Pursuing More Aggressive Timelines in the Surgical Treatment of Traumatic Spinal Cord Injury (TSCI): A Retrospective Cohort Study with Subgroup Analysis

Background: The optimal timing of surgical therapy for traumatic spinal cord injury (TSCI) remains unclear. The purpose of this study is to evaluate the impact of “ultra-early” (<4 h) versus “early” (4–24 h) time from injury to surgery in terms of the likelihood of neurologic recovery. Methods: The effect of surgery on neurological recovery was investigated by comparing the assessed initial and final values of the American Spinal Injury Association (ASIA) Impairment Scale (AIS). A post hoc analysis was performed to gain insight into different subgroup regeneration behaviors concerning neurological injury levels. Results: Datasets from 69 cases with traumatic spinal cord injury were analyzed. Overall, 19/46 (41.3%) patients of the “ultra-early” cohort saw neurological recovery compared to 5/23 (21.7%) patients from the “early” cohort (p = 0.112). The subgroup analysis revealed differences based on the neurological level of injury (NLI) of a patient. An optimal cutpoint for patients with a cervical lesion was estimated at 234 min. Regarding the prediction of neurological improvement, sensitivity was 90.9% with a specificity of 68.4%, resulting in an AUC (area under the curve) of 84.2%. In thoracically and lumbar injured cases, the estimate was lower, ranging from 284 (thoracic) to 245 min (lumbar) with an AUC of 51.6% and 54.3%. Conclusions: Treatment within 24 h after TSCI is associated with neurological recovery. Our hypothesis that intervention within 4 h is related to an improvement in the neurological outcome was not confirmed in our collective. In a clinical context, this suggests that after TSCI there is a time frame to get the right patient to the right hospital according to advanced trauma life support (ATLS) guidelines.

Acute and Post-Acute COVID-19 Severity and Mortality in Patients with Hematologic Malignancies: A Population-Based Registry Study

Introduction: The severity of acute clinical outcomes and mortality in hematologic malignancy (HM) patients infected by SARS-CoV-2 was exhaustively documented in the first weeks of the pandemic. A consistent increased mortality compared to non-cancer patients was observed across studies. In this study we aimed to estimate survival in COVID-19 HM patients by type of malignancy, to describe acute and post-acute clinical outcomes, and to compare outcomes in early and later pandemic periods. Methods: In this population-based registry study sponsored by the Madrid Society of Hematology (Asociación Madrileña de Hematología y Hemoterapia), we collected de-identified data on clinical characteristics, treatment and acute and post-acute outcomes in adult patients with hematologic malignancies and confirmed SARS-CoV-2 infection within the Madrid region of Spain. Our case series included all eligible patients admitted to 26 regional health service hospitals and 5 private healthcare centers between February 28, 2020 and February 18, 2021 with a coverage of 98% on a population of 6.6 million inhabitants. The study outcomes were all-cause mortality, severity of disease (WHO), oxygen support, ICU admission, and follow-up symptoms and signs and complications. Survival probabilities were estimated with the actuarial method and reported overall and stratified by type of malignancy and for two study periods (early cohort,-COVID-19 diagnosis from February 28 to 31 May, 2020, and later cohort, up to February 18, 2021). Results: Of the 1408 patients reported to the HEMATO-MADRID COVID-19 registry, 1166 were included in the present analyses; 839 (72%) had a lymphoid malignancy, including 325 (28%) with non-Hodgkin lymphoma, 50 (4%) with Hodgkin lymphoma and 263 (23%) with multiple myeloma; and 327 (28%) had a myeloid malignancy, including 115 (10%) with myelodysplastic syndrome, 92 (8%) with acute myeloid leukemia (AML) and 87 (7%) with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms. Overall COVID-19 clinical severity was classified as critical in 19% of patients, severe in 36%, moderate in 22%, and mild in 22%; 10% were admitted to an ICU; 8% were on mechanical ventilation and 19% on noninvasive ventilation. Mild disease increased between early and later period from 15% to 38% of patients; severe disease decreased from 42% to 24%, p&lt;0.001. COVID-19 treatment with steroids increased from 38% to 59%, p&lt;0.001. At follow-up, 22% reported persistent symptoms related to COVID-19 at 2 months, 16% at 4 months and 14% at 6 months. 381 of 1166 (33%) patients died. Overall 30-day survival was 68%; 2 and 3-month overall survival probabilities were 56% and 53%, respectively. Survival was more favorable for patients with myeloproliferative neoplasms (82%, 69% and 65% at 30-days, 2 and 3 months, respectively) than for those with lymphoid malignancies (68%, 56% and 54%) or myelodysplastic syndrome/acute myeloid leukemia (61%, 51%, 46%), p=001. 285 (37%) patients died in the early period vs 96 (24%) in the later, p&lt;0.001, but median (interquartile range) follow-up time was much higher in the early vs later, 45 (20-116) days vs. 26 (11-86), respectively. Overall survival was not different between periods, p=0.5 (hazard ratio [95%C], 0.93 [0.73-1.17]). In the later cohort, 30 and 60-day survival probabilities were 71% and 56% vs. 67% and 56% in the early cohort Conclusions. A population-based registry in Spain provided strong evidence that although COVID-19 severity decreased over year 1 of the pandemic, mortality remained high, and survival was stable over time in the group of patients with hematological malignancy infected by SARS-Coc-2. A relevant proportion of the infected patients (1 in 6) referred persistent symptoms attributable to COVID-19. The improved clinical management of severe COVID-19 in non-cancer patients that followed the dissemination of evidence-based recommendations did not translate in more favorable survival in patients with hematological malignancies. Research is needed to address the specific characteristics and improve the clinical management of this vulnerable population. Disclosures Martinez-Lopez: Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Incyte: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Astellas: Research Funding, Speakers Bureau. Jiménez-Yuste: Pfizer: Consultancy, Honoraria, Research Funding; Grifols: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; NovoNordisk: Consultancy, Honoraria, Research Funding; BioMarin: Consultancy; Sobi: Consultancy, Honoraria, Research Funding; Octapharma: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding. Kwon: Gilead: Honoraria.

The Cost Effectiveness of Delaying Filgrastim Administration after Autologous Stem Cell Transplant in Patients with Multiple Myeloma - a Single Institution Experience

Background ASCO clinical guidelines recommends administration of WBC growth factors after autologous stem cell transplant (ASCT) to reduce the duration of severe neutropenia (Smith TJ et al., Recommendations for the use of WBC growth factors: American society of clinical oncology clinical practice guideline update. J Clin Oncol, 33(28):3199-3212, 2015). But there is conflicting data regarding the optimal timing of granulocyte colony stimulating factor (G-CSF) initiation post-transplantation and a lack of recent cost effectiveness analysis. Based on single center studies showing similar results between an early approach and a delayed one, we changed our institutional standard to a delayed strategy since June 2020. Methods We retrospectively compared the outcomes of adult multiple myeloma ASCT patients who received G-CSF either on day 2 (early) or day 5 (late) at Roger Williams Medical Center. Sixteen consecutive patients received day 2 G-CSF between July 2018 and June 2020 (D+2 cohort) while seven received day 5 since implementing the change in June 2020 (D+5 cohort). The doses of G-CSF given were 300 mcg, 480 mcg, 600 mcg or 960 mcg. One-way factorial ANOVA and Fit Y by X was used for comparison of variables. Descriptive statistics were used where appropriate. Results Baseline characteristics were comparable between the D+2 and D+5 cohorts (median age 62 vs 63 years, median CD34+cells 4.01 vs 4.54 x10 6/kg respectively). The median number of prior treatments, conditioning intensity, disease status at transplant and G-CSF doses were similar in both cohorts. Median ANC at G-CSF initiation was different (3300 in D+2 vs 100 in D+5). The median follow-up for survivors was 215 days for D+5 cohort (range: 135-404 days) and 699 days for D+2 cohort (range: 418-923 days). The results are summarized in table 1. For the primary outcome, median time to neutrophil engraftment was 13 days versus 10 days in the early and late cohorts, respectively (p=0.07). Median days from administration of GCSF to hospital discharge was noted to be shorter in the late cohort (13 vs 17.5 days, p=0.05). There was no statistically significant difference in the incidence of febrile neutropenia or transfusion requirements with late initiation of G-CSF. While engraftment syndrome and duration of antibiotics were noted to be more in the early cohort, these were not statistically significant. Median length of hospital stay was a day and half shorter in the late cohort. 6-month OS favored the D+5 cohort (p=0.03); this was likely due to transplant related deaths in early cohort. The average cost saving per patient by implementing the late strategy was 887.4 $. Conclusions Late initiation of G-CSF following autologous ASCT in patients with multiple myeloma was associated with a shorter time to neutrophil engraftment and length of stay post transplantation with no difference in overall outcomes. Cost benefit analysis favors delaying initiation of GCSF for autologous SCT at our center. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Targeting of the CD80/86 proinflammatory axis as a therapeutic strategy to prevent severe COVID-19

