Ibrutinib followed by ofatumumab consolidation in previously untreated patients with chronic lymphocytic leukemia (CLL): GELLC-7 trial from the Spanish group of CLL (GELLC).

Background: BTK inhibitors have been concurrently administered with anti-CD20 monoclonal antibodies (mAbs) in chronic lymphocytic leukemia (CLL). However, the optimal regimen for combining these two drugs remains pending. Methods: This multi-center phase 2 study aimed to analyze whether consolidation with ofatumumab improved the response in patients with CLL receiving front-line treatment with ibrutinib. Patients received 12 cycles of ibrutinib monotherapy. Those who achieved CR after this induction were maintained on ibrutinib. Conversely, those who did not attain CR continued with ibrutinib in addition to a consolidation, which involved 7 doses of ofatumumab. The primary objective was the complete response (CR) rate at cycle 20. This study is registered within the EU Clinical Trials Register (EudraCT 2016-004937-26). Findings: Between September 8, 2017, and May 21, 2018, 84 patients (median age, 69 years) were included. After completion of 12 cycles of ibrutinib (n = 80), 4 patients (5%) were in CR, 67 (84%) in partial response (PR), and 6 patients (7%) had a PR with lymphocytosis (PRL). After consolidation with ofatumumab, 20 patients improved the response from PR to CR and 6 patients with PRL obtained a PR. Seventy-one patients (85%) completed 20 cycles of treatment, with a CR rate of 24/71 (34%). According to the intention-to-treat analysis at cycle 20, the ORR was 69/84 (82.2%), with a CRR of 24/84 (28.6%). Progression-free survival and overall survival at 48-months were 89.9% (CI: 82.4-95.5) and 92.2% (CI: 85.3-97.1), respectively. Interpretation: These findings underscore the potential for a consolidation strategy in CLL, wherein the addition of a mAb in patients with low tumor burden might enhance the quality of the response. Funding: The study was funded by Janssen that also supplied ibrutinib, whereas ofatumumab was supplied by Novartis.

Incremental hemodialysis and vascular access complications: a 12-year experience in a hospital hemodialysis unit.

BACKGROUND: Incremental hemodialysis (HD) is considered a valid alternative for patients with residual kidney function. Evidence concerning its effect on vascular access is scarce. We present our 12-year experience of an incremental hemodialysis program with the aim of evaluating survival and complications of arteriovenous fistula in these patients compared to the thrice-weekly scheme. METHODS: From January 1st, 2006 to December 31st, 2017, 220 incident patients started hemodialysis, 132 (60%) of whom began hemodialysis with two sessions per week and 88 (40%) with three sessions per week. Demographic and clinical variables were assessed at the start of treatment. Data regarding arteriovenous fistula survival and complications were collected. RESULTS: Both groups had similar baseline sociodemographic and clinical characteristics. A total of 188 (85%) patients were dialyzed with an arteriovenous fistula during follow-up. Eighty-three patients had one or more fistula complications, with no differences between incremental and conventional groups (p = 0.55). Fistula survival rates showed no significant difference between the two groups, whether analyzed from the date of fistula creation (Log Rank p = 0.810) or from the date of initial fistula cannulation (Log Rank p = 0.695). CONCLUSIONS: We found no differences in arteriovenous fistula survival or complication rate between patients who started HD with an incremental versus a conventional treatment scheme. Randomized controlled clinical trials may be warranted to achieve a higher degree of evidence.

Patient-Reported Outcomes After Intramedullary Nailing of Oncologic Impending or Pathologic Fractures With Carbon Fiber or Titanium Implant.

