A reduction in tumor volume exceeding 65% predicts a good histological response to neoadjuvant chemotherapy in patients with Ewing sarcoma.

OBJECTIVE: No consensus exists for tumor volume response criteria in patients with Ewing sarcoma. This study aimed to identify an optimal cutoff for predicting a good histological response by analyzing tumor volume changes and tumor necrosis after neoadjuvant chemotherapy. MATERIALS AND METHODS: We performed a retrospective analysis of 184 Ewing sarcoma patients, analyzing tumor volume changes before and after neoadjuvant chemotherapy. Patients were divided into two groups based on histological response: good (tumor necrosis ≥ 95%) and poor (tumor necrosis < 95%) responders. The receiver operating characteristic (ROC) area under the curve (AUC) method was used to determine the optimal thresholds for predicting the histological response. Additionally, the prognostic value of this cutoff for relapse-free survival was assessed. RESULTS: Out of 184 patients, 83 (45%) had tumor necrosis ≥ 95%, while 101 (55%) had tumor necrosis < 95%. ROC analysis identified the optimal cutoff for a good histological response as over 65% tumor volume reduction (AUC = 0.69; p < 0.001). Patients with volume reduction of ≥ 65% had a higher likelihood of a good histological response than those with lesser reductions (p = 0.004; odds ratio = 2.61). Multivariable analysis indicated a correlation between poor histological response and reduced relapse-free survival (hazard ratio = 2.17; p = 0.01), while tumor volume reduction itself did not impact survival. CONCLUSION: We reported that a tumor volume reduction of ≥ 65% was able to predict a good histological response in Ewing sarcoma patients. We recommend preoperative tumor volume assessment to identify patients at greater risk for poor histological response who could benefit from more intensive chemotherapy protocols or additional radiotherapy.

A COVID-19 specific multiparametric and ECG-based score for the prediction of in-hospital mortality: ELCOVID score.

We aimed to develop and validate a COVID-19 specific scoring system, also including some ECG features, to predict all-cause in-hospital mortality at admission. Patients were retrieved from the ELCOVID study (ClinicalTrials.gov identifier: NCT04367129), a prospective, multicenter Italian study enrolling COVID-19 patients between May to September 2020. For the model validation, we randomly selected two-thirds of participants to create a derivation dataset and we used the remaining one-third of participants as the validation set. Over the study period, 1014 hospitalized COVID-19 patients (mean age 74 years, 61% males) met the inclusion criteria and were included in this analysis. During a median follow-up of 12 (IQR 7-22) days, 359 (35%) patients died. Age (HR 2.25 [95%CI 1.72-2.94], p < 0.001), delirium (HR 2.03 [2.14-3.61], p = 0.012), platelets (HR 0.91 [0.83-0.98], p = 0.018), D-dimer level (HR 1.18 [1.01-1.31], p = 0.002), signs of right ventricular strain (RVS) (HR 1.47 [1.02-2.13], p = 0.039) and ECG signs of previous myocardial necrosis (HR 2.28 [1.23-4.21], p = 0.009) were independently associated to in-hospital all-cause mortality. The derived risk-scoring system, namely EL COVID score, showed a moderate discriminatory capacity and good calibration. A cut-off score of ≥ 4 had a sensitivity of 78.4% and 65.2% specificity in predicting all-cause in-hospital mortality. ELCOVID score represents a valid, reliable, sensitive, and inexpensive scoring system that can be used for the prognostication of COVID-19 patients at admission and may allow the earlier identification of patients having a higher mortality risk who may be benefit from more aggressive treatments and closer monitoring.

Malawer type I/V proximal humerus reconstruction after tumor resection: a systematic review.

