the latest follow-up (p < < 0.01). Additionally, patients with a pre-operative VAS score greater than 8 were found to show greater clinical and functional benefits compared with patients with VAS score lower than 8. CONCLUSIONS: The knee injection of aASCs associated to arthroscopic debridement increased significantly the clinical and functional scores in patients with early KOA at a mid-term follow-up, especially those with higher pre-operative VAS scores.

ECM Remodeling in Breast Cancer with Different Grade: Contribution of 2D-DIGE Proteomics.

Tumor extracellular matrix (ECM) plays a pivotal role in outcome of breast cancer (BC) patients. Overexpression of 58 genes, encoding 43 structural ECM proteins, has been identified to determine a specific cluster of BC with accelerated metastatic potential only in the undifferentiated (grade III) phenotype. The scope of this study is to characterize protein repertoire able to predict patient outcome in BC according to ECM gene expression pattern and histological grade. The differential proteomic analysis is based on 2D-differential gel electrophoresis, MALDI-MS, bioinformatics, and immunoblotting. Results suggest a relationship among ECM remodeling, signal mechanotransduction, and metabolic rewiring in BCs characterized by a specific mRNA ECM signature and identified a set of dysregulated proteins characteristic of hormone receptors expression as fibrinogen-ß chain, collagen α-1(VI) chain, and α-1B-glycoprotein. Furthermore, in triple negative tumors with ECM signature, the FGG and α5ß1/αvß3 integrins increase whereas detyrosinated α-tubulin and mimecan decrease leading to unorganized integrin presentation involving focal adhesion kinase, activation of Rho GTPases associated to epithelial mesenchymal transition. In hormone receptors negative BCs characterized by a specific ECM gene cluster, the differentially regulated proteins, identified in the present study, can be potentially relevant to predict patient's outcome.

Tibial internal rotation negatively affects clinical outcomes in total knee arthroplasty: a systematic review.

PURPOSE: The aim of this systematic review is to analyze the effect of tibial rotational alignment after total knee arthroplasty (TKA) on clinical outcomes and assess the eventual cut-off values for tibial TKA rotation leading to poor outcomes. METHODS: A detailed and systematic search from 1997 to 2017 of the Pubmed, Medline, Cochrane Reviews, and the Google Scholar databases was performed using the keyword terms "total knee arthroplasty", "total knee replacement", "tibial alignment", "tibial malalignement", "tibial rotation", "rotational error", "axis", "angle", "tibial malrotation", "clinical outcome", in several combinations. The modified Coleman scoring methodology (mCMS) was used. All the primary TKAs studies analyzing correlation between clinical results and tibial rotation were included. RESULTS: Five articles met the inclusion criteria. A total of 333 arthroplasties were included in this review; 139 had tibial component malalignment, while 194 were in control groups. The mean age of patients was 67.3 (SD 0.57) years. The mean average postoperative follow-up delay was 34.7 months (range 21-70). The mean mCMS score was 59.2 points indicating good methodological quality in the included studies. Functional outcomes were assessed through KSS, OKS, KOOS and VAS, negatively related to tibial internal rotation. CONCLUSIONS: Our review confirmed that excessive internal rotation of the tibial TKA component represents a significant risk factor for pain and inferior functional outcomes after TKA (> 10° of internal rotation demonstrated the common value), since external rotation does not affect the results. However, a universal precise cut-off value has not been found in the available literature and there remains a debate about CT rotation assessment and surgical intra-operative landmarks. LEVEL OF EVIDENCE: III.

Good clinical results with autologous matrix-induced chondrogenesis (Amic) technique in large knee chondral defects.