INTRODUCTION: Despite the benefits of intramedullary nailing (IMN) of impending or pathologic fractures in oncologic patients, literature on patient-reported outcomes (PROs) is scarce in patients treated with carbon fiber (CF) nails. Our study compared postoperative PROs after IMN with CF or titanium implants. METHODS: We conducted a retrospective propensity score-matched cohort study of patients treated at our institution with CF or titanium nails for impending or pathologic fractures from metastatic bone disease. Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Short Form (SF) Physical, Mental, and Physical Function 10a scores were collected. Pain was assessed using visual analog scale (VAS). Absolute and differential scores were compared between groups. RESULTS: We included 207 patients, 51 treated with CF and 156 with titanium nails. One month postoperatively, patients had a one-point decrease in the pain VAS score while PROMIS scores did not improve. At 3 months, PROMIS SF Physical and SF 10a scores improved from preoperative values. Six months postoperatively, median PROMIS SF Physical, SF Mental, and SF 10a scores were higher than preoperative scores. Absolute and differential PROMIS and pain VAS scores were similar between groups at the 6-month and 1-year marks. CONCLUSION: Patient-reported outcomes were similar after intramedullary nailing with either CF or titanium implants.

Incidence and survival outcomes of patients with high-grade appendicular bone sarcoma and isolated regional lymph node metastasis: A national cohort database study.

BACKGROUND: While distant metastases in primary bone sarcomas have been extensively studied, the impact of isolated regional lymph node (LN) metastasis on survival remains unknown. In patients with primary bone sarcomas, we sought to assess the prevalence of isolated regional LN metastasis and the survival of this population. METHODS: A total of 6651 patients with histologically-confirmed high-grade osteosarcoma, Ewing sarcoma, or chondrosarcoma were retrieved from the SEER database. We defined four subgroups for our analysis: localized disease (N0 M0), isolated regional LN metastasis (N1 M0), isolated distant metastasis (N0 M1), and combined regional LN and distant metastasis (N1 M1). Disease-specific survival (DSS) was assessed using the Kaplan-Meier method. RESULTS: Prevalence of isolated regional LN metastasis (N1 M0) was highest in Ewing sarcoma (27/1097; 3.3 %), followed by chondrosarcoma (18/1702; 1.4 %) and osteosarcoma (26/3740; 0.9 %). In all three histologies, patients with isolated regional LN metastasis had a worse 2-year, 5-year, and 10-year DSS than those with localized disease. Chondrosarcoma patients with isolated regional LN (N1 M0) metastasis had a significantly higher DSS in comparison to those with only distant metastasis (N0 M1) at the 5- and 10-year marks; for osteosarcoma and Ewing sarcoma, only a pattern towards higher survival was seen. Risk factors for presenting isolated regional LN metastasis included tumor location in lower-limb (OR = 2.01) or pelvis (OR = 2.49), diagnosis of Ewing sarcoma (OR = 2.98), and tumor >10 cm (OR = 1.96). CONCLUSIONS: Isolated regional LN metastases in primary bone sarcomas is an infrequent presentation associated with worse survival than localized disease. LEVEL OF EVIDENCE: III.

Theoretical Study of Cyanidin-Resveratrol Copigmentation by the Functional Density Theory.

Anthocyanins are colored water-soluble plant pigments. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood-brain barrier (BBB). Research based on population studies suggests that including anthocyanin-rich sources in the diet lowers the risk of neurodegenerative diseases. The copigmentation caused by copigments is considered an effective way to stabilize anthocyanins against adverse environmental conditions. This is attributed to the covalent and noncovalent interactions between colored forms of anthocyanins (flavylium ions and quinoidal bases) and colorless or pale-yellow organic molecules (copigments). The present work carried out a theoretical study of the copigmentation process between cyanidin and resveratrol (CINRES). We used three levels of density functional theory: M06-2x/6-31g+(d,p) (d3bj); ωB97X-D/6-31+(d,p); APFD/6-31+(d,p), implemented in the Gaussian16W package. In a vacuum, the CINRES was found at a copigmentation distance of 3.54 Å between cyanidin and resveratrol. In water, a binding free energy ∆G was calculated, rendering -3.31, -1.68, and -6.91 kcal/mol, at M06-2x/6-31g+(d,p) (d3bj), ωB97X-D/6-31+(d,p), and APFD/6-31+(d,p) levels of theory, respectively. A time-dependent density functional theory (TD-DFT) was used to calculate the UV spectra of the complexes and then compared to its parent molecules, resulting in a lower energy gap at forming complexes. Excited states' properties were analyzed with the ωB97X-D functional. Finally, Shannon aromaticity indices were calculated and isosurfaces of non-covalent interactions were evaluated.

Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease.

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.

Postoperative Outcomes of Total Humerus Replacement for Oncologic Reconstruction of the Upper Limb: A Systematic Review of the Literature.

BACKGROUND: Total humerus replacement (THR) is a reconstruction procedure performed after resection of massive humeral tumors. However, there is limited literature on the rates of failure and functional outcomes of this implant. Our study aimed to determine the main failure modes, implant survival, and postoperative functional outcomes of THR. METHODS: A comprehensive search of the PubMed and Embase databases was conducted. We registered our study on PROSPERO (448684) and used the Strengthening the Reporting of Observational Studies in Epidemiology checklist for quality assessment. The Henderson classification was used to assess endoprosthesis failure and the Musculoskeletal Tumor Society (MSTS) score for functional outcomes. Weighted means and standard deviations were calculated. RESULTS: Ten studies comprising 171 patients undergoing THR were finally included. The overall failure rate was 32.2%. Tumor progression (12.6%) and prosthetic infections (9.4%) were the most common failure modes, followed by soft-tissue failures (5.9%), aseptic loosening (3.5%), and structural failure (1.8%). Two-year, 5-year, and 10-year implant survival rates for the entire cohort were 86%, 81%, and 69.3%. Ten-year implant survival for primary THRs was 78.3%, compared with 38.6% for revision THRs (p = 0.049). The mean MSTS score at the last follow-up was 77%. Patients whose implants did not fail had a higher MSTS score (79.3%) than those with failed implants (71.4%) (p = 0.02). CONCLUSION: One-third of THR will fail, mostly due to tumor progression and prosthetic infection. Overall functional scores were acceptable, with MSTS scores displaying great hand and elbow function but limited shoulder function. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

Wound-Healing Effects of Common Antineoplastic Agents and Perioperative Considerations for the Orthopaedic Surgeon.

In oncologic patients, optimal postoperative wound healing is crucial for the maintenance of systemic therapies and improved survival. Although several risk factors for postoperative wound complications have been identified, the clinical effect of new antineoplastic agents on wound healing remains uncertain. The available literature on the effect of antineoplastic agents in wound healing is complex to analyze because of other confounding risk factors such as radiation therapy and certain patient-specific variables. Available perioperative drug recommendations are based on database opinion and case reports from adverse event alerts. This review highlights the characteristics of old and new antineoplastic agents commonly used in the treatment of sarcoma, carcinoma, and other cancers and their potential effects on the wound-healing process. It also aims to provide perioperative treatment cessation recommendations to guide orthopaedic surgeons and prevent drug-related wound complications to the fullest extent possible.

Wound vacuum-assisted closure temporization after tumor resection of soft tissue sarcomas-A cost analysis in a propensity-score matched population.

BACKGROUND: Vacuum-assisted closure (VAC) temporization is a technique associated with high local control rates used in myxofibrosarcoma. We sought to compare the costs and postoperative outcomes of VAC temporization and single-stage (SS) excision/reconstruction. METHODS: We conducted a retrospective analysis of patients with myxofibrosarcoma surgically treated at our institution between 2000 and 2022. Variables of interest included total, direct, and indirect costs for initial episode of care, 90 days and 1 year after initial admission, and postoperative outcomes. Costs were compared between the VAC temporization and SS groups. RESULTS: After matching, 13 patients in the SS group and 23 in the VAC group were analyzed. We found no difference in median and mean total inpatient costs, between the VAC temporization and SS group. While total 90-day and 1-year costs were higher in the VAC group compared to the SS group, mean costs were similar. There were no differences in postoperative complications between groups. A subanalysis of the entire cohort (n = 139) revealed lower local recurrence and overall death rates in the VAC temporization group. CONCLUSION: VAC temporization had similar inpatient costs and postoperative outcomes to SS excision/reconstruction. While median 90-day and 1-year costs were higher in the VAC group, mean costs did not differ.

