Simultaneous Bilateral Total Knee Arthroplasty in Elderly: Are There Factors that Can Influence Safety and Clinical Outcome?

Objective: The aim of this study was to look for preoperative patients' related factors correlating with worse clinical outcomes in a cohort of elderly patients undergoing simultaneous bilateral total knee arthroplasty (SiBTKA) to search for risk factors, which may influence clinical outcomes and safety. Subjects and Methods. The hospital database was mined searching for patients older than 70 years that underwent SiBTKA for severe bilateral knee osteoarthritis (OA) between 2012 and 2016. Preoperative clinical information, Oxford Knee Score (OKS), and Knee Injury and Osteoarthritis Outcome Score (KOOS) prior to surgery were recorded. The OKS and the KOOS were submitted again after a minimum of 5 years of follow-up (FU). Results: An improvement was observed in all clinical scores at last FU. The major complication rate was 5.4%. No patients' clinical data showed correlation with perioperative complications or need for transfusions. Functional scores at the last FU were negatively affected by age at surgery and positively affected by preoperative clinical scores. Discussion. In the setting of severe symptomatic bilateral knee OA, SiBTKA seems to be effective in improving symptoms at midterm follow-up, with acceptable rates of perioperative complications in patients older than 70. Higher age at surgery and lower preoperative functional scores are associated with worse clinical outcomes at FU. This could assist surgeons in advising patients that delay of surgical treatment could worsen outcomes.

Synovial mast cells from knee and hip osteoarthritis: histological study and clinical correlations.

PURPOSE: The aim of this study was to investigate the presence of synovial mast cells (MCs) in hip and knee tissue from osteoarthritis (OA) patients and to correlate them with clinical and radiological data. METHODS: Synovial tissue was obtained during arthroplasty from 60 patients, 30 with knee OA and 30 with hip OA. Control synovial tissue was obtained from 30 patients without OA, 15 undergoing above-knee amputation and 15 receiving a hip replacement for fracture. Before surgery, the radiographic findings were graded according to the Kellgren-Lawrence system and clinical data including pain (VAS) and functional information (KOOS and HOOS) was collected. The tissue was stained with hematoxylin-eosin and toluidine blue for histochemistry and incubated with CD117 and CD31 antibodies for immunohistochemistry. MC and vessel number and synovitis score were determined in all samples. RESULTS: Mean MC number, synovitis score and vessel number were significantly higher in the OA samples (p < 0.05) than in control tissue. MC number correlated with the synovitis score and disease severity in both patient groups. CONCLUSIONS: The prevalence of MCs in synovium from OA patients and their association with synovial inflammation and pain suggest a role for them in OA pathophysiology.

The use of augmented reality for limb and component alignment in total knee arthroplasty: systematic review of the literature and clinical pilot study.

PURPOSE: A systematic review of the literature has been carried out to assess the actual evidence of the use of augmented reality in total knee arthroplasty (TKA). We then conducted a pilot clinical study to examine the accuracy of the Knee + augmented reality navigation in performing TKA. The present augmented reality (AR) system allows the surgeon to view the tibial and femur axis superimposed on the surgical field through the smart glasses. It provides real-time information during surgery and intraoperative feedback. METHODS: A systematic review of the PubMed, MEDLINE, and Embase databases up to May 2021 using the keywords "augmented reality", "knee arthroplasty", "computer assisted surgery", "navigation knee arthroplasty" was performed by two independent reviewers. We performed five TKAs using the Knee + system. Patients were 4 females, with mean age of 76.4 years old (range 73-79) and mean Body Max Index (BMI) of 31.9 kg/m2 (range 27-35). The axial alignment of the limb and the orientation of the components were evaluated on standardized pre and postoperative full leg length weight-bearing radiographs, anteroposterior radiographs, and lateral radiographs of the knee. The time of tourniquet was recorded. The perception of motion sickness was assessed by Virtual Reality Sickness Questionnaire (VRSQ) subjected to surgeon immediately after surgery. RESULTS: After duplicate removal, a total of 31 abstracts were found. However, only two studies concerned knee arthroplasty. Unfortunately, both were preclinical studies. Knee + system is able to perform a cutting error of less than 1° of difference about coronal alignment of femur and tibia and less than 2° about flexion/extension of femur and posterior tibial slope. The absolute differences between the values obtained during surgery and the measurement of varus femur, varus tibia, posterior slope, and femur flexion angle on post-operative radiographs were 0.6° ± 1.34°, 0.8° ± 0.84°, 0.8° ± 1.79°, and 0.4 mm ± 0.55 mm, respectively. CONCLUSIONS: On light of our preliminary results, the Knee + system is accurate and effective to perform TKA. The translation from pilot study to high-level prospective studies is warranted to assess accuracy and cost-effective analysis compared to conventional techniques. LEVEL OF EVIDENCE: IV.

