Do Patients Treated With an Unplanned Resection for Small Superficial Soft Tissue Sarcomas Have Worse Long-term Survival Than Those Initially Treated With an Oncologic Resection?

BACKGROUND: Histologic grade, size, and depth are well-known prognostic factors in soft tissue sarcomas (STS). Small (< 5 cm) and superficial STS generally have an excellent prognosis when treated with appropriate surgery. However, they are often misdiagnosed and mistreated. We reported that in midterm follow-up (5 to 7 years), patients with unplanned resections of tumors with positive margins who immediately underwent a reoperation with margin-widening re-resection and postoperative radiotherapy had survival comparable to that of patients who were initially treated correctly. In that article, we included STS larger than 5 cm, deep STS, and individuals with local recurrence. However, we wanted to evaluate the impact of unplanned resection on the survival of patients who had STS with the best prognosis, small and superficial STS, with two groups that were as homogeneous as possible. QUESTION/PURPOSE: Do patients with small and superficial STS who underwent an unplanned resection have worse prognosis in the long term than those who were initially treated correctly? METHODS: We exclusively evaluated patients with small (< 5 cm) and superficial (to the deep fascia) STS. We systematically excluded deep STS. Among this subset, we identified 93 patients with superficial STS. We excluded patients with local relapse, metastatic disease, superficial STS of the head or neck, those with insufficient clinical or dosimetric information, and patients with follow-up of less than 2 years. Furthermore, our focus on investigating the most benign and homogeneous STS prompted us to exclude patients with superficial tumors greater than or equal to 5 cm. This selection was driven by the presumed better prognosis associated with smaller tumors, inevitably leading to a smaller pool of patients for direct comparison with patients who had unplanned resections. The initial expectation was to observe similar survival outcomes between cohorts. Between 1990 and 2019, a total of 17 patients underwent surgical treatment at our private, medium-size center. Of those, 29% (5 patients) were lost to follow-up before 2 years without meeting a study endpoint (relapse, metastasis or revision, reoperation, or death), leaving a total of 71% (12 patients) of the original group who had either follow-up of at least 2 years or who met a study endpoint before that minimum surveillance duration. They were treated with surgery alone. During that same period, another 51 patients were referred to us after undergoing an unplanned resection of a lesion that subsequently was determined to be a soft tissue malignancy. Of those, 18% (9 patients) were lost to follow-up before 2 years without meeting a study endpoint, leaving 82% (42 patients) of the original group who had either follow-up of at least 2 years or who met a study endpoint before that minimum surveillance duration. They were treated with re-excision and postoperative radiotherapy. Patients with unplanned resections had an older mean age (51± 5 versus 44 ± 7 years; p = 0.1) and a higher proportion of female patients (58% versus 38%; p = 0.07), but the groups did not differ in terms of largest diameter, histologic type, or tumor location. However, patients with planned resections had a higher proportion of high-grade STS (75% versus 55%; p = 0.07). No metastases were present in either group at diagnosis. We performed a univariate analysis of the groups. We could not perform a multivariate analysis because of the small sample. We compared the groups in terms of local recurrence and all-cause mortality using the Kaplan-Meier survivorship estimator. RESULTS: According to the Kaplan-Meier survivorship estimator, survivorship free from local recurrence at a mean of 20 years of follow-up was better in the planned resection group than in the unplanned resection group (92% [95% CI 63% to 100%] versus 69% [95% CI 54% to 81%]; p = 0.04). Furthermore, overall survivorship at 5 years was higher in the planned resection group than in the unplanned resection group (100% [95% CI 72% to 100%] versus 70% [95% CI 54% to 81%]; p = 0.04). Similarly, the planned resection group exhibited superior survivorship at 20 years of follow-up (100% [95% CI 72% to 100%] versus 62% [95% CI 47% to 75%]; p = 0.01). Metastatic disease was absent in the planned resection group, while it occurred in 12 patients in the unplanned resection group (28% [95% CI 17% to 44%]). CONCLUSION: Unplanned resection for patients with small and superficial STS was associated with a decrease in overall survival in the long term, despite the use of postoperative radiotherapy. An unplanned resection may be an important prognostic factor. Nevertheless, larger and prospective studies are needed to validate our findings. Although small and superficial lumps are usually benign, nonsarcoma surgeons should be aware that some masses may be malignant, and if in doubt, MR imaging, a biopsy before excision, or consultation with or referral to a sarcoma center should be considered before removing the mass. LEVEL OF EVIDENCE: Level III, therapeutic study.

Long-term efficacy of autologous bone marrow mesenchymal stromal cells for treatment of knee osteoarthritis.

Knee osteoarthritis is the most prevalent joint disease and a frequent cause of pain, functional loss and disability. Conventional treatments have demonstrated only modest clinical benefits whereas cell-based therapies have shown encouraging results, but important details, such as dose needed, long-term evolution or number of applications required are scarcely known. Here we have reanalyzed results from two recent pilot trials with autologous bone marrow-derived mesenchymal stromal cells using the Huskisson plot to enhance quantification of efficacy and comparability. We find that cell doses of 10, 40 and 100 million autologous cells per knee provided quite similar healing results and that much of the effect attained 1 year after cell application remained after 2 and 4 years. These results are encouraging because they indicate that, apart from safety and simplicity: (i) the beneficial effect is both significant and sizeable, (ii) it can be achieved with a single injection of cells, and (iii) the effect is perdurable for years.Trial registration: EudraCT 2009-017405-11; NCT02123368. Registered 25 April 2014-Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT02123368?term=02123368&draw=2&rank=1.

Phase II multicenter randomized controlled clinical trial on the efficacy of intra-articular injection of autologous bone marrow mesenchymal stem cells with platelet rich plasma for the treatment of knee osteoarthritis.

BACKGROUND: Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100 × 106 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF®) as adjuvant in a randomized clinical trial. METHODS: A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF® or intraarticular administration of 100 × 106 cultured autologous BM-MSCs plus PRGF®. Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. RESULTS: No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF® and BM-MSC with PRGF® went from 5 (1.8) to 4.5 (2.2) (p = 0.389) and from 5.3 (1.9) to 3.5 (2.5) (p = 0.01), respectively at 12 months. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF® was 31.9 (16.2) and 22.3 (15.8) respectively (p = 0.002) while that for patients treated with BM-MSC plus PRGF® was 33.4 (18.7) and 23.0 (16.6) (p = 0.053). Although statistical significances between groups have been not detected, only patients being treated with BM-MSC plus PRGF® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage. CONCLUSIONS: Treatment with BM-MSC associated with PRGF® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy. Trial registration Clinical Trials.gov identifier NCT02365142. Nº EudraCT: 2011-006036-23.

Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: long-term follow up of a multicenter randomized controlled clinical trial (phase I/II).

BACKGROUND: Mesenchymal stromal cells (MSCs) are a promising option to treat knee osteoarthritis (OA). Their safety and usefulness have been reported in several short-term clinical trials but less information is available on the long-term effects of MSC in patients with osteoarthritis. We have evaluated patients included in our previous randomized clinical trial (CMM-ART, NCT02123368) to determine their long-term clinical effect. MATERIALS: A phase I/II multicenter randomized clinical trial with active control was conducted between 2012 and 2014. Thirty patients diagnosed with knee OA were randomly assigned to Control group, intraarticularly administered hyaluronic acid alone, or to two treatment groups, hyaluronic acid together with 10 × 106 or 100 × 106 cultured autologous bone marrow-derived MSCs (BM-MSCs), and followed up for 12 months. After a follow up of 4 years adverse effects and clinical evolution, assessed using VAS and WOMAC scorings are reported. RESULTS: No adverse effects were reported after BM-MSCs administration or during the follow-up. BM-MSCs-administered patients improved according to VAS, median value (IQR) for Control, Low-dose and High-dose groups changed from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 7 (6, 7), 2 (2, 5) and 3 (3, 4), respectively at the end of follow up (Low-dose vs Control group, p = 0.01; High-dose vs Control group, p = 0.004). Patients receiving BM-MSCs also improved clinically according to WOMAC. Control group showed an increase median value of 4 points (- 11;10) while Low-dose and High-dose groups exhibited values of - 18 (- 28;- 9) and - 10 (- 21;- 3) points, respectively (Low-dose vs Control group p = 0.043). No clinical differences between the BM-MSCs receiving groups were found. CONCLUSIONS: Single intraarticular injection of in vitro expanded autologous BM-MSCs is a safe and feasible procedure that results in long-term clinical and functional improvement of knee OA.

Sesamoid Position in Healthy Volunteers Without Deformity: A Computed Tomography Study.