Cassia angustifolia and tacrolimus interaction in a liver transplant patient, a case report.

Cassia angustifolia is a species of plant from the Senna family that has traditionally been used as a laxative in different herbal products and commercial medicines. Even though there are few documented drug-plant interactions, the use of C. angustifolia with different drugs may have additive effects, such as with other laxatives or potassium-depleting diuretics. Its use also increases peristalsis which, may reduce drug absorption. The combination with digoxin has been associated with an increased risk of digoxin toxicity, probably due to an increase in plasma digoxin concentrations and hypokalaemia. We present a case with supratherapeutic trough concentration of tacrolimus, an immunosuppressive agent, and a herbal product in a liver transplant patient after concomitant intake of tacrolimus and a herbal product based on C. angustifolia, suggesting a possible drug-lant interaction through by P-glycoprotein. We observed an increase in the patient's blood concentration 2.8-fold and the area under the curve at steady state 2.1-fold. This interaction could be of clinical relevance, given the dose-dependent side effects of tacrolimus, such as nephrotoxicity, neurotoxicity, hypertension, hyperglycaemia, or electrolyte alterations.

Neoplastic pathologic hip fractures are associated with a higher risk of post-operative bleeding and thromboembolic events.

INTRODUCTION: Surgical treatment of hip fractures leads to significant post-operative complications. Although pathologic fractures (PF) are associated with worse outcomes, most studies do not differentiate between etiology (neoplastic and non-neoplastic PF). We seek to compare 30-day complication rates between 1) native hip fractures and neoplastic PF, and 2) neoplastic and non-neoplastic PF. MATERIALS AND METHODS: A total of 127,819 patients with hip fractures and 5104 with PF diagnosed from 2005 to 2021 were retrieved from the NSQIP database. We included 1843 patients with neoplastic PF and 3261 with non-neoplastic PF. Demographics, pre-operative labs and co-morbidities, and post-operative outcomes were analyzed. Propensity-score matching was conducted to control for confounders. RESULTS: Patients with a neoplastic PF had a significantly higher rate of deep venous thrombosis (DVT) (4 % vs 1.2 %, p = 0.001) and pulmonary embolism (PE) (2.4 % vs 0.7 %, p < 0.001), than native hip fractures. Rates of post-operative bleeding were significantly higher in the neoplastic PF group (29.3 % vs 23.9 %, p < 0.001) than non-neoplastic PF. No differences in soft tissue complications were found. When comparing neoplastic and non-neoplastic PF, the former had a higher rate of PE (2.5 % vs 1.0 %, p = 0.015) and post-operative bleeding (27.6 % vs 22.0 %, p = 0.009). Unplanned readmission rates and 30-day mortality rate were also higher in the neoplastic PF group. CONCLUSION: Neoplastic PF of the hip are associated with higher risk of thromboembolic event rates and post-operative bleeding than both native hip fractures and non-neoplastic PF. No differences in rates of soft tissue complications were found between groups.

Complications and Functional Outcomes after Reconstruction of the Proximal Humerus with Allograft-Prosthetic Composite - A Systematic Review of the Literature.