PURPOSE: Autologous matrix-induced chondrogenesis (AMIC) is a treatment for focal full-thickness cartilage defects combining microfracturing with an exogenous I/III collagen matrix (Chondro-Gide). The aim of the present study was to determine the 7 years outcomes of patients treated with the AMIC technique for knee chondral defects larger than 2 cm2. The hypothesis was that the positive short-term outcomes achieved in the previous series would not deteriorate at a 7-year follow-up. METHODS: Twenty-one patients treated with the AMIC technique were retrospectively analysed. Patients were assessed through the IKDC subjective knee evaluation questionnaire and the Lysholm scoring system. All patients underwent a complete imaging study including radiographs and magnetic resonance. The median defect size was found to be 4.3 (range 2.9-8) cm2. RESULTS: At a median follow-up of 7 (±1.4) years, the mean IKDC score improved from 31.7 (±8.9) points preoperatively, to 80.6 (±5.3) at the latest follow-up (p < 0.05). The mean Lysholm score improved from 38.8 (±12.4) points preoperatively to 72.6 (±19.5) points at the last follow-up (p < 0.05). At the last follow-up, 76.2% of patients were satisfied or extremely satisfied with their outcomes, while 66.6% of patients showed good quality repair tissue on magnetic resonance imaging. CONCLUSION: AMIC was found to be an effective method to treat full-thickness knee chondral defects larger than 2 cm2, with significant clinical and functional improvement maintained over a 7-year follow-up. LEVEL OF EVIDENCE: IV.

Myriocin treatment of CF lung infection and inflammation: complex analyses for enigmatic lipids.

Our aim was to use quantitative and qualitative analyses to gain further insight into the role of ceramide in cystic fibrosis (CF). Sphingolipid ceramide is a known inflammatory mediator, and its accumulation in inflamed lung has been reported in different types of emphysema, chronic obstructive pulmonary disease and CF. CF is caused by a mutation of the chloride channel and associated with hyperinflammation of the respiratory airways and high susceptibility to ongoing infections. We have previously demonstrated that de novo ceramide synthesis is enhanced in lung inflammation and sustains Pseudomonas aeruginosa pulmonary infection in a CF murine model. We used liquid chromatography and matrix-assisted laser desorption/ionization (MALDI) imaging coupled with mass spectrometry, confocal laser scan microscopy and histology analyses to reveal otherwise undecipherable information. We demonstrated that (i) upregulated ceramide synthesis in the alveoli is strictly related to alveolar infection and inflammation, (ii) alveolar ceramide (C16) can be specifically targeted by nanocarrier delivery of the ceramide synthesis inhibitor myriocin (Myr) and (iii) Myr is able to downmodulate pro-inflammatory lyso-PC, favouring an increase in anti-inflammatory PCs. We concluded that Myr modulates alveolar lipids milieu, reducing hyperinflammation and favouring anti-microbial effective response in CF mouse model.

Indications for prophylactic osteosynthesis associated with curettage in benign and low-grade malignant primitive bone tumors of the distal femur in adult patients: a case series.

BACKGROUND: The aim of the study was to evaluate whether the use of preventive osteosynthesis after curettage in benign and primitive low-grade malignant bone tumor localized in the distal femur in adult patients provides sufficient mechanical stability to the system as to allow weight-bearing and reduce the risk of postoperative fracture. Additionally, lower limb function after curettage and preventive osteosynthesis was evaluated. MATERIALS AND METHODS: We analyzed twelve cases of benign and low-grade malignant bone lesions of the distal femur in adult patients treated in our orthopedic department between 2008 and 2011 with curettage, bone filling and preventive osteosynthesis. All patients were treated with curettage with the use of high-speed cutters, plus liquid nitrogen as local adjuvant in low-grade malignant lesions, and filling of the lesion with bone graft or allograft or acrylic cement, followed by osteosynthesis. RESULTS: No fractures or major complications were observed; good function of the knee was observed. CONCLUSION: We recommend preventive osteosynthesis after curettage in patients with very large lesions (>5 cm, >60 cm3) or high functional requirements, in obese patients, and when local adjuvants are used. LEVEL OF EVIDENCE: Level IV retrospective case-series study.

Articulated spacer provides long-term knee improvement after two-stage reimplantation.

