Spinal Fractures in Ankylosing Spondylitis: Patterns, Management, and Complications in the United States – Analysis of Latest Nationwide Inpatient Sample Data

Objective: Ankylosing spondylitis (AS) is a rheumatic inflammatory disease marked by chronic inflammation of the axial skeleton. This condition, particularly when severe, can lead to increased risk of vertebral fractures attributed to decreased ability of the stiffened spinal column to sustain normal loads. However, little focus has been placed on understanding the locations of spinal fractures and associated complications and assessing the correlation between these. In this review, we aim to summarize the complications and treatment patterns in the United States in AS patients with spinal fractures, using the latest Nationwide Inpatient Sample (NIS) database (2016–2018).Methods: We analyzed the NIS data of years 2016–2018 to compare the fracture patterns and complications.Results: A total of 5,385 patients were included. The mean age was 71.63 years (standard deviation [SD], 13.21), with male predominance (83.8%). The most common population is Whites (77.4%), followed by Hispanics (7.9%). The most common fracture level was thoracic level (58.3%), followed by cervical level (38%). Multiple fracture levels were found in 13.3% of the patients. Spinal cord injury (SCI) was associated with 15.8% of the patients. The cervical level had a higher proportion of SCI (26.5%), followed by thoracic level (9.2%). The mean Elixhauser comorbidity score was 4.82 (SD, 2.17). A total of 2,365 patients (43.9%) underwent surgical treatment for the fractures. The overall complication rate was 40.8%. Respiratory complications, including pneumonia and respiratory insufficiency, were the predominant complications in the overall cohort. Based on the regression analysis, there was no significant difference (p = 0.45) in the complication rates based on the levels. The presence of SCI increased the odds of having a complication by 2.164 times (95% confidence interval, 1.722–2.72; p ≤ 0.001), and an increase in Elixhauser comorbidity score predicted the complication and in-hospital mortality rate (p ≤ 0.001).Conclusion: In conclusion, AS patients with spinal fractures have higher postoperative complications than the general population. The most common fracture location was thoracic in our study, although it differs with few studies, with SCI occurring in 1/6th of the patients.

Assessment of Metabolic Dysfunction in Sepsis in a Retrospective Single-Centre Cohort

Objective. Our primary aim was to assess selected metabolic dysfunction parameters, both independently and as a complement to the SOFA score, as predictors of short-term mortality in patients with infection admitted to the intensive care unit (ICU). Methods. We retrospectively enrolled all consecutive adult patients admitted to the eight ICUs of Lille University Hospital, between January 2015 and September 2016, with suspected or confirmed infection. We selected seven routinely measured biological and clinical parameters of metabolic dysfunction (maximal arterial lactatemia, minimal and maximal temperature, minimal and maximal glycaemia, cholesterolemia, and triglyceridemia), in addition to age and the Charlson’s comorbidity score. All parameters and SOFA scores were recorded within 24 h of admission. Results. We included 956 patients with infection, among which 295 (30.9%) died within 90 days. Among the seven metabolic parameters investigated, only maximal lactatemia was associated with higher risk of 90-day hospital mortality in SOFA-adjusted analyses (SOFA-adjusted OR, 1.17; 95%CI, 1.10 to 1.25; p < 0.001 ). Age and the Charlson’s comorbidity score were also statistically associated with a poor prognosis in SOFA-adjusted analyses. We were thus able to develop a metabolic failure, age, and comorbidity assessment (MACA) score based on scales of lactatemia, age, and the Charlson’s score, intended for use in combination with the SOFA score. Conclusions. The maximal lactatemia level within 24 h of ICU admission is the best predictor of short-term mortality among seven measures of metabolic dysfunction. Our combined “SOFA + MACA” score could facilitate early detection of patients likely to develop severe infections. Its accuracy requires further evaluation.

National Norms for the Elixhauser and Charlson Comorbidity Indexes Among Hospitalized Adults

Multimorbidity has become the defining focus of in-patient geriatric clinical practice and research. Comorbidity assessment burden is often completed using the Elixhauser (ECI) and Charlson comorbidity indexes (CCI), which can predict mortality risk, hospital length of stay and readmission, and healthcare utilization. Yet, the national norms for ECI and CCI have not been reported. Therefore, this study aimed to report comorbidity score national norms of hospitalized patients based on age, race, and sex. Using the 2017 US National Inpatient Sample, ICD-10 coding data from 7,159,694 adult patient’s (≥18years) was abstracted to calculate ECI and CCI scores. Scores were stratified into 5-year age increments from age 45-89. Adults aged&lt;45 and &gt;89 were included in the analysis, however not age-stratified. Overall mean comorbidity score for the population using the ECI was 2.76 (95%CI 2.76, 2.76) and CCI was 1.22 (95% CI 1.22, 1.22). Mean scores for both indexes increased with age until age 90, and this increase was independent of race and sex (all p-values&lt;0.001). Some individual comorbidities increased with age including congestive heart failure and dementia, while others including diabetes and chronic obstructive pulmonary disease increased with age but peaked between 60-74 years and declined in older age. Importantly, a report of US national norms for comorbidity burden among hospitalized adults can provide a reference for determining if clinical and research populations have greater or lesser comorbidity than typical hospitalized adults for their age, race, and sex.

Factors Associated with Changes in the Objectively Measured Physical Activity among Japanese Adults: A Longitudinal and Dynamic Panel Data Analysis

Background: Factors of dynamic changes associated with changes in the objectively measured physical activity have not been well understood. We aimed to 1) evaluate the longitudinal change in the physical activity trajectory associated with age according to sex and to 2) determine the dynamic changes factors associated with the change in physical activity-related variables across a wide age range among Japanese adults.Methods: This longitudinal prospective study included 689 Japanese adults (3914 measurements) aged 26–85 years, whose physical activity data in at least two surveys were available. Physical activity-related variables, such as intensity (inactive, light [LPA; 1.5 to 2.9 metabolic equivalents (METs)], moderate to vigorous [MVPA; ≥3.0 METs]), total energy expenditure (TEE), physical activity level (PAL), and step count, were evaluated using a validated triaxial accelerometer. The inactive times were calculated by subtracting the sum of sedentary (<1.5 METs) and non-wearing periods from 1440 minutes. Statistical analysis involved the latent growth curve models and random-effect panel data multivariate regression analysis. The covariates for multivariate analysis included the age, sex, region, body mass index, waist/hip ratio, comorbidity score, smoking status, alcohol intake, energy intake, diet quality score, hemoglobin, heart rate, hand grips, leg power, and trunk flexibility.Results: During a mean follow-up period of 6.8 years, physical activity was assessed 5.1 times in men and 5.9 times in women on average. The profiles for the inactive time, LPA (only men), MVPA, step count, PAL, and TEE showed clear curvature, indicating an accelerated rate of change around the age of 70. In contrast, other variables exhibited minimal or no curvature over the age span. The MVPA trajectory was positively associated with alcohol consumption, hand grips, leg power, and trunk flexibility, and negatively associated with age, local area, BMI, comorbidity score, and heart rate over time.Conclusions: Our results indicated that the physical activity trajectory showed clear curvature, accelerated rate of change around the age of 70, and determined physical health and fitness and BMI as dynamic changes factors associated physical activity changes. These findings may be useful to help support populations to achieve and maintain the recommended level of physical activity.

Combined Resistance to Ceftolozane-Tazobactam and Ceftazidime-Avibactam in Extensively Drug-Resistant (XDR) and Multidrug-Resistant (MDR) Pseudomonas aeruginosa: Resistance Predictors and Impact on Clinical Outcomes besides Implications for Antimicrobial Stewardship Programs

A retrospective case-control study was conducted at Modena University Hospital from December 2017 to January 2019 to identify risk factors and predictors of MDR/XDR Pseudomonas aeruginosa (PA) isolation with resistance to ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T), and of mortality among patients infected/colonized. Among 111 PA isolates from clinical/surveillance samples, 60 (54.1%) were susceptible to both drugs (S-CZA-C/T), while 27 (24.3%) were resistant to both (R-CZA-C/T). Compared to patients colonized/infected with S-CZA-C/T, those with R-C/T+CZA PA had a statistically significantly higher Charlson comorbidity score, greater rate of previous PA colonization, longer time before PA isolation, more frequent presence of CVC, higher exposure to C/T and cephalosporins, longer hospital stay, and higher overall and attributable mortality. In the multivariable analysis, age, prior PA colonization, longer time from admission to PA isolation, diagnosis of urinary tract infection, and exposure to carbapenems were associated with the isolation of a R-C/T+CZA PA strain, while PA-related BSI, a comorbidity score > 7, and ICU stay were significantly associated with attributable mortality. C/T and CZA are important therapeutic resources for hard-to-treat PA-related infections, thus specific antimicrobial stewardship interventions should be prompted in order to avoid the development of this combined resistance, which would jeopardize the chance to treat these infections.

