Anti-tumor necrosis factor α: originators versus biosimilars, comparison in clinical response assessment in a multicenter cohort of patients with inflammatory arthropathies.

OBJECTIVE: To compare etanercept and adalimumab biosimilars (SB4 and ABP501) and respective bioriginators in terms of safety and efficacy in a real-life contest. METHODS: We consequently enrolled patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with SB4, and ABP501, or with corresponding originators, belonging to the main biological prescribing centers in the Lazio region (Italy), from 2017 to 2020. Data were collected at recruitment and after 4, 8, 12, and 24 months of therapy. RESULTS: The multicenter cohort was composed by 455 patients treated with biosimilars [SB4/ABP501 276/179; female/male 307/146; biologic disease-modifying anti-rheumatic drug (b-DMARD) naïve 56%, median age/ interquartile range 55/46-65 years] and 436 treated with originators (etanercept/adalimumab 186/259, female/ male 279/157, b-DMARD naïve 67,2%, median age/interquartile range 53/43-62 years). No differences were found about safety, but the biosimilar group presented more discontinuations due to inefficacy (p<0.001). Female gender, being a smoker, and being b-DMARD naïve were predictive factors of reduced drug survival (p=0.05, p=0.046, p=0.001 respectively). The retention rate at 24 months was 81.1% for bioriginators and 76.5% for biosimilars (median retention time of 20.7 and 18.9 months, respectively) (p=0.002). Patients with remission/low disease activity achievement at 4 months showed a cumulative survival of 90% to biosimilar therapy until 24 months (p=0.001); early adverse reactions instead represented a cause of subsequent drug discontinuation (p=0.001). CONCLUSIONS: Real-life data demonstrated a similar safety profile between biosimilars and originators, but a reduced biosimilar retention rate at 24 months. Biosimilars could be considered a valid, safe, and less expensive alternative to originators, allowing access to treatments for a wider patient population.

COVID-19 lockdown and hip arthroplasty rehabilitation changes: mid-term clinical outcomes.

OBJECTIVE: Hip arthroplasty is one of the most performed surgeries in orthopedics. Rehabilitation process after surgery allows rapid recovery of joint functions in absence of pain in most patients. During COVID-19 pandemic, rehabilitation clinics have reduced the number of beds available. Thus, an increasing number of patients were forced to home rehabilitation programs. Our study aimed at determining any significant differences in clinical and functional outcomes between those patients who underwent a home rehabilitation program and those others who were granted a place in a Rehabilitation clinic during COVID-19 pandemic, at mid-term follow-up. PATIENTS AND METHODS: An observational retrospective single-center study was designed. The patients included were 63, divided into two groups: Group A (29 patients) for home rehabilitation, and Group B (34 patients) for clinic rehabilitation. Follow-up was performed at 1, 6 and 12 months after surgery. Clinical evaluation was assessed through Oxford Hip Score for hip function, Visual Analogue Scale (VAS) for pain and hip range of motion (ROM) to evaluate joint recovery. RESULTS: ROM was compared at follow-up with significant differences 12 months after surgery (107.93° group A vs. 104.7° group B; p=0.0168). Pain felt by patients according to the VAS scale showed no significant differences at follow-up (1 month 3.27 vs. 3.65 p=0.1489; 6 months 1.89 vs. 2.18 p=0.105; 12 months 0.58 vs. 0.68 p=0.6263). Regarding the Oxford Hip score, significant differences emerged at 1-month follow-up (38.75 group A vs. 37.94 group B; p=0.0498). CONCLUSIONS: At mid-term follow-up, little differences were found between patients who went through home rehabilitation and those who went to a rehabilitation clinic. Therefore, decreasing the number of beds available in rehab clinics during COVID-19 pandemic was not an obstacle for elective surgery for orthopedic surgeons.

Medial gastrocnemius flap for the treatment of infected knee prostheses.