BACKGROUND: Several reconstruction methods exist for Malawer type I/V proximal humerus reconstruction after bone tumor resection; however, no consensus has been reached regarding the preferred methods. METHODS: We conducted a literature search on various types of proximal humerus oncologic reconstruction methods. We collected data on postoperative functional outcomes assessed based on Musculoskeletal Tumor Society (MSTS) scores, 5-year reconstruction survival rates, and complications. We calculated each reconstruction's weighted mean based on the sample size and standard errors. Complications were categorized based on the Henderson classification. Based on these integrated data, our primary objective is to propose an optimal strategy for proximal humerus reconstruction after bone tumor resection. RESULTS: We examined various reconstruction techniques, including modular prosthesis (752 patients in 21 articles), osteoarticular allograft (142 patients in six articles), allograft prosthesis composites (236 patients in 12 articles), reverse shoulder total arthroplasty (141 patients in 10 articles), composite reverse shoulder total arthroplasty (33 patients in four articles), claviculo-pro-humero technique (51 patients in six articles), and cement spacer (207 patients in four articles). Weighted mean MSTS scores were: modular prosthesis (73.8%), osteoarticular allograft (74.4%), allograft prosthesis composites (79.2%), reverse shoulder total arthroplasty (77.0%), composite reverse shoulder total arthroplasty (76.1%), claviculo-pro-humero technique (75.1%), and cement spacer (69.1%). Weighted 5-year reconstruction survival rates were modular prosthesis (85.4%), osteoarticular allograft (67.6%), allograft prosthesis composites (85.2%), reverse shoulder total arthroplasty (84.1%), and cement spacer (88.0%). Reconstruction survival data was unavailable for composite reverse shoulder total arthroplasty and claviculo-pro-humero technique. Major complications included shoulder joint instability: modular prosthesis (26.2%), osteoarticular allograft (41.5%), allograft prosthesis composites (33.9%), reverse shoulder total arthroplasty (17%), composite reverse shoulder total arthroplasty (6.1%), claviculo-pro-humero technique (2.0%), and cement spacer (8.7%). Aseptic loosening of the prosthesis occurred: modular prosthesis (3.9%) and reverse shoulder total arthroplasty (5.7%). Allograft fracture was observed in 54.9% of patients with osteoarticular allograft. CONCLUSION: The complication profiles differed among reconstruction methods. Weighted mean MSTS scores exceeded 70% in all methods except cement spacer, and the 5-year reconstruction survival rate surpassed 80% for all methods except osteoarticular allograft. Proximal humerus reconstruction after bone tumor resection should consider potential complications and patients' individual factors.

Ultrasound-Guided Venous Axillary Access Versus Standard Fluoroscopic Technique for Cardiac Lead Implantation: ZEROFLUOROAXI Randomized Trial.

BACKGROUND: Axillary vein puncture (AVP) and cephalic vein surgical cutdown are recommended in international guidelines because of their low risk of pneumothorax and chronic lead complications. Directly visualizing and puncturing the axillary vein under ultrasound guidance reduces radiation exposure, provides direct needle visualization, and lowers periprocedural complications. Our hypothesis is that ultrasound-guided axillary access is safer and more feasible than the standard fluoroscopic technique. OBJECTIVES: The purpose of this study was to assess the efficacy and safety of ultrasound-guided axillary venous access during cardiac lead implantation for pacemakers (PMs) and implantable cardioverter-defibrillator (ICD) implantations. METHODS: Patients were randomized in a 1:1 fashion to either axillary venous access under fluoroscopic guidance or ultrasound-guided axillary venous access. The composite outcome, including pneumothorax, hemothorax, inadvertent arterial puncture, pocket hematoma, pocket infection, lead dislodgement, and death, was evaluated 30 days after implantation. RESULTS: We randomized 270 patients into 2 groups: the standard group for fluoroguided AVP (n = 134) and the experimental group for ultrasound-guided AVP (n = 136). No disparities in baseline characteristics were observed between the groups. The median age of the patients was 81 years, with women comprising 41% of the population. The majority of patients received single- and dual-chamber PMs (87% vs 88%; P = 1.00), and slightly over 10% in both groups received ICDs (13% vs 12%; P = 0.85). In total, we placed 357 leads in PMs and 48 leads in ICDs. Among these, 295 leads were inserted via axillary vein access and 110 via cephalic vein access. Notably, the subclavian vein was never used as a vascular access. The composite outcome was lower in the ultrasound group according to intention-to-treat analysis (OR: 0.55; 95% CI: 0.31-0.99; P = 0.034). The main difference within the composite outcome was the lower incidence of inadvertent axillary arterial puncture in the experimental group (17% vs 6%; P = 0.004). The ultrasound group also exhibited lower total procedural x-ray exposure (10,344 µGy × cm2 vs 7,119 µGy × cm2; P = 0.002) while achieving the same rate of success at the first attempt (61% vs 69%; P = 0.375). CONCLUSIONS: Ultrasound-guided AVP is safer than the fluoroscopy-guided approach because it achieves the same rate of acute success while maintaining low total procedural radiation exposure. Ultrasound AVP should be considered the optimal venous access method for cardiac lead implantation. (Ultrasound Guided Axillary Access vs Standard Fluoroscopic Technique for Cardiac Lead Implantation [ZEROFLUOROAXI]; NCT05101720).