PURPOSE: The purpose of this study was to determine the long-term outcome in patients who underwent two-stage reimplantation with an articulated spacer following a chronic periprosthetic knee infection. The hypothesis was that the use of an articulated spacer provides significant improvement of clinical results and knee functionality through a long follow-up period, and therefore a durable revision TKA. METHODS: Forty-six consecutive patients (46 knees) who underwent two-stage reimplantation with an articulated spacer for a chronic periprosthetic knee infection were retrospectively analysed. An articulated cement spacer, moulded in surgery room, was implanted in all cases. Patients were followed for a median period of 12 (range 6-16) years, and no patients were lost to follow-up. Patients were assessed preoperatively and postoperatively through the IKS knee and function scores and ROM. RESULTS: Two-stage reimplantation was successful in controlling the infection in 91.3 % of patients. In the 42 patients with a successful two-stage revision, the median IKS knee and function scores were 36 (range 16-56) points and 25 (range 15-35) points, respectively, before the operation, and 76 (range 52-94) points and 70 (range 55-90) points (p < 0.001) at the last follow-up. The median ROM increased from 80 (range 60-110) degrees preoperatively to 115 (range 100-128) degrees (p < 0.01) at the last follow-up. CONCLUSIONS: Two-stage septic revision with an articulated cement spacer provided a significant long-term improvement of preoperative clinical and functional knee scores and therefore a durable revision TKA. LEVEL OF EVIDENCE: Retrospective case series, Level IV.

Protein Kinase A Activation Promotes Cancer Cell Resistance to Glucose Starvation and Anoikis.

Cancer cells often rely on glycolysis to obtain energy and support anabolic growth. Several studies showed that glycolytic cells are susceptible to cell death when subjected to low glucose availability or to lack of glucose. However, some cancer cells, including glycolytic ones, can efficiently acquire higher tolerance to glucose depletion, leading to their survival and aggressiveness. Although increased resistance to glucose starvation has been shown to be a consequence of signaling pathways and compensatory metabolic routes activation, the full repertoire of the underlying molecular alterations remain elusive. Using omics and computational analyses, we found that cyclic adenosine monophosphate-Protein Kinase A (cAMP-PKA) axis activation is fundamental for cancer cell resistance to glucose starvation and anoikis. Notably, here we show that such a PKA-dependent survival is mediated by parallel activation of autophagy and glutamine utilization that in concert concur to attenuate the endoplasmic reticulum (ER) stress and to sustain cell anabolism. Indeed, the inhibition of PKA-mediated autophagy or glutamine metabolism increased the level of cell death, suggesting that the induction of autophagy and metabolic rewiring by PKA is important for cancer cellular survival under glucose starvation. Importantly, both processes actively participate to cancer cell survival mediated by suspension-activated PKA as well. In addition we identify also a PKA/Src mechanism capable to protect cancer cells from anoikis. Our results reveal for the first time the role of the versatile PKA in cancer cells survival under chronic glucose starvation and anoikis and may be a novel potential target for cancer treatment.

Prosthetic knee infection by resistant bacteria: the worst-case scenario.

PURPOSE: The aim of the present paper was to determine (1) the incidence of failure (defined as the persistence or the recurrence of the infection), (2) the incidence of prosthesis (or even limb) loss (defined as the final need for an arthrodesis, resection arthroplasty or amputation) and (3) what factors could influence the failure in patients treated with a two-stage reimplantation for periprosthetic knee infections caused by resistant bacteria. METHODS: The authors retrospectively reviewed 29 total knee arthroplasties infected by resistant bacteria in 29 patients who underwent a two-stage revision. Between the stages, intravenous-targeted antibiotics were administered for a median period of 8 (range 6-12) weeks. Median follow-up was 10 (range 7-14) years. RESULTS: The authors found that failure occurred in 5 of 29 patients (17.2 %). When methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) were involved, failure rate was 10 % (2 of 20). When vancomycin-resistant enterococcus (VRE), multidrug-resistant (MDR) Acinetobacter baumannii and MDR Pseudomonas aeruginosa were involved, the failure rate was 33.3 % (3 of 9). Of those five patients, two underwent amputations, one chronic suppressive antibiotic therapy, one arthrodesis and one resection arthroplasty; among them, three lost the limb (10.3 % of the overall group). Timing of reimplantation and patient comorbidities did not significantly influence the failure. CONCLUSIONS: Two-stage protocol resulted in a viable option for patients with infections by some resistant organisms (MRSA and MR-CoNS). However, when highly resistant organisms were involved (VRE, MDR Acinetobacter Baumannii and MDR Pseudomonas aeruginosa), the failure rate was much higher. In all cases of failure of the two-stage reimplantation, prosthesis (or even limb) loss occurred. Consequently, patients should be counselled that when highly resistant bacteria are involved, two-stage reimplantation could not be successful, with high final risk of prosthesis (or even limb) loss. LEVEL OF EVIDENCE: Retrospective case series, Level IV.

