Prospective Registry Data Research Articles

Efficacy of laser interstitial thermal therapy (LITT) for newly diagnosed and recurrent IDH wild-type glioblastoma.

BackgroundTreatment options for unresectable new and recurrent glioblastoma remain limited. Laser ablation has demonstrated safety as a surgical approach to treating primary brain tumors. The LAANTERN prospective multicenter registry (NCT02392078) data were analyzed to determine clinical outcomes for patients with new and recurrent IDH wild-type glioblastoma.MethodsDemographics, intraprocedural data, adverse events, KPS, health economics, and survival data were prospectively collected and then analyzed on IDH wild-type newly diagnosed and recurrent glioblastoma patients who were treated with laser ablation at 14 US centers between January 2016 and May 2019. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable differences in survival, and median survival numbers.ResultsA total of 29 new and 60 recurrent IDH wild-type WHO grade 4 glioblastoma patients were treated. Positive MGMT promoter methylation status was present in 5/29 of new and 23/60 of recurrent patients. Median physician-estimated extent of ablation was 91%-99%. Median overall survival (OS) was 9.73 months (95% confidence interval: 5.16, 15.91) for newly diagnosed patients and median post-procedure survival was 8.97 months (6.94, 12.36) for recurrent patients. Median OS for newly diagnosed patients receiving post-LITT chemo/radiation was 16.14 months (6.11, not reached). Factors associated with improved survival were MGMT promoter methylation, adjuvant chemotherapy within 12 weeks, and tumor volume <3 cc.ConclusionsLaser ablation is a viable option for patients with new and recurrent glioblastoma. Median OS for IDH wild-type newly diagnosed glioblastoma is comparable to outcomes observed in other tumor resection studies when those patients undergo radiation and chemotherapy following LITT.

Rearrest during hospitalisation in adult comatose out-of-hospital cardiac arrest patients: Risk factors and prognostic impact, and predictors of favourable long-term outcomes

BackgroundRearrest occurs commonly after initial resuscitation following out-of-hospital cardiac arrest (OHCA). We determined (1) the predictors of rearrest during hospitalisation that can be identified in the hours immediately after OHCA, (2) the association between rearrest and favourable long-term outcomes, and (3) the predictors of favourable long-term outcomes in rearrest patients. MethodsConditional multivariable logistic regression analyses were performed using the Korean Hypothermia Network prospective registry data, which included details of adult OHCA patients treated with targeted temperature management at 22 teaching hospitals in South Korea. ResultsAmong the 1,233 patients, 260 (21.1%) experienced rearrest. Of the 192 patients resuscitated from first rearrest, 33 (17.2%) achieved 6-month favourable outcomes. Arrhythmia, heart failure, ST-segment elevation, lower initial Glasgow coma scale (GCS) motor score, higher initial lactate level, and antiarrhythmic drug use within 1 h were independently associated with rearrest. Higher lactate level and antiarrhythmic drug use were associated with shockable first rearrest, while arrhythmia, heart failure, ST-segment elevation, and lower GCS motor score were associated with non-shockable first rearrest. Rearrest was independently associated with a lower likelihood of 6-month favourable outcomes (P = 0.003). Initial shockable rhythm after OHCA, absence of diabetes, shorter cumulative time to restoration of spontaneous circulation, coronary angiography, and hypophosphataemia within 7 d were independently associated with 6-month favourable outcomes in the patients resuscitated from first rearrest. ConclusionsRearrest during hospitalisation after OHCA was inversely associated with 6-month favourable outcomes. We identified several risk factors for rearrest and prognostic factors for patients resuscitated from first rearrest.

Development and validation of visual grading system for stenosis in intracranial atherosclerotic disease on time-of-flight magnetic resonance angiography.

Although the overestimation problem of time-of-flight magnetic resonance angiography (TOF-MRA) applying the warfarin-aspirin symptomatic intracranial disease (WASID) method to assess intracranial arterial stenosis has often been suggested, no pertinent grading system for TOF-MRA has been developed. We aimed to develop and evaluate the performance of a visual grading system for intracranial arterial stenosis on TOF-MRA (MRAVICAST). This single-center cohort study analyzed prospective observational registry data from a comprehensive stroke center between January 2014 and February 2020. Patients with confirmed stenosis of the intracranial large arteries who underwent confirmative digital subtraction angiography (DSA) were included; a 4-point grading system was developed based on physical characteristics of TOF-MRA. The overall diagnostic accuracies of MRAVICAST for each grade, interobserver reproducibility, and positive predictive values for > 50% and > 70% stenoses were evaluated. We analyzed 132 segments with intracranial atherosclerotic stenosis from 71 patients (34 men and 37 women; mean age, 61.0 ± 15.25years; range, 21-89years). The overall diagnostic accuracy of MRAVICAST (93.9%, 124/132) was higher than that of MRAWASID (50.8%, 67/132) for each grade. The degree of stenosis did not differ significantly between MRAVICAST and DSAWASID (p = .849). Regarding reproducibility, MRAVICAST demonstrated excellent interobserver agreement (ICC, 0.989; 95% CI, 0.979-0.999). The positive predictive values of MRAVICAST for the diagnosis of > 50% and > 70% stenoses were 97.3% and 100.0%, respectively. The new intuitive grading system accurately and reliably determined the degree of stenosis in intracranial arterial atherosclerosis patients. MRAVICAST could be a versatile alternative to MRAWASID for evaluating intracranial arterial stenosis. • In this retrospective diagnostic study (sample: 132 stenotic segments), the overall accuracy of the visual grading system (MRAVICAST) was 94%, and positive predictive value for > 50% stenosis was 97%. • In the era of medical treatment for intracranial atherosclerotic stenosis, MRAVICAST could be a versatile alternative method to MRAWASID for evaluating intracranial arterial stenosis.

Development and validation of a prognostic tool: Pulmonary embolism short-term clinical outcomes risk estimation (PE-SCORE).

Develop and validate a prognostic model for clinical deterioration or death within days of pulmonary embolism (PE) diagnosis using point-of-care criteria. We used prospective registry data from six emergency departments. The primary composite outcome was death or deterioration (respiratory failure, cardiac arrest, new dysrhythmia, sustained hypotension, and rescue reperfusion intervention) within 5 days. Candidate predictors included laboratory and imaging right ventricle (RV) assessments. The prognostic model was developed from 935 PE patients. Univariable analysis of 138 candidate variables was followed by penalized and standard logistic regression on 26 retained variables, and then tested with a validation database (N = 801). Logistic regression yielded a nine-variable model, then simplified to a nine-point tool (PE-SCORE): one point each for abnormal RV by echocardiography, abnormal RV by computed tomography, systolic blood pressure < 100 mmHg, dysrhythmia, suspected/confirmed systemic infection, syncope, medico-social admission reason, abnormal heart rate, and two points for creatinine greater than 2.0 mg/dL. In the development database, 22.4% had the primary outcome. Prognostic accuracy of logistic regression model versus PE-SCORE model: 0.83 (0.80, 0.86) vs. 0.78 (0.75, 0.82) using area under the curve (AUC) and 0.61 (0.57, 0.64) vs. 0.50 (0.39, 0.60) using precision-recall curve (AUCpr). In the validation database, 26.6% had the primary outcome. PE-SCORE had AUC 0.77 (0.73, 0.81) and AUCpr 0.63 (0.43, 0.81). As points increased, outcome proportions increased: a score of zero had 2% outcome, whereas scores of six and above had ≥ 69.6% outcomes. In the validation dataset, PE-SCORE zero had 8% outcome [no deaths], whereas all patients with PE-SCORE of six and above had the primary outcome. PE-SCORE model identifies PE patients at low- and high-risk for deterioration and may help guide decisions about early outpatient management versus need for hospital-based monitoring.

Response Team Management of Acute Serious Pulmonary Embolism.

Response Team Management of Acute Serious Pulmonary Embolism.

Prospective Validation of the Use It or Lose It Paradigm: Secondary Analysis of Sub-Acute Dietary Outcomes by Eat and Exercise Status During Oropharyngeal Radiotherapy

<h3>Purpose/Objective(s)</h3> The investigators' 2013 use it or lose it study suggested functional benefit of two pharyngeal activities during head and neck radiotherapy (RT) – maintenance of oral intake (EAT) and swallowing exercise. EAT and EXERCISE independently associated with better odds of resuming a regular diet in long term survivorship and shorter duration of gastrostomy (FT) dependence. The prior work is limited by the retrospective nature of the dataset and historically far higher FT utilization. Our aim was to validate the previous work in a contemporary cohort of oropharyngeal cancer (OPC) survivors treated with RT using prospectively acquired validated outcome measures. <h3>Materials/Methods</h3> Endpoints included subacute diet after RT per the performance status scale for head and neck cancer (PSS-HN; solid food diet coded as ≥60 and no FT) and length of FT-dependence in days. Primary independent variables included oral intake (PO) at the end of RT (nothing per oral/NPO; partial PO; full PO) and swallow exercise adherence. Multiple linear regression and logistic regression models were analyzed adjusting for tumor location, baseline diet, chemotherapy and N and T stage. <h3>Results</h3> Analysis included 595 patients treated with primary radiotherapy (RT; 19% 111) /chemoradiation (CRT; 73% 434) or primary TORS + CRT (8% 50) for OPC (base of tongue/glossopharyngeal sulcus [46% 276]; tonsil [44% 263]; other [9% 56]). At the end of RT 9% of patients were NPO (55), 19% partial PO (115), 71% full PO (425). Statistically significant (<i>P</i> < 0.05) covariates for EAT and/or EXERCISE included tumor location, chemotherapy, N and T stage. Fifty-seven percent of patients (340) reported adherence to swallow exercises. Overall, 66% (394) of patients returned to a solid diet by 3-6 months. In adjusted models, EAT and EXERCISE during RT were independently, significantly (<i>P</i> < 0.01) associated with sub-acute diet recovery and FT duration. Patients who maintained full PO during RT were 2.5 times more likely to eat a solid diet by 3-6 months (OR 2.5, 95% CI: 1.3, 5) when compared to those who were NPO during treatment. Patients who exercised were 2.9 times more likely to return to a solid diet (OR 2.9, 95% CI: 1.8, 4.4) relative to those who did not. Thirty-eight percent of patients received a FT (231) and the median duration of tube dependence was 89 days (IQR: 28-142). EAT was independently associated with FT duration (<i>P</i> < 0.001, Coefficient, -123.6, 95% CI: -148.7, -98.4), while EXERCISE was not (<i>P</i> = .73). <h3>Conclusion</h3> These prospective registry data validate prior work that indicate independent benefit of EAT and swallowing EXERCISE adherence during RT on subacute functional outcomes. Patients who maintained full PO and/or exercise were more likely to eat solid foods by 3-6 months after treatment, while patients who EAT during treatment expectedly have the shortest feeding tube dependence.

Ten-Year Experience in Implementing Single-Fraction Lung SBRT for Medically Inoperable Early-Stage Lung Cancer.

To review 10 years of using single-fraction lung stereotactic body radiation therapy (SF-SBRT) for medically inoperable peripheral early-stage lung cancer. An institutional review board-approved prospective lung SBRT data registry was surveyed until the end of December 2019 for all patients receiving SF-SBRT with minimum 6-month follow-up. Doses used were either 34 Gy or 30 Gy. Outcomes of interest included rates of local failure and overall survival (OS), as well as treatment-related toxicity graded per Common Terminology Criteria for Adverse Events version 3.0. A total of 229 patients met the study criteria. Patient characteristics included female sex (55%); median age, 74.6 years (range, 47-94); and median Karnofsky Performance Status 80 (range, 50-100). Tumor characteristics included median diameter, 1.6 cm (range, 0.7-4.1); median positron emission tomography standardized uptake value maximum 6.1 (range, 0.8-24.3); and 63.6% of patients biopsied. SF-SBRT dose was 34 Gy in 72.1% cases and 30 Gy in 27.9%, with patient and tumor characteristics balanced between cohorts. Overall median follow-up times for 30 Gy and 34 Gy were 36.7 and 17.2 months, respectively (P < .0001). At analysis, 55.9% patients were alive. Two (0.9%) patients developed grade 3 toxicities, and none had grade 4/5 toxicities. Grades 1 to 2 pneumonitis and chest wall toxicity were seen in 7% and 12.7% patients, respectively. Median overall survival was 44.1 months. Rates of 2-year local, nodal, and distant failure were 7.3%, 9.4%, and 12.2%, respectively. There were no significant differences in outcomes by dose. This is the largest institutional series to date reporting on SF-SBRT outcomes for medically inoperable peripheral early-stage lung cancer and the first to report on a decade's experience in implementing this schedule. Outcomes from this analysis are comparable to published results from 2 randomized trials and validate the use of this schedule in routine practice. In the absence of phase 3 trials, this study should encourage increased use of SF-SBRT for inoperable tumors.

P05.02 Does Non-Small Cell Lung Cancer Histologic Type Influence Outcomes with Single-Fraction Stereotactic Body Radiotherapy?

For early stage medically inoperable Non-Small Cell Lung Cancer (NSCLC) treated with fractionated stereotactic body radiotherapy (SBRT), when compared by biologically equivalent dose (BED) higher rates of local failure have been associated with squamous (SqC) histology compared to adenocarcinoma (AC) for equivalent BEDs. We sought to determine if histology outcomes differed when using single-fraction schedules (SF-SBRT). An IRB-approved prospective lung SBRT data registry was surveyed from 12/2009 till 12/2019 for all patients (pts) receiving SF-SBRT with minimum 6-month follow up with biopsy-proven AC or SqC excluding bronchoalveolar and “NSCLC not-otherwise specified” cases. Doses employed were either 34 Gy, planned per RTOG 0915, or 30 Gy, planned per RPCI-124407. Outcomes of interest included cumulative incidence rates of local (LF), nodal (NF), and distant (DF) failure and overall survival (OS), as well as treatment-related toxicity graded per CTCAE version 3.0. 229 SF-SBRT pts treated over 10 years had a 2-year LF rate of 7.28%. For this analysis 113 (49.3%) met study’s pathology criteria and had a 2-year LF rate of 8.41%. No association was seen between histology type and the SF-SBRT dose given: 65 pts (57.5%) had AC, of these 19 (29.2%) and 46 (70.8%) received 30 Gy and 34 Gy, respectively. Of 48 SqC pts (42.5%), 17 (35.4%) and 31 (64.6%) received 30 Gy and 34 Gy, respectively. Median follow up was 22.9 months. Patient characteristics were balanced between histologies. Median tumor size was 1.9 cm and 2.05 cm for AC and SqC, respectively. When comparing tumor features for each histology or by dose group, there were no significant (NS) differences including specifically tumor distance from the chest wall. Comparing total Ac vs. SqC cohorts, 2-year LF rates in % were 7.32 vs. 9.64, respectively (p=0.9805). In %, 2-year LF, NF, DF and OS rates for AC for 30 Gy and 34 Gy, respectively, were 10.84 vs. 6.41; 10.53 vs. 16.24; 15.79 vs. 13.04; 77.9 vs.71.2 (all NS). In %, 2-year LF, NF, DF, and OS rates for SqC for 30 Gy and 34 Gy, respectively, were 11.76 vs. 8.08; 5.88 vs. 17.94; 23.53 vs. 9.68; 70.6 vs. 77.1 (all NS). There were no grade 4/5 toxicities and NS differences in any other toxicity rate by histology or dose. For AC pts, pneumonitis rates were: 4 pts (6.2%) with grades 1-2; chest wall toxicity rates were: 7pts (10.8%) with grade 1-2 and 1 (1.5%) with grade 3. For SqC, pneumonitis rates were: 4 pts (8.3%) with grade 1-2 rates pneumonitis; chest wall toxicity rates were: 10 (20.8%) with grade 1-2 only. SqC LF rates are similar to AC’s with either SF-SBRT schedule and no significant differences were seen for other outcomes or for toxicity profiles by histology and dose. This suggests equivalent efficacy for SF-SBRT doses independent of NSCLC histology

Importance of In-Hospital Prospective Registry and Infectious Endocarditis Heart Team to Monitor and Improve Quality of Care in Patients with Infectious Endocarditis.

Aim: To investigate the value of prospective in-hospital registry data and the impact of an infectious endocarditis heart team approach (IEHT) on improvement in quality of care and monitor outcomes in hospitalized patients with IE. Methods: Between December 2014 and the end of 2019, 160 patients were hospitalized in one centre with the definite diagnosis of infectious endocarditis (IE) and entered in a prospective registry. From 2017, an IEHT was introduced. Propensity score matching was used to assess the impact of an IEHT approach on clinical outcomes. Results: Median age was 72.5 y (62.75–80.00), diabetes was present in 33.1%, chronic kidney disease in 27.5%, COPD in 17.5%, and a history of ischaemic heart disease in 30.6%. Prosthetic valve IE was observed in 43.8% and device-related IE in 16.9% of patients. Staphylococcus (37.5%) was the most frequent pathogen followed by streptococcus (24.4%) and enterococcus (23.1%). Overall, 30-day and 1-year mortality were 19.4% and 37.5%, respectively. The introduction of prospective data collection and IE heart team was associated with a trend towards reduction of adjusted 1-year mortality (26.5% IEHT vs. 41.2% controls, p = 0.0699). An IEHT clinical decision-making approach was independently associated with a shorter length of stay (p = 0.04). Conclusions: Use of a prospective registry of IE coupled with a heart team approach was associated with more efficient patient management and a trend towards lower mortality. Prospective data collection and dedicated IEHT have the potential to improve patient care and clinical outcomes.

Development and Validation of an Arterial Pressure-Based Cardiac Output Algorithm Using a Convolutional Neural Network: Retrospective Study Based on Prospective Registry Data.

BackgroundArterial pressure-based cardiac output (APCO) is a less invasive method for estimating cardiac output without concerns about complications from the pulmonary artery catheter (PAC). However, inaccuracies of currently available APCO devices have been reported. Improvements to the algorithm by researchers are impossible, as only a subset of the algorithm has been released.ObjectiveIn this study, an open-source algorithm was developed and validated using a convolutional neural network and a transfer learning technique.MethodsA retrospective study was performed using data from a prospective cohort registry of intraoperative bio-signal data from a university hospital. The convolutional neural network model was trained using the arterial pressure waveform as input and the stroke volume (SV) value as the output. The model parameters were pretrained using the SV values from a commercial APCO device (Vigileo or EV1000 with the FloTrac algorithm) and adjusted with a transfer learning technique using SV values from the PAC. The performance of the model was evaluated using absolute error for the PAC on the testing dataset from separate periods. Finally, we compared the performance of the deep learning model and the FloTrac with the SV values from the PAC.ResultsA total of 2057 surgical cases (1958 training and 99 testing cases) were used in the registry. In the deep learning model, the absolute errors of SV were 14.5 (SD 13.4) mL (10.2 [SD 8.4] mL in cardiac surgery and 17.4 [SD 15.3] mL in liver transplantation). Compared with FloTrac, the absolute errors of the deep learning model were significantly smaller (16.5 [SD 15.4] and 18.3 [SD 15.1], P<.001).ConclusionsThe deep learning–based APCO algorithm showed better performance than the commercial APCO device. Further improvement of the algorithm developed in this study may be helpful for estimating cardiac output accurately in clinical practice and optimizing high-risk patient care.

Place de la radiothérapie de la tumeur primitive et/ou des métastases du cancer de la prostate oligométastatique

Oligometastatic prostate cancer is among the most studied oligometastatic cancers in the literature. However few prospective studies have assessed stereotactic body radiotherapy (SBRT) for prostate cancer oligometastases. Two randomised phase II trials show a progression-free survival benefit compared with observation. Prospective registry data show very good local control and low toxicity too. Inclusion in ongoing trials should be strongly encouraged to define the role of SBRT in addition to systemic therapy. Radiation therapy to the primary tumour has been studied in randomised trials and provides an overall survival benefit in patients with low metastatic burden. The benefit is inversely correlated with the number of bone lesions using conventional imaging, up to three metastases. Radiotherapy to the primary tumour is recommended by the learned societies for patients with low metastatic burden. Its role in combination with second generation anti androgen therapy needs to be clarified.

Prevalence of sarcopenia in idiopathic dropped head syndrome patients is similar to healthy volunteers

Dropped head syndrome (DHS) exhibits cervical deformity due to weakness of the cervical extensor group, and sarcopenia is characterized by progressive and systemic reduction in skeletal muscle mass. These clinical finding are associated with reduced activity of daily living, reduced quality of life, and increased risk of mortality. We collected and reviewed prospective registry data for 16 patients with idiopathic DHS continuously collected without dropping out and 32 healthy individuals who matched their gender and age. The prevalence of sarcopenia and body composition data were compared. There were no differences in the prevalence of sarcopenia, appendicular muscle mass, and leg muscle mass between DHS patients and the healthy elderly. Trunk muscle mass in DHS patients was significantly lower than that in healthy individuals. A significant correlation was found between appendicular muscle mass and trunk muscle mass in healthy subjects but not in DHS patients. Sarcopenia was not associated with the onset of idiopathic DHS. The prevalence of sarcopenia was not high in patients with idiopathic DHS due to the preservation of their appendicular skeletal muscle mass. Patients with DHS were characterized by a significant loss of trunk muscle mass that may be related to the disease but not aging.

Immune Checkpoint Inhibitors in the Aged.

Large phase III trials have established the benefit of checkpoint blockade across multiple tumor types, but patient representation is limited in some subgroups including the aged population. There are several changes in the immune system that occur with age (termed immunosenescence) that could potentially limit efficacy in aged populations. Despite the concerns stated above, available evidence from prospective trials, retrospective cohorts, and registry data suggest that elderly patients achieve similar benefit with immune checkpoint blockade in comparison to the general population and do not have increased toxicity. However, as patients age, they are at higher risk of developing a decline in multiple physiologic systems (including the immune system) and reduced ability to recover from illness. Clinical evidence shows that patients who have a poor performance status have inferior outcomes and limited clinical benefit from checkpoint blockade. Clinicians should take an individualized approach that accounts for each patient's health status rather than considering age alone when determining who should be offered checkpoint blockade therapy.

High Neutrophil-Lymphocyte Ratio Predicts Post-stroke Cognitive Impairment in Acute Ischemic Stroke Patients.

