Ruthenium-based assemblies incorporating tetrapyridylporphyrin panels: a photosensitizer delivery strategy for the treatment of rheumatoid arthritis by photodynamic therapy.

Ruthenium-based assemblies containing tetrapyridylporphyrins (TPyP) in their structure have been evaluated as photosensitizers (PS) to treat rheumatoid arthritis (RA) by photodynamic therapy (PDT). TPyP is useless by itself as a PS due to its low solubility in biological media, however, incorporated in metallacages it can be internalized in cells. The study shows a cellular antiproliferative activity in fibroblast-like synoviocyte (FLS) in the lower nanomolar range in the presence of light, and no dark toxicity at 1 µM concentration, thus having an excellent photoactivity index. The presence of diamagnetic (Zn2+) and paramagnetic (Co2+) metals in the center of TPyP impairs the effectiveness of PDT, showing no (Co) or reduced (Zn) photoactivity. A total of five metallacages with different structural characteristics have been evaluated, and our results suggest that the incorporation of PS in metalla-assemblies is not only an elegant method to increase solubility in biological media for TPyP but also appears to be an efficient hybrid system to treat RA by PDT.

Femoral shaft fractures treated by antegrade locked intramedullary nailing: EOS stereoradiographic imaging evaluation of rotational malalignment having a functional impact.

INTRODUCTION: The standard treatment of femoral shaft fractures is intramedullary nailing. One of the most frequent complications is femoral malrotation. Our study sought to: 1) use EOS imaging to determine the amount of rotational malalignment after intramedullary nailing that has an impact on 6-month functional results; 2) determine the incidence of femoral malrotation based on EOS imaging; 3) determine the risk factors for postoperative femoral malrotation that impacts the 6-month functional results. The hypothesis was that EOS imaging can be used to determine the amount of femoral malrotation that has a functional impact in patients treated by percutaneous femoral intramedullary nailing. MATERIAL AND METHODS: We performed a prospective, single-center study between September 2017 and February 2020. Patients who had suffered a femoral shaft fracture treated with antegrade intramedullary nailing were included in this study. Femoral anteversion was measured at 6 months with an EOS stereoradiographic imaging system. Patients were assessed at 6 months with the WOMAC, Oxford, Harris and MDP functional scores. The SF-12 quality of life score was also determined. RESULTS: Thirty patients were evaluated at 6 months postoperatively, 15 women (50%) and 15 men (50%) who were 47 years old on average [16; 94]. The average anteversion was 19.9°C [-23°; 75°]. The functional scores (Oxford and Harris) were altered when there was 14° or more difference in femoral torsion between the operated side and the healthy side with a sensitivity of 0.88 and a specificity of 0.77. The risk factors for femoral malrotation were age under 35 years (p=0.01), urgent surgical management (p=0.008), location in middle third of femoral shaft (p=0.05), and short spiral fracture (p=0.02). CONCLUSION: The use of EOS imaging allowed us to demonstrate that functional hip outcomes are altered at 6 months postoperatively when greater than 14° femoral malrotation is present compared to the contralateral side after femoral intramedullary nailing. The risk factors that contributed to intraoperative rotational malalignment were age less than 35 years, urgent surgical management, mid-shaft femoral fracture and short spiroid fractures. LEVEL OF EVIDENCE: II.

User satisfaction with single-use instruments versus reusable instruments for treating distal radius fractures with locking volar plates.

INTRODUCTION: The adoption of single-use instruments (SUI) in orthopedic and trauma surgery continues at a rapid pace. Economics studies on this topic have come to contradictory conclusions about whether these SUI have a cost advantage. The aims of our study were to (1) compare the satisfaction of operating room staff between SUI and reusable instruments (RUI) in the context of distal radius fracture fixation with locking volar plates; (2) compare the immediate postoperative and medium-term radiological outcomes of patients operated these two types of instrument sets. We hypothesized that users will be more satisfied with SUI in the context of distal radius fracture fixation with locking volar plates. MATERIALS AND METHODS: This was a prospective, single-center study performed between April 2019 and July 2020. The inclusion criteria were patients more than 18 years of age who had a distal radius fracture with indication for fixation with volar locking plate, and whose initial treatment and follow-up were completed in our surgery department. Two groups of patients were created: SUI and RUI. The satisfaction of the surgeons and scrub nurses was determined using a 10-item questionnaire. RESULTS: The analysis was done on 91 procedures for which a satisfaction questionnaire was completed by the primary surgeon and the scrub nurse. The satisfaction scores were always significantly better in the RUI group than in the SUI group (p<0.05). DISCUSSION: This study found that surgeons and scrub nurses in our surgery department liked the RUI better than the SUI. At a time when SUI kits become more popular in orthopedic and trauma surgery, based on cost arguments that still need to be confirmed, taking into account the operating room staff's opinion is an important criterion for improving RUI kits. LEVEL OF EVIDENCE: II.