What Is the Revision-free Survival of Resurfaced Allograft-prosthesis Composites for Proximal Humerus Reconstruction in Children With Bone Tumors?

BACKGROUND: Reconstruction of the proximal humerus in children who undergo bone tumor resection is challenging because of patients' small bone size and possible limb length discrepancy at the end of skeletal growth due to loss of the physis. There are several options for proximal humerus reconstruction in children, such as clavicula pro humero, free vascularized fibula grafting, massive bone osteoarticular allografting, endoprostheses, and allograft-prosthesis composites, but no consensus exists on the best method for reconstruction. Resurfaced allograft-prosthesis composites could be an alternative surgical option, but little is known about the results of this surgical technique. QUESTIONS/PURPOSES: (1) What are the complications and what is the survivorship free from reconstruction failure associated with resurfaced allograft-prosthesis composites in a small, single-center case series? (2) What Musculoskeletal Tumor Society scores do patients achieve after reconstructions with resurfaced allograft-prosthesis composites? METHODS: This study was a retrospective, single-arm case analysis in a single institution. We generally considered resurfaced allograft-prosthesis composites in children with malignant bone tumors involving the metaepiphysis of the proximal humerus in whom there was no evidence of joint contamination and in whom axillary nerve preservation was possible. Between 2003 and 2021, we treated 100 children (younger than 15 years) with bone tumors of the humerus. Thirty children (30%) with diaphyseal tumors (21 children) or distal tumors (9 children) were excluded. Among the potentially eligible children, 52 were not analyzed because they were treated with other procedures such as amputation, modular prostheses, cement spacers, free vascularized fibula grafting, and massive bone osteoarticular allografts. We included 18 children (26% of the potentially eligible children) who were treated with resurfaced allograft-prosthesis composites. There were 9 boys and 9 girls, with a median age of 10 years (range 4 to 15 years) at the time of diagnosis. A long stem (≥ 6 cm) in the resurfaced allograft-prosthesis composite was used in 9 children and a short stem (< 6 cm) was used in the remaining 9. One of the 18 children had a follow-up of less than 2 years. The median follow-up of the remaining 17 children was 4.7 years (range 2 to 19 years). The children' medical records were reviewed for clinical and functional outcomes. We performed a competing risk analysis to calculate the reconstruction failure-free survival of resurfaced allograft-prosthesis composites. Reconstruction failure was defined as removal of the implant or allograft because of implant loosening or breakage and allograft fracture or resorption. We analyzed the children's postoperative complications and functional outcomes at the end of the follow-up period using the Musculoskeletal Tumor Society functional scoring system. RESULTS: The competing risk analysis revealed that reconstruction failure was 25% (95% confidence interval 7% to 40%) at 3 years, reaching a plateau. Four of 18 children underwent surgical revision with a new reconstruction. The reasons for reconstruction revision were resorption of the allograft at the proximal part (2 children) and fracture of the allograft (2 children). Reconstruction revision was performed in 3 of 9 children who underwent reconstruction with a short stem and in 1 of 9 children who underwent reconstruction with a long stem. Several children had other complications that did not result in removal of the allograft. Allograft resorption was observed in 4 of 18 children, but no additional surgical treatment was performed. Shoulder instability or subluxation was observed in 4 of 18 children, but only 1 child underwent surgery with a reverse shoulder arthroplasty without removal of the resurfaced allograft-prosthesis composite. Limited elbow motion because of plate impingement was observed in 1 child who underwent surgical cutting of the protruding distal part of the plate. Incomplete radial nerve palsy after surgery occurred in 1 child, with spontaneous resolution after 2 months. Screw loosening occurred in 2 children who underwent surgery with removal of loose screws. Two children had a nonunion at the graft-host bone junction; 1 child underwent surgery with bone grafting and refixation of the graft-host bone junction, and the other child with both nonunion and plate breakage was treated with bone grafting and refixation of the graft-host bone junction with a new plate. Among 17 children who had a follow-up longer than 2 years, the median Musculoskeletal Tumor Society functional score at the last follow-up interval was 23 of 30 (range 20 to 26); 1 child was considered to have an excellent result (functional score ≥ 26), 15 children were considered to have a good result (functional score 21 to 25), and 1 child was considered to have a fair result (functional score ≤ 20). The Musculoskeletal Tumor Society functional score did not change after excluding 4 children who underwent replacement of resurfaced allograft-prosthesis composites (24 of 30 [range 20 to 26]). The median angle of flexion of the shoulder was 40° (range 20º to 90°), and the median angle of abduction was 30° (range 20º to 90°). CONCLUSION: Resurfaced allograft-prosthesis composites showed a high risk of complications, but not all complications resulted in removal of the reconstructed allograft. We used this technique mainly for very young children with small bones and for older children who underwent axillary nerve preservation. Although its success may be limited owing to a high risk of complications, a resurfaced allograft-prosthesis composite could be an alternative surgical option in order to preserve the bone stock and achieve good functional outcomes in very young children. We recommend using a long-stem resurfaced allograft-prosthesis composite, which may reduce the risk of complications. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Coronary Physiology Guidance vs Conventional Angiography for Optimization of Percutaneous Coronary Intervention: The AQVA-II Trial.

