Should age be a factor in treatment choice of periprosthetic Vancouver B2-B3 proximal femur fractures? A retrospective analysis of mortality and functional outcomes in elderly patients

Background and aim of the work Revision Arthroplasty (RA) is considered the treatment of choice for periprosthetic femur fractures (PFF) presenting with a loose stem. In the elderly RA may be associated with high post-operative mortality and complications. The aim of this study is to compare mortality and functional outcomes of open reduction internal fixation (ORIF) and RA for B2-B3 PFF in the elderly. Methods The study population included 29 patients (>65 years) surgically treated for B2-B3 PFF at the Orthopedic and Traumatology Unit of Cattinara University Hospital in Trieste (Italy) between January 2015 and December 2019. 16 patients were treated with ORIF and 13 with RA. Mortality and functional outcomes were analyzed. Results In-hospital (6,25% vs 7,69%) and 3 months (6,25 vs 15,38%) mortality was higher in the RA group. Mortality rates were particularly high in the > 85-year-old patients within four months from RA treatment. One year (38,46% and 16,67%) and overall mortality (69,22% and 25%) was higher after ORIF. Average time to weight-bearing and ambulation was 2.6 and 5.25 months for ORIF patients and 1.3 and 2.4 months for RA. A correlation was found between delayed weight-bearing and overall mortality. Conclusions Age is a risk factor for short term mortality following RA. Patients >85 years of age could benefit from a less invasive procedure such as ORIF. Long term outcomes are generally better for patients who undergo RA but further studies are necessary to evaluate the risk-benefit ratio of RA treatment compared to ORIF in elderly patients

Predictors of cut-out after cephalomedullary nail fixation of pertrochanteric fractures: a retrospective study of 813 patients

BACKGROUND: Cut-out is the most common mechanical complication of the osteosynthesis of pertrochanteric fractures. This complication determines a significant increase in morbidity in elderly patient. Cut-out is defined as the varus collapse of the femoral head-neck fragment with the extrusion of the cephalic screw. Surgical treatment of cut-out might lead to further complications, longer rehabilitation, increased social burden and healthcare system costs. The aim of the study is to identify the predictors of cut-out to prevent its occurrence. MATERIALS AND METHODS: Study population included all patients affected by extracapsular fracture of the proximal femur who were admitted and treated with short cephalomedullary nailing at the Cattinara Hospital-ASUITS of Trieste between 2009 and 2014. A retrospective analysis of clinical and radiographic data was carried out and cut-out cases recorded. The data collected on the study population were analyzed to find an eventual correlation with the occurrence of cut-out. The independent variables were age, gender, side of the fracture, ASA class, Evans classification, nailing system, quality of reduction, TAD, CalTAD, and Parker ratio. RESULTS: The study population counted 813 cases, with an F:M ratio of 4:1 and a mean age of 84.7 years. The cut-out was recorded in 18 cases (2.2%). There was no statistically significant association between cut-out and age, sex, side of fracture, ASA class, and nailing system. The Evans classification, the quality of reduction, the TAD, the CalTAD, and the Parker's ratio demonstrated a significant correlation at univariate analysis with cut-out. The results of multivariate analysis confirmed that TAD, Parker AP, and quality of reduction were independently significantly correlated to cut-out. CONCLUSION: The results of the present study demonstrate that good quality of reduction and correct position of the lag screw are likely to decrease the risk of cut-out complication. A nomogram for cut-out prediction is proposed for clinical validation

Flexor hallucis longus transfer and composite anterolateral thigh fascio-cutaneous flap for reconstruction of massive chronic and infected Achilles tendon lesion. A case report and review of the literature

Achilles tendon reconstruction with substance loss and infection in the overlying soft tissues is a challenge. There is no standardized treatment in literature for these cases. We describe a one-stage tendon reconstruction, using flexor hallucis longus (FHL) tendon transfer and an anterolateral thigh flap with vascularized fascia lata in a patient with re-rupture of the Achilles tendon, soft tissue infection and a tendon defect of 10 cm in length. The surgical procedure has had a successful outcome; patient has recovered normal gait, has recovered complete ankle range of motion with only a partial loss in plantar flexion of the big toe, without any loss in strength. No complications have emerged at follow-up. This technique is promising in treating large Achilles tendon defects with overlying soft tissue infection in a one-stage procedure

Poor nutritional status but not cognitive or functional impairment per se independently predict 1 year mortality in elderly patients with hip-fracture

