Citations

Background: Multiple publications demonstrate an association between time to initiation of corticosteroids and outcomes such as mortality and reversal of shock. However, the optimal time to initiate hydrocortisone remains unknown. Objective: To evaluate the impact of early versus late initiation of hydrocortisone in septic shock patients. Methods: A retrospective, multicentered, observational study was conducted. Adults admitted from July 1, 2014, to August 31, 2019, diagnosed with septic shock receiving vasopressors and low-dose hydrocortisone were evaluated. Participants were divided into the “early” group if hydrocortisone was initiated within 12 hours or “late” group if initiated after 12 hours of vasopressor initiation. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included in-hospital mortality, intensive care unit (ICU) and hospital length of stay (LOS), vasopressor utilization, fluids administered, and need for renal replacement therapy. Results: A total of 198 patients were identified for inclusion in this propensity score–weighted cohort: 99 in the early group and 99 in the late group. Early initiation was associated with shorter time to vasopressor discontinuation compared with late initiation (40.7 vs 60.6 hours; P = 0.0002). There was also a reduction in ICU LOS (3.6 vs 5.1 days; P = 0.0147) and hospital LOS (8.9 vs 10.9 days; P = 0.0220) seen in the early group. There was no difference in mortality between groups. Conclusion and Relevance: In this propensity-matched cohort, administration of hydrocortisone within 12 hours from the onset of septic shock was associated with improved time to vasopressor discontinuation and reduced ICU and hospital LOS.

7022 Background: Philadelphia-like Acute Lymphoblastic Leukemia (Ph-like ALL) is a high-risk subset of adult ALL. Until recently, there has not been a systematic platform to recognize this entity in clinical practice. Furthermore, data regarding the role of allogeneic hematopoietic cell transplantation (allo-HCT) is lacking. We conducted this study to identify patients with Ph-like ALL and describe their outcomes in comparison to Ph+ and Ph- ALL with emphasis on the role of allo-HCT. Methods: To identify cases of Ph-like ALL, available diagnostic cytogenetic pellets for patients in the Mayo Clinic ALL cohort (N=365) were tested using a targeted fluorescence in situ hybridization (FISH) panel developed by the Mayo Clinic Genomics Laboratory and includes probes to detect Ph-like-specific rearrangements (i.e., ABL1, ABL2, PDGFRB, JAK2 and CRLF2). Results: Thirty-three (9%) patients with Ph-like ALL were identified, the remaining patients were classified as Ph+ (N=132, 36%) or Ph- ALL (N=200, 55%). Patients with Ph-like ALL were younger (Median: 39 vs. 50 vs. 49 years, P=.01), had higher WBC (Median: 27.9 vs. 21.5 vs. 4.5 x109/L, P<.001), were less likely to achieve CR (91% vs. 99% vs. 96%, P=.02), more likely to be MRD+ (64% vs. 34% vs. 36%, P=.03), had a higher relapse rate (5-year: 39% vs. 24% vs. 38%, P=.01) and lower OS (5-year: 41% vs. 64% vs. 49%, P=.02), see Table. Patients who achieved MRD negativity had better OS (MRD+ vs MRD-, P=.01). Importantly, no statistically significant difference in OS, relapse or non-relapse mortality were noted between the 3 groups in patients who underwent allo-HCT in CR1. Conclusions: Ph-like ALL is a high risk subgroup with increased prevalence in younger adults. Allo-HCT appears to offset the poor prognosis associated with this entity. A targeted FISH panel offers timely recognition of this entity in a clinical setting.[Table: see text]

AimsThis study aimed to determine outcomes of isolated tibial insert exchange (ITIE) during revision total knee arthroplasty (TKA).MethodsFrom 1985 to 2016, 270 ITIEs were performed at one institution for instability (55%, n = 148), polyethylene wear (39%, n = 105), insert fracture/dissociation (5%, n = 14), or stiffness (1%, n = 3). Patients with component loosening, implant malposition, infection, and extensor mechanism problems were excluded.ResultsSurvivorship free of any re-revision was 68% at ten years. For the indication of insert wear, survivorship free of any re-revision at ten years was 74%. Re-revisions were more frequent for index diagnoses other than wear (hazard ratio (HR) 1.9; p = 0.013), with ten-year survivorships of 69% for instability and 37% for insert fracture/dissociation. Following ITIE for wear, the most common reason for re-revision was aseptic loosening (33%, n = 7). For other indications, the most common reason for re-revision was recurrence of the original diagnosis. Mean Knee Society Scores improved from 54 (0 to 94) preoperatively to 77 (38 to 94) at ten years.ConclusionAfter ITIE, the risk and reasons for re-revision correlated with preoperative indications. The best results were for polyethylene wear. For other diagnoses, the re-revision rate was higher and the failure mode was most commonly recurrence of the original indication for the revision TKA. Cite this article: Bone Joint J 2021;103-B(6):1103–1110.

Aims The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis. Methods Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm3 and ≥ 65% for TKA and ≥ 3,000 cells/mm3 and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the reference standard to evaluate test performances. Results were compared using McNemar’s test and area under the receiver operating characteristic curve (AUC) analysis. Results Expert consensus classified 18 arthroplasies as having failed due to PJI and 81 due to aseptic failure. Using these classifications, the calculated sensitivity and specificity of AD LFA was 83.3% (95% confidence interval (CI) 58.6 to 96.4) and 93.8% (95% CI 86.2 to 98.0), respectively. Sensitivity and specificity of AD ELISA was 83.3% (95% CI 58.6 to 96.4) and 96.3% (95% CI 89.6 to 99.2), respectively. There was no statistically significant difference between sensitivity (p = 1.000) or specificity (p = 0.157) of the two AD assays. AUC for AD LFA was 0.891. In comparison, AUC for synovial WBC count, PMN%, and the combination of the two values was 0.821 (sensitivity p = 1.000, specificity p < 0.001), 0.886 (sensitivity p = 0.317, specificity p = 0.011), and 0.926 (sensitivity p = 0.317, specificity p = 0.317), respectively. Conclusion The diagnostic accuracy of synovial AD for PJI diagnosis is comparable and not statistically superior to that of synovial WBC count plus PMN% combined. Cite this article: Bone Joint J 2021;103-B(6):1119–1126.

Aims To describe the risk of periprosthetic joint infection (PJI) and reoperation in patients who have an acute, traumatic wound dehiscence following total knee arthroplasty (TKA). Methods From January 2002 to December 2018, 16,134 primary TKAs were performed at a single institution. A total of 26 patients (0.1%) had a traumatic wound dehiscence within the first 30 days. Mean age was 68 years (44 to 87), 38% (n = 10) were female, and mean BMI was 34 kg/m2 (23 to 48). Median time to dehiscence was 13 days (interquartile range (IQR) 4 to 15). The dehiscence resulted from a fall in 22 patients and sudden flexion after staple removal in four. The arthrotomy was also disrupted in 58% (n = 15), including a complete extensor mechanism disruption in four knees. An irrigation and debridement with component retention (IDCR) was performed within 48 hours in 19 of 26 knees and two-thirds were discharged on antibiotic therapy. The mean follow-up was six years (2 to 15). The association of wound dehiscence and the risk of developing a PJI was analyzed. Results Patients who sustained a traumatic wound dehiscence had a 6.5-fold increase in the risk of PJI (95% confidence interval (CI) 1.6 to 26.2; p = 0.008). With the small number of PJIs, no variables were found to be significant risk factors. However, there were no PJIs in any of the patients who were treated with IDCR and a course of antibiotics. Three knees required reoperation including one two-stage exchange for PJI, one repeat IDCR for PJI, and one revision for aseptic loosening of the tibial component. Conclusion Despite having a traumatic wound dehiscence, the risk of PJI was low, but much higher than experienced in all other TKAs during the same period. We recommend urgent IDCR and a course of postoperative antibiotics to decrease the risk of PJI. A traumatic wound dehiscence increases risk of PJI by 6.5-fold. Cite this article: Bone Joint J 2021;103-B(6 Supple A):191–195.

AimsIt remains difficult to diagnose early postoperative periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). We aimed to validate the optimal cutoff values of ESR, CRP, and synovial fluid analysis for detecting early postoperative PJI in a large series of primary TKAs.MethodsWe retrospectively identified 27,066 primary TKAs performed between 2000 and 2019. Within 12 weeks, 169 patients (170 TKAs) had an aspiration. The patients were divided into two groups: those evaluated ≤ six weeks, or between six and 12 weeks postoperatively. The 2011 Musculoskeletal Infection Society (MSIS) criteria for PJI diagnosis in 22 TKAs. The mean follow-up was five years (two months to 17 years). The results were compared using medians and Mann-Whitney U tests and thresholds were analyzed using receiver operator characteristic curves.ResultsWithin six weeks, the median CRP (101 mg/l vs 35 mg/l; p = 0.011), synovial WBCs (58,295 cells/μl vs 2,121 cells/μl; p ≤ 0.001), percentage of synovial neutrophils (91% vs 71% (p < 0.001), and absolute synovial neutrophil count (ANC) (50,748 cells/μl vs 1,386 cells/μl (p < 0.001) were significantly higher in infected TKAs. Between six and 12 weeks, the median CRP (85 mg/l vs 5 mg/l (p < 0.001)), ESR (33 mm/hr vs 14 mm/hr (p = 0.015)), synovial WBCs (62,247 cells/μl vs 620 cells/μl (p < 0.001)), percentage of synovial neutrophils (93% vs 54% (p < 0.001)), and ANC (55,911 cells/μl vs 326 cells/μl (p < 0.001)) were also significantly higher in infected TKAs. Optimal thresholds at ≤ six weeks were: CRP ≥ 82 mg/l (sensitivity 70%, specificity 77%), synovial WBCs ≥ 8,676 cells/μl (83%, 90%), percentage of synovial neutrophils ≥ 88% (67%, 78%), and ANC ≥ 8,346 cells/μl (83%, 91%). Between six and 12 weeks, thresholds were: CRP ≥ 34 mg/l (90%, 93%), synovial WBCs ≥ 1,983 cells/μl (80%, 85%), percentage of synovial neutrophils ≥ 76% (80%, 81%), and ANC ≥ 1,684 cells/μl (80%, 87%).ConclusionEarly PJI after TKA should be suspected within six weeks if the CRP is ≥ 82 mg/l, synovial WBCs are ≥ 8,676 cells/μl, the percentage of synovial neutrophils is ≥ 88%, and/or the ANC is ≥ 8,346 cells/μl. Between six and 12 weeks, thresholds include a CRP of ≥ 34 mg/l, synovial WBC of ≥ 1,983 cells/μl, a percentage of synovial neutrophils of ≥ 76%, and/or an ANC of ≥ 1,684 cells/μl. Cite this article: Bone Joint J 2021;103-B(6 Supple A):177–184.

Background: Most North American surgeons predominantly use uncemented stems in primary total hip arthroplasties (THAs) and reserve cemented stems for selected older patients and those with poor bone quality. However, data on this “selective use” strategy for cemented stems in the population at risk for periprosthetic fracture and implant loosening are limited. The purpose of this study was to describe implant survivorship, complications, and radiographic results of a specific collarless, polished, tapered cemented stem (Exeter; Stryker) used selectively in a predominantly elderly population undergoing primary THA. Methods: We identified 386 patients who underwent a total of 423 primary THAs with selectively utilized Exeter stems for the treatment of osteoarthritis between 2006 and 2017. In the same time period, 11,010 primary THAs were performed with uncemented stems and 961 with non-Exeter cemented stems. The mean patient age was 77 years, 71% were female, and the mean body mass index was 29 kg/m 2 . Competing risk analysis accounting for death was utilized to determine cumulative incidences of revision and reoperation. The mean follow-up was 5 years (range, 2 to 12 years). Results: The 10-year cumulative incidence of any femoral component revision in this patient cohort was 4%, with 10 stems revised at the time of the latest follow-up. There were no intraoperative femoral fractures. The indications for revision were postoperative periprosthetic femoral fracture (n = 6), dislocation (n = 3), and infection (n = 1). There were no revisions for femoral loosening. The 10-year cumulative incidence of reoperation was 10%. The 10-year cumulative incidence of Vancouver B periprosthetic femoral fracture was 2%. Radiographically, there were no cases of aseptic loosening or osteolysis. There was a significant improvement in median Harris hip score, from 53 preoperatively to 92 at a mean follow-up of 5 years (p < 0.001). Conclusions: The strategy of selectively utilizing a collarless, polished, tapered cemented stem produced a low (4%) cumulative incidence of stem revision at 10 years postoperatively and resulted in no cases of aseptic loosening. The use of the Exeter stem did not eliminate postoperative femoral fractures in this predominantly elderly, female patient population. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Background: The management of patients with triple-negative breast cancer (TNBC) is challenging with several controversies and unmet needs. During the 12th Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020, a panel of 35 breast cancer experts from 13 countries voted on consensus guidelines for the clinical management of TNBC. The consensus was subsequently updated based on the most recent data evolved lately. Methods: A consensus conference approach adapted from the American Society of Clinical Oncology (ASCO) was utilized. The panellists voted anonymously on each question, and a consensus was achieved when ≥75% of voters selected an answer. The final consensus was later circulated to the panellists for critical revision of important intellectual content. Results and conclusion: These recommendations represent the available clinical evidence and expert opinion when evidence is scarce. The percentage of the consensus votes, levels of evidence and grades of recommendation are presented for each statement. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials.

Abstract Genomic classification has improved risk assignment of pediatric, but not adult B-lineage acute lymphoblastic leukemia (B-ALL). The international UKALLXII/ECOG-ACRIN E2993 (#NCT00002514) trial accrued 1229 adolescent/adult patients with BCR-ABL1− B-ALL (aged 14 to 65 years). Although 93% of patients achieved remission, 41% relapsed at a median of 13 months (range, 28 days to 12 years). Five-year overall survival (OS) was 42% (95% confidence interval, 39, 44). Transcriptome sequencing, gene expression profiling, cytogenetics, and fusion polymerase chain reaction enabled genomic subtyping of 282 patient samples, of which 264 were eligible for trial, accounting for 64.5% of E2993 patients. Among patients with outcome data, 29.5% with favorable outcomes (5-year OS 65% to 80%) were deemed standard risk (DUX4-rearranged [9.2%], ETV6-RUNX1/-like [2.3%], TCF3-PBX1 [6.9%], PAX5 P80R [4.1%], high-hyperdiploid [6.9%]); 50.2% had high-risk genotypes with 5-year OS of 0% to 27% (Ph-like [21.2%], KMT2A-AFF1 [12%], low-hypodiploid/near-haploid [14.3%], BCL2/MYC-rearranged [2.8%]); 20.3% had intermediate-risk genotypes with 5-year OS of 33% to 45% (PAX5alt [12.4%], ZNF384/-like [5.1%], MEF2D-rearranged [2.8%]). IKZF1 alterations occurred in 86% of Ph-like, and TP53 mutations in patients who were low-hypodiploid (54%) and BCL2/MYC-rearranged (33%) but were not independently associated with outcome. Of patients considered high risk based on presenting age and white blood cell count, 40% harbored subtype-defining genetic alterations associated with standard- or intermediate-risk outcomes. We identified distinct immunophenotypic features for DUX4-rearranged, PAX5 P80R, ZNF384-R/-like, and Ph-like genotypes. These data in a large adult B-ALL cohort treated with a non–risk-adapted approach on a single trial show the prognostic importance of genomic analyses, which may translate into future therapeutic benefits.