An excessive immune response known as cytokine storm is the hallmark of severe COVID-19. The cause of this cytokine rampage is yet not known. Based on recent epidemiological evidence, we hypothesized that CD80/86 signaling is essential for this hyperinflammation, and that blocking this proinflammatory axis could be an effective therapeutic approach to protect against severe COVID-19. Here we provide exploratory evidence that abatacept, a drug that blocks CD80/86 co-stimulation, produces changes at the systemic level that are highly antagonistic of the proinflammatory processes elicited by COVID-19. Using RNA-seq from blood samples from a longitudinal cohort of n = 38 rheumatic patients treated with abatacept, we determined the immunological processes that are significantly regulated by this treatment. We then analyzed available blood RNA-seq from two COVID19 patient cohorts, a very early cohort from the epicenter of the pandemic in China (n = 3 COVID-19 cases and n = 3 controls), and a recent and larger cohort from the USA (n = 49 severe and n = 51 mild COVD-19 patients). We found a highly significant antagonism between SARS-CoV-2 infection and COVID-19 severity with the systemic response to abatacept. Analysis of previous single-cell RNA-seq data from bronchoalveolar lavage fluid from mild and severe COVID-19 patients and controls, reinforce the implication of the CD80/86 proinflammatory axis. Our functional results further support abatacept as a candidate therapeutic approach to prevent severe COVID-19.

All-cause and Cause-specific Mortality in Systemic Lupus Erythematosus: A Population-based Study

Objective To investigate all-cause and cause-specific mortality in SLE patients between two time periods, 1997-2005 and 2006-2014. Methods We used an administrative health database from the province of British Columbia, Canada to match all incident SLE patients to 10 non-SLE individuals on sex, age and index date. Cohorts were divided into two sub-groups, according to diagnosis year: early cohort 1997-2005 and late cohort 2006-2014. The outcome was death (all-cause, renal disease, cancer, infection, cardiovascular disease (CVD), and other). Hazard ratios (HR and 95% confidence intervals) were estimated using univariate and multivariable Cox models. Results Among 6,092 SLE patients and 60,920 non-SLE individuals, there were 451 and 1,910 deaths, respectively. The fully-adjusted all-cause mortality HR (95% CI) in the overall SLE cohort was 1.85 (1.66-2.06), with no statistically significant improvement between early and late cohorts (1.95 (1.69-2.26) versus 1.74 (1.49-2.04). There was excess mortality from renal disease (3.04 (2.29-4.05)), infections (2.74 (2.19-3.43)) and CVD (2.05 (1.77-2.38)), but not cancer (1.18 (0.96-1.46)), in the overall SLE cohort. There was no statistically significant improvement in cause-specific mortality between early and late cohorts for renal disease (3.57 (2.37-5.36) versus 2.65 (1.78-3.93)), infection (2.94 (2.17-3.98) versus 2.54 (1.84-3.51)), and CVD (1.95 (1.60-2.38) versus 2.18 (1.76-2.71)). There was no increase in cancer-related mortality in either cohort (1.27 (0.96-1.69) versus 1.10 (0.82-1.48)). Conclusion This population-based study demonstrates a persisting mortality gap in all-cause and cause-specific deaths in SLE patients, compared to the general population.

Early Chemoprophylaxis Against Venous Thromboembolism in Patients With Traumatic Brain Injury

Introduction Timing to start of chemoprophylaxis for venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) remains controversial. We hypothesize that early administration is not associated with increased intracranial hemorrhage. Methods A retrospective study of adult patients with TBI following blunt injury was performed. Patients with penetrating brain injury, any moderate/severe organ injury other than the brain, need for craniotomy/craniectomy, death within 24 hours of admission, or progression of bleed on 6 hour follow-up head computed tomography scan were excluded. Patients were divided into early (≤24 hours) and late (>24 hours) cohorts based on time to initiation of chemoprophylaxis. Progression of bleed was the primary outcome. Results 264 patients were enrolled, 40% of whom were in the early cohort. The average time to VTE prophylaxis initiation was 17 hours and 47 hours in the early and late groups, respectively ( P < .0001). There was no difference in progression of bleed (5.6% vs. 7%, P = .67), craniectomy/-craniotomy rate (1.9% vs. 2.5%, P = .81), or VTE rate (0% vs. 2.5%, P = .1). Conclusion Early chemoprophylaxis is not associated with progression of hemorrhage or need for neurosurgical intervention in patients with TBI and a stable head CT 7 hours following injury.

Factors associated with syphilis seroprevalence in women with and at-risk for HIV infection in the Women’s Interagency HIV Study (1994–2015)