Evaluation of Ruthenium-Based Assemblies as Carriers of Photosensitizers to Treat Rheumatoid Arthritis by Photodynamic Therapy.

For the first time, ruthenium-based assemblies have been used as carriers for photosensitizers in the treatment of rheumatoid arthritis by photodynamic therapy (PDT). These metallacages are totally soluble in physiological media and can transport photosensitizers (PS) in their cavity. After an incubation period, the PS is released in the cytoplasm and irradiation can take place. This strategy allows photosensitizers with low or null solubility in biological media to be evaluated as PDT agents in rheumatoid arthritis. The systems in which 21H,23H-porphine and 29H,31H-phthalocyanine are encapsulated show excellent photocytotoxicity and no toxicity in the dark. On the other hand, systems in which metalated derivatives such as Mg(II)-porphine and Zn(II)-phthalocyanine are used show good photocytotoxicity, but to a lesser extent than the previous two. Furthermore, the presence of Zn(II)-phthalocyanine significantly increases the toxicity of the system. Overall, fifteen different host-guest systems have been evaluated, and based on the results obtained, they show high potential for treating rheumatoid arthritis by PDT.

Factors influencing the mid-term radiological and functional outcomes of 41 post-fracture bipolar radial head arthroplasty cases at a mean follow-up of 87 months.

INTRODUCTION: When treating comminuted radial head fractures that cannot be adequately fixed, the next option is arthroplasty (radial head replacement). We hypothesized that the radiological and functional outcomes of bipolar mobile cup radial head arthroplasty is not influenced by the length of follow-up but instead by the correct positioning of the implant intraoperatively and by the presence of associated bone or ligament injuries. PATIENTS AND METHODS: Between May 1998 and December 2016, 82 cases of radial head arthroplasty were performed at our hospital. The mean age of patients at the time of arthroplasty was 53 years (22-81). Ligament or bone injuries complicated the radial head fractures in 70% of patients. RESULTS: For the final assessment, 41 patients were reviewed and included in the statistical analysis with a mean of 82 months (12-228). The mean MEPS at the final assessment was 88.7 (61-100). There were 23 excellent, 9 good, 9 average and 0 poor results. The average DASH score was 18.7 (0-55). The average VAS for pain was 1.0 (0-5). Five patients (12%) required surgical revision, including one implant change. Our statistical analysis found no relationship between follow-up time and functional outcomes. The appearance of periprosthetic radiolucent lines was not affected by the length of follow-up. Associated bone or ligament injuries significantly increased the probability of periprosthetic radiolucent lines, humeroulnar joint degeneration and decentering of the implanted cup. Radiological evidence of a suspended implant was associated with significantly worse functional outcomes. CONCLUSION: This study confirms the long-term stability of the clinical outcomes of radial head arthroplasty. There was no relationship between worsening radiological appearance of the implant and the clinical outcomes. It is critical that this implant not be oversized or suspended, as this can trigger premature capitellar erosion and painful stiffness of the operated elbow. LEVEL OF EVIDENCE: IV; systematic retrospective analysis.

Impact of orthogeriatric management on the average length of stay of patients aged over seventy five years admitted to hospital after hip fractures.