INTRODUCTION: Allograft prosthetic composite (APC) reconstruction is performed after resection of proximal humerus tumors or failure of arthroplasty implants. There is limited literature on the postoperative outcomes of this technique. We sought to assess implant survival, failure rates, and postoperative functional outcomes after APC reconstruction of the proximal humerus. METHODS: A systematic review of the PubMed and Embase databases was conducted. The study was registered on PROSPERO (ID: 448663). The STROBE checklist was used for quality assessment. Implant failure was determined using the Henderson classification for biological reconstruction. Functional outcome was primarily assessed using the Musculoskeletal Tumor Society (MSTS) score at last follow-up. RESULTS: Twenty-five studies with a total of 488 patients were included. Mean follow-up in reporting studies ranged from 2.5 to 10 years. Five-year revision-free survival for implants ranged from 41 to 92%. Overall implant failure rate ranged from 9 to 54%, and reoperation rate ranged from 0 to 55%. Graft-host non-union (type 2) was the most common mode of failure, with rates ranging from 0 to 75%. The mean MSTS scores at last follow-up ranged from 57 to 90% across studies. A trend towards better functional outcomes was seen in patients having an APC with a reverse total shoulder arthroplasty (rTSA) compared with those with hemiarthroplasty (HA). CONCLUSIONS: APCs show promise in proximal shoulder reconstruction, with heterogenous functional outcomes that are non-inferior to other reconstruction techniques. Graft host non-union is a common mode of failure and remains a concern in this type of prosthesis. Future studies should compare rTSA-APCs and rTSA endoprostheses while controlling for potential confounders.

Transcriptomic characterization of the response to a microalgae extract in Arabidopsis thaliana and Solanum lycopersicum.

BACKGROUND: The steady world population growth and the current climate emergency crisis demand the development of sustainable methods to increase crop performance and resilience to the abiotic and biotic stresses produced by global warming. Microalgal extracts are being established as sustainable sources to produce compounds that improve agricultural yield, concurrently contributing during their production process to atmospheric CO2 abatement through the photosynthetic activity of microalgae. RESULTS: In the present study, we characterize the transcriptomic response in the model plant Arabidopsis thaliana and the plant of horticultural interest Solanum lycopersicum to the foliar application of a microalgae-based commercial preparation LRM™ (AlgaEnergy, Madrid, Spain). The foliar spray of LRM™ has a substantial effect over both transcriptomes potentially mediated by various compounds within LRM™, including its phytohormone content, activating systemic acquired resistance, possibly mediated by salicylic acid biosynthetic processes, and drought/heat acclimatization, induced by stomatal control and wax accumulation during cuticle development. Specifically, the agronomic improvements observed in treated S. lycopersicum (tomato) plants include an increase in the number of fruits, an acceleration in flowering time and the provision of higher drought resistance. The effect of LRM™ foliar spray in juvenile and adult plants was similar, producing a fast response detectable 2 h from its application that was also maintained 24 h later. CONCLUSION: The present study improves our knowledge on the transcriptomic effect of a novel microalgal extract on crops and provides the first step towards a full understanding of the yield and resistance improvement of crops. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Enhancement of the CO2 adsorption and hydrogenation to CH4 capacity of Ru-Na-Ca/γ-Al2O3 dual function material by controlling the Ru calcination atmosphere.

Integrated CO2 capture and utilization (ICCU) technology requires dual functional materials (DFMs) to carry out the process in a single reaction system. The influence of the calcination atmosphere on efficiency of 4% Ru-8% Na2CO3-8% CaO/γ-Al2O3 DFM is studied. The adsorbent precursors are first co-impregnated onto alumina and calcined in air. Then, Ru precursor is impregnated and four aliquotes are subjected to different calcination protocols: static air in muffle or under different mixtures (10% H2/N2, 50% H2/N2 and N2) streams. Samples are characterized by XRD, N2 adsorption-desorption, H2 chemisorption, TEM, XPS, H2-TPD, H2-TPR, CO2-TPD and TPSR. The catalytic behavior is evaluated, in cycles of CO2 adsorption and hydrogenation to CH4, and temporal evolution of reactants and products concentrations is analyzed. The calcination atmosphere influences the physicochemical properties and, ultimately, activity of DFMs. Characterization data and catalytic performance discover the acccomodation of Ru nanoparticles disposition and basic sites is mostly influencing the catalytic activity. DFM calcined under N2 flow (RuNaCa-N2) shows the highest CH4 production (449 µmol/g at 370°C), because a well-controlled decomposition of precursors which favors the better accomodation of adsorbent and Ru phases, maximizing the specific surface area, the Ru-basic sites interface and the participation of different basic sites in the CO2 methanation reaction. Thus, the calcination in a N2 flow is revealed as the optimal calcination protocol to achieve highly efficient DFM for integrated CO2 adsorption and hydrogenation applications.