Axial and rotational alignment of lower limb in a Caucasian aged non-arthritic cohort.

BACKGROUND: The alignment of human lower limb has been an area of ongoing study for decades. The purpose of this study was to analyze the axial and rotational alignment from hip to ankle in a Caucasian aged non-arthritic cohort. METHODS: A non-arthritic cohort of aged patients was retrospectively analyzed by computer tomography. Anatomical-mechanical angle of femur (AMA), femur inclination (FI), femoral anteversion (FA), posterior condylar angle (PCA), proximal tibial torsion (TEAs-PTC and TEAs-PTT) and tibial fibular torsion (PTC-TFA) were measured. RESULTS: The median age of the patients was 76 years (range 67 to 91 years). Regarding axial alignment, the AMA was 5 (2.94; 6.80). No significance differences were reported by side and age. AMA was significantly lower in men. The FI was 125.3 (120.0; 134.8) with no differences in terms of side, age or gender. Regarding torsion alignment, the median values of FA, PTC-TFA and TEAs-PTT were, respectively, 16.8, 28.5 and - 1.4. No differences were reported by age. Right tibia was externally rotated by 1.5 degrees as compared to the left side (P 0.035). CONCLUSION: The broad variability of the parameters analyzed highlights the necessity for a more anatomical and individualized approach during surgery of lower limb. The present study offers the fundament to understand and treat lower limb deformities. Hence, these data can constitute the normal reference values useful to investigate lower limb malalignment. Moreover, it helps to assess the possible changes of axial and rotational alignment in idiopathic OA of lower limb. LEVEL OF EVIDENCE III: Retrospective cohort study.

Effects of NGF and BDNF on chondrocytes: a microarray analysis.

Osteoarthritis (OA) represents an inflammation-driven injury of articular tissues, progressively leading to structural and functional joint impairment. The main symptom of OA is pain. Although it has been well established that OA represents a whole joint disease, the source of pain remains to be clarified. Nowadays, it has been well established that neurotrophines expression is evident in joints affected by OA. In addition, elevated NGF levels are found in the synovial fluid of patients with inflammatory or degenerative rheumatic diseases, including OA, rheumatoid arthritis and spondylarthritis. Growing evidences indicate that blocking NGF signaling using an anti NGF agent (i.e. tanezumab) provides effective pain relief. This study analyzed the effects of NGF and BDNF on cultured human chondrocytes by evaluating and their effects on chondrogenesis, chondrocyte differentiation and cartilage degeneration through a microarray analysis. The whole transcriptome analysis performed in this study highlighted how NGF and BDNF could be able to induce a proinflammatory response in human chondrocytes. Moreover, NGF and BDNF treatments seems to be able to induce the activation of several genes involved in the OA pathogenesis as IL17AR, HLA-DRB1, GDF-15, NR1D1, MCF2L and TGF-Beta.

Synovial and serum levels of NGF in osteoarthritis and rheumatic diseases: a systematic review.