Background and Aims: Systemic inflammation is associated with an increased risk of cognitive impairment and dementia, but the associations between them in stroke patients are less clear. We examined the impact of systemic inflammation represented as the neutrophil-lymphocyte ratio (NLR) on the development of post-stroke cognitive impairment (PSCI) and domain-specific cognitive outcomes 3-month after ischemic stroke.Methods: Using prospective stroke registry data, we consecutively enrolled 345 participants with ischemic stroke whose cognitive functions were evaluated 3-month after stroke. Their cognition was assessed with the Korean version of the Vascular Cognitive Impairment Harmonization Standards and the Korean-Mini Mental Status Examination. PSCI was defined as a z-score of < -2 standard deviations for age, sex, and education adjusted means in at least one cognitive domain. The participants were categorized into five groups according to the quintiles of NLR (lowest NLR, Q1). The cross-sectional association between NLR and PSCI was assessed using multiple logistic regression, adjusting for age, sex, education, vascular risk factors, and stroke type.Results: A total of 345 patients were enrolled. The mean age was 63.0 years and the median NIHSS score and NLR were 2 [1–4] and 2.26 [1.65–2.91], respectively. PSCI was identified in 71 (20.6%) patients. NLR was a significant predictor for PSCI both as a continuous variable (adjusted OR, 1.14; 95% CI, 1.00–1.31) and as a categorical variable (Q5, adjusted OR, 3.26; 95% CI, 1.17–9.08). Patients in the Q5 group (NLR ≥ 3.80) showed significantly worse performance in global cognition and in visuospatial and memory domains.Conclusions: NLR in the acute stage of ischemic stroke was independently associated with PSCI at 3 months after stroke, and high NLR was specifically associated with cognitive dysfunction in the memory and visuospatial domains. Thus, systemic inflammation may be a modifiable risk factor that may influence cognitive outcomes after stroke.

A Prospective Multi-Centered Registry Is Feasible in Sickle Cell Disease: Globin Regional Network for Data and Discovery (GRNDaD)

Background: Multi-centered longitudinal observational and interventional trials over five decades have shifted SCD from a disease of childhood to a disease of young and middle-aged adults, with an average life expectancy extending into the fifth decade. However, the aging SCD patient, who may have faced early mortality decades ago, now faces novel, complex, and uncharacterized disease manifestations in an era of fragmented care and little coordination. Single-center studies, limited to local institutional data sets, lack sufficient breadth to inform evidence-based clinical guidelines, and the natural history of the patient with SCD in the current era is not known. Web-based data collection and the electronic health record (EHR) have the potential to transform SCD care in the US. Using these tools, providers at multiple academic health centers together developed a multi-centered prospective database to characterize the expanding transition population and adult cohort in the modern era. Our objective is to demonstrate the feasibility of this prospective collaborative data network, the (GRNDaD) registry.Methods: GRNDaD is recruiting adult and pediatric patients at four sites (Baltimore, Cleveland, Milwaukee, and Oakland, Ca.). Through an iterative process using existing registries at the participating sites and broadly validated measures (PhenX), a set of variables were agreed upon by the site investigators and created in REDCap. The full registry has 117 unique variables from the medical record, 72 of which are mandatory during annual updates. Survey data, including ASCQ-Me and the brief pain inventory, are available for direct patient entry. A detailed codebook with variable definitions has been developed. The registry includes an output template that provides patient specific routine health maintenance information for review during clinical care. Here, we report on 166 participants with a minimum dataset entered over 6 months, estimated to be 15% of the cumulative population at our sites. All lab studies entered are those measured at a routine follow-up visit. Ttests and chi -square were used to compare differences in lab values and complications between those with sickle cell anemia (SCA) and variant sickle hemoglobinopathies.Results: 471 patients consented to the registry, with <5% refusal (n=18). Those with full data in the registry includes 118 patients with phenotypic SCA, with an average age of 35.4 years. There are 48 patients with sickle variants: 27 with SC, 18 with Sβ+ Thalassemia, and 3 others, with an average age of 38.5 years. 48% of participants had documentation of pneumococcal vaccination. Notably, 82% of patients with SCA are on disease modifying therapy. Likely as a consequence, LDH values do not differ significantly between SCA and variant SCD in GRNDaD, which is not seen in other registry reports. Lab values and disease modifying therapy can be seen in Tables 1 and 2.Conclusions: These data represent care provided at the four comprehensive sickle programs involved in this project. Two additional sites are joining GRNDaD in late 2017, and the goal is to continue to expand. Using a web-available user-friendly portal, prospective registry data can be collected in a timely fashion at multiple centers. Currently data are extracted manually, but code is being developed to extract data directly from the EHR to improve efficiency. This will provide a unique snapshot of the current state of care of large groups of individuals with SCD. Registry participation is well received by potential subjects. One limitation identified early is that vaccinations may be provided outside of the comprehensive center (in primary care clinics) and so alternative strategies may be needed to reliably collect this data. Patient-specific data output from GRNDaD, for use clinically, is being optimized. Over time, as we collect data on important outcomes, we anticipate that GRNDaD will allow the recognition of novel phenotypic subpopulations and risk profiles, and will optimize clinical management, therapeutic product development, and quality assurance for our patients. [Display omitted] DisclosuresLanzkron:Pfizer: Research Funding; Global Blood Therapeutics: Research Funding; Bayer: Research Funding; HRSA: Research Funding; Prolong: Research Funding; PCORI: Research Funding. Field:NKT Therapeutics: Honoraria, Research Funding; Astellas: Research Funding; Prolong Pharmaceuticals: Research Funding; Incyte: Research Funding. Hoppe:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Little:Hemex Health: Equity Ownership.