Reconstruction of the elbow with distal humerus endoprosthetic replacement after tumor resection: a systematic review of the literature and institutional case series.

BACKGROUND: Distal humerus replacement (DHR) is a modular endoprosthesis mainly used for bone reconstruction after resection of primary or metastatic bone lesions. Studies on DHR failure rates and postoperative functional outcomes are scarce. We sought to assess implant survival, modes of failure, and functional outcomes in patients undergoing DHR for oncologic indications. METHODS: A systematic review of the PubMed and Embase databases was performed. PRISMA guidelines were followed for this manuscript. Our study was registered on PROSPERO (457,260). Quality appraisal of included studies was conducted using the STROBE checklist. Prosthetic failure was assessed using the Henderson classification for megaprosthetic failures. We additionally performed a retrospective review of patients treated with a DHR for oncologic indications at a large tertiary care academic center. Weighted means were calculated to pool data. RESULTS: Eleven studies with a total of 162 patients met the inclusion criteria. Mean follow-up was 3.7 years (range, 1.66-8 years). Henderson type 2 failures (aseptic loosening) were the most common mode of failure, occurring in 12% of cases (range, 0%-33%). Five-year implant survival was 72% (range, 49%-93.7%). Mean postoperative Musculoskeletal Tumor Society (MSTS) score was 81.1 (range, 74-84.3). In our institutional case series, 2 out of 5 patients had DHR revision for periprosthetic fracture and aseptic loosening at 16 and 27 months after surgery, respectively. CONCLUSIONS: Distal humerus replacement is a successful reconstruction strategy for tumors of the distal humerus, with high implant survival and good to excellent functional outcomes.

Phosphaturic mesenchymal tumor: management and outcomes of ten patients treated at a single institution.

BACKGROUND: Phosphaturic mesenchymal tumor (PMT) is a rare tumor that causes tumor-induced osteomalacia. Patients present with non-specific symptoms secondary to renal phosphate wasting and decreased bone mineralization. We sought to assess: (1) What are the common presenting features, laboratory and imaging findings, histologic findings of phosphaturic mesenchymal tumors? (2) What are the available treatment strategies for phosphaturic mesenchymal tumors and their long-term outcomes in terms of local recurrence and symptom control after treatment? METHODS: We retrospectively identified patients with a histologic diagnosis of PMT located in the axial or appendicular skeleton, or surrounding soft tissues. A total of 10 patients were finally included in our study. RESULTS: Median tumor size was 1.9 cm (range, 1.1 to 6.1) and median time from symptom onset to diagnosis was 3 years (range, 0.5 to 15 years). All patients but one presented with hypophosphatemia (median 1.9 mg/dL, range 1.2 to 3.2). Pre-operative FGF-23 was elevated in all cases (median 423.5 RU/mL, range 235 to 8950). Six patients underwent surgical resection, three were treated percutaneously (radiofrequency ablation or cryoablation), and one refused treatment. Only one patient developed local recurrence and no patients developed metastatic disease. At last follow-up, nine patients showed no evidence of disease and one was alive with disease. CONCLUSION: Phosphaturic mesenchymal tumor is a rare tumor presenting with non-specific symptoms. Surgery is the standard treatment when negative margins can be achieved without significant morbidity. In patients with small tumors in surgically-inaccessible areas, radiofrequency ablation or cryoablation can be performed successfully.