BACKGROUND: The debate surrounding the efficacy of coronary physiological guidance compared with conventional angiography in achieving optimal post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) values persists. OBJECTIVES: The primary aim of this study was to demonstrate the superiority of physiology-guided PCI, using either angiography or microcatheter-derived FFR, over conventional angiography-based PCI in complex high-risk indicated procedures (CHIPs). The secondary aim was to establish the noninferiority of angiography-derived FFR guidance compared with microcatheter-derived FFR guidance. METHODS: Patients with obstructive coronary lesions and meeting CHIP criteria were randomized 2:1 to receive undergo physiology- or angiography-based PCI. Those assigned to the former were randomly allocated to angiography- or microcatheter-derived FFR guidance. CHIP criteria were long lesion (>28 mm), tandem lesions, severe calcifications, severe tortuosity, true bifurcation, in-stent restenosis, and left main stem disease. The primary outcome was invasive post-PCI FFR value. The optimal post-PCI FFR value was defined as >0.86. RESULTS: A total of 305 patients (331 study vessels) were enrolled in the study (101 undergoing conventional angiography-based PCI and 204 physiology-based PCI). Optimal post-PCI FFR values were more frequent in the physiology-based PCI group compared with the conventional angiography-based PCI group (77% vs 54%; absolute difference 23%, relative difference 30%; P < 0.0001). The occurrence of the primary outcome did not differ between the 2 physiology-based PCI subgroups, demonstrating the noninferiority of angiography- vs microcatheter-derived FFR (P < 0.01). CONCLUSIONS: In CHIP patients, procedural planning and guidance on the basis of physiology (through either angiography- or microcatheter-derived FFR) are superior to conventional angiography for achieving optimal post-PCI FFR values. (Physiology Optimized Versus Angio-Guided PCI [AQVA-II]; NCT05658952).

Diagnostic challenges in low-grade central osteosarcoma.

Aims: Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes. Methods: We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder's grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome. Results: Based on imaging, 35 of 49 patients (71.4%) exhibited malignant features. Overall, 40 of 49 patients (81.6%) had undergone a biopsy before en-bloc resection: 27 of 40 patients (67.5%) were diagnosed on the first biopsy, which was more accurate when carried out by open rather than needle biopsy (91.3% vs 35.3% diagnostic accuracy, respectively; p < 0.001). Of the 40 patients treated by en-bloc resection, surgical margins were wide in 38 (95.0%) and marginal in two (5.0%). Furthermore, nine of 49 patients (18.4%) underwent curettage (intralesional margin) without previous biopsy. All patients with a positive margin developed local recurrence. Distant metastases occurred in five of 49 patients (10.2%). The mean five-year overall survival (OS) and distant relapse-free survival (D-RFS) were 89.3% (SD 5.1%) and 85.7% (SD 5.5%), respectively. Univariate analysis showed that the occurrence of distant metastasis was a poor prognostic factor for OS (hazard ratio 11.54, 95% confidence interval (CI) 1.92 to 69.17; p < 0.001). Local recurrence was a poor prognostic factor for D-RFS (HR 8.72, 95% CI 1.69 to 45.0; p = 0.002). Conclusion: The diagnosis of LGCOS can be challenging because it may present with non-malignant features and has a low diagnostic accuracy on biopsy. If precisely diagnosed, LGCOS can be successfully treated by surgical excision with wide margins.

Lengthening Patients Previously Treated for Massive Lower Limb Reconstruction for Bone Tumors with the PRECICE 2 Nail.