The Association of Antibiotic (ATB) exposure prior to immune checkpoint inhibitor (ICI) treatment on early emergency room and hospitalization utilization: A population-based study.

304 Background: ICIs are becoming a common therapeutic option for many solid tumors. Prior studies have shown that ATB exposure can negatively impact ICI outcomes through gut microbiome changes leading to poorer overall survival; however, less is known about the potential impact of ATB exposure on toxicities from ICI. We undertook a population-based retrospective cohort study in patients receiving ICIs to evaluate the impact of ATB exposure on early acute care use, defined as emergency department visit or hospitalization, within 30 days of initiation of ICI therapy. Methods: Administrative data was utilized to identify a cohort of cancer patients > 65 years of age receiving ICIs from June 2012 to October 2018 in Ontario, Canada. We linked databases deterministically to obtain socio-demographic and clinical co-variates, ATB prescription claims and acute care utilization. Patients were censored if they died within 30 days of initiating ICI therapy. The impact of ATB exposure within 60 days prior to starting ICI on early acute care use was evaluated using multi-variable logistic regression models, adjusted for age, gender, rurality, recent hospitalization within 60 days prior to starting ICI and comorbidity score. Results: Among 2737 patients (median age 73 years), 43% received Nivolumab, 41% Pembrolizumab and 13% Ipilimumab, most commonly for lung cancer (53%) or melanoma (34%). Of these patients, 19% had ATB within 60 days prior to ICI with a median ATB treatment duration of 9 days (SD = 13). 647 (25%) patients had an acute care episode within 30 days of starting ICIs; 182 (7%) patients passed away within 30 days without acute care use and were censored from further analyses. Any ATB exposure within 60 days prior to ICI was associated with greater likelihood of acute care use (aOR = 1.34 95% CI [1.07-1.67] p = 0.01). A dose effect was seen based on weeks of ATB exposure within 60 days prior to ICI (aOR = 1.12 per week [1.04-1.21] p = 0.004) and early acute care use. ATB class analysis identified that exposure to penicillins (aOR = 1.54 [1.11-2.15] p = 0.01) and fluoroquinolones (aOR = 1.55 [1.11-2.17] p = 0.01) within 60 days of starting ICIs were associated with a greater likelihood of acute care use, while there was no significant association between cephalosporin exposure and early acute care use (p > 0.05). Conclusions: Exposure to ATBs, specifically fluoroquinolones and penicillins, prior to ICI therapy is associated with greater likelihood of hospitalization or emergency room visits within 30 days after initiation of ICIs, even after adjustment for relevant co-variates including age, comorbidity score and recent hospitalization prior to ICI initiation. Further studies are required to better understand the mechanisms of recent ATB exposure on early acute care use among patients receiving ICIs.

Subtyping Hyperchloremia among Hospitalized Patients by Machine Learning Consensus Clustering

Background and Objectives: Despite the association between hyperchloremia and adverse outcomes, mortality risks among patients with hyperchloremia have not consistently been observed among all studies with different patient populations with hyperchloremia. The objective of this study was to characterize hyperchloremic patients at hospital admission into clusters using an unsupervised machine learning approach and to evaluate the mortality risk among these distinct clusters. Materials and Methods: We performed consensus cluster analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 11,394 hospitalized adult patients with admission serum chloride of >108 mEq/L. We calculated the standardized mean difference of each variable to identify each cluster’s key features. We assessed the association of each hyperchloremia cluster with hospital and one-year mortality. Results: There were three distinct clusters of patients with admission hyperchloremia: 3237 (28%), 4059 (36%), and 4098 (36%) patients in clusters 1 through 3, respectively. Cluster 1 was characterized by higher serum chloride but lower serum sodium, bicarbonate, hemoglobin, and albumin. Cluster 2 was characterized by younger age, lower comorbidity score, lower serum chloride, and higher estimated glomerular filtration (eGFR), hemoglobin, and albumin. Cluster 3 was characterized by older age, higher comorbidity score, higher serum sodium, potassium, and lower eGFR. Compared with cluster 2, odds ratios for hospital mortality were 3.60 (95% CI 2.33–5.56) for cluster 1, and 4.83 (95% CI 3.21–7.28) for cluster 3, whereas hazard ratios for one-year mortality were 4.49 (95% CI 3.53–5.70) for cluster 1 and 6.96 (95% CI 5.56–8.72) for cluster 3. Conclusions: Our cluster analysis identified three clinically distinct phenotypes with differing mortality risks in hospitalized patients with admission hyperchloremia.