NGF has raised interest as a target molecule in the treatment of OA, after the clinical evidences that antagonization of NGF axis provides symptoms relief in OA. Thus, we conducted a systematic review of the literature to investigate the evidence of NGF being overexpressed during OA. We conducted a database search on Medline using keywords including NGF, serum, synovial fluid, AND osteoarthritis or arthritis. We included study conducted on human, with serum or synovial specimens and an OA cohort. Nine studies met the inclusion criteria. Serum levels ranged from non-detectable to 153.5±28.6 pg/ml. Synovial fluid levels ranged from non-detectable to nearly 210±82 pg/ml. One study supported the evidence of an increased level of NGF in SF and serum of OA patients. The concentration of NGF reported in these studies is controversial and evidence of overexpression of NGF is low.

The metabolic effects of quinolones and steroids on human ligament cells: an in vitro study.

The toxic effects of fluoroquinolones and steroid on tendon cells have been well established, but their role on human ligamentocytes remain unclear. We have investigated the effects of ciprofloxacin and methylprednisolone on human anterior cruciate ligamentocytes after 7 and 14 days of culture. We evaluated cell viability, Annexin V-FITC/PI assay, senescence-associated ß-galactosidase staining, and collagen type I detection. Regarding quinolones administration, we observed that ligament cells treated with ciprofloxacin have characterized by a significantly decrease of cell viability and collagen type I expression and an increase of apoptotic cells. In cells treated with high dose of steroid we observed a significantly decrease of cell viability and collagen type I expression and the presence of senescent cells. Therefore, ciprofloxacin and methylprednisolone might have cytotoxic effects on ligamentocytes by two distinct mechanisms. Quinolones seem to induce cell apoptosis, while steroids might be able to induce cellular senescence. Hence their use should be avoided in athletes and in orthopedic surgery.

Primary reverse shoulder arthroplasty for acute proximal humerus fractures: A 5-year long term retrospective study of elderly patients.

BACKGROUND: Reverse shoulder arthroplasty (RSA) in complex shoulder fractures is ever more frequently. This study compares clinical and radiologic results of patients with comminuted proximal humeral fractures (PHFs) treated with RSA, with and without tuberosities grafting. METHODS: Between January 2009 and June 2014, 55 patients aged ≥65 years with 3- and 4-part PHFs were treated surgically. Patients' files and the hospital's digital database were reviewed retrospectively with at least 5-year of follow up. We constituted three groups according to the tuberosity consolidation: patients in whom the tuberosities showed anatomic consolidation (Group I) and patients either with secondary displacement of the tuberosities (Group II) or without tuberosity repair (Group III). RESULTS: The 74% of the repaired tuberosities consolidated in anatomic position. Among range of motion (ROM), we reported that forward elevation, abduction and external rotation were significantly better in Group I than those in Group II-III. Furthermore, quick Dash score and Constant score showed more satisfied results in Group I. Regarding complications, not infection or instability were found in group I. On the other hand, in group II, we reported one patient with deep infection, leading to two steps surgery. In group III, we recorded two patients with instability required implant revision and one with deep infection treated by revision. CONCLUSION: RSA showed satisfied results even at 5 year follow up. Preservation of the tuberosities in anatomic position improves active forward elevation and external rotation as well as patient satisfaction with less complications.

Characterization of human costal cartilage: is it an adapt tissue as graft for articular cartilage repair?