The objective of this study was to determine the efficacy of the PRECICE 2® nail in the treatment of lower limb length discrepancy in patients with a history of bone tumors. This study reports on outcomes, complications, and the safety of the PRECICE 2 limb lengthening nail in a cohort of pediatric patients with limb length discrepancy after surgery for bone tumors. Seventeen patients were treated with intramedullary magnetic nails. The average patient age at the time of surgery was 19 (range 11-32). The PRECICE 2 nail was used on 14 femurs (6 retrograde and 8 anterograde) and 3 tibias. The average consolidation time was 141 days (range 50-360) with a mean CI of 31 ± 12 days/cm. The ASAMI bone score showed 14 (82%) excellent results, 1 (6%) good result, and 2 (12%) poor results. The ASAMI functional score showed 13 (84.6%) excellent results, 3 (11.5%) good results, and 1 (3.8%) fair result. Patients treated with chemotherapy for bone cancer did not show any increase in distraction time or consolidation time. A total of 3 (17%) problems, 1 obstacle (5.5%), and 1 complication (5.5%) were encountered in our case series. The PRECICE 2 nail allows for effective and accurate lengthening preserving the range of motion in patients treated for bone tumors.

The Prognostic Value of Serum Biomarkers for Survival of Children with Osteosarcoma of the Extremities.

BACKGROUND: Osteosarcoma is a highly aggressive malignant bone tumor that affects mainly adolescents and young adults. We analyzed serum biomarkers for their prognostic significance in children with osteosarcoma. METHODS: In this retrospective study, we investigated the prognostic factors in 210 children who were treated for appendicular osteosarcoma, including patient age and sex, tumor site and size (≥8 cm or <8 cm), presence of metastasis, chemotherapy-induced tumor necrosis, serum levels of alkaline phosphatase (AP), C-reactive protein, serum hemoglobin, lactate dehydrogenase, erythrocyte sedimentation rate (ESR), leukocyte counts, platelet count, and neutrophil-lymphocyte ratio. RESULTS: A multivariate Cox regression model showed that high level of AP [HR of 1.73; 95% CI, 1.02 to 2.94], poor chemotherapy-induced tumor necrosis [HR of 2.40; 95% CI, 1.41 to 4.08] and presence of metastases at presentation [HR of 3.71; 95% CI, 2.19 to 6.29] were associated with poor prognosis at 5 years (p < 0.05). Inadequate surgical margins [HR 11.28; 95% CI, 1.37 to 92.79] and high levels of ESR [HR 3.58; 95% CI, 1.29 to 9.98] showed a greater risk of local recurrence at 5 years follow-up (p < 0.05). CONCLUSIONS: AP and ESR can identify osteosarcoma-diagnosed children with a greater risk of death and local recurrence, respectively.

Acute Prosthetic Joint Infections with Poor Outcome Caused by Staphylococcus Aureus Strains Producing the Panton-Valentine Leukocidin.

The aim of this study was to investigate whether the presence of Staphylococcus aureus (SA) producing the Panton-Valentine leukocidin (PVL) affects the outcome of Prosthetic Joint Infection (PJI). Patients with acute and chronic PJI sustained by SA were prospectively enrolled at the orthopedic unit of "Casa di Cura Santa Maria Maddalena", from January 2019 to October 2021. PJI diagnosis was reached according to the diagnostic criteria of the International Consensus Meeting on PJI of Philadelphia. Synovial fluid obtained via joint aspirations was collected in order to isolate SA. The detection of PVL was performed via real-time quantitative PCR (RT-qPCR). The outcome assessment was performed using the criteria of the Delphi-based International Multidisciplinary Consensus. Twelve cases of PJI caused by SA were included. Nine (75%) cases were acute PJI treated using debridement, antibiotic and implant retention (DAIR); the remaining three (25%) were chronic PJI treated using two-stage (n = 2) and one-stage revision (n = 1), respectively. The SA strains that tested positive for PVL genes were 5/12 (41.6%,). Treatment failure was documented in three cases of acute PJI treated using DAIR, all supported by SA-PVL strains (p < 0.045). The remaining two cases were chronic PJI treated with a revision arthroplasty (one and two stage, respectively), with a 100% eradication rate in a medium follow-up of 24 months. Although a small case series, our study showed a 100% failure rate in acute PJI, probably caused by SA PVL-producing strains treated conservatively (p < 0.04). In this setting, toxin research should guide radical surgical treatment and targeted antibiotic therapy.

Psychological Well-Being, Self-Esteem, Quality of Life and Gender Differences as Determinants of Post-Traumatic Growth in Long-Term Knee Rotationplasty Survivors: A Cohort Study.