Lupus, vaccinations and COVID-19: What we know now.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus causing Coronavirus disease 2019 (COVID-19), has had a huge impact on health services, with a high mortality associated with complications including pneumonia and acute respiratory distress syndrome. Patients with systemic lupus erythematosus (SLE) are at increased risk of viral infections, and recent data suggests they may be at an increased risk of poor outcomes with COVID-19. This may be particularly true for those on rituximab or high dose steroids. A huge international effort from the scientific community has so far resulted in the temporary authorisation of three vaccines which offer protection against SARS-CoV-2, with over 30 other vaccines being evaluated in ongoing trials. Although there has historically been concern that vaccines may trigger disease flares of SLE, there is little convincing evidence to show this. In general lupus patients appear to gain good protection from vaccination, although there may be reduced efficacy in those with high disease activity or those on immunosuppressive therapies, such as rituximab or high dose steroids. Recent concerns have been raised regarding rare clotting events with the AstraZeneca/Oxford vaccine and it is currently unknown whether this risk is higher for those patients with secondary antiphospholipid syndrome. With the possibility of annual COVID vaccination programmes in the future, prospective data collection and registries looking at the effect of vaccination on SLE disease control, the incidence of COVID-19 in SLE patients and severity of COVID-19 disease course would all be useful. As mass vaccination programmes begin to roll out across the world, we assess the evidence of the use of vaccines in SLE patients and in particular vaccines targeting SARS-CoV-2.

Prognostic Value of the Time-to-Positivity in Blood Cultures from Septic Shock Patients with Bacteremia Receiving Protocol-Driven Resuscitation Bundle Therapy: A Retrospective Cohort Study.

Introduction: To evaluate the prognostic value of the time-to-positivity in patients with culture-positive septic shock. Methods: Retrospective study using a prospective data registry was performed at the emergency department of a tertiary hospital. Consecutive adult patients with septic shock (N = 2499) were enrolled between 2014 and 2018. Bacteremia was defined using blood cultures, and viral and fungal pathogens were excluded. The primary outcome was the 28-day mortality. Results: In 803 (46.7%) septic shock patients with bacteremia, median TTP was 10.1 h. The most prevalent isolated bacterial pathogens were Escherichia coli (40.8%) and Klebsiella (23.4%). Although the TTP correlated with a higher sequential organ failure assessment score (Spearman’s rho = −0.12, p < 0.01), it showed no significant difference between the 28-day survivors and non-survivors (10.2 vs. 9.4 days, p = 0.35). In subgroup analysis of the Escherichia coli and Klebsiella bacteremia cases, a shorter TTP showed prognostic value for predicting the 28-day mortality. The optimal TTP cut-off for Escherichia coli and Klebsiella was 10 h and 8 h, respectively. Conclusions: The prognostic value of the TTP in septic shock patients receiving bundle therapy may be limited and its clinical interpretation should only be made on a pathogen-specific basis.

Central sensitization inventory in endometriosis.

A key clinical problem is identifying the patient with endometriosis whose pain is complicated by central nervous system sensitization, where conventional gynecologic treatment (eg, hormonal therapy or surgery) may not completely alleviate the pain. The Central Sensitization Inventory (CSI) is a questionnaire previously validated in the chronic pain population. The objective of this study was an exploratory proof-of-concept to identify a CSI cutoff in the endometriosis population to discriminate between individuals with significant central contributors (identified by central sensitivity syndromes [CSS]) to their pain compared to those without. We analyzed a prospective data registry at a tertiary referral center for endometriosis, and included subjects aged 18 to 50 years with endometriosis who were newly or re-referred to the center in 2018. The study sample consisted of 335 subjects with a mean age of 36.0 ± 7.0 years. An increasing number of CSS was significantly correlated with dysmenorrhea, deep dyspareunia, dyschezia, and chronic pelvic pain scores (P < 0.001), and with the CSI score (0-100) (r = 0.731, P < 0.001). Receiver operating characteristic analysis indicated that a CSI cutoff of 40 had a sensitivity of 78% (95% CI: 72.7%-84.6%) and a specificity of 80% (95% CI: 70.3%-84.5%) for identifying a patient with endometriosis with ≥3 CSS. In the group with CSI ≥ 40, 18% retrospectively self-reported pain nonresponsive to hormonal therapy and 40% self-reported daily pain, compared with 6% and 20% in the CSI < 40 group (P = 0.003 and 0.002, respectively). In conclusion, a CSI ≥ 40 may be a practical tool to help identify patients with endometriosis with pain contributors related to central nervous system sensitization.