OBJECTIVE: Muscular flaps may represent a valid treatment option for prosthetic infection after knee arthroplasty. PATIENTS AND METHODS: We present the results of 20 consecutive patients treated with the use of medial gastrocnemius flap for the management of different types of injuries or integumentary defects after total knee arthroplasty. Tissue necrosis or dehiscence occurred within 1 and 2 months after arthroplasty. The mean follow-up was 23.4 (12-60) months. Clinical outcome was evaluated according to the infection control rate and post-operative Knee Society Score (KSS). RESULTS: Prosthesis salvage and complete restoration of skin coverage were achieved in all patients. Functional assessment was performed using the KSS score. The final knee KSS score was classified as excellent (score: 80-100) in 0 patients, good (score: 70-79) in 17 patients, fair (score: 60-69) in 2 patients, and poor (score: 60) in 1 patient. Residual Extension Deficit: 0-20°; Very Satisfactory in 17 patients. 30-70° Satisfactory in 2 patients, 80-90° Unsatisfactory in 1 patient. Patients who successfully underwent flap treatment experienced a much greater increase in both components of the KSS score. CONCLUSIONS: The results highlight the effectiveness of medial gastrocnemius muscular flap for the treatment of prosthetic knee infection, in terms of function, limb salvage, cost-effectiveness and post-surgery quality of life. Further larger studies may consolidate these findings.

Survivorship of proximal femoral replacement in neoplastic and non-neoplastic elderly patients.

OBJECTIVE: Massive bone loss is a serious problem in the elderly. Joint replacement with modular prostheses represents the most common reconstructive technique after oncological and non-oncological resections. Megaprostheses are broadly available, adaptable and versatile and allow early mobilization and rehabilitation. Although segmental endoprosthetic implants are now widely used and despite innovations, complications remain far high. Our purpose is to establish what happens to megaprostheses of a specific anatomical site in the long term in a population with oncologic and non-oncologic indications treated at a single center solely by a few skilled surgeons. MATERIALS AND METHODS: We retrospectively reviewed our institutional database. We collected 35 patients who underwent endoprosthetic reconstruction exclusively of the proximal femur for neoplastic and non-neoplastic disease between 2008 and 2021. The minimum follow-up was 12 months. Complications were collected and classified, and also adapted to the non-oncological setting. RESULTS: Taking into consideration the entire population, 94% of this survived the follow-up at 6 months, subsequently 85% at 1 year and 82% at 2 years. At follow-ups after 5 years, 79% of megaprostheses showed no mechanical failure. Analyzing prosthetic survival in the two groups, this was >50% at 24 months after surgery in both groups, with better survival for the oncological one. CONCLUSIONS: Proximal femur replacement can be a valid option in treatment of oncological and non-oncological cases. Due to the high complication rate, only selected cases should undergo this kind of surgical procedure.

Proximal humerus fractures treatment in adult patients with bone metastasis.

OBJECTIVE: The humerus is the second long bone most affected by pathological fractures. According to Capanna and Campanacci criteria, surgical choice is based on bone metastasis location, on the patient's status and on the residual functional capacity. Metadiaphysis is an area of conflict in the choice between megaprosthesis implant and intramedullary nail osteosynthesis. This study compares these two surgical procedures in terms of reacquired functionality and local control of metastasis. PATIENTS AND METHODS: Thirty-eight patients (17 males and 21 females; mean age: 66 years old) treated in our institution between January 2010 and December 2020 for pathological humeral metadiaphyseal fractures caused by metastasis, were included in this study. We choose the Musculoskeletal Tumor Society rating system (MSTS) and the Quick Disability of Arm-Shoulder-Hand (QuickDASH) scores for the evaluation of the upper limb function after surgery. RESULTS: Eighteen (47%) pathological fractures were treated by resection and megaprosthesis implantation, twenty (53%) were treated by medullary nail osteosynthesis. A reduction in pain and greater mechanical stability in the immediate post-operative period was found in all patients. Twenty-two patients died (58%) and sixteen survived (42%). Long-term functional recovery of patients undergoing osteosynthesis is greater than megaprothesis group. CONCLUSIONS: Both medullary nail osteosynthesis and resection and megaprosthesis implantation guarantee excellent recovery at 72 months after surgery, improvement in quality of life and pain relief.  Patients treated with osteosynthesis showed a great short-term functional recovery since the joint portion of the limb is not involved, whereas patients treated with megaprosthesis showed better local oncologic control. It is therefore possible to define the type of treatment not only on the localization of the fracture (diaphysis or epiphysis) but above all on the conditions and characteristics of the patient.

Safety of rituximab in the routine treatment of rheumatoid arthritis in Italy in patients refractory to anti-TNFa drugs: results from the observational retrospective-prospective RUBINO study.

The paper reports the results from the observational retrospective-prospective RUBINO study conducted in Italy to assess the safety of rituximab in the treatment of rheumatoid arthritis (RA) in routine clinical practice. The percentage of patients who manifested at least one grade 3 or 4 adverse event (AE) assessed by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v.3) during the observation period (primary objective) was evaluated. The percentage of patients manifesting a severe AE (SAE), clinical response to rituximab treatment, clinical remission according to disease activity score for 28 joints (DAS28) criteria, markers of disease and quality of life were also assessed. Fifty-three Italian rheumatology centers took part in the study. Patients with a diagnosis of RA and inadequate response to anti-tumor necrosis factor b (anti-TNFa) drugs were enrolled. Participating patients had previously received at least one cycle of rituximab, and treatment was still ongoing at the time of recruitment. Out of 205 patients enrolled, 60% manifested no form of AE, 14.2% had at least one grade 3 or 4 AE, and 11.2% patients reported an SAE. The overall percentage of patients manifesting AEs (40%) was lower compared to the DANCER (81% and 85%), REFLEX (85%) and RESET (85% and 69%) studies, but higher than that observed in the CERERRA registry (from 10.2% to 13.9%). This difference may be due to the shorter observation period applied in the CERERRA registry (only 12 months) compared to the RUBINO study (up to 3 years). All parameters of RA activity (erythrocyte sedimentation rate, C-reactive protein, health assessment questionnaire score, DAS28) improved significantly during the study.

Anti-endothelial cell antibodies in rheumatic heart disease.

To evaluate the anti-endothelial cell antibodies (AECA), anti-cardiolipin antibodies (aCL) and serum mannose-binding lectin (MBL) profiles of a large cohort of Yemeni patients with rheumatic heart disease (RHD) and to correlate these findings with clinical features of the disease. Patients (n = 140) were recruited from Al-Thawra Hospital in Sana'a, Yemen. All had RHD diagnosed according to modified Jones' criteria. We also studied 140 sex- and age-matched healthy blood donors from the same area. Echocardiography was performed according to the recommendations of the American Society of Echocardiography. Solid phase enzyme-linked immunosorbent assays (ELISAs) were used to measure AECA and aCL titres and serum MBL levels. Forty per cent of the patients were AECA-positive, but only 7·8% were positive for aCL antibodies. Serum MBL levels were significantly lower in the RHD group (median 4221 ng/ml versus 5166 ng/ml in healthy controls). AECA titres were correlated positively with patient age, duration of RHD and the severity of aortic stenosis, as determined by echocardiographic findings. In several autoimmune rheumatic diseases, such as systemic lupus erythematosus, vasculitis and scleroderma, AECA have been shown to play pathogenic roles by producing proinflammatory and procoagulant effects (increased expression of adhesion molecules and tissue factors, increased cytokine release) in endothelial cells. In RHD, these autoantibodies might represent a pathological link between activation of the valvular endothelium and valvular damage.

Central pontine myelinolysis induced by hypophosphatemia following Wernicke's encephalopathy.

A 62-year-old woman, after a resection and ileostomy for multiple perforations of the terminal ileum and prolonged postoperative parenteral nutrition, developed thiamine deficiency with clinical and magnetic resonance imaging features of Wernicke's disease. Later on the patient developed central pontine myelinolysis. For this condition, a pathogenetic role of a transient hypophosphatemia was suggested by both laboratory data and course of the disease.