ObjectiveSyphilis rates among women in the USA more than doubled between 2014 and 2018. We sought to identify correlates of syphilis among women enrolled in the Women’s Interagency HIV Study (WIHS) to inform targeted interventions.MethodsThe retrospective cross-sectional analysis of secondary data included women with HIV or at-risk of HIV who enrolled in the multisite US WIHS cohort between 1994 and 2015. Syphilis screening was performed at baseline. Infection was defined serologically by a positive rapid plasma reagin test with confirmatory treponemal antibodies. Sociodemographic and behavioural characteristics stratified by baseline syphilis status were compared for women enrolled during early (1994–2002) and recent (2011–2015) years. Multivariable binomial modelling with backward selection (p>0.2 for removal) was used to model correlates of syphilis.ResultsThe study included 3692 women in the early cohort and 1182 women in the recent cohort. Syphilis prevalence at enrolment was 7.5% and 3.7% in each cohort, respectively (p<0.01). In adjusted models for the early cohort, factors associated with syphilis included age, black race, low income, hepatitis C seropositivity, drug use, HIV infection and >100 lifetime sex partners (all p<0.05). In the recent cohort, age (adjusted prevalence OR (aPOR) 0.2, 95% CI 0.1 to 0.6 for 30–39 years; aPOR 0.5, 95% CI 0.2 to 1.0 for 40–49 years vs ≥50 years), hepatitis C seropositivity (aPOR 2.1, 95% CI 1.0 to 4.1) and problem alcohol use (aPOR 2.2, 95% CI 1.1 to 4.4) were associated with infection.ConclusionsSyphilis screening is critical for women with HIV and at-risk of HIV. Targeted prevention efforts should focus on women with hepatitis C and problem alcohol use.

Adoption of Robotic-Arm-Assisted Total Knee Arthroplasty Is Associated with Decreased Use of Articular Constraint and Manipulation under Anesthesia Compared to a Manual Approach

Haptic robotic-arm-assisted total knee arthroplasty (RATKA) seeks to leverage three-dimensional planning, intraoperative assessment of ligament laxity, and guided bone preparation to establish and achieve patient-specific targets for implant position. We sought to compare (1) operative details, (2) knee alignment, (3) recovery of knee function, and (4) complications during adoption of this technique to our experience with manual TKA. We compared 120 RATKAs performed between December 2016 and July 2018 to 120 consecutive manual TKAs performed between May 2015 and January 2017. Operative details, lengths of stay (LOS), and discharge dispositions were collected. Tibiofemoral angles, Knee Society Scores (KSS), and ranges of motion were assessed until 3 months postoperatively. Manipulations under anesthesia, complications, and reoperations were tabulated. Mean operative times were 22 minutes longer in RATKA (p < 0.001) for this early cohort, but decreased by 27 minutes (p < 0.001) from the first 25 RATKA cases to the last 25 RATKA cases. Less articular constraint was used to achieve stability in RATKA (93 vs. 55% cruciate-retaining, p < 0.001; 3 vs. 35% posterior stabilized (PS), p < 0.001; and 4 vs. 10% varus-valgus constrained, p_ = _0.127). RATKA had lower LOS (2.7 vs. 3.4 days, p < 0.001). Discharge dispositions, tibiofemoral angles, KSS, and knee flexion angles did not differ, but manipulations were less common in RATKAs (4 vs. 17%, p = 0.013). We observed less use of constraint, shorter LOS, and fewer manipulations under anesthesia in RATKA, with no increase in complications. Operative times were longer, particularly early in the learning curve, but improved with experience. All measured patient-centered outcomes were equivalent or favored the newer technique, suggesting that RATKA with patient-specific alignment targets does not compromise initial quality. Observed differences may relate to improved ligament balance or diminished need for ligament release.

Persistent premature mortality gap in dermatomyositis and polymyositis: a United Kingdom general population-based cohort study

Objective DM and PM are associated with substantial morbidity and mortality. We aimed to examine recent trends. Methods Using The Health Improvement Network, we identified patients with incident DM/PM (defined by ≥1 Read diagnosis code) aged 18–89 years with ≥1 year of continuous enrolment prior to the cohort entry date and up to 10 comparators matched on age, sex and entry year. The cohort was divided in two based on the year of DM/PM diagnosis: the early cohort (1999–2006) and late cohort (2007–2014). We calculated multivariable hazard ratios (HR) for death using a Cox-proportional hazards model and multivariable rate differences (RD) using an additive hazard model. Results We identified 410 DM cases (mean age: 58 years, 66% female) and 407 PM cases (mean age: 59 years, 61% female). Both DM cohorts had excess mortality compared with the comparison cohorts (71.5 vs 12.9 deaths/1000 person-years [PY] in the early cohort and 49.1 vs 10.4 deaths/1000 PY in the late cohort). The multivariable HRs were 7.51 (95% CI: 4.20, 13.42) in the early cohort and 5.42 (95% CI: 3.11, 9.45) in the late cohort (P-value for interaction = 0.59), and multivariable RDs were 56.2 (95% CI: 31.8, 81.2) in the early cohort and 36.3 (95% CI: 19.6, 53.0) in the late cohort (P-value for interaction = 0.15). A similar trend existed in PM. Conclusion The premature mortality gap in DM/PM has not considerably improved in recent years, highlighting an unmet need for therapeutic improvement.