We used coronal computed tomography to determine the normal sesamoid position in 20 healthy volunteers. The sample involved 40 feet (20 left [50%] and 20 right [50%]) in 20 volunteers, including 11 females (55%) and 9 males (45%). The relationship between the first metatarsal head and the sesamoid complex was categorized as Yildirim grade 0 in every case (100%). The mean width of the foot was 77.7 ± 5.8 mm, and the ratio of the foot width to the distance from the second metatarsal head to the tibial sesamoid was 39.6% ± 2.02%. Based on our findings, we consider Yildirim grade 0 to be the normal sesamoid alignment.

The Relationship Between the Sesamoid Complex and the First Metatarsal After Hallux Valgus Surgery Without Lateral Soft-Tissue Release: A Prospective Study.

Some investigators have emphasized restoring the relationship between the sesamoid complex and the first metatarsal head to reduce the risk of hallux valgus recurring after surgical reconstruction. In a prospective study, we analyzed whether the first metatarsophalangeal joint could be realigned after scarf-Akin bunionectomy without lateral soft tissue release. A total of 25 feet, in 22 patients, were prospectively enrolled and analyzed using anteroposterior radiographs and coronal computed tomography scans obtained before and 3 months after surgery. The Yildirim sesamoid position decreased from a preoperative of 2 (range 1 to 3) to a postoperative position of 0 (range 0 to 1; p < .001), the mean first intermetatarsal angle decreased from 12.6° ± 2.4° to 5.8° ± 2.1° (p < .001), and the mean distance between the second metatarsal and the tibial sesamoid changed from 25.7 ± 4.6 to 25.9 ± 4.6 (p = .59). Our findings suggest that dislocation of the sesamoid complex is actually caused by displacement of the first metatarsal. In conclusion, the scarf-Akin bunionectomy adequately restores the alignment of the first metatarsophalangeal joint, including restoration of the sesamoid apparatus, without direct plantar-lateral soft tissue release.

Vitamin E Cup Cross-linked Polyethylene in Total Hip Arthroplasty: A Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: The goal of this study was to assess the efficacy and safety of vitamin E cup cross-linked polyethylene (VEPE) liners compared with standard polyethylene (PE) liners in total hip arthroplasty. METHODS: A systematic search of the PubMed, EMBASE, Scopus, and Cochrane Collaboration Library databases was conducted. The evaluated outcomes were radiological parameters, functional scores (Harris Hip Score, Numeric Rating Scale, and Activity Scale from the University of California), and adverse events. Odds ratios and mean differences (MD) were calculated for the dichotomous and continuous variables. Meta-analysis was done using Review Manager. RESULTS: Seven randomized controlled trials (n = 990) were included. VEPE liners showed markedly lower penetration at the last follow-up (MD, -0.15; 95% confidence interval [CI], -0.18 to -0.11) and penetration rate at last follow-up (MD, -0.01; 95% CI, -0.01 to -0.00) than standard PE liners. However, no notable differences were observed in cup migration, inclination, anteversion, or patient-reported outcomes. The complication rate was not markedly different between the groups (odds ratio, 1.07; 95% CI, 0.42 to 2.73). DISCUSSION: This meta-analysis found that while VEPE demonstrated decreased penetration rates in total hip arthroplasty, no differences were observed in patient outcomes or complications compared with standard PE. However, the clinical relevance of penetration rate reduction remains uncertain, given the short follow-up period.

Causes and risk factors for same-day discharge failure after total hip and knee arthroplasty: a meta-analysis.

In recent decades, the trend toward early same-day discharge (SDD) after surgery has dramatically increased. Efforts to develop adequate risk stratification tools to guide decision-making regarding SDD versus prolonged hospitalization after total hip arthroplasty (THA) remain largely incomplete. The purpose of this report is to identify the most frequent causes and risk factors associated with SDD failure in patients undergoing THA and total knee arthroplasty (TKA). A systematic search following PRISMA guidelines of four bibliographic databases was conducted for comparative studies between patients who were successfully discharged on the same day and those who failed. Outcomes of interests were causes and risk factors associated with same-day discharge failure. Odds ratios (OR) were calculated for dichotomous variables, whereas mean differences (MD) were calculated for continuous variables. Meta-analysis was performed using RevMan software. Random effects were used if there was evidence of heterogeneity. Eight studies with 3492 patients were included. The most common cause of SDD failure was orthostatic hypotension, followed by inadequate physical condition, nausea/vomiting, pain, and urinary retention. Female sex was a risk factor for failure (OR 0.77, 95% CI 0.63-0.93), especially in the THA subgroup. ASA score IV (OR 0.33, 95% CI 0.14-0.76) and III (OR 0.72, 95% CI 0.52-0.99) were risk factors, as were having > 2 allergies and smoking patients. General anesthesia increased failure risk (OR 0.58, 95% CI 0.42-0.80), while spinal anesthesia was protective (OR 1.62, 95% CI 1.17-2.24). The direct anterior and posterior approaches showed no significant differences. In conclusion, orthostatic hypotension was the primary cause of SDD failure. Risk factors identified for SDD failure in orthopedic surgery include female sex, ASA III and IV classifications, a higher number of allergies, smoking patients and the use of general anesthesia. These factors can be addressed to enhance SDD outcomes.