A modified Austin/chevron osteotomy for treatment of hallux valgus and hallux rigidus.

UNLABELLED: The purpose of this brief paper is to present the preliminary results of a modified Austin/chevron osteotomy for treatment of hallux valgus and hallux rigidus. In this procedure, the dorsal arm of the osteotomy is performed orthogonal to the horizontal plane of the first metatarsal, the main advantage being that this allows much easier and more accurate multiplanar correction of first metatarsal deformities. From 2010 to 2013, 184 consecutive patients with symptomatic hallux valgus and 48 patients with hallux rigidus without severe metatarsophalangeal joint degeneration underwent such modified chevron osteotomy. Mean patient age was 54.9 (range 21-70) years, and mean follow-up duration was 41.7 (range 24-56) months. Ninety-three percent of patients were satisfied with the surgery. Mean American Orthopaedic Foot and Ankle Society (AOFAS) score improved from 56.6 preoperatively to 90.6 at last follow-up, and mean visual analog scale (VAS) pain score decreased from 5.7 preoperatively to 1.6 at final follow-up (p < 0.05). In patients treated for hallux valgus, mean hallux valgus angle decreased from 34.1° preoperatively to 6.2° at final follow-up, and mean intermetatarsal angle decreased from 18.5° preoperatively to 4.1° at final follow-up (p < 0.05). One patient developed postoperative transfer metatarsalgia, treated successfully with second-time percutaneous osteotomy of the minor metatarsals, whilst one patient had wound infection that resolved with systemic antibiotics. LEVEL OF EVIDENCE: Level IV.

Unicompartmental knee arthroplasty is effective: ten year results.

PURPOSE: Unicompartmental knee arthroplasty (UKA) presents low morbidity and complication risk and provides excellent outcomes and fast recovery. Despite these facts, knee-replacement registries have shown high failure rates for UKA, especially when compared with traditional TKA. The purpose of this study was therefore to report outcomes, complications, and ten year survivorship rate of medial ZUK unicompartmental knee prosthesis. METHODS: We retrospectively analysed 136 medial UKAs in 124 patients, with a maximum follow-up of ten years. Patients were assessed through the International Knee Society (IKS) scores and range of motion (ROM). A complete X-ray study was performed in all patients. Limb alignment was assessed by measuring the femorotibial mechanical alignment. At surgery, bone resections were performed according to proximal tibial epiphyseal axis. RESULTS: Mean IKS knee score improved from 45.7 (range 35-63) points preoperatively to 87.2 (range 71-100) points at the latest follow-up. Mean IKS function score improved from 50.9 (range 40-70) points to 89.1 (range 75-100) points (p < 0.05). Mean ROM increased from 106.1° (range 98-123°) to 128.6° (range 116-139°) (p < 0.01). Four cases (2.9 %) were revised due to failure for any cause, so that survivorship was 97.1 % at the latest follow-up. CONCLUSIONS: This study demonstrates excellent outcomes and survivorship for the ZUK unicompartmental knee prosthesis. Based on our findings, we believe that the ZUK prosthesis offers an effective and durable solution for treating medial degeneration of the knee. Level of Evidence IV - Retrospective case series study.

A CASQ1 founder mutation in three Italian families with protein aggregate myopathy and hyperCKaemia.

