Median Charlson Comorbidity Index Research Articles

Immune related adverse events: Timing, identification patterns, and impact on survival.

e14705 Background: Increased use of immune checkpoint inhibitors (ICI) has resulted in a rise in immune related adverse events (irAEs), which many non-oncology clinicians may underrecognize. Controversy exists surrounding whether irAE presence has an impact on survival. Our primary goal was to evaluate the timing between detection to diagnosis of irAE, and determine the department responsible for making the irAE diagnosis. We also assess the incidence of single vs multisystem irAEs, impact of irAE on survival, and assess whether standard irAEs (s-irAEs) those diagnosed within 90 days of initial ICI administration vs delayed irAE (d-irAEs) those diagnosed >90 days impacts survival. Methods: We performed an IRB approved retrospective study of patients 18 years and older who received ICIs for a malignancy at Gundersen Health System between January 1, 2011 and December 31, 2021. Statistical analysis included Chi-square, Fisher’s Exact, and Wilcoxon rank sum tests and Kaplan-Meier survival analysis. All analysis was completed in R version 4.2.3 with a p-value <0.05 considered significant. Results: Our study included 664 patients who were 99.6% white, 60% male, and an average age of 67 years. Median Charlson Comorbidity Index was 10. There were 245 (36.8%) patients with at least 1 irAE, and 62 (9.3%) with a multisystem irAE. While 28 (11%) irAEs were initially detected by non-oncology providers, only 10 (4.1%) irAEs were diagnosed by a non-oncology department. Median time (days) from symptoms to diagnosis was 3 for those diagnosed in non-oncology departments and 0 for those diagnosed in oncology (p<0.01). A total of 142 (58.0%) s-irAEs were detected with grades 1-2-3-4-5 accounting for 21.1%-54.9%-19.7%-1.4%-2.8%. There were 103 (42.0%) d-irAEs with grades 1-2-3-4-5 accounting for 23.3%-53.4%-17.4%-5.8%-0%. Of the d-irAEs, 17 (16.5%) occurred >365 days from initiation of ICI. The 3 most common irAE in this patient population included thyroiditis (34%), dermatitis (21%), and pneumonitis (12%). Our data shows a significant survival difference in patients with an irAE compared to those without (p<.01). No significant survival difference was noted between patients who had s-irAE vs d-irAE (p=.069). Conclusions: Our results show that irAEs may be underrecognized and often not formally diagnosed by non-oncology providers. However, median time to diagnosis is short within this context. This may be due to non-oncology providers feeling uncomfortable making the final decision, which emphasizes the importance for oncologists to finalize irAE diagnoses. We did see a positive impact on survival with irAE presence. While oncologists often clinically expect irAEs to surface within the first 6-10 weeks of treatment, our study demonstrates that 42% of irAEs occur after 12 weeks from ICI initiation. There is no difference in survival between s-irAEs vs d-irAEs, and overall grade distribution between these two groups appears similar.

Immune-related adverse events in patients treated with immunotherapy according to corticosteroid exposure.

e14709 Background: Patients with cancer require treatment with corticosteroids for multiple reasons, including prevention of chemotherapy-related side effects. Although corticosteroid use has been associated with lower efficacy of immune checkpoint inhibitors (ICI) in some studies, whether corticosteroid exposure affects the presence and severity of immune-related adverse events (irAEs) remains unclear. Methods: Retrospective single-center study of patients diagnosed with solid tumors treated with ICI. Eligible patients were those who received at least one cycle of ICI and had at least 1 month of follow-up post-ICI initiation. Patient data were extracted from electronic medical records. Comparisons between groups were made based on steroid exposure (defined as the administration of >10 mg of prednisone or its equivalent for >10 days within a 30-day period or at any point during ICI treatment, excluding steroid treatment for irAEs). Associations between variables were assessed using independent samples T-test, Chi-square, and Fisher’s exact tests. Results: We included 135 patients (mean age 61 years, SD 13); 72 (54%) were male. Forty-two (31%) had been exposed to steroids (mean prednisone equivalent of 427 mg, SD 298). Most patients received ICI as palliative treatment for advanced disease (105/135; 78%), primarily as first-line therapy (79/105; 75%). Patients exposed to corticosteroids were more likely to have received ICI with chemotherapy (76% vs 1%, p<0.001), were younger (56 vs. 63 years, p=0.009), more likely to be female (62% vs. 39, p=0.014), and had lower median Charlson Comorbidity Index scores (2 vs. 3, p=0.026). Steroid-exposed patients were more likely to have employed ICI in the neoadjuvant or adjuvant settings (36 vs. 16%, p=0.024) or as third or subsequent line therapy (26 vs. 8%, p=0.044). There were no statistically significant differences in the frequency of irAEs of any grade based on steroid exposure (31% vs 41%, p=0.252). However, patients who were exposed to steroids were significantly less likely to delay or suspend ICI (10% vs. 32%, p=0.005). No other parameters were associated with the rate or severity of irAEs. Conclusions: Our findings suggest that corticosteroid exposure does not increase the frequency of irAEs in patients treated with ICI, but it is associated with a reduced likelihood of discontinuing ICI due to irAEs. These observations suggest that corticosteroids may play a beneficial role in managing patients undergoing immunotherapy, particularly in sustaining treatment continuity despite irAEs. This study underscores the need for further investigation into optimal steroid use strategies to enhance patient outcomes with immunotherapy, especially in situations when they are commonly prescribed, such as premedication for chemotherapy.