One-Stage Versus Two-Stage Revision Surgery for Periprosthetic Hip Infection: An Updated Systematic Review and Meta-Analysis of Clinical Outcomes.

INTRODUCTION: The primary objective of this meta-analysis was to evaluate and compare the functional outcomes, postoperative reinfection rates, and complication rates in patients undergoing one-stage versus two-stage surgical revision for periprosthetic hip infection. METHODS: The study population included adult patients who had undergone revision hip arthroplasty. Comparative studies have compared two-stage and one-stage revision strategies. Searches were conducted using the major databases. Review Manager software was used to estimate the effects. A sensitivity analysis was also conducted. RESULTS: Nine cohort studies including 2,502 hips were included. The success rate did not show significant differences between the groups (odds ratio [OR] 0.42, 95% confidence interval 0.05 to 3.37). No difference was noted in reinfection (OR 0.81, 95% CI 0.56-1.19). Life quality per Harris Hip Score was higher for one-stage revision strategies (mean difference [MD] 9.00, 95% CI 2.23-15.78). No differences were noted in mortality, aseptic loosening, or revision rates. Age (MD 2.32, 95% CI 1.34-3.29) and body mass index (BMI) (MD 1.88, 95% CI 0.38-3.38) were lower in the two-stage group. Sinus tract presence was higher in the one-stage group (OR 1.44, 95% CI 1.05-1.95). Paprosky I acetabulum was higher in the one-stage group, and Paprosky III was higher in the two-stage group. CONCLUSIONS: The results did not demonstrate notable clinical differences between one-stage and two-stage hip arthroplasties, regardless of the treated microorganism. However, the quality of life may be somewhat better in the one-stage group. Age, body mass index, and Paprosky classification are factors that influence procedure selection.

Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide.

While myelodysplastic syndromes with del(5q) (del(5q) MDS) comprises a well-defined hematological subgroup, the molecular basis underlying its origin remains unknown. Using single cell RNA-seq (scRNA-seq) on CD34+ progenitors from del(5q) MDS patients, we have identified cells harboring the deletion, characterizing the transcriptional impact of this genetic insult on disease pathogenesis and treatment response. Interestingly, both del(5q) and non-del(5q) cells present similar transcriptional lesions, indicating that all cells, and not only those harboring the deletion, may contribute to aberrant hematopoietic differentiation. However, gene regulatory network (GRN) analyses reveal a group of regulons showing aberrant activity that could trigger altered hematopoiesis exclusively in del(5q) cells, pointing to a more prominent role of these cells in disease phenotype. In del(5q) MDS patients achieving hematological response upon lenalidomide treatment, the drug reverts several transcriptional alterations in both del(5q) and non-del(5q) cells, but other lesions remain, which may be responsible for potential future relapses. Moreover, lack of hematological response is associated with the inability of lenalidomide to reverse transcriptional alterations. Collectively, this study reveals transcriptional alterations that could contribute to the pathogenesis and treatment response of del(5q) MDS.

Monitoring different sources of marine pollution in the Canarian intertidal zone using Anemonia sulcata as a bioindicator.

Sea anemones have often been used as bioindicators of contamination because they are semisessile organisms that rarelly leave their niche, which is why they are conducive to affecting the ecosystem at the local level. The objective of this work is to determine whether the concentrations of heavy metals and trace elements in the anemone Anemonia sulcata vary depending on the source of contamination present. In 2021 seventy specimens were collected at five sampling points and fourteen specimens were collected in each point (Control Zone, Thermal Power Plant, Sewage Pipe, Harbour and Tourism) in 2021, on the island of Tenerife. All the areas studied characterized by a pollution condition had higher concentrations of metals and trace elements than the control area. The anemones from Harbour presented a greater number of metals with a higher concentration than the other study areas.