A comparison of comorbidity measures for predicting mortality after elective hip and knee replacement: A cohort study of data from the National Joint Registry in England and Wales

Background The risk of mortality following elective total hip (THR) and knee replacements (KR) may be influenced by patients’ pre-existing comorbidities. There are a variety of scores derived from individual comorbidities that can be used in an attempt to quantify this. The aims of this study were to a) identify which comorbidity score best predicts risk of mortality within 90 days or b) determine which comorbidity score best predicts risk of mortality at other relevant timepoints (30, 45, 120 and 365 days). Patients and methods We linked data from the National Joint Registry (NJR) on primary elective hip and knee replacements performed between 2011–2015 with pre-existing conditions recorded in the Hospital Episodes Statistics. We derived comorbidity scores (Charlson Comorbidity Index—CCI, Elixhauser, Hospital Frailty Risk Score—HFRS). We used binary logistic regression models of all-cause mortality within 90-days and within 30, 45, 120 and 365-days of the primary operation using, adjusted for age and gender. We compared the performance of these models in predicting all-cause mortality using the area under the Receiver-operator characteristics curve (AUROC) and the Index of Prediction Accuracy (IPA). Results We included 276,594 elective primary THRs and 338,287 elective primary KRs for any indication. Mortality within 90-days was 0.34% (N = 939) after THR and 0.26% (N = 865) after KR. The AUROC for the CCI and Elixhauser scores in models of mortality ranged from 0.78–0.81 after THR and KR, which slightly outperformed models with ASA grade (AUROC = 0.77–0.78). HFRS performed similarly to ASA grade (AUROC = 0.76–0.78). The inclusion of comorbidities prior to the primary operation offers no improvement beyond models with comorbidities at the time of the primary. The discriminative ability of all prediction models was best for mortality within 30 days and worst for mortality within 365 days. Conclusions Comorbidity scores add little improvement beyond simpler models with age, gender and ASA grade for predicting mortality within one year after elective hip or knee replacement. The additional patient-specific information required to construct comorbidity scores must be balanced against their prediction gain when considering their utility.

Analysis of patterns of care and benefit of thoracic radiotherapy for patients with stage IV NSCLC in the immunotherapy-era from a national hospital-based registry.

9123 Background: Metastatic non-small cell lung cancer (mNSCLC) has classically been treated with platinum-doublet chemotherapy. Recent studies have established immunotherapy as an integral part of therapy for mNSCLC without targetable mutations. There are limited data on the role of consolidative thoracic radiotherapy (TRT) for patients with mNSCLC in the immunotherapy-era. A secondary analysis of KEYNOTE-001 showed significant improvement in overall survival in patients who received radiotherapy with pembrolizumab compared to patients not previously receiving radiotherapy. Methods: We queried the National Cancer Database (NCDB) for patients with metastatic presentation, stage IVA/IVB non-small cell lung cancer between the ages of 18-90 years treated between 2012-2017 with a combination of chemotherapy, immunotherapy, and thoracic radiotherapy. Patients with unknown treatment status, follow up time, or vital status were excluded. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between treatment groups utilizing log-rank testing. A 3:1 nearest-neighbor propensity-score matching was performed utilizing clinical and demographic covariates to reduce the impact of potential confounders of overall survival on the probability of receipt of TRT. Cox proportional hazards regression was used to identify predictors of overall survival. Results: A total of 81,382 patients were identified that met inclusion criteria. The median age was 68 (18-90) years. The majority of patients (n = 51,681, 64%) had chemotherapy, while 7,929 (10%) patients received immunotherapy, and 15,984 (20%) received TRT. The median follow-up was 6.18 (range 0-76.9) months. For the entire cohort of patients receiving immunotherapy, 2 year OS was 29.4% with TRT compared to 32.7% without. Following propensity matching by age, sex, race, and comorbidity score, a total number of 4,264 patients receiving immunotherapy were matched. The 2 year OS was 27.7% in patients receiving TRT and immunotherapy vs. 22.2% in patients with immunotherapy alone (p = 0.004). On multivariable analysis receipt of TRT was a significant predictor of OS after adjustment for age, race, comorbidity score, sex, and median income (p = 0.0003, HR 0.87, 95% CI 0.80 - 0.94). For patients receiving BED10 > 39 Gy (equivalent to 30 Gy in 10 fractions), 2 year OS was significantly improved at 37.0% vs 18.1% (p < 0.0001). Conclusions: In patients with mNSCLC, the addition of TRT to immunotherapy is associated with improved overall survival at 2 years. Receipt of a higher BED10 is associated with further improved survival. Selection of mNSCLC patients receiving immunotherapy for TRT approaching definitive doses warrants further investigation. Data from prospective, randomized trials may better elucidate this benefit and identify a potential mechanism.