INTRODUCTION: Hip fracture is a frequent and serious condition in the elderly. We conducted a retrospective cohort study to answer the following questions: (1) Could treatment in an orthogeriatric unit help to reduce the average length of stay for patients aged over 75 years admitted to hospital for the treatment of a hip fracture?; and (2) Could such treatment influence the post-operative outcomes of patients with hip fracture? METHODS AND MATERIALS: Our study included 534 patients admitted to hospital between January 2017 and December 2018 for surgical treatment of a hip fracture. We compared 246 patients who received traditional orthopaedic care with 288 patients treated in an orthogeriatric unit. RESULTS: Our cohort included 410 women (77%). The average age was 87.5 ± six years, and 366 patients (68%) were living at home prior to the fracture. A statistically significant difference in median length of stay (from 10 to 9 days) was observed between patients who did and did not receive orthogeriatric unit treatment (groups 1 and 2; 95% CI: 0.64; 2.59; p = 0.001). There was no difference in pre-operative delay, intra-hospital mortality rate, place of recovery, rate of institutionalisation after six months, or the number of new fractures at 6 months between the groups. The mortality rate after six months was 23.6% and 21.3% in groups 1 and 2, respectively; the difference was not significant. DISCUSSION: Orthogeriatric unit treatment reduced the median length of stay by one day, in line with most previous studies. According to Pablos-Hernandez et al., multifaceted orthogeriatric treatment is most effective. In our study, only 38% of the patients received surgical treatment within 48 hours, where early surgery is key for reducing the length of hospital stay. The intrahospital mortality rate was 2.6%, which is comparable to literature data. The discharge rate did not differ by orthogeriatric treatment status, which is also consistent with previous findings (e.g. Gregersen et al.). Lastly, the mortality rate after six months was slightly reduced by orthogeriatric care. In line with this, Boddaert et al. reported a difference in mortality rate after six months between groups who did and did not receive orthogeriatric treatment (15% vs. 24%).

Orthogeriatric assessment of patients over 75 years of age with a proximal femur fracture: Predictors of 6-month mortality.

INTRODUCTION: Proximal femur fractures are common and dangerous in older adults, given the high short-term mortality rate. While surgical treatment is vital, medical orthogeriatric care may reduce the 6-month mortality rate; however, this has not been determined on a broad scale in France. This led us to conduct a retrospective study to answer the following questions: (1) Does delayed surgical treatment impact the 6-month mortality rate? (2) Are there correctable medical factors that impact the 6-month mortality? HYPOTHESIS: Delayed surgical treatment is not an isolated risk factor for higher 6-month mortality after proximal femur fracture. METHODS: We included all patients 75 years or older who had suffered a proximal femur fracture requiring surgical treatment. This allowed us to analyze the medical records of 476 patients retrospectively. We documented their comorbidities and pre-, intra- and postoperative characteristics. A univariate then multivariate analysis was done to identify risk factors for mortality at 6 months. RESULTS: In the univariate analysis, time to surgery of more than 48hours increased the risk of dying at 6 months by 1.5 fold (Odds ratio (OR)=1.57/95% CI: 1-2.48/p=0.04). However, this risk factor was not significant in the multivariate analysis since it is not an independent risk factor. In the multivariate analysis, anticoagulants (OR=2/95% CI: 1.13-3.50/p=0.02), dementia (OR=2.2/95% CI: 1.32-3.59/p=0.002), peripheral artery disease (OR=2.9/95% CI: 1.10-7.70/p=0.03), 2-point drop in hemoglobin count from preoperative to postoperative (OR=1.9/95% CI: 1.05-3.12/p=0.04), male sex (OR=1.82/95% CI: 1.05-3.12/p=0.04), age above 85 years (OR=5.26/95% CI: 1.49-5.26/p=0.002) and Charlson comorbidity index≥7 (OR=2.13/95% CI: 1.29-3.52/p=0.003) were statistically associated with mortality at 6 months. DISCUSSION/CONCLUSION: Our study found that the patients most at risk for dying within 6 months of a hip fracture were males, older than 85 and have associated medical conditions (Charlson index≥7). Prior anticoagulant treatment increases the time to surgery in our study and therefore increases the risk of these patients dying within 6 months. Treatment of these at-risk patients should ensure that their underlying medical conditions are not made worse, while providing treatment within 48hours. Patients taking anticoagulants must be monitored carefully to ensure surgical treatment is not delayed. LEVEL OF EVIDENCE: IV, retrospective study without control group.

Analysis of the effects of arthrodesis of the hallux metatarsophalangeal joint on gait cycle: results of a GAITRite® treadmill test.

INTRODUCTION: Approximately 80% of patients are satisfied with the outcome of arthrodesis of the hallux metatarsophalangeal (MTP) joint. The hypothesis of this study was that MTP arthrodesis does not influence the walking cycle. The aim of this study was to evaluate the effect of MTP arthrodesis on gait cycle and to measure the functional outcome of MTP arthrodesis after a minimum of two year follow-up. METHOD: This was an observational prospective cohort study performed at a single centre that included 26 patients (32 ft) who underwent unilateral or bilateral MTP arthrodesis during the period 2004-2014. An X-ray assessment based on the American Orthopaedic Foot and Ankle Society score was performed pre-operatively and at the last follow-up (average follow-up duration 8.3 years). The walking cycle was analysed at the final follow-up using a GAITRite® treadmill test. RESULTS: Twenty unilateral and six bilateral MTP arthrodeses were included in this study. The average age of the patients was 70 years. No significant difference was found in the walking cycle between the operated and non-operated sides for unilaterally MTP arthrodesis. However, we observed a non-significant increase in the percentage of contact time after MTP arthrodesis (65% on the operated side vs. 63% on the non-operated side). We also observed a significant decrease in the average walking rate, and a decrease in walking speed, in cases of bilateral MTP arthrodesis compared with normal walking cycle data from a laboratory study. CONCLUSIONS: MTP joint arthrodesis does not appear to have any effect on the walking cycle, but reduced patient pain and increased the walking distance. The patients reported satisfaction with the surgical outcomes and would recommend it to a relative with the same pathology.