Rotationplasty (RP) is a special surgical technique for bone tumors of the lower limb and is the chosen procedure for children under 6 with bone sarcoma in the distal femur. Leg reconstruction results in an unusual aspect of the limb potentially giving life-long emotional outcomes, especially considering the young age of most RP patients. Although the high level of the quality of life of these patients has been previously reported, aspects related to long-term psychological well-being, self-esteem and life satisfaction, particularly regarding the gender, procreation and parenting, have never been explored. The aim of this study was to assess the general degree of psychological well-being of RP patients, with specific reference to gender, procreation and parenting. Twenty long-term RP survivors of high-grade bone sarcoma participated in the study. They were administered the following validated questionnaires: HADS for psychological well-being (degree of anxiety and depression), Temperament and Character Inventory (TCI), RSES for self-esteem, SF-36 for quality of life, SWLS extended to life satisfaction, and ABIS for body image integration. Data on education, marriage, employment and parenthood were gathered. All the scores obtained were very close to normal references. The only gender difference was found for the TCI Cooperativeness scale, which was higher in women than in men. A satisfactory psychological well-being in terms of both self-esteem and integration of the prosthetic joint limb into one's body image, with relatively limited amount of anxiety/depression, good quality of life, and good temperament and character traits, was found. No major gender differences were reported.

QFR-Based Virtual PCI or Conventional Angiography to Guide PCI: The AQVA Trial.

BACKGROUND: Post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) values ≥0.90 are associated with a low incidence of adverse events. OBJECTIVES: The AQVA (Angio-based Quantitative Flow Ratio Virtual PCI Versus Conventional Angio-guided PCI in the Achievement of an Optimal Post-PCI QFR) trial aims to test whether a QFR-based virtual percutaneous coronary intervention (PCI) is superior to a conventional angiography-based PCI at obtaining optimal post-PCI QFR results. METHODS: The AQVA trial is an investigator-initiated, randomized, controlled, parallel-group clinical trial. A total of 300 patients (356 study vessels) undergoing PCI were randomized 1:1 to receive either QFR-based virtual PCI or angiography-based PCI (standard of care). The primary outcome was the rate of study vessels with a suboptimal post-PCI QFR value, which was defined as <0.90. Secondary outcomes were procedure duration, stent length/lesion, and stent number/patient. RESULTS: Overall, 38 (10.7%) study vessels missed the prespecified optimal post-PCI QFR target. The primary outcome occurred significantly more frequently in the angiography-based group (n = 26, 15.1%) compared with the QFR-based virtual PCI group (n = 12 [6.6%]; absolute difference = 8.5%; relative difference = 57%; P = 0.009). The main cause of a suboptimal result in the angiography-based group is the underestimation of a diseased segment outside the stented one. There were no significant differences among secondary endpoints, although stent length/lesion and stent number/patient were numerically lower in the virtual PCI group (P = 0.06 and P = 0.08, respectively), whereas procedure length was higher in the virtual PCI group (P = 0.06). CONCLUSIONS: The AQVA trial demonstrated the superiority of QFR-based virtual PCI over angiography-based PCI with regard to post-PCI optimal physiological results. Future larger randomized clinical trials that demonstrate the superiority of this approach in terms of clinical outcomes are warranted. (Angio-based Quantitative Flow Ratio Virtual PCI Versus Conventional Angio-guided PCI in the Achievement of an Optimal Post-PCI QFR [AQVA]; NCT04664140).

The Prognostic Value of the Serum Level of C-Reactive Protein for Survival of Children with Ewing's Sarcoma.

The purpose of the present study was to evaluate the prognostic role of C-reactive protein (CRP) in children with Ewing's sarcoma. We conducted a retrospective study on 151 children undergoing multimodal treatment for Ewing's sarcoma in the appendicular skeleton from December 1997 to June 2020. Univariate Kaplan-Meier analyses of laboratory biomarkers and clinical parameters showed that CRP and metastatic disease at presentation were poor prognostic factors associated with overall survival and disease recurrence at 5 years (p < 0.05). A multivariate Cox regression model showed that pathological CRP (≥1.0 mg/dL) [HR of 3.67; 95% CI, 1.46 to 10.42] and metastatic disease [HR of 4.27; 95% CI, 1.58 to 11.47] were associated with a higher risk of death at 5 years (p < 0.05). In addition, pathological CRP (≥1.0 mg/dL) [HR of 2.66; 95% CI, 1.23 to 6.01] and metastatic disease [HR of 2.56; 95% CI, 1.13 to 5.55] were associated with a higher risk of disease recurrence at 5 years (p < 0.05). Our findings demonstrated that CRP was associated with the prognosis of children with Ewing's sarcoma. We recommend pre-treatment measurement of the CRP in order to recognize children with Ewing's sarcoma who are at greater risk of death or local recurrence.