Hip fractures are strongly associated with mortality in the elderly. Studies investigating predisposing factors have suggested a negative impact of poor nutritional, cognitive and functional status on patient survival, however their independent prognostic impact as well as their interactions remain undefined. This study aimed to determine whether poor nutritional status independently predicts 1 year post-fracture mortality after adjusting for cognitive and functional status and for other clinically relevant covariates. METHODS: 1211 surgically treated hip fracture elderly (age 65 65) patients consecutively admitted to the Orthopaedic Surgery Unit of the "Azienda Sanitaria Universitaria Integrata Trieste" (ASUITs), Cattinara Hospital, Trieste, Italy and managed by a dedicated orthogeriatric team. Pre-admission nutritional status was evaluated by Mini Nutritional Assessment (MNA) questionnaire, cognitive status by Short Portable Mental Status Questionnaire (SPMSQ) and functional status by Activity of Daily Living (ADL) questionnaire. All other clinical data, including comorbidities, type of surgery, post-operative complications (delirium, deep vein thrombosis, cardiovascular complications, infections, need for blood transfusions) were obtained by hospital clinical records and by mortality registry. RESULTS: Poor nutritional status (defined as MNA 6423.5), increased cognitive and functional impairment were all associated with 3-, 6- and 12 month mortality (p < 0.001). Both cognitive and functional impairment were associated with poor nutritional status (p < 0.001). Logistic regression analysis demonstrated that the association between nutritional status and 3-, 6- and 12- month mortality was independent of age, gender, comorbidities, type of surgery and post-operative complications as well as of cognitive and functional impairment (p < 0.001). In contrast, the associations between mortality and cognitive and functional impairment were independent (p < 0.001) of demographic (age, gender) and clinical covariates but not of malnutrition. Kaplan-Meier analysis showed a lower mean survival time (p < 0.001) in patients with poor nutritional status compared with those well-nourished. CONCLUSIONS: In hip fracture elderly patients, poor nutritional status strongly predicts 1 year mortality, independently of demographic, functional, cognitive and clinical risk factors. The negative prognostic impact of functional and cognitive impairment on mortality is mediated by their association with poor nutritional statu

Rewiring innate and adaptive immunity with TLR9 agonist to treat osteosarcoma

Background Osteosarcoma (OS) is the most common primary bone tumor in children and adolescent. Surgery and multidrug chemotherapy are the standard of treatment achieving 60-70% of event-free survival for localized disease at diagnosis. However, for metastatic disease, the prognosis is dismal. Exploiting immune system activation in the setting of such unfavorable mesenchymal tumors represents a new therapeutic challenge. Methods In immune competent OS mouse models bearing two contralateral lesions, we tested the efficacy of intralesional administration of a TLR9 agonist against the treated and not treated contralateral lesion evaluating abscopal effect. Multiparametric flow cytometry was used to evaluate changes of the tumor immune microenviroment. Experiments in immune- deficient mice allowed the investigation of the role of adaptive T cells in TLR9 agonist effects, while T cell receptor sequencing was used to assess the expansion of specific T cell clones. Results TLR9 agonist strongly impaired the growth of locally-treated tumors and its therapeutic effect also extended to the contralateral, untreated lesion. Multiparametric flow cytometry showed conspicuous changes in the immune landscape of the OS immune microenvironment upon TLR9 engagement, involving a reduction in M2-like macrophages, paralleled by increased infiltration of dendritic cells and activated CD8 T cells in both lesions. Remarkably, CD8 T cells were needed for the induction of the abscopal effect, whereas they were not strictly necessary for halting the growth of the treated lesion. T cell receptor (TCR) sequencing of tumor infiltrating CD8 T cells showed the expansion of specific TCR clones in the treated tumors and, remarkably, their selected representation in the contralateral untreated lesions, providing the first evidence of the rewiring of tumor-associated T cell clonal architectures. Conclusions Overall these data indicate that the TLR9 agonist acts as an in situ anti-tumor vaccine, activating an innate immune response sufficient to suppress local tumor growth while inducing a systemic adaptive immunity with selective expansion of CD8 T cell clones, which are needed for the abscopal effect

Triggering CD40 on endothelial cells contributes to tumor growth

Inflammatory cells can either promote or inhibit tumor growth. Here we studied whether CD40, a key molecule for adaptive immune response, has any role in mammary carcinogenesis of BALB/NeuT transgenic tumor-prone mice. We transferred the HER2/neu oncogene into CD40-null background to obtain the CD40-KO/NeuT strain. CD40-KO/NeuT mice showed delayed tumor onset and reduced tumor multiplicity. BM (BM) transplantation experiments excluded a role of BM-derived cells in the reduced tumorigenicity associated with CD40 deficiency. Rather, CD40 expressed by endothelial cells (ECs) takes part to the angiogenic process. Accordingly, large vessels, well organized around the tumor lobular structures, characterize BALB/NeuT tumors, whereas tiny numerous vessels with scarce extracellular matrix are dispersed in the parenchyma of poorly organized CD40-KO/NeuT tumors

Cardiac rehabilitation outcome after transcatheter aortic valve implantation.

Patients with severe aortic stenosis are increasingly treated with transcatheter aortic valve implantation (TAVI) as a safer option to surgical aortic valve replacement (sAVR). Similar to many other heart diseases, after the specific therapeutic intervention patients are eligible for cardiac rehabilitation (CR) for the purpose of functional recovery. Thus far, CR after both sAVR and TAVI has been used to a limited extent, as shown by the availability of only two meta-analyses including 5 studies and 6 studies, respectively. Recent observational studies reported a significant improvement in functional indexes such as the Barthel scale and the 6-minute walk test (6MWT). We evaluated the outcome of CR in patients after TAVI treatment by measuring changes in the commonly used Barthel scale and 6MWT and adding the short physical performance battery (SPPB) scale as an index to assess lower extremity function. All indexes demonstrated a significant improvement, namely p<0.001 with the Barthel scale, p=0.043 for the 6MWT, and p=0.002 for SPPB. These results confirm the significant improvement of the Barthel scale and 6MWT reported in the previous meta-analysis and suggest the utility of SPPB as a further index of efficacy of CR in patients with severe aortic stenosis treated with TAVI

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P &lt; 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p &lt; 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription