Risk Factor For Inferior Outcomes Research Articles

Kidney re-transplantation in the ipsilateral iliac fossa: a surgeon's perspective on perioperative outcome.

Compared with primary transplantation, ipsilateral renal re-transplantation is associated with an increased risk of surgical complications and inferior graft outcomes. This study investigates whether an ipsilateral re-transplantation approach per se is an independent risk factor for surgical complications and early graft loss. In this retrospective, single-centre analysis, surgical complications and early graft outcomes of ipsilateral kidney re-transplantations from January 2007 to December 2017 were compared with primary transplantations and contralateral re-transplantations. Univariate and multivariate binary logistic regression analyses were performed to identify risk factors for surgical complications requiring surgical revision and graft loss within the first year after transplantation. Of the 1489 kidney transplantations, 51 were ipsilateral, 159 were contralateral re-transplantations and 1279 were primary transplantations. Baseline characteristics did not differ between the ipsilateral and contralateral re-transplant recipients except for current and highest panel reactive antibody levels. Major complications requiring surgical revision were significantly more frequent in ipsilateral re-transplantations (P=.010) than in primary transplantations but did not differ between ipsilateral and contralateral re-transplantations (P=.217). Graft loss within the first year after transplant was 15.7% in the ipsilateral versus 8.8% in the contralateral re-transplant group (P=.163) versus 6.4% in the primary transplantation group (P=.009). In a multivariate regression model, ipsilateral re-transplantation was not identified as an independent risk factor for complications requiring surgical revision or first-year graft loss. Ipsilateral renal re-transplantation is not a risk factor for inferior outcomes. Graft implantation into a pre-transplanted iliac fossa is a feasible and valid therapeutic option.

Clinical Outcomes and Return to Preinjury Sports After Anatomic Reconstruction With a Gracilis Autograft Versus the Modified Broström Procedure in Patients With Generalized Joint Laxity

Background: Generalized joint laxity (GJL) is a risk factor for inferior outcomes after the modified Broström procedure for chronic lateral ankle instability, while anatomic reconstruction with tendons is more inclined to be recommended. However, whether anatomic reconstruction could achieve better results than the modified Broström procedure in patients with GJL is unknown. Purpose: To compare clinical outcomes and return to sports between anatomic reconstruction and the modified Broström procedure in patients with GJL. Study Design: Cohort study; Level of evidence, 3. Methods: Patients with GJL (Beighton score ≥4) who underwent either the modified Broström procedure or anatomic reconstruction with gracilis autografts between 2017 and 2020 were reviewed. Included were 19 patients who underwent anatomic reconstruction (reconstruction group) and 49 patients who underwent the modified Broström procedure (MBP group). Clinical outcomes were compared using the Foot and Ankle Outcome Score (FAOS) and the Karlsson score. The rates of return to preinjury level in high-demand sports, sprain recurrence, and range of motion between the 2 groups were also compared. Results: The mean follow-up duration was 38.3 months in the reconstruction group and 43.7 months in the MBP group. The FAOS and Karlsson scores improved significantly after surgery in both groups ( P < .001 for all), with the reconstruction group having significantly higher postoperative FAOS-Sports scores (87.9 ± 8.9 vs 80.5 ± 11.6; P = .015) and Karlsson scores (86.9 ± 6.1 vs 82 ± 8.4; P = .025) than the MBP group. The rate of return to preinjury high-demand sports was higher in the reconstruction group than in the MBP group (73.3% vs 38.9%; P = .034). The MBP group had a significantly higher rate of sprain recurrence (22.4% vs 0%; P = .027). More patients reported dorsiflexion restriction in the reconstruction group (n = 4; 21.1%) than in the MBP group (n = 1; 2%) ( P = .019); nonetheless, there was no noticeable effect on daily life and sports. Conclusion: Better clinical outcomes, less sprain recurrence, and a higher rate of return to preinjury high-demand sports were found after anatomic reconstruction with free tendons compared with the modified Broström procedure in patients with GJL. Anatomic tendon reconstruction can be recommended for such patients, especially those participating in high-demand sports.

Addition of single dose gemtuzumab ozogamicin to intensive induction chemotherapy in core-binding factor acute myeloid leukemia

In a meta-analysis of 5 trials, the addition of gemtuzumab ozogamicin (GO) to intensive induction chemotherapy led to a survival benefit in patients with core-binding factor (CBF) acute myeloid leukemia (AML). Given the heterogeneous incorporation of GO in clinical trials, the ideal dose and schedule remains unclear. We conducted a single-center retrospective analysis to compare outcomes of patients with CBF-AML treated with intensive induction chemotherapy, with or without a single dose of GO 3 mg/m2, during induction only. We included 87 patients (GO=32, control=55). The composite complete remission (cCR) rate was higher in the control group (93%) compared to the GO group (82%) (p<0.001). The rate of measurable residual disease (MRD) negative cCR, by flow cytometry, was similar between both groups. There were no significant differences between the two groups in terms of toxicity. The 3-year relapse-free survival (RFS) for both groups was similar (71% vs 68%, p=0.5). The 3-year overall survival (OS) for the GO group was 68%, compared to 66% for the control group (p=0.9).In multivariable analysis, age and MRD positive status were risk factors for inferior outcomes. We find that survival of patients with CBF-AML is favorable in the real-world setting. The addition of single-dose GO, during induction, did not lead to a higher remission rate or survival benefit, when compared to intensive chemotherapy without GO. Further investigation into the incorporation of GO in the treatment algorithm for CBF-AML is needed.

Predisposing Factors for Postoperative Complications in the Year Following Fronto-Orbital Advancement and Remodeling: A Single Institution Study of 267 Patients.

Fronto-orbital advancement and remodeling (FOAR) is a common surgical approach used for craniosynostosis conferring functional and aesthetic benefit. There are few reports examining predisposing factors for postoperative complications within the first year after surgery. This study aimed to establish complication rates and identify risk factors for inferior outcomes in a large population of patients undergoing FOAR. All patients who underwent fronto-orbital advancement and remodeling from 2013-2022 at our institution were retrospectively studied. Perioperative and postoperative data were collected to yield outcomes analyses. Multivariable logistic regression with backwards selection was performed to identify predictors of postoperative complications. 267 patients underwent FOAR. The overall complication rate was 14.2%, most commonly delayed wound healing (7.4%), postoperative blood transfusion (5.8%), and infection requiring readmission (1.9%). Tense closure independently predicted delayed wound healing (p<0.001) and infection requiring readmission (p=0.03). Syndromic patients were more likely than non-syndromic children to have undergone prior craniofacial surgery (45.3% vs 23.8%, p=0.003). Syndromic status and prior craniofacial surgery were associated with increased risk of developing infection requiring readmission (p=0.012 and p=0.004, respectively). A greater proportion of malnourished patients experienced postoperative complications compared to patients without malnourishment (24.4% vs 12.1%, p=0.031), though there were no significant differences in individual postoperative outcomes. Identified risk factors for complications included syndromic status, tense closure, and prior craniofacial surgery. Most complications were managed nonoperatively. These factors may be considered in preoperative planning and when counseling patient families.

Validation and Retraining of the Stellae-123 Gene Expression Signature Improved Risk Stratification in Taiwanese Acute Myeloid Leukemia Patients

The European Leukemia Net (ELN) recommendations provide valuable guidance in treatment decisions of patients with acute myeloid leukemia (AML). However, the genetic complexity and heterogeneity of AML are not fully covered, despite the critical role of gene expression analysis in risk stratification. Addressing this gap, the Stellae-123 score, an AI-based model that captures gene expression patterns, has demonstrated promising results in predicting survival of AML patients in four western cohorts. This study aims to assess the applicability of Stellae-123 in a Taiwanese cohort. Our cohort included 233 de novo AML patients, who were diagnosed and treated at the National Taiwan University Hospital and received standard induction therapy with 7+3 chemotherapy (or 5+2 in elder fit patients). All patients had sufficient bone marrow samples for DNA and RNA sequencing at diagnosis. The median age of the cohort was 41 years. Among the patients, ELN-2022 risk groups were distributed as follows: favorable (53.4%), intermediate (27.6%), and adverse (19%). Appling the original Stellae-123 model, which derived gene expression signatures from the BeatAML cohort RNA-seq data, our patients were categorized into low-, intermediate-, and high-risk groups, each representing 33% of the cohort. Overall, there were no differences in clinical features among these risk groups. The Stellae-123 risk groups partially aligned with the ELN risk groups, with more ELN low-risk patients in the Stellae-123 low-risk group and a higher proportion of ELN-high risk patients in the Stellae-123 high-risk group. Intriguingly, aside from mutations listed in ELN-2022, the Stellae-123 high-risk group had significantly less NRAS mutations than others. Cumulative hazards predicted by Stellae-123 model yielded a c-index of 0.612 for overall survival (OS), and the three risk groups had significantly different OS (p&amp;lt;0.001). We next postulated that since Stellae-123 relies on molecular features derived from the leukemic cells, it might serve as a biomarker of biological risk to predict relapse-free survival (RFS). The c-index calculated by Stellae-123 to predict RFS was 0.607, suggesting a reasonable ability to discriminate between different risk levels for RFS. Recognizing the potential variation between the original training cohort and the Taiwanese population, we addressed this concern by retraining the Stellae-123 model using Taiwanese RNAseq data. As a result, the model retraining led to significant improvements in the cross-validated c-indexes, with values of 0.656 (OS) and 0.636 (RFS), leading to an even more robust risk stratification (p&amp;lt;0.001, Figure 1A). As we noticed overlapping grouping between Stellae-123 and ELN-2022 in both pretrained and retrained models, we explored if Stellae-123's prognostic power was independent of ELN risk status by conducting a multivariable analysis. Remarkably, in both the pretrained and retrained Stellae-123 models, whether calculated as continuous values or categorized into three groups, they consistently demonstrated discriminative power in predicting OS and RFS, irrespective of age and ELN-2022 risk, suggesting that Stellae-123 could offer additional valuable information in predicting patient outcomes. Considering recent data showing that incorporating age helped improve the prognostication performance of ELN-2022 and that age was an independent risk factor for inferior outcome in our cohort, we examined how age could complement current risk stratification. Serial model testing revealed significant improvement of the prognostic models when age and transcriptomic data, especially the locally retrained Stellae-123 model, were combined with ELN-2022, evident by drastically declined Akaike Information Criterion (AIC) values. Time-dependent ROC curve analysis confirmed the potential of incorporating Stellae-123 and age to complement current risk stratification system (Figure 1B). In summary, we showed that the Stellae-123 predicted both OS and relapse risk in AML patients from Taiwan. Furthermore, we demonstrated that model retraining could improve prognostication by adapting the Stellae-123 to the particularities of Taiwanese patients. Given the remarkable extrapolation of the signature, it's suggested gene expression profile be incorporated in the risk stratification of AML patients who are candidates to intensive therapy.

Preoperative Depression Is Associated With Increased Complications Following Distal Radius Fracture Surgery

Background: Depression is a known risk factor for inferior outcomes after orthopedic procedures, but its specific relationship with distal radius fractures remains unknown. This study investigates the relationship between preoperative diagnosed depression and common postoperative complications occurring within the first year after open reduction internal fixation (ORIF) for distal radius fractures. Methods: This retrospective study used Truven MarketScan database and the Current Procedural Terminology (CPT) codes to identify distal radius fracture patients who underwent ORIF in the United States between January 1, 2009, and December 31, 2019. International Classification of Diseases (ICD) codes were used to identify patients with and without a diagnosis of preoperative depression. Univariate, multivariate, t test, and χ2 analyses were performed to determine the association between preoperative depression and postoperative complications following a distal radius fracture surgery. Results: Of the 75 098 eligible patients, 9.9% had at least one ICD code associated with preoperative depression. Preoperative depression was associated with increased odds for surgical site infection (odds ratio [OR] 1.25, confidence interval [CI] 1.14-1.37), emergency department visits for postoperative pain (OR 1.28, CI 1.15-1.36), hardware complication (OR 1.18, CI 1.07-1.30), removal of hardware within 1 year (OR 1.16, CI 1.09-1.27), wound complication (OR 1.17, CI 1.08-1.27), and 30-day readmission (OR 1.21, CI 1.07-1.31). Conclusions: Preoperative diagnosed depression is associated with increased complications following distal radius fracture surgery. These results can help guide preoperative and postoperative protocols in these higher risk patients. More research is needed to investigate if depression is a modifiable risk factor, as depression treatment could potentially improve postsurgical outcomes.

Outcomes of patients with advanced liver disease undergoing cardiac surgery

ObjectiveLiver disease (LD) is considered a risk factor for inferior outcomes in general and cardiac surgery, yet current cardiac surgery risk estimators exclude LD, and literature on the topic remains scant. We sought to evaluate whether the presence of advanced LD is associated with inferior outcomes following cardiac surgery. MethodsThis single-center, retrospective, observational study included 285 patients diagnosed with LD who underwent cardiac surgery in 2010 to 2020. The cohort contained 3 groups, Child-Turcotte-Pugh (CTP) class A (n = 219), CTP early-class B (n = 34), and CTP advanced-class B (n = 32). A model for end-stage liver disease score of 12.7 points (determined using a receiver-operating characteristic curve analysis on 30-day mortality) dichotomized class B into early- and advanced-groups. Univariate and multivariate logistic regression analyses were performed to identify predictors of 30-day mortality. ResultsPatients in CTP advanced-class B had the longest length of stay (14 days), highest incidence of prolonged ventilation (46.9%), renal failure (21.9%), 30-day mortality (18.8%), and in-hospital mortality (18.8%). Incidence of ≥1 postoperative complication was higher in CTP advanced-class B (59.4%), compared with CTP class A (37.9%) and CTP early-class B (38.2%). Multivariate logistic regression analysis demonstrated that female sex (odds ratio, 3.01; 95% CI, 1.07-8.77; P = .037) and peripheral vascular disease (odds ratio, 4.01; 95% CI, 1.33-12.2; P = .013) were independent predictors of 30-day mortality in patients with advanced LD. ConclusionsSeverity of LD influences perioperative outcomes following cardiac surgery. Our data suggest that patients in CTP class A and selected patients in CTP class B (model for end-stage liver disease score <12.7) can undergo surgery with acceptable risk.

Favorable Outcomes of DDX41-Mutated MDS and Low Blast Count AML Treated with Azacitidine with or without Lenalidomide (ALLG MDS4 Trial)

Introduction. The Australasian Leukaemia and Lymphoma Group (ALLG) MDS4 phase II trial randomized 160 patients (pts) with higher risk (by IPSS) myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and low blast acute myeloid leukemia (AML) to either azacitidine (AZA) or combination AZA with lenalidomide (LEN, from cycle 3 onwards) (Kenealy, Haematologica 2019; ANZCTR12610000271000). Whilst the combination of LEN and AZA was tolerable, there was no improvement in clinical benefit, response rates or overall survival in patients compared to treatment with AZA alone. We performed a post-hoc genomic analysis of pts on this trial to further understand the molecular changes in this cohort and any correlation with outcomes. Methods. A unique molecular index (UMI) based QIAseq targeted DNA panel (QIAGEN) was performed as previously described (Blombery, Blood 2020). Sensitivity for variant calling was 0.5% variant allele frequency (VAF). HumanCytoSNP-12 BeadChip array (SNP-A) was previously performed and reported (Kenealy, Haematologica 2019). Primary endpoint of the study was ongoing clinical benefit at 12 months, defined as being alive and progression-free. Logistic regression and Cox proportional hazards regression were used respectively to assess the differences in response rates and overall survival between two treatment groups according to the molecular subgroups. Results. A total of 66 pts, representative of the 160 enrolled, had baseline gDNA available for targeted panel testing; 36 and 30 pts on AZA alone and AZA+LEN therapy, respectively. Median age was 71.6 years. IPSS-R risk groups were very low or low (n=20), intermediate (n=18), high or very high (n=25), and not available (n=3 due to missing karyotype). Disease subtypes were MDS (n=52), CMML (n=9), and AML (n=5). 47% of pts had an abnormal SNP-A, including 18% with complex (≥3) copy number changes. The most common gene mutations observed were ASXL1 (48.5%), TET2 (47%) and RUNX1 (30%) (Figure 1). Overall clinical benefit at 12 months was achieved in 39 pts (59%). TET2 was the only gene mutation associated with significantly improved benefit when treated with AZA alone (OR 10 [95% CI, 2 to 81]). Median follow up among survivors was 49 months and the median overall survival was 33.2 months (95% CI, 21.7 - NE). Mutations in TP53, U2AF1, EZH2 and SRSF2 were associated with inferior overall survival. Molecular subgroup analyses did not identify any significant difference between the two treatment arms. Given the recent discovery of DDX41 mutations in MDS/AML and early data supporting a favorable response to AZA/LEN, we focused on 6/66 (9%) patients with detectable DDX41 mutations. All 6 pts had a second mutation detectable in DDX41 as well as no detectable abnormalities on SNP-A. The most commonly co-mutated gene in this group was ASXL1 (in 4/6). One patient with DDX41 mutation died before receiving any therapy. Best responses achieved in DDX41 mutated patients were complete remission (CR, n=1), marrow CR (n=1), hematologic improvement (HI, n=1), and stable disease (SD, n=2). Remarkably, of the 5 patients that received treatment (4 AZA, 1 AZA+LEN), the overall survival at 52 months (range 47-58) follow up was 100% (Figure 2), despite having intermediate (n=3) and high (n=2) R-IPSS. Mutations were also serially assessed on therapy in 45 pts: ≤2 cycles in 38 pts, and ≥4 cycles in 7 pts (2 AZA+LEN). Of 166 mutations observed at baseline, majority (67%) were stable with <10% change in VAF (median +2%). Overall, 27 (60%) pts had clearance or >10% VAF reduction in ≥1 variant, including clearance in 20 (12%) variants (most commonly TET2 [n=4] and RUNX1 [n=3]), and reduction in 33 (20%) variants (ASXL1 [n=6], SF3B1, SRSF2 and TET2 [n=5 each], but no pt had complete molecular clearance. In contrast, new mutations (n=18 variants) or >10% VAF increase (n=2 variants) were observed in 14 (31%) pts, most commonly TET2 (n=6), RUNX1 (n=4), and DNMT3A and BRAF (n=3 each). Conclusions. In summary, our correlative molecular analysis of the ALLG MDS4 trial of AZA vs AZA+LEN in MDS/AML has identified, in addition to established molecular risk factors for inferior outcomes, that pts with DDX41 mutations are associated with highly favorable outcomes with either AZA or AZA+LEN. This observation and subgroup of patients warrants further study in randomized trials. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

High percentages of peripheral blood T-cell activation in childhood Hodgkin's lymphoma are associated with inferior outcome.

The aims of this study were to investigate the activation of T lymphocytes in peripheral blood from children with Hodgkin's lymphoma (HL) and explore their roles for prognosis in HL. A cohort of 52 newly diagnosed children with HL during the past 10 years was enrolled for analysis in this study. Peripheral blood samples of the patients were acquired before treatment in our hospital, and T-cell subsets were detected by a four-color flow cytometer. CD4+ T cells and CD4+/CD8+ T-cell ratio decreased significantly in patients with HL vs. healthy controls. CD8+ T cells, CD3+CD4+HLA-DR+ T cells, and CD3+CD8+HLA-DR+ T cells increased markedly in patients with HL vs. healthy controls. Receiver-operating characteristic (ROC) curve analysis showed that CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells each distinguished the high-risk group from the low- and intermediate-risk group. The area under the ROC curve for predicting high-risk patients was 0.795 for CD3+CD4+HLA-DR+ T cell and 0.784 for CD3+CD8+HLA-DR+ T cell. A comparison of peripheral blood T-cell subsets that responded differently to therapy showed significantly higher percentages of CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells in patients who achieved complete remission compared to those who did not achieve complete remission. In addition, high percentages of both CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells were associated with inferior event-free survival. Peripheral immune status may be related to disease severity in HL. CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells may be a novel indicator for risk stratification of HL and may be an independent risk factor for inferior outcome in childhood HL.

The Effect of Joint Line Elevation on Patient-Reported Outcomes After Contemporary Revision Total Knee Arthroplasty.

Joint line elevation in revision total knee arthroplasty (rTKA) is considered a risk factor for inferior outcomes, engendering a dogmatic protocol of joint line restoration. However, this precedent is based on historical data using rudimentary revision systems and unvalidated outcome measures. This study's purpose was to evaluate the effect of joint line height elevation on validated patient-reported outcome measures (PROMs) using modern revision implants. A total of 327 rTKAs performed at a single institution were reviewed. Surgical technique prioritized flexion-extension gap balancing and accepted joint line elevation if necessary to achieve a balanced flexion space. Radiographic measurements included changes in joint line height (from preoperative and calculated "intended" anatomic/native) and change in posterior condylar offset. Prospectively collected PROMs were evaluated using multivariate regression. The mean joint line elevation from preoperative and "intended" to postoperative joint line was 4.9±5.7 mm and 7.2±6.6 mm, respectively. The mean increase in posterior condylar offset was 1.0±4.6 mm. Patients within ±5 mm of preoperative joint line height were 3.88× more likely to achieve the substantial clinical benefit for Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (P= .004). An increase from intended joint line height >5 mm was not associated with differences in any other PROMs (P ≥ .165). In contemporary rTKA, recreating the joint line within 5 mm of preoperative improves knee-specific health outcomes. These data support approximating native joint line height as a viable technique to optimize flexion gap balance and subsequent patient outcomes in rTKA. Level III retrospective cohort study.

Concomitant Glenolabral Articular Disruption (GLAD) Lesion is Not Associated With Inferior Clinical Outcomes After Arthroscopic Bankart Repair for Shoulder Instability: A Retrospective Comparative Study

PurposeThe purpose of this study was to compare outcomes between anterior shoulder instability patients with and without glenolabral articular disruption (GLAD) lesions after undergoing arthroscopic Bankart repair and to evaluate potential risk factors for inferior outcomes and recurrent instability.MethodsProspectively collected data were retrospectively reviewed for patients who underwent arthroscopic Bankart repair with and without GLAD lesions at a minimum of 2 years follow-up. Consecutive patients were matched by age, sex, and number of anchors. Patient-reported outcomes (PROs) were evaluated before and after surgery, including American Shoulder and Elbow Surgeons, Single Assessment Numeric Evaluation, Quick Disabilities of the Arm, Shoulder and Hand, Short Form-12 score, and satisfaction. Recurrent dislocation, subjective instability, and reoperation were analyzed. Additionally, PROs were assessed on the basis of GLAD lesion characteristics.ResultsA total of 54 patients (27 GLAD, 27 control) with a mean age of 28.9 ± 11.6 years were analyzed at mean 4.5 ± 1.9 years (range, 2-9 years) follow-up. Thirty-eight (70.3%) of the participants were male. Patients in both groups experienced significant improvements in all PROs (P ≤ .006 for all measures) and reported high median satisfaction (scale 1-10: 10 vs 10, P = .290) at final follow-up. Two patients in the GLAD cohort and 1 in the control cohort underwent reoperation (P = .588). Four (14.8%) patients in each group reported recurrent dislocation (P = 1.0). Additionally, 2 (7.4%) GLAD patients and 1 (3.7%) control patient reported subjective shoulder instability after surgery (P = 1.0). No significant differences in PROs were observed based on anchor/labral advancement or treatment with microfracture, nor were significant correlations observed between GLAD lesion size and PROs (P > .05 for all).ConclusionArthroscopic Bankart repair in patients with GLAD lesions resulted in significantly improved outcomes with high satisfaction, which was no different when compared with those without GLAD lesions.Level of EvidenceLevel III, retrospective comparative study.

Isolated Bioinductive Repair Of High-Grade Partial-Thickness Rotator Cuff Tears In Patients With Established Risk Factors For Inferior Outcomes

To analyze clinical results of isolated bioinductive repair (IBR) of high-grade partial-thickness rotator cuff tears in patients with established risk factors for inferior outcomes using data from a multi-center registry.

Characteristics and Outcome of Elderly Patients (>55 Years) with Acute Lymphoblastic Leukemia.

Simple SummaryDisease-specific mortality of acute lymphoblastic leukemia (ALL) increases with age. So far, only a few analyses have investigated disease characteristics of elderly patients (>55 years) with newly diagnosed ALL. The aim of our retrospective study was to evaluate the treatment results of 93 elderly patients who received intensive chemotherapy between May 2003 and October 2020. We identify poor performance status and older age at the time of diagnosis as risk factors for inferior outcomes, while ALL immunophenotype, BCR::ABL1 status, the complexity of karyotype, and intensity of treatment did not significantly affect overall survival (OS). With 17.3% of patients dying while in complete remission (CR), an event-free survival (EFS) and OS of 32.9% and 47.3% at 3 years, our data suggest that intensive treatment of elderly ALL patients is feasible but associated with significant toxicity. These results underline the need for novel, less toxic treatment approaches for this vulnerable cohort of patients.Prognosis of elderly ALL patients remains dismal. Here, we retrospectively analyzed the course of 93 patients > 55 years with B-precursor (n = 88) or T-ALL (n = 5), who received age-adapted, pediatric-inspired chemotherapy regimens at our center between May 2003 and October 2020. The median age at diagnosis was 65.7 years, and surviving patients had a median follow-up of 3.7 years. CR after induction therapy was documented in 76.5%, while the rate of treatment-related death within 100 days was 6.4%. The OS of the entire cohort at 1 and 3 year(s) was 75.2% (95% CI: 66.4–84.0%) and 47.3% (95% CI: 36.8–57.7%), respectively, while the EFS at 1 and 3 years(s) was 59.0% (95% CI: 48.9–69.0%) and 32.9% (95% CI: 23.0–42.8%), respectively. At 3 years, the cumulative incidence (CI) of relapse was 48.3% (95% CI: 38.9–59.9%), and the CI rate of death in CR was 17.3% (95% CI: 10.9–27.5%). Older age and an ECOG > 2 represented risk factors for inferior OS, while BCR::ABL1 status, immunophenotype, and intensity of chemotherapy did not significantly affect OS. We conclude that intensive treatment is feasible in selected elderly ALL patients, but high rates of relapse and death in CR underline the need for novel therapeutic strategies.

Impact of frailty on clinical outcomes and resource use following emergency general surgery in the United States.

BackgroundFrailty has been recognized as an independent risk factor for inferior outcomes, but its effect on emergency general surgery (EGS) is understudied.ObjectiveThe purpose of the present study was to define the impact of frailty on risk-adjusted mortality, non-home discharge, and readmission following EGS operations.MethodsAdults undergoing appendectomy, cholecystectomy, small bowel resection, large bowel resection, repair of perforated ulcer, or laparotomy within two days of an urgent admission were identified in the 2016–2017 Nationwide Readmissions Database. Frailty was defined using diagnosis codes corresponding to the Johns Hopkins Adjusted Clinical Groups frailty indicator. Multivariable regression was used to study in-hospital mortality and non-home discharge by operation, and Kaplan Meier analysis to study freedom from unplanned readmission at up to 90-days follow-up.ResultsAmong 655,817 patients, 11.9% were considered frail. Frail patients most commonly underwent large bowel resection (37.3%) and cholecystectomy (29.2%). After adjustment, frail patients had higher mortality rates for all operations compared to nonfrail, including those most commonly performed (11.9% [95% CI 11.4–12.5%] vs 6.0% [95% CI 5.8–6.3%] for large bowel resection; 2.3% [95% CI 2.0–2.6%] vs 0.2% [95% CI 0.2–0.2%] for cholecystectomy). Adjusted non-home discharge rates were higher for frail compared to nonfrail patients following all operations, including large bowel resection (68.1% [95% CI 67.1–69.0%] vs 25.9% [95% CI 25.2–26.5%]) and cholecystectomy (33.7% [95% CI 32.7–34.7%] vs 2.9% [95% CI 2.8–3.0%]). Adjusted hospitalization costs were nearly twice as high for frail patients. On Kaplan-Meier analysis, frail patients had greater unplanned readmissions (log rank P<0.001), with 1 in 4 rehospitalized within 90 days.ConclusionsFrail patients have inferior clinical outcomes and greater resource use following EGS, with the greatest absolute differences following complex operations. Simple frailty assessments may inform expectations, identify patients at risk of poor outcomes, and guide the need for more intensive postoperative care.

Allogeneic stem cell transplantation for AML patients with RUNX1 mutation in first complete remission: a study on behalf of the acute leukemia working party of the EBMT

Acute myeloid leukemia with runt-related transcription factor 1 gene mutation (RUNX1+ AML) is associated with inferior response rates and outcome after conventional chemotherapy. We performed a retrospective, registry-based analysis to elucidate the prognostic value of RUNX1 mutation after allogeneic stem cell transplantation (alloSCT). All consecutive adults undergoing alloSCT for AML in first complete remission (CR1) between 2013 and 2019 with complete information on conventional cytogenetics and RUNX1 mutational status were included. Endpoints of interest were cumulative relapse incidence, non-relapse mortality, overall and leukemia-free survival (OS/LFS), and GvHD-free/relapse-free survival. A total of 674 patients (183 RUNX1+, 491 RUNX1−) were identified, with >85% presenting as de novo AML. Median follow-up was 16.4 (RUNX1+) and 21.9 (RUNX1−) months. Survival rates showed no difference between RUNX1+ and RUNX1− patients either in univariate or multivariate analysis (2-year OS: 67.7 vs. 66.1%, p = 0.7; 2-year LFS: 61.1 vs. 60.8%, p = 0.62). Multivariate analysis identified age, donor type and poor cytogenetics as risk factors for inferior outcome. Among patients with RUNX+ AML, older age, reduced intensity conditioning and minimal residual disease at alloSCT predicted inferior outcome. Our data provide evidence that the negative influence of RUNX1 mutations in patients with AML can be overcome by transplantation in CR1.

Osteoarthrosis, Advanced Age, and Female Sex Are Risk Factors for Inferior Outcomes After Hip Arthroscopy and Labral Debridement for Femoroacetabular Impingement Syndrome: Case Series With Minimum 10-Year Follow-Up

(1) To determine the cumulative survivorship using the endpoint of total hip arthroplasty (THA) correlated with osteoarthrosis (Tönnis grade ≤ 1 vs Tönnis grade > 1) at a minimum 10-year follow-up and (2) to identify risk factors for THA conversion. This study examined 112 patients who underwent hip arthroscopy for femoroacetabular impingement syndrome (FAIS) between 2007 and 2009. The inclusion criterion was primary hip arthroscopy to treat FAIS with corresponding chondrolabral pathologies. The exclusion criteria were secondary hip pathologies, revision hip arthroscopy, or dysplasia. The mean follow-up period was 11 years. Cumulative survival was estimated by Kaplan-Meier analysis using the endpoint of THA. Risk factors for THA conversion were identified using a multivariate Cox proportional hazards model. Forty patients underwent THA. The cumulative survivorship rate at 11 years was 86% for patients with a Tönnis grade of 1 or less and 46% for those with a Tönnis grade greater than 1. Osteoarthrosis, advanced age, and female sex were associated with lower hip survival rates. In particular, the risk of THA conversion was 24% higher for patients with an advanced age at the time of surgery, 97% higher for female patients, and 133% higher for hips with a Tönnis grade greater than1. The survivorship rate at a mean 11-year follow-up after arthroscopic FAIS therapy was 86.3% in the group with a Tönnis grade of 1 or less and 46.4% in the group with a Tönnis grade greaterthan 1. The presence of osteoarthrosis, advanced age, and female sex adversely affected the outcome. Level III, retrospective comparative study.

Weight Loss Predicts Inferior Outcome in Polycythemia Vera Patients

Background: Conventional risk factors for inferior outcomes in polycythemia vera (PV) include elevated hematocrit, white blood cell (WBC) count, age, and abnormal karyotype. Weight loss adversely impacts survival in cancer patients. JAK2 myeloproliferative neoplasms (MPN) upregulate tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-8 and induce decreased leptin levels leading to weight loss. The impact of weight loss in PV patients receiving best supportive care (i.e. frontline hydroxyurea [HU] therapy, phlebotomy) on overall survival (OS) is largely unknown. In this study, we seek to investigate: (1) differential effect on survival for weight loss, and (2) variables with predictive value for weight loss among JAK2 inhibitor-naïve PV patients. Methods: After IRB approval, 46 patients at the Michael E. DeBakey VA Medical Center diagnosed with PV between 2000 and 2016 were selected for analysis. Our outcome of interest was OS among PV patients exhibiting weight loss versus patients who maintained, gained weight or had minor weight loss. To objectively estimate weight changes overtime, the difference between baseline BMI [BMI-B] at the time of diagnosis and BMI at last follow-up (BMI-L) was obtained for each patient. Survival analysis was performed for PV patients exhibiting more than 10% weight loss (&amp;gt;10%) versus all other patients (less than 10% loss, stable and increased weight) (&amp;lt;10%) over time. Kaplan-Meier (KM) method was used to determine OS. Cox regression model was performed to assess independent role of different variables including age, blood cell counts and ferritin level Statistical analysis was performed using SAS software. Results: Median BMI loss was 10% (0.03-36.72%); 33/46 (71.7%) and 13/46 (28.2%) patients developed &amp;lt;10% and &amp;gt;10% BMI loss, respectively. Baseline characteristics are summarized in Table 1. Median BMI at last follow up was 21 for PV patients exhibiting &amp;gt;10% BMI loss and 27.7 for PV patients exhibiting &amp;lt;10% BMI loss (p&amp;lt;0.01). Median age was higher among patients exhibiting &amp;gt;10% BMI loss (68 vs 56 y, respectively, p=0.006). A non-significant clinical trend for higher WBC was observed among patients losing &amp;gt;10% BMI (10.9 vs 7.6 K/uL, p=0.08). Median Hemoglobin (Hb), hematocrit (Hct) and ferritin were intriguingly lower in the &amp;gt;10% loss group at 16 vs 18.3 g/dL (p=0.01), 49.3 vs 54.2% (p=0.04) and 29.8 vs 50.6 ng/mL (p=0.09) respectively, while median RDW was higher at 18 vs 15.1% (p=0.01). OS was 9125 days vs 5364 days, in patients with &amp;lt;10% and &amp;gt;10% BMI loss, respectively (p=0.02, HR=0.20; CI 95% 0.04-0.84) (Figure 1). On multivariate analysis, age (hazard ratio [HR], 1.34; p&amp;lt;0.02) and WBC count (HR, 1.57; p&amp;lt;0.01), were predictive of OS. Conclusions: A subgroup of PV patients exhibit progressive weight loss. Over 10% BMI reduction is associated with decreased survival, suggesting that "early weight loss" is an independent clinical variable that predicts high risk PV. While a larger study is needed to validate this observation, this small study highlights the role of leukocytosis, advanced age and weight loss in PV. Confirmation of the observations reported here could unveil an important role for pharmacologic and/or dietary interventions to improve survival among high-risk PV patients. Disclosures Rivero: agios: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees.

An Endovascular-First Approach for Aortoiliac Occlusive Disease is Safe: Prior Endovascular Intervention is Not Associated with Inferior Outcomes after Aortofemoral Bypass

Although prior endovascular intervention is a risk factor for inferior outcomes after infrainguinal bypass, there are few studies evaluating the effect of prior aortoiliac endovascular intervention (AIEI) on outcomes after aortofemoral bypass (AFB). We sought to determine if prior AIEI was predictive of adverse events after AFB. The Vascular Quality Initiative was queried for all patients who underwent AFB form 2009 to 2019. Urgent/emergent cases and repeat procedures were excluded. Primary outcomes were major perioperative complications, major adverse limb event (MALE)-free survival, and long-term survival. Multivariable logistic regression identified predictors of major complications. Predictors of MALE-free survival were identified with Cox proportional hazards modeling. There were 3,056 patients who underwent AFB; 618 had a prior AIEI. Mean age was 60.3±8.7years, and 58.7% of patients were men. There was no difference in major complications between the 2 groups (AIEI: 23.8%, no AIEI: 24.5%; P-value=0.70). Factors associated with major complications were chronic obstructive pulmonary disease (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.07-1.54; P=0.008), simultaneous lower extremity intervention (endarterectomy, bypass, or transluminal intervention, OR 1.41, 95% CI: 1.18-1.69; P<0.001), congestive heart failure (CHF) (OR 1.58, 95% CI: 1.15-2.16; P=0.004), increased age (OR 1.03 per year, 95% CI: 1.02-1.04; P<0.001), increasing operative blood loss (OR 1.35 per liter, 95% CI: 1.21-1.50; P<0.001), increasing operative time (OR 1.07 per hour, 95% CI: 1.02-1.13; P=0.008), and end-to-side proximal anastomosis (OR 1.23, 95% CI: 1.03-1.46; P=0.022). One-year MALE-Free survival was 88.2% (95% CI: 85.2-90.7%) for the prior AIEI group and 89.7% (95% CI: 88.3-90.7%) for the group without prior AIEI (logrank P-value=0.201). Predictors of MALEs/death were history of a bypass (hazard ratio [HR] 1.51, 95% CI: 1.16-1.96; P=0.002), increasing degree of ischemia on presentation (HR 1.28 per increasing level of ischemia, 95% CI: 1.16-1.41; P<0.001), diabetes (HR 1.29, 95% CI: 1.05-1.59; P=0.014), simultaneous peripheral vascular intervention (HR 2.06, 95% CI: 1.02-4.15; P=0.044), CHF (HR 1.60, 95% CI: 1.18-2.18; P=0.002), end-stage renal disease on hemodialysis (HR 5.07, 95% CI: 2.45-10.48; P<0.001), and presenting hemoglobin<9g/dl (HR 1.76, 95% CI: 1.02-3.02; P=0.041). One-year survival for the prior AIEI group was 94.5% (95% CI: 92.2-96.1%) and 94.0% (95% CI: 92.9-94.9%) for the group with no prior AIEI (logrank P=0.486). Prior AIEI did not predict any of the primary outcomes in multivariable analysis. An endovascular-first approach for aortoiliac occlusive disease appears to be safe and does not portend to inferior results after AFB.

An Endovascular First Approach for Aortoiliac Occlusive Disease Is Safe: Prior Endovascular Intervention Not Associated With Inferior Outcomes After Aortofemoral Bypass

While prior endovascular intervention is a risk factor for inferior outcomes after infrainguinal bypass, there are few studies evaluating the effect of prior aortoiliac endovascular intervention (AIEI) on outcomes after aortofemoral bypass (AFB). We sought to determine if prior AIEI was predictive of adverse events after AFB.

Conversion to Everolimus was Beneficial and Safe for Fast and Slow Tacrolimus Metabolizers After Renal Transplantation.

Fast tacrolimus (TAC) metabolism (concentration/dose (C/D) ratio <1.05 ng/mL/mg) is a risk factor for inferior outcomes after renal transplantation (RTx) as it fosters, e.g., TAC-related nephrotoxicity. TAC minimization or conversion to calcineurin-inhibitor free immunosuppression are strategies to improve graft function. Hence, we hypothesized that especially patients with a low C/D ratio profit from a switch to everolimus (EVR). We analyzed data of 34 RTx recipients (17 patients with a C/D ratio <1.05 ng/mL/mg vs. 17 patients with a C/D ratio ≥1.05 ng/mL/mg) who were converted to EVR within 24 months after RTx. The initial immunosuppression consisted of TAC, mycophenolate, prednisolone, and basiliximab induction. During an observation time of 36 months after changing immunosuppression from TAC to EVR, renal function, laboratory values, and adverse effects were compared between the groups. Fast TAC metabolizers were switched to EVR 4.6 (1.5–21.9) months and slow metabolizers 3.3 (1.8–23.0) months after RTx (p = 0.838). Estimated glomerular filtration rate (eGFR) did not differ between the groups at the time of conversion (baseline). Thereafter, the eGFR in all patients increased noticeably (fast metabolizers eGFR 36 months: + 11.0 ± 11.7 (p = 0.005); and slow metabolizers eGFR 36 months: + 9.4 ± 15.9 mL/min/1.73 m2 (p = 0.049)) vs. baseline. Adverse events were not different between the groups. After the switch, eGFR values of all patients increased statistically noticeably with a tendency towards a higher increase in fast TAC metabolizers. Since conversion to EVR was safe in a three-year follow-up for slow and fast TAC metabolizers, this could be an option to protect fast metabolizers from TAC-related issues.