Corrigendum: Serum IgG antibodies from pregnant women reacting to mimotopes of Simian virus 40 large T antigen, the viral oncoprotein.

[This corrects the article DOI: 10.3389/fimmu.2017.00411.].

The role of conventional radiography to assess the outcome of oncologic skeletal reconstructions of lower limbs aided by vascularized fibular autograft.

INTRODUCTION: Vascularized fibular autografts (VFA) are used in the oncologic skeletal reconstructions of long bones, alone or combined with massive bone allografts (MBA). Data regarding the role of imaging in assessing these complex skeletal reconstructions are lacking, and have mainly focused on Computed Tomography (CT). Our aim was to evaluate if early conventional radiography (CR) findings are correlated with the outcome of these skeletal reconstructions. MATERIALS AND METHODS: All consecutive patients who underwent oncologic resection of lower limbs long bones followed by VFA reconstruction were included in this single-center retrospective study. We compared the CR obtained immediately after surgery with the CR at the 6-month control, as well as the CR at 6 months with the CT at 6 months when available. The following scores were assigned to the VFA: 0 (unchanged), 1 (osteopenia-cortical bone thinning), 2 (increase in bone density-cortical thickening). We then investigated whether this score correlated with the implant outcome within 12 months (optimal integration, suboptimal integration, integration requiring further surgery or lack of integration) using Kaplan-Meier and Cox regression analyses, considering the occurrence of integration and the duration time before the surgical removal of the whole bone reconstruction. RESULTS: Forty-five patients were included (32 men [71.1%], mean age 14.6 years), 26 affected by osteosarcoma, 14 by Ewing sarcoma, 3 by adamantinoma and 2 operated for the failure of previous reconstructions for bone sarcoma. VFA changes on 6-month CR were significantly associated with optimal integration of the implants (log-rank P = 0.0137, multivariate Hazard ratio = 7.62, 95% confidence interval = 1.13-51.25). None of the other clinical and surgical features were associated with the implant outcome. The findings on 6-month CR and CT follow-up were not significantly different. CT at 6 months was available in 36 patients (80.0%). CONCLUSION: The assessment of VFA morphological changes on CR performed at 6 months can predict the outcome of the skeletal implant. This data should be considered for clinical decision-making, selecting patients requiring additional images (CT), and possible subsequent revision surgical procedures.

Impact of trans-stent gradient on outcome after PCI: results from a HAWKEYE substudy.

To test whether quantitative flow ratio (QFR)-based trans-stent gradient (TSG) is associated with adverse clinical events at follow-up. A post-hoc analysis of the multi-center HAWKEYE study was performed. Vessels post-PCI were divided into four groups (G) as follows: G1: QFR ≥ 0.90 TSG = 0 (n = 412, 54.8%); G2: QFR ≥ 0.90, TSG > 0 (n = 216, 28.7%); G3: QFR < 0.90, TSG = 0 (n = 37, 4.9%); G4: QFR < 0.90, TSG > 0 (n = 86, 11.4%). Cox proportional hazards regression model was used to analyze the effect of baseline and prognostic variables. The final reduced model was obtained by backward stepwise variable selection. Receiver operating characteristic (ROC) was plotted and area under the curve (AUC) was calculated and reported. Overall, 449 (59.8%) vessels had a TSG = 0 whereas (40.2%) had TSG > 0. Ten (2.2%) vessel-oriented composite endpoint (VOCE) occurred in vessels with TSG = 0, compared with 43 (14%) in vessels with TSG > 0 (p < 0.01). ROC analysis showed an AUC of 0.74 (95% CI: 0.67 to 0.80; p < 0.001). TSG > 0 was an independent predictor of the VOCE (HR 2.95 [95% CI 1.77-4.91]). The combination of higher TSG and lower final QFR (G4) showed the worst long-term outcome while low TSG and high QFR showed the best outcome (G1) while either high TSG or low QFR (G2, G3) showed intermediate and comparable outcomes. Higher trans-stent gradient was an independent predictor of adverse events and identified a subgroup of patients at higher risk for poor outcomes even when vessel QFR was optimal (> 0.90).

Circulating Biomarkers of Endothelial Dysfunction and Inflammation in Predicting Clinical Outcomes in Diabetic Patients with Critical Limb Ischemia.