Characteristics and comorbidities of veterans treated with enzalutamide or abiraterone.

e17022 Background: Prostate cancer (PCa) is the most common male malignancy and is the fourth leading cause of cancer-related death in males worldwide. Enzalutamide (ENZ) and Abiraterone (AA) are used in the treatment of castrate resistant PCa after androgen deprivation therapy (ADT), however these agents have not been directly compared. These drugs have various adverse effects with different mechanisms of action and may be selected based on comorbid conditions. In this study, we aim to identify patient characteristics and comorbidities of patients treated with ENZ versus AA. Methods: Patients treated with AA or ENZ between September 10, 2014 and June 3, 2017 were identified in the Veterans Health Administration and followed until April 2020. Only patients with a pathologic diagnosis of PCa and treatment with ADT prior to AA or ENZ were included. Age at initiation of treatment, Elixhauser comorbidity score, PSA at initiation of AA or ENZ, Gleason score at diagnosis, treatment with ADT, docetaxel, and cabazitaxel was collected. Months of filled prescriptions were used to determine length of treatment. Results: Of 2575 patients, 1095 (42.5%) were initially treated with ENZ, 1480 (57.5%) with AA, and 1330 (51.7%) received both agents. Overall, 756 (29.4%) of patients were of black race. Docetaxel was used in 32.3% of patients and cabazitaxel in 11.7% of patients, with no differences between ENZ or AA cohorts. There were no significant differences in time from pathologic diagnosis to initial ADT therapy, or subsequently to treatment with ENZ or AA in either group. Furthermore, there were no differences in PSA (n = 1243, median AA 33.7 vs ENZ 30.7, p = 0.538) or Gleason scores (n = 1816, mean AA 7.85 vs ENZ 7.94, p = 0.142). Patients initially treated with ENZ compared to AA were older (mean 74.2 vs. 73.7 years, p = 0.032), had higher mean comorbidity score (7.1 vs. 6.7, p = 0.002), and had a longer duration of first treatment (median 10.5 months vs. 9.0 months, p < 0.001). As a second agent, ENZ also had a longer duration of treatment (median 5.0 vs. 4.2 months, p < 0.001). Patients treated initially with ENZ were more likely to have heart failure (18.2% vs. 13.7%, p = 0.002), cardiac arrhythmia (42.1% vs 36.6%, p = 0.004), valvular disease (13.7% vs 10.3%, p = 0.009), peripheral vascular disorders (26.8% vs 22.7%, p = 0.016), uncomplicated hypertension (86.8% vs 83.6%, p = 0.024), complicated hypertension (20.2% vs 16.9%, p = 0.033), uncomplicated diabetes (43.9% vs 37.4%, p = 0.001), complicated diabetes (26.0% vs 19.9%, p = 0.000), renal failure (28.3% vs 22.6%, p = 0.001). Conclusions: Overall, we found that patients initially treated with ENZ were older and had higher rates of cardiovascular disease and diabetes compared to those initially treated with AA. Assessment of comorbidities may be helpful in treatment selection to facilitate personalized medicine in prostate cancer, prevent adverse events, and improve outcomes.