BACKGROUND: Protein aggregate myopathies are increasingly recognised conditions characterised by a surplus of endogenous proteins. The molecular and mutational background for many protein aggregate myopathies has been clarified with the discovery of several underlying mutations. Familial idiopathic hyperCKaemia is a benign genetically heterogeneous condition with autosomal dominant features in a high proportion of cases. METHODS: In 10 patients from three Italian families with autosomal dominant benign vacuolar myopathy and hyperCKaemia, we performed linkage analysis and exome sequencing as well as morphological and biochemical investigations. RESULTS AND CONCLUSIONS: We show, by Sanger and exome sequencing, that the protein aggregate myopathy with benign evolution and muscle inclusions composed of excess CASQ1, affecting three Italian families, is due to the D244G heterozygous missense mutation in the CASQ1 gene. Investigation of microsatellite markers revealed a common haplotype in the three families indicating consanguinity and a founder effect. Results from immunocytochemistry, electron microscopy, biochemistry and transfected cell line investigations contribute to our understanding of pathogenetic mechanisms underlining this defect. The mutation is common to other Italian patients and is likely to share a founder effect with them. HyperCKaemia in the CASQ1-related myopathy is common and sometimes the sole overt manifestation. It is likely that CASQ1 mutations may remain undiagnosed if a muscle biopsy is not performed, and the condition could be more common than supposed.

Proteomic analysis of human glioblastoma cell lines differently resistant to a nitric oxide releasing agent.

Glioblastoma multiforme is the most aggressive astrocytoma characterized by the development of resistant cells to various cytotoxic stimuli. Nitric oxide (NO) is able to overcome tumor resistance in PTEN mutated rat C6 glioma cells due to its ability to inhibit cell growth by influencing the intracellular distribution of ceramide. The aim of this study is to monitor the effects of NO donor PAPANONOate on ceramide trafficking in human glioma cell lines, CCF-STTG1 (PTEN-mutated, p53-wt) and T98G (PTEN-harboring, p53-mutated), together with the assessment of their differential molecular signature by 2D-DIGE and MALDI mass spectrometry. In the CCF-STTG1 cell line, the results indicate that treatment with PAPANONOate decreased cell proliferation (<50%) and intracellular trafficking of ceramide, assessed by BODIPY-C5Cer, while these events were not observed in the T98G cell line. Proteomic results suggest that CCF-STTG1 cells are characterized by an increased expression of proteins involved in NO-associated ER stress (i.e. protein disulfide-isomerase A3, calreticulin, 78 kDa glucose-regulated protein), which could compromise ceramide delivery from ER to Golgi, leading to ceramide accumulation in ER and partial growth arrest. Conversely, T98G cell lines, resistant to NO exposure, are characterized by increased levels of cytosolic antioxidant proteins (i.e. glutathione-S-transferase P, peroxiredoxin 1), which might buffer intracellular NO. By providing differential ceramide distribution after NO exposure and differential protein expression of two high grade glioma cell lines, this study highlights specific proteins as possible markers for tumor aggressiveness. This study demonstrates that, in two different high grade glioma cell lines, NO exposure results in a different ceramide distribution and protein expression. Furthermore, this study highlights specific proteins as possible markers for tumor aggressiveness.

Low-grade periprosthetic knee infection: diagnosis and management.

UNLABELLED: Diagnosis and management of low-grade periprosthetic knee infection are still controversial and debatable. The diagnosis of low-grade infection after total knee arthroplasty is often complex, as clinical symptomatology and diagnostic studies are highly conflicting and knees often exhibit well-fixed components. Although the criterion standard for staged reimplantation is interim placement of an antibiotic-loaded spacer, less-invasive surgical procedures have been advocated for managing infections caused by low-virulence bacteria. Debridement with polyethylene exchange and single-stage reimplantation could offer advantages, such as fewer surgeries, reduced potential for intraoperative complications, and lower direct social costs. The aim of this narrative review was to analyze the literature to evaluate the effectiveness of different surgical procedures in managing low-grade periprosthetic knee infections. Additionally, the most reliable investigations for diagnosing total knee infection caused by low-virulence bacteria were reviewed. LEVEL OF EVIDENCE: Level V.