Incidence and risk factors for stroke after hip fracture: a meta-analysis.

Hip fractures represent a high burden and are associated with mortality in up to 30% of the cases. Stroke complications can be devastating and increase mortality and disability in elderly patients. This study aimed to determine the overall incidence and risk factors for stroke in patients with hip fractures. A systematic search of the literature using PubMed, EMBASE, Scopus, and Cochrane Collaboration Library databases was carried out. Studies have reported the incidence of stroke in patients > 50 years of age with hip fractures. Data were extracted according to PRISMA guidelines (PROSPERO: CRD42023384742). Data were combined using Review Manager version 5.4. A random-effects model was adopted if a significant heterogeneity was observed. The primary outcome was the incidence of stroke in patients with hip fractures. The secondary outcomes of interest included the influence on the incidence of demographic factors, associated conditions, habits, and analytical parameters. Of the 635 initially retrieved studies, 18 were included, with 256,197 patients. The mean age of the patients ranged from 55 to 84 years old. The overall incidence of stroke in patients with hip fracture was 6.72% (95% CI 4.37-9.07%. The incidence of stroke by region was highest in the American continent (8.09%, 95% CI 3.60-12.58%; P > 0.001). Regarding associated conditions diabetes significantly increased the risk of stroke (OR 1.80, 95% CI 1.41-2.30). Respect to patient characteristics, BMI greater than 24.4 and female gender did not significantly increase the risk of stroke: (OR 1.07, 95% CI 0.74-1.56) and (OR 1.15, 95% CI 0.91-1.46). Lastly, lower albumin concentrations were a risk factor for stroke in patients with hip fracture (MD - 3.18, 95% CI - 4.06 to 2.31). In conclusion, the incidence of stroke after hip fracture was 6.72%. The incidence of stroke increases over time, and the closely associated risk factors are diabetes and low albumin level.

Efficacy and safety of arthroscopy in femoroacetabular impingement syndrome: a systematic review and meta-analysis of randomized clinical trials.

This study aimed to compare the efficacy and safety of arthroscopy with physiotherapy or joint lavage in patients with femoroacetabular impingement (FAI). A meta-analysis using PubMed, Embase, Scopus, and the Cochrane Collaboration Library databases was performed in September 2022. We included studies focusing on patients with FAI who underwent arthroscopic surgery versus those who underwent physiotherapy or arthroscopic lavage. The outcomes were functional scores (iHOT-33 and HOS ADL) and adverse events. Randomized clinical trials were included in the study. The risk of bias in each study was assessed according to Cochrane guidelines for clinical trials. The data were combined using Review Manager version 5.4. (PROSPERO CRD42022375273). Six RCTs were included, from a pool of 839 patients (407 females). The iHOT-33 and HOS ADL scales showed significant differences at 12 months in favor of the arthroscopy group (MD, 10.65; 95% CI 6.54-4.76) and (MD, 8.09; 95% CI 3.11-13.07). MCID was not achieved through arthroscopy in functional variables. The rates of osteoarthritis (OR, 6.18; 95% CI 1.06-36.00) and numbness (OR, 73.73; 95% CI 10.00-43.92) were significantly higher in the arthroscopy group. Arthroscopic surgery showed statistical superiority over the control group without exceeding the MCID in most studies; however, the results might have been influenced by secondary variables. Finally, arthroscopic surgery results in a high rate of conversion to osteoarthritis.

An engineered periosteum for efficient delivery of rhBMP-2 and mesenchymal progenitor cells during bone regeneration.

During bone regeneration, the periosteum acts as a carrier for key regenerative cues, delivering osteochondroprogenitor cells and crucial growth factors to the injured bone. We developed a biocompatible, 3D polycaprolactone (PCL) melt electro-written membrane to act as a mimetic periosteum. Poly (ethyl acrylate) coating of the PCL membrane allowed functionalization, mediated by fibronectin and low dose recombinant human BMP-2 (rhBMP-2) (10-25 µg/ml), resulting in efficient, sustained osteoinduction in vitro. In vivo, rhBMP-2 functionalized mimetic periosteum demonstrated regenerative potential in the treatment of rat critical-size femoral defects with highly efficient healing and functional recovery (80%-93%). Mimetic periosteum has also proven to be efficient for cell delivery, as observed through the migration of transplanted periosteum-derived mesenchymal cells to the bone defect and their survival. Ultimately, mimetic periosteum demonstrated its ability to deliver key stem cells and morphogens to an injured site, exposing a therapeutic and translational potential in vivo when combined with unprecedentedly low rhBMP-2 doses.