Several techniques and different biological or artificial tissues have been proposed as graft to restore articular defects. However, among the numerous and heterogeneous procedures proposed over time, the current literature findings are not conclusive. The aim of the current study is to evaluate if human costal cartilage can be suitable as graft for restoring articular cartilage defects. Knee articular cartilage and costal cartilage samples were obtained respectively from patients that underwent anterior cruciate ligament reconstruction (samples from notch plasty) or knee joint replacement and ear reconstruction or rhinoplasty through rib graft. The samples were stained with hematoxylin eosin, safranine-O, Gomori paraldehyde-fuchsin and Von Kossa for light microscopy. Immunohistochemistry was performed using anti-collagen I, II, IV and anti-SOX9 antibodies. Furthermore, samples were analyzed by transmission electron microcopy (TEM). In both cartilage, the cells are arranged in quite similar layers and the matrix show the same hyaline appearance: presence of type II collagen and solphated glycosaminoglycans, and absence of type I collagen and SOX-9. The bigger difference between the two hyaline tissues is the presence of perichondrium that surrounds all the specimens of costal cartilage. It consists of two separate layers where the inner one seems to get thinner with aging. The results show that rib cartilage seems to be an adapt tissue as graft for articular cartilage repair from a histological point of view. However, to date its therapeutic potential remains to be clearly defined by animal and clinical studies.

Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals.

Preclinical evidence suggests that ghrelin, a peptide synthesized by endocrine cells of the stomach and a key component of the gut-brain axis, is involved in alcohol seeking as it modulates both central reward and stress pathways. However, whether and how ghrelin administration may impact alcohol intake in humans is not clear. For, we believe, the first time, this was investigated in the present randomized, crossover, double-blind, placebo-controlled, human laboratory study. Participants were non-treatment-seeking alcohol-dependent heavy-drinking individuals. A 10-min loading dose of intravenous ghrelin/placebo (3 mcg kg-1) followed by a continuous ghrelin/placebo infusion (16.9 ng/kg/min) was administered. During a progressive-ratio alcohol self-administration experiment, participants could press a button to receive intravenous alcohol using the Computerized Alcohol Infusion System. In another experiment, brain functional magnetic resonance imaging was conducted while participants performed a task to gain points for alcohol, food or no reward. Results showed that intravenous ghrelin, compared to placebo, significantly increased the number of alcohol infusions self-administered (percent change: 24.97±10.65, P=0.04, Cohen's d=0.74). Participants were also significantly faster to initiate alcohol self-administration when they received ghrelin, compared to placebo (P=0.03). The relationships between breath alcohol concentration and subjective effects of alcohol were also moderated by ghrelin administration. Neuroimaging data showed that ghrelin increased the alcohol-related signal in the amygdala (P=0.01) and modulated the food-related signal in the medial orbitofrontal cortex (P=0.01) and nucleus accumbens (P=0.08). These data indicate that ghrelin signaling affects alcohol seeking in humans and should be further investigated as a promising target for developing novel medications for alcohol use disorder.

Nerve growth factor administration on cultured human ligamentocytes: an in vitro pilot study.

Nerve growth factor (NGF) is involved in several joint pathologies. It has been demonstrated that its concentration increases in synovial fluid and tissue from arthritis. However, its role in joint homeostasis and pathophysiology still remain to be clarified. This study analyzed the effect of 200 ng/ml on cultured human ligamentocytes by evaluating cell proliferation, cell phenotype and gene expression. The MTT test excluded an influence on cell viability at 7 and 14 days. Regarding cell phenotype, we observed that NGF might promote the synthesis of COL1A1. On the other hand, real time PCR showed that NGF did not influence gene expression of COL3A1, FGF-BETA, IGF1, MMP2, MMP3, MMP9 and MMP13. However, COL1A1 gene was significantly upregulated in treated cell at 14 days. Our results suggest that NGF may have an anabolic effect on ligament. Additional investigations are necessary to determine how NGF may influence ligamentocytes..

The effect of anti-IgE therapy in knee osteoarthritis: a pilot observational study.

Osteoarthritis is a whole-joint disease and its pathogenesis remains poorly understood. Recent evidence proposed the importance of the innate immune system as trigger of synovium inflammation following the degeneration of cartilage. Moreover, synovial mast cells (MCs) might be correlated with pain and disability reported by patients. Anti IgE therapy represents a new class of MCs stabilizing agent, licensed for people with asthma and chronic urticaria. Therefore, we studied if the stabilizing effect of anti IgE would improve the pain and disability in patients affected by knee osteoarthritis and atopic disease. This pilot study provides the first evidence that anti IgE treatment induces a short-term clinical improvement supporting the role of MCs in osteoarthritis.