Reverse Fragility Index: Comparing Revision Rates Between Direct Anterior and Other Approaches in Total Hip Arthroplasty. A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Despite increasing adoption of the direct anterior (DA) approach in total hip arthroplasty (THA), uncertainty persists regarding its outcomes beyond the 1-year mark in comparison to other approaches. We used the reverse fragility index (RFI) to evaluate the robustness of reported findings in the literature. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) comparing implant revision rates between DA and other approaches in THA, defined as all those different from DA. Our primary outcome was the RFI, which gauges the number of events needed for a nonsignificant result to become significant, in the revision rate between DA and other approaches. We also calculated the reverse fragility quotient by dividing the RFI by each study's sample size. Median values and interquartile ranges (IQRs) were displayed. RESULTS: A total of 10 RCTs with a total of 971 patients were included. The median RFI was 5 (IQR, 4 to 5), indicating the study's results would be statistically significant if the outcomes of 5 patients in 1 treatment arm were reversed. The median reverse fragility quotient was 0.049 (IQR, 0.04 to 0.057), indicating that a change of outcome in 4.9% of patients would render the revision rate significant. The median number of patients lost to follow-up was 4 (IQR, 0 to 7). Of the 10 RCTs, 6 had more patients lost to follow-up than their respective RFI values. CONCLUSIONS: Notable fragility was evidenced in most studies comparing DA to other approaches for THA. Surgeons should not solely rely on the P value to determine clinical significance and instead use multiple metrics. LEVEL OF EVIDENCE: II.

A Bibliometric Analysis of the 500 Most Cited Papers in Orthopaedic Oncology.

BACKGROUND: Despite notable progress over time, broad insight into the scientific landscape of orthopaedic oncology is lacking. We conducted a bibliometric analysis of the 500 most cited papers in the field. METHODS: We searched the Science Citation Index Expanded database of the Web of Science Core Collection to find the 500 most cited articles in the field. RESULTS: Citation count ranged from 81 to 1,808. Articles were published from 1965 to 2018. Over half of all articles were published in the United States (53.6%). The 2000s was the most productive decade with 170 (34%) articles. All articles were written in English and were published across 29 journals. Female participation as first authors significantly increased from the 1960s to the 2010s (0% vs 14.6%, P = 0.0434). Similarly, female involvement as senior authors grew from the 1960s to the 2010s (0% vs 12.2%, P = 0.0607). Primary bone sarcomas were the most cited topic among articles from the 1970s to the 1980s. From studies produced in the 1990s up until the 2010s, reconstruction procedures were the most cited topic. CONCLUSION: Trends over the years have resulted in an emphasis on a surgical technique. Notable progress has been made regarding gender diversity, yet disparities still exist.

Is Unplanned Excision of Soft Tissue Sarcomas Associated with Worse Oncological Outcomes?-A Systematic Review and Meta-Analysis.

BACKGROUND: Soft tissue sarcomas are a group of rare neoplasms which can be mistaken for benign masses and be excised in a non-oncologic fashion (unplanned excision). Whether unplanned excision (UE) is associated with worse outcomes is highly debated due to conflicting evidence. METHODS: We performed a systematic review and meta-analysis following PRISMA guidelines. Main outcomes analyzed were five-year overall survival (OS), five-year local recurrence-free survival (LRFS), amputation rate and plastic reconstruction surgery rate. Risk ratios were used to compare outcomes between patients treated with planned and unplanned excision. RESULTS: We included 16,946 patients with STS, 6017 (35.5%) with UE. UE was associated with worse five-year LRFS (RR 1.35, p = 0.019). Residual tumor on the tumor bed was associated with lower five-year LRFS (RR = 2.59, p < 0.001). Local recurrence was associated with worse five-year OS (RR = 1.82, p < 0.001). UE was not associated with a worse five-year OS (RR = 0.90, p = 0.16), higher amputation rate (RR = 0.77, p = 0.134), or a worse plastic reconstruction surgery rate (RR = 1.25, p = 0.244). CONCLUSIONS: Unplanned excision of Soft Tissue Sarcomas and the presence of disease in tumor bed after one were associated with worse five-year LRFS. Tumor bed excision should remain the standard approach, with special consideration to the presence of residual disease.