High Chloride Burden and Clinical Outcomes in Critically Ill Patients With Large Hemispheric Infarction.

Background: In general, disease severity has been found to be associated with abnormal chloride levels in critically ill patients, but hyperchloremia is associated with mixed results regarding patient-centered clinical outcomes. We aimed to investigate the impact of maximum serum chloride concentration on the clinical outcomes of critically ill patients with large hemispheric infarction (LHI).Methods: We conducted a retrospective observational cohort study using prospective institutional neurocritical care registry data from 2013 to 2018. Patients with LHIs involving over two-thirds of middle cerebral artery territory, with or without infarction of other vascular territories, and a baseline National Institutes of Health Stroke Scale score of ≥13 were assessed. Those with a baseline creatinine clearance of <15 mL/min and required neurocritical care for <72 h were excluded. Primary outcome was in-hospital mortality. Secondary outcomes included 3-month mortality and acute kidney injury (AKI) occurrence. Outcomes were compared to different maximum serum chloride levels (5 mmol/L increases) during the entire hospitalization period using multivariable logistic regression analyses.Results: Of 90 patients, 20 (22.2%) died in-hospital. Patients who died in-hospital had significantly higher maximum serum chloride levels than did those who survived up to hospital discharge (139.7 ± 8.1 vs. 119.1 ± 10.4 mmol/L; p < 0.001). After adjusting for age, sex, and Glasgow coma scale score, each 5-mmol/L increase in maximum serum chloride concentration was independently associated with an increased risk of in-hospital mortality (adjusted odds ratio (aOR), 4.34; 95% confidence interval [CI], 1.98–9.50; p < 0.001). Maximum serum chloride level was also an independent risk factor for 3-month mortality (aOR, 1.99 [per 5 mmol/L increase]; 95% CI, 1.42–2.79; p < 0.001) and AKI occurrence (aOR, 1.57 [per 5 mmol/L increase]; 95% CI, 1.18–2.08; p = 0.002).Conclusions: High maximum serum chloride concentrations were associated with poor clinical outcomes in critically ill patients with LHI. This study highlights the importance of monitoring serum chloride levels and avoiding hyperchloremia in this patient population.

Criteria for failure and worsening after surgery for lumbar spinal stenosis: a prospective national spine registry observational study

Background contextCriteria for success after surgical treatment of lumbar spinal stenosis (LSS) have been defined previously; however, there are no clear criteria for failure and worsening after surgery as assessed by patient-reported outcome measures (PROMs). PurposeWe aimed to quantify changes in standard PROMs that most accurately identified failure and worsening after surgery for LSS. Study design /settingRetrospective analysis of prospective national spine registry data with 12-months follow-up. Patient sampleWe analyzed 10,822 patients aged 50 years and older operated in Norway during a decade, and 8,258 (76%) responded 12 months after surgery. Outcome measures (PROMs)We calculated final scores, absolute changes, and percentage changes for Oswestry Disability Index (ODI), Numeric Rating Scale (NRS) for back and leg pain (0-10), and EuroQol-5D (EQ-5D). These 12 PROM derivates were compared to the Global Perceived Effect (GPE), a 7-point Likert scale. MethodsWe used ODI, NRS back and leg pain, and EQ-5D 12 months after surgery to identify patients with failure (no effect) and worsening (clinical deterioration). The corresponding GPE at 12-months was graded as failure (GPE=4-7) and worsening (GPE=6-7) and used as an external criterion. To quantify the most accurate cut-off values corresponding to failure and worsening, we calculated areas under the curves (AUCs) of receiver operating characteristics (ROC) curves for the respective PROM derivates. ResultsMean (95% CI) age was 68.3 (68.1 – 68.5) years, and 52% were females. There were 1,683 (20%) failures, and 476 (6%) patients were worse after surgery. The mean (95% CI) pre- and postoperative ODIs were 39.8 (39.5 – 40.2) and 23.7 (23.3 – 24.1), respectively. At 12 months, the mean difference (95% CI) in ODI was 16.1 (15.7 – 16.4), and the mean (95% CI) percentage improvement 38.8% (37.8 – 38.8).The PROM derivates identified failure and worsening accurately (AUC>0.80), except for the absolute change in EQ-5D. The ODI derivates were most accurate to identify both failure and worsening. We found that less than 20% improvement in ODI most accurately identified failure (AUC=0.89 [95% CI: 0.88 to 0.90]), and an ODI final score of 39 points or more most accurately identified worsening (AUC =0.91 [95% CI: 0.90 – 0.92]). ConclusionsIn this national register study, ODI derivates were most accurate to identify both failure and worsening after surgery for degenerative lumbar spinal stenosis. We recommend use of ODI percentage change and ODI final score for further studies of failure and worsening in elective spine surgery.