Biobehavioral effects of baclofen in anxious alcohol-dependent individuals: a randomized, double-blind, placebo-controlled, laboratory study.

Baclofen has been suggested as a potential pharmacotherapy for alcohol use disorder, but the clinical data are conflicting. Here we investigated the biobehavioral effects of baclofen in a sample of anxious alcohol-dependent individuals. This was a randomized, double-blind, placebo-controlled, human laboratory study in non-treatment seeking alcohol-dependent individuals with high trait anxiety (N=34). Participants received baclofen (30 mg per day) or placebo for at least 8 days, then performed an experimental session consisting of alcohol cue-reactivity followed by alcohol administration procedure (alcohol priming, then alcohol self-administration). Total amount of alcohol self-administered was the primary outcome; alcohol craving, subjective/physiological responses and mood/anxiety symptoms were also evaluated. There was no significant medication effect on the total amount of alcohol consumed during the alcohol self-administration (P=0.76). Baclofen blunted the positive association between maximum breath alcohol concentration during priming and the amount of alcohol consumption (significant interaction, P=0.03). Ratings of feeling intoxicated were significantly higher in the baclofen group after consuming the priming drink (P=0.006). During the self-administration session, baclofen significantly increased ratings of feeling high (P=0.01) and intoxicated (P=0.01). A significant reduction in heart rate (P<0.001) and a trend-level increase in diastolic blood pressure (P=0.06) were also detected in the baclofen group during the alcohol laboratory session. In conclusion, baclofen was shown to affect subjective and physiological responses to alcohol drinking in anxious alcohol-dependent individuals. These results do not support an anti-craving or anti-reinforcing effect of baclofen, but rather suggest that baclofen may act as a substitution medication for alcohol use disorder.

Rapid adaptation drives invasion of airway donor microbiota by Pseudomonas after lung transplantation.

In cystic fibrosis (CF) patients, chronic airway infection by Pseudomonas leads to progressive lung destruction ultimately requiring lung transplantation (LT). Following LT, CF-adapted Pseudomonas strains, potentially originating from the sinuses, may seed the allograft leading to infections and reduced allograft survival. We investigated whether CF-adapted Pseudomonas populations invade the donor microbiota and adapt to the non-CF allograft. We collected sequential Pseudomonas isolates and airway samples from a CF-lung transplant recipient during two years, and followed the dynamics of the microbiota and Pseudomonas populations. We show that Pseudomonas invaded the host microbiota within three days post-LT, in association with a reduction in richness and diversity. A dominant mucoid and hypermutator mutL lineage was replaced after 11 days by non-mucoid strains. Despite antibiotic therapy, Pseudomonas dominated the allograft microbiota until day 95. We observed positive selection of pre-LT variants and the appearance of novel mutations. Phenotypic adaptation resulted in increased biofilm formation and swimming motility capacities. Pseudomonas was replaced after 95 days by a microbiota dominated by Actinobacillus. In conclusion, mucoid Pseudomonas adapted to the CF-lung remained able to invade the allograft. Selection of both pre-existing non-mucoid subpopulations and of novel phenotypic traits suggests rapid adaptation of Pseudomonas to the non-CF allograft.

Homologous platelet-rich plasma for the treatment of knee involvement in primary Sjögren’s syndrome.

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease characterized by dry eyes, dry mouth, and other clinical manifestations. The most common extraglandular manifestation of pSS is articular involvement and to date their management is unclear. The aims of the current pilot study were to assess the safety and the outcomes of homologous platelet-rich plasma (HPRP) injections in pSS cohort affected by knee arthralgia/arthritis at short-term follow up. This pilot study provides the first evidence that HPRP injections are a safe treatment and induce a short-term clinical improvement. Although the lack of a control group, randomization and long-term follow up prevents the assessment of the real effectiveness of this treatment, further studies are needed to confirm these findings and to determine the mechanism of action, biological changes and disease-modifying properties of PRP.

Human tissue engineering allows the identification of active miRNA regulators of glioblastoma aggressiveness.

Glioblastoma multiforme (GBM) is among the most aggressive cancers associated with massive infiltration of peritumoral parenchyma by migrating tumor cells. The infiltrative nature of GBM cells, the intratumoral heterogeneity concomitant with redundant signaling pathways likely underlie the inability of conventional and targeted therapies to achieve long-term remissions. In this respect, microRNAs (miRNAs), which are endogenous small non-coding RNAs that play a role in cancer aggressiveness, emerge as possible relevant prognostic biomarkers or therapeutic targets for treatment of malignant gliomas. We previously described a tissue model of GBM developing into a stem cell-derived human Engineered Neural Tissue (ENT) that allows the study of tumor/host tissue interaction. Combined with high throughput sequencing analysis, we took advantage of this human and integrated tissue model to understand miRNAs regulation. Three miRNAs (miR-340, -494 and -1293) active on cell proliferation, adhesion to extracellular matrix and tumor cell invasion were identified in GBM cells developing within ENT, and also confirmed in GBM biopsies. The components of miRNAs regulatory network at the transcriptional and the protein level have been also revealed by whole transcriptome analysis and Tandem Mass Tag in transfected GBM cells. Notably, miR-340 has a clinical relevance and modulates the expression of miR-494 and -1293, emphasizing its biological significance. Altogether, these findings demonstrate that human tissue engineering modeling GBM development in neural host tissue is a suitable tool to identify active miRNAs. Collectively, our study identified miR-340 as a strong modulator of GBM aggressiveness which may constitute a therapeutic target for treatment of malignant gliomas.

The genome of an Encephalitozoon cuniculi type III strain reveals insights into the genetic diversity and mode of reproduction of a ubiquitous vertebrate pathogen.

Encephalitozoon cuniculi is a model microsporidian species with a mononucleate nucleus and a genome that has been extensively studied. To date, analyses of genome diversity have revealed the existence of four genotypes in E. cuniculi (EcI, II, III and IV). Genome sequences are available for EcI, II and III, and are all very divergent, possibly diploid and genetically homogeneous. The mechanisms that cause low genetic diversity in E. cuniculi (for example, selfing, inbreeding or a combination of both), as well as the degree of genetic variation in their natural populations, have been hard to assess because genome data have been so far gathered from laboratory-propagated strains. In this study, we aim to tackle this issue by analyzing the complete genome sequence of a natural strain of E. cuniculi isolated in 2013 from a steppe lemming. The strain belongs to the EcIII genotype and has been designated EcIII-L. The EcIII-L genome sequence harbors genomic features intermediate to known genomes of II and III lab strains, and we provide primers that differentiate the three E. cuniculi genotypes using a single PCR. Surprisingly, the EcIII-L genome is also highly homogeneous, harbors signatures of heterozygosity and also one strain-specific single-nucleotide polymorphism (SNP) that introduces a stop codon in a key meiosis gene, Spo11. Functional analyses using a heterologous system demonstrate that this SNP leads to a deficient meiosis in a model fungus. This indicates that EcIII-L meiotic machinery may be presently broken. Overall, our findings reveal previously unsuspected genome diversity in E. cuniculi, some of which appears to affect genes of primary importance for the biology of this pathogen.

Whole-Genome Shotgun Sequence of Bacillus amyloliquefaciens Strain UASWS BA1, a Bacterium Antagonistic to Plant Pathogenic Fungi.

We report here the whole-genome shotgun sequence of Bacillus amyloliquefaciens strain UASWS BA1, isolated from inner wood tissues of a decaying Platanus × acerifolia tree. This strain proved to be antagonistic to several plant pathogenic fungi and oomycetes and can be developed as a biological control agent in agriculture.