A Reassessment of the Barrier Effect of the Physis against Metaphyseal Osteosarcoma: A Comprehensive Pathological Study with Its Radiological and Clinical Follow-Up Correlations.

Osteosarcoma is a primary malignant bone tumor usually arising at the metaphysis of long bones, particularly around the knee. The physis has been regarded as a barrier capable of blocking tumor extension, thus allowing it to preserve their epiphysis and therefore improve functional results. With the objective of clarifying how effective the physis is as a barrier to tumor spread, a large series of skeletally immature patients with osteosarcoma were reviewed. From 452 metaphyseal osteosarcomas a selection of 282 cases in which the tumor was close or crossing the physis were carried out. This sub-sample was split into two groups according to the surgical treatment (epiphyseal preservation or not). The specimens obtained by resection were studied, and the physeal and metaphyseal areas were studied by multiple sections. Immunostaining against VEGF of physis was obtained in selected cases. In about half of the patients affected by metaphyseal malignant bone tumors, the growth plate and epiphysis were not compromised by the tumor. Three sequential invasive growth patterns of an osteosarcoma in its relationship with the physis could be distinguished. An intense angiogenesis and osteoclastic reaction could be observed in the growth plate in the free zone between the tumor and the physis. The local recurrence incidence was lower in the epiphyseal preservation treated patients than it was in the conventional treatment (8% vs. 12%). Most local recurrences appeared in the first 2 years. The overall survival of patients treated with epiphyseal preservation was better than that of the patients treated without preserving the epiphysis (73% vs. 59%; p = 0.03) at a mean follow-up of 18 years. We have described an angiogenic and osteoclastic reaction in the base of the growth plate in the proximity of the advance front of the tumor, which could facilitate the osteosarcoma invasion. It is also shown that the preoperative imaging method for examination is a valid approach for the decision to carry out epiphyseal preservation. Finally, we concluded that epiphyseal preservation combined with protective chemotherapy is an excellent clinical approach for selected patients with metaphyseal osteosarcoma.

Risk Factors of DAIR Failure and Validation of the KLIC Score: A Multicenter Study of Four Hundred Fifty-Five Patients.

Background: Debridement, antibiotic agents, and implant retention (DAIR) is a currently accepted approach for the treatment of early prosthetic joint infections (PJI). The success of a DAIR procedure has shown variable results throughout the published literature. Scoring systems such as the Kidney, Liver, Index surgery, Cemented prosthesis, and C-reactive protein value (KLIC) score for the selection of patients that are likely to benefit from DAIR have proved to be helpful in decision making. Our study aims to further validate the KLIC score using a large external multicentric cohort and to evaluate other risk factors for failure. Patients and Methods: A retrospective analysis of patients with an early acute PJI who were treated with DAIR and recorded in a database of eight Spanish university hospitals was performed. According to pre-operative variables of the KLIC study, patients were categorized into five groups: group A, ≤2 points; group B, 2.5-3.5 points; group C, 4-5 points; group D, 5.5-6.5 points; and group E, ≥7 points. Failure rates were compared between groups at 60 days and after 60 days of DAIR. Further variables for risk of failure were also analyzed. Results: A total of 455 patients with early acute PJI were included in the analyses. At 60 days, patients presenting with pre-operative elevated C-reactive protein serum levels, Staphylococcus aureus, and polymicrobial infections were associated with failure. Failure rates recorded were 12% for group A (n = 210), 18% for group B (n = 83), 26% for group C (n = 89), 24% for group D (n = 66), and 0% for group E (n = 7). Univariable analysis between consecutive groups of the KLIC score showed no differences for failure before 60 days of the DAIR procedure. Scheduled surgery and having the procedure performed by a specialized unit were also identified as important factors for DAIR success. Conclusions: Our results suggest the KLIC score was not useful for predicting failure in our cohort. Furthermore, our results indicate a specialized unit should conduct DAIR procedures.

Preneoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma.