Lower-limb Flip-Flap: A simple reliable modification of adipofascial flap for extensive tibial crest cutaneous defect.

INTRODUCTION: Large cutaneous defects exposing the whole tibial crest are difficult to cover and are conventionally best treated with free flaps. This article describes a technical modification of the adipofascial flap in this indication. METHODS: The "flip-flap" is vascularized by the posterior tibial artery perforators harvested on the medial aspect of the leg. The hypodermal and fascial tissue is de-epidermized and elevated from the posterior midline up to the medial edge of the soleus muscle, then folded over the exposed tibial crest like a page of a book. RESULTS: A 27×6cm effect was successfully covered on a 72 year-old patient with vascular status precluding free flap. The flap healed by day 21. DISCUSSION/CONCLUSION: This technical modification is simple and allows coverage of large tibial crest skin defect when a free flap is not possible.

Treatment of cephalotuberosity fractures in elderly patients treated by reverse shoulder prosthesis: a study of functional results in relation to deltoid tension.

INTRODUCTION: The treatment of proximal humerus fractures is a therapeutic challenge in the elderly as the functional demands of these patients are high. We postulated that there may be a relationship between functional results and deltoid tension when these fractures are treated with a reverse prosthesis. This study was performed to determine the optimal tension of the deltoid. The primary outcome was the constant score in relation to humeral length at the final follow-up. MATERIALS AND METHODS: Our retrospective cohort consisted of 45 patients treated with a reverse fracture prosthesis during the period from January 2010 to July 2017. The fractures were all classified as Neer III or IV, 91% of our patients were women and the average age was 82 years. RESULTS: Constant score and antepulsion were improved with humeral elongation between 10 and 25 mm (p < 0.02 and p < 0.05, respectively). External rotation was improved with humeral elongation (p < 0.03). CONCLUSION: Tuberosity reinsertion improves mobility in patients treated surgically for a reverse fracture prosthesis. The recovery of anatomical retroversion seems of fundamental importance, and we confirmed that deltoid tension that must also be taken into account to improve functional results of reverse shoulder prosthesis on fracture. The ideal humeral elongation seems to be between 10 and 25 mm, in relation to the contralateral side, to obtain better functional results.

Are orthopedic surgeons exposed to excessive eye irradiation? A prospective study of lens irradiation in orthopedics and traumatology.

INTRODUCTION: Numerous studies in recent years highlighted an increased risk of pathologies related to ionizing radiation in caregivers. A new French decree was adopted on June 4, 2018, dividing by 7.5 the radiation dose authorized in the lens for exposed workers. HYPOTHESIS: The hypothesis of the present study was that ocular irradiation in orthopedic surgeons was below the new legal threshold. METHOD: The equivalent dose (mSv) received by the lens was prospectively assessed in 10 orthopedic surgeons (5 senior, 5 residents), using 3 passive dosimeters placed at the forehead and either temple. Each intervention of each operator was recorded, with dose per area in the operating room at each use of the fluoroscope. RESULTS: All equivalent doses to the lens at the end of the 4 month study period were well below threshold. Doses were not significantly different between forehead and either temple (p=0.7, p=0.6 for the 2 temples). There was no difference according to side of the head (p=0.3). The dose received in the lens correlated with the dose delivered in the room (p=0.004). There were no significant differences in irradiation according to the surgeon's experience (p=0.2) or trauma activity rate (p=0.4). DISCUSSION: No studies have reported equivalent doses to the lens exceeding the authorized limit. But none previously measured equivalent dose to the lens according to the axis of irradiation in the eyes. The present study showed that orthopedic surgeons received as much eye radiation laterally as frontally. Ocular radiation protection needs therefore to be as effective laterally as frontally. The surgeon's experience did not emerge as a protective factor against ocular irradiation.

Is non-operative treatment still relevant for Garden Type I fractures in elderly patients? The femoral neck impaction angle as a new CT parameter for determining the indications of non-operative treatment.

BACKGROUND: The indications of non-operative treatment of undisplaced femoral neck fractures are controversial. The objective of this study was to assess whether two computed tomography (CT) parameters, the femoral neck impaction angle (IA) and the femoral neck posterior tilt angle (PTA), were effective in predicting the risk of secondary displacement after non-operative treatment of Garden I femoral neck fractures in patients aged 65 years or over. HYPOTHESIS: The working hypotheses were that the IA in the coronal plane and PTA in the axial plane predicted secondary displacement after non-operative treatment of Garden I femoral neck fractures, could be reproducibly and reliably measured on CT scans, and could serve to identify Garden I fractures at risk for secondary displacement after non-operative treatment. METHODS: Forty-nine patients aged 65 years or over with Garden I fractures treated non-operatively were included in a prospective single-centre study. CT images were used to measure the IA as the position of the fracture line relative to the femoral head in the coronal plane and the PTA as the position of the femoral head centre relative to the femoral neck axis in the axial plane. RESULTS: After non-operative treatment, secondary displacement occurred in 22 (45%) patients. The PTA was not significantly different between the groups with vs. without secondary displacement (p=0.62). IA values≤135° were significantly associated with secondary displacement (odds ratio, 11.73; 95% confidence interval [95%CI], 3.04-45.28; p=0.004). An IA≤135° was 72.73% sensitive and 81.48% specific for predicting secondary displacement. IA measurement was reproducible, with intra-class and inter-class Cohen's kappa values of 0.94 (95%CI, 0.90-0.97) and 0.9011 (95%CI, 0.83-0.94), respectively. DISCUSSION: The IA measured on CT images may hold promise for identifying Garden I hip fractures at high risk for secondary displacement after non-operative treatment. IA measurement is reproducible and reliable and may help to determine the indications of non-operative treatment. LEVEL OF EVIDENCE: II, prospective cohort study.

Hemiarthroplasty for Complex Distal Radius Fractures in Elderly Patients.

Background In elderly patients, distal radius fractures frequently occur in osteoporotic bone and may be nonreconstructable. It is our hypothesis that a hemiarthroplasty replacment of the articular surface can provide satisfactory results in terms of range of motion, pain, and function for immediate salvage of a fracture that is not amenable to internal fixation. Methods Between July 2009 and January 2012, eight elderly patients were treated with insertion of a Sophia distal radius implant (Biotech, Paris, France). Inclusion criteria consisted of an isolated AO type C2 distal radius fracture in patients over 70 years old. All patients were reviewed by an independent surgeon. Results The mean follow-up was 25 months (range, 17-36 months). Mean wrist range of motion (ROM) was 45° (40-50°) of flexion, 44° (40-50°) of extension, and a mean pronation-supination arc of 160°. Mean grip force was 18 kgf. The mean QuickDASH (Disabilities of the Arm, Shoulder and Hand) was 18.2/100 (6.82-29.55), and the mean visual analog scale (VAS) was 2.33 (0-4). X-ray images did not demonstrate implant loosening or ulnar translation of the carpus. Conclusions The Sophia hemiarthroplasty provided rapid recovery of independence in elderly patients with a nonreconstructable comminuted distal radius fracture.

Endostatin cDNA/cationic liposome complexes as a promising therapy to prevent lung metastases in osteosarcoma: study in a human-like rat orthotopic tumor.

Antiangiogenesis or destruction of tumor neovessels is an effective strategy to prevent tumor growth. Endostatin, one of the many inhibitors of angiogenesis that have been discovered, has shown conflicting results in preclinical assays. We studied the therapeutic potential of lipid/DNA complexes consisting of cationic liposomes and an endostatin-coding plasmid (Endo cDNA/CLP) in an orthotopic osteosarcoma model in rats. Empty plasmid without the endostatin gene complexed with cationic liposomes served as control. Animals were treated intravenously three times a week starting on the day tumors were detectable by (18)FDG tomoscintigraphy. During treatment, tumor progression was followed by PET scan and angioscintigraphy, and the effects of antivascular therapy on primary tumor, metastases, and tumor vascular density were confirmed by histologic analysis. Our results demonstrate that therapy using Endo cDNA/CLP is associated with pronounced delay in tumor growth. Moreover, it effectively prevented the occurrence of lung metastases, the major reason for bad prognosis and death in osteosarcoma patients. This approach could be used as an adjuvant therapy for osteosarcoma.