Critical limb ischemia (CLI) is a severe manifestation of peripheral artery disease characterized by ischemic pain, which is frequently associated with diabetes and non-healing lesions to inferior limbs. The clinical management of diabetic patients with CLI typically includes percutaneous transluminal angioplasty (PTA) to restore limb circulation and surgical treatment of diabetic foot ulcers (DFU). However, even after successful treatment, CLI patients are prone to post-procedure complications, which may lead to unplanned revascularization or foot surgery. Unfortunately, the factors predicting adverse events in treated CLI patients are only partially known. This study aimed to identify potential biomarkers that predict the disease course in diabetic patients with CLI. For this purpose, we measured the circulating levels of a panel of 23 molecules related to inflammation, endothelial dysfunction, platelet activation, and thrombophilia in 92 patients with CLI and DFU requiring PTA and foot surgery. We investigated whether these putative biomarkers were associated with the following clinical endpoints: (1) healing of the treated DFUs; (2) need for new revascularization of the limb; (3) appearance of new lesions or relapses after successful healing. We found that sICAM-1 and endothelin-1 are inversely associated with DFU healing and that PAI-1 and endothelin-1 are associated with the need for new revascularization. Moreover, we found that the levels of thrombomodulin and sCD40L are associated with new lesions or recurrence, and we show that the levels of these biomarkers could be used in a decision tree to assign patients to clusters with different risks of developing new lesions or recurrences.

Intercalary reconstruction of long bones by massive allograft: Comparison of construct stability ensured by three different host-graft junctions and two types of fixations in a synthetic femur model.

An intercalary segmental allograft is an option for limb salvage in bone tumours. Stable and congruent intercalary reconstructions are a prerequisite for achieving host-graft union. However, a too rigid fixation could increase the risk of late complications correlated with negative bone remodelling. This study compared the reconstruction stiffness achieved by three different host-graft junctions, namely, end-to-end, modified step-cut, and taper. A low-stiffness bone plate was used as the fixation method, except for the taper junction where a low-stiffness intramedullary nail was also used to investigate the effects of different types of fixation on construct stiffness. Composite femora were tested under four loading conditions to determine coronal and sagittal bending stiffness, as well as torsional stiffness in opposite directions. Stiffness values were expressed as a percentage of intact host bone stiffness (%IBS). While a reduction of coronal bending stiffness was found with taper junctions (76%IBS) compared with the high values ensured by end-to-end (96%IBS) and modified step-cut junctions (92%IBS), taper junctions significantly increased stiffness under sagittal bending and torsion in intra- and extra-direction: end-to-end 29%IBS, 7%IBS, 7%IBS, modified step-cut 38%IBS, 20%IBS, 21%IBS, and taper junction 52%IBS, 55%IBS, 56%IBS, respectively. Construct stiffness with taper junctions was decreased by 11-41%IBS by replacing the bone plate with an intramedullary nail. Taper junctions can be an alternative to achieve intercalary reconstructions with more homogeneous and, in three out of four loading conditions, significantly higher construct stability without increasing bone plate stiffness. The risk of instability under high torsional loads increases when taper junctions are associated with a low-stiffness intramedullary nail.

Renin-Angiotensin-Aldosterone System Inhibitors, Statins, and Beta-Blockers in Diabetic Patients With Critical Limb Ischemia and Foot Lesions.

Medical therapy for secondary prevention is known to be under-used in patients with peripheral artery disease (PAD). Few data are available on the subgroup with critical limb ischemia (CLI). Prescription of cardiovascular preventive therapies was recorded at discharge in a large, prospective cohort of patients admitted for treatment of CLI and foot lesions, stratified for coronary artery disease (CAD) diagnosis. All patients were followed up for at least 1 year. The primary endpoint was major adverse cardiovascular events (MACE). 618 patients were observed for a median follow-up of 981 days. Renin-angiotensin-aldosterone system (RAAS) inhibitors, statins, beta-blockers, and antithrombotic drugs were prescribed in 52%, 80%, 51%, and 99% of patients, respectively. However, only 43% of patients received optimal medical therapy (OMT), defined as the combination of RAAS inhibitor plus statin plus at least one antithrombotic drug. It was observed that the prescription of OMT was not affected by the presence of a CAD diagnosis. On the other hand, it was noticed that the renal function affected the prescription of OMT. OMT was independently associated with MACE (HR 0.688, 95%CI 0.475-0.995, P = .047) and, after propensity matching, also with all-cause mortality (HR 0.626, 95%CI 0.409-0.958, P = .031). Beta-blockers prescription was not associated with any outcome. In conclusion, patients with critical limb ischemia are under-treated with cardiovascular preventive therapies, irrespective of a CAD diagnosis. This has consequences on their prognosis.