Normal cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B lymphocytes before lymphoma remains uncertain. We sequenced multiple stages of the B lineage in elderly individuals and patients with lymphoplasmacytic lymphoma, a singular disease for studying lymphomagenesis because of the high prevalence of mutated MYD88. We observed similar accumulation of random mutations in B lineages from both cohorts and unexpectedly found MYD88L265P in normal precursor and mature B lymphocytes from patients with lymphoma. We uncovered genetic and transcriptional pathways driving malignant transformation and leveraged these to model lymphoplasmacytic lymphoma in mice, based on mutated MYD88 in B cell precursors and BCL2 overexpression. Thus, MYD88L265P is a preneoplastic event, which challenges the current understanding of lymphomagenesis and may have implications for early detection of B cell lymphomas.

Salvage brachytherapy for locally recurrent prostate cancer after single-fraction 19 Gy high-dose-rate brachytherapy: toxicity, prostate-specific antigen kinetics, and cancer control.

PURPOSE: To evaluate toxicity, prostate-specific antigen (PSA) kinetics, and cancer control of high-dose-rate brachytherapy (HDR-BT) as a salvage modality for men with locally recurrent prostate cancer, after primary HDR-BT failure. MATERIAL AND METHODS: Twelve patients with biochemical failure and a local relapse after 19 Gy single-fraction high-dose-rate brachytherapy (HDR-BT 19 Gy) were salvaged using two HDR-BT fractions. Salvage treatment consisted of two HDR-BT applications, one week apart, delivering 12 Gy to the prostate per application (HDR-BT 12 × 2). RESULTS: Median age and initial PSA prior to rescue treatment were 74 years (range, 65-80) and 5.29 ng/ml (range, 2.37-16.40), respectively. Forty-two percent had a low-risk and 58% presented with intermediate-risk prostate cancer. Median follow-up period was 26 months (range, 10-42). Median time to PSA nadir was 12 months, with a median value of 0.21 ng/ml. Most of the patients (11 of 12) achieved a PSA decline ≥ 90%. Acute grade 2 genitourinary (GU) toxicity occurred in 4 patients (33.3%) and none presented with acute gastrointestinal (GI) toxicity. Two patients (16.7%) suffered from late GU grade 2 toxicity. No grade 3 toxicity were recorded. To date, 2 patients (16.7%) have experienced biochemical failure after salvage treatment. CONCLUSIONS: Salvage HDR-BT 12 × 2 is a feasible and well-tolerated treatment, with acceptable toxicity rates for men with locally recurrent prostate cancer, who failed after HDR-BT with 19 Gy. Moreover, PSA kinetics and cancer control after salvage treatment suggest that this strategy might be efficacious in this clinical setting.

Cemented Dual Mobility Cup for Primary Total Hip Arthroplasty in Elder Patients with High-Risk Instability.

Several studies have shown that double mobility (DM) cups reduce postoperative dislocations. Does the cemented dual mobility cup reduce dislocations in a specific cohort of elder patients with a high dislocation risk? Our hypothesis is that this implant is optimal for elder patients because it reduces early dislocation. We have retrospectively reviewed elder patients who underwent total hip arthroplasty (THA) with cemented double mobility cup between March 2009 and January 2018. The inclusion criteria were patients (>75 years) who were operated on for primary THA (osteoarthritis or necrosis) with a cemented dual mobility cup and a high-risk instability (at least two patient-dependent risk factors for instability). The exclusion criteria were revision surgeries or hip fracture. In all the cases, the same surgical approach was performed with a Watson Jones modified approach in supine position. We have collected demographic data, instability risk factors. Patients were classified using the Devane's score, Merle d'Aubigné score and the patient's likelihood of falling with the Morse Fall Scale. Surgical and follow-up complications were collected from their medical history. Sixty-eight arthroplasties (68 patients) were included in the study. The median age was 81.7 years (SD 6.4), and the American Society of Anesthesiologists (ASA) score showed a distribution: II 27.94%, III 63.24% and IV 8.82%. Devane's score was less than five in all of the cases. At least two patient-dependent risk factors for instability (87% had three or more) were present in each case. The median follow-up time was 49.04 months (SD 22.6). Complications observed were two cases of infection and one case of aseptic loosening at 15 months which required revision surgery. We did not observe any prosthetic dislocation. The cemented dual mobility cup is an excellent surgical option on primary total hip arthroplasties for elder patients with high-risk instability.