Extracorporeal Membrane Oxygenation for Acute Lung Injury in Idiopathic Inflammatory Myopathies-A Potential Lifesaving Intervention.

Idiopathic inflammatory myopathies (IIM) can present with acute IIM-related lung injury and respiratory failure, leading to a high mortality risk in intensive care units (ICU). Extracorporeal membrane oxygenation (ECMO) in acute respiratory distress syndrome can be lifesaving. We aimed to report a case series of IIM patients that received ECMO. Patients with IIM from tertiary care centers in Belgium, Canada, Denmark, United States, and Sweden who underwent ECMO were reviewed to describe clinical characteristics, disease outcomes and hospitalization course. Clinical characteristics at admission and during ICU stay including ECMO complications and mortality causes were summarized. The study included 22 patients (50% female, mean±SD age at admission 47 ± 12 years) with anti-MDA5 positive dermatomyositis (68%), anti-synthetase syndrome (14%), polymyositis (9%), overlap myositis (5%) and non-MDA5 dermatomyositis (5%). Patients had low comorbidity scores and 46% had received immunosuppression before their ICU admission. Eight (36%) patients died in the ICU, six (27%) were bridged to recovery and eight (36%) were bridged to transplant. When comparing patients bridged to recovery and those who died in the ICU, those who died were older (p= 0.03) and had higher median Charlson comorbidity index scores (p= 0.05). Both groups had similar frequencies of ECMO-related complications (33% vs 50%, p= 0.94). In the patients exposed to ECMO in this case series, 14 were successfully bridged to recovery or transplant, while 8 died in the ICU. Large studies are needed to collect data on clinical outcomes in patients with IIM-ILD exposed to ECMO to identify the best candidates for the intervention.

#807 Presepsin and procalcitonin levels are associated with acute kidney injury in sepsis patients

Abstract Background and Aims Acute kidney injury (AKI) is a leading cause of death in patients with sepsis. Presepsin is a novel biomarker which has been used to predict sepsis and the outcomes of sepsis. Presepsin was also demonstrated in a small clinical trial to be associated with AKI in sepsis patients. Procalcitonin is a biomarker which was well-studied in sepsis and AKI patients. We aimed to study the association of presepsin and procalcitonin with AKI and outcomes of AKI in sepsis patients. Method We conducted a multicenter prospective trial in eight tertiary-care hospitals in Thailand. We included suspected sepsis patients aged 18 years or older who entered the emergency room during January 2021 to July 2022. We excluded patients with pregnancy, previous trauma, and postcardiac arrest. We also excluded dialysis patients and patients with estimated glomerular filtration rate (eGFR) less than 30 ml/min/1.73 m2 from our study. We measured blood presepsin and procalcitonin at day 0, 3 and 7 along with other investigation for usual intensive care of sepsis. We calculated the level of presepsin and procalcitonin that could distinguish between sepsis patients with and without AKI. We also analyzed whether presepsin and procalcitonin were associated between severity of AKI determined by Kidney Disease: Improving Global Outcomes (KDIGO) staging of AKI. Results We recruited 621 patients who was diagnosed sepsis at emergency department. AKI was diagnosed in 246 patients (39.6%). Of these AKI patients, maximal KDIGO stage of AKI were stage 1, 2 and 3 in 140 (56.9%), 64 (26.0%) and 42 (17.1%) patients, respectively. The median age was 70.1 years with 54.6% was male patients. The median BMI was 21.9 kg/m2. The median Charlson comorbidity index (CCI) was 5 (IQR 4-7). The median presepsin level in AKI patients was 1012 pg/mL (IQR 528-1719 pg/mL), which was significantly higher (P < 0.001) than the median presepsin level in non-AKI patients, which was 594 pg/mL (IQR 337-1138 pg/mL). The median procalcitonin level in AKI patients was 1.24 ng/mL (IQR 0.22-6.06 ng/mL), which was significantly higher (P < 0.001) than the median presepsin level in non-AKI patients, which was 0.50 ng/mL (IQR 0.09-2.34 ng/mL). The cut-point of presepsin level and the procalcitonin level of ≥795 pg/mL and ≥0.9 ng/mL was associated with AKI in sepsis patients respectively. The higher level of presepsin and procalcitonin also significantly associated with higher KGIDO staging of AKI as shown in Fig. 1. However, the mortality rate in both groups were not significantly different (24.0% in AKI group vs. 21.1% in non-AKI group, P = 0.39) Conclusion To date, this is one of the largest studies to evaluate the association between presepsin level, procalcitonin level and AKI in sepsis patients. The presepsin level and the procalcitonin level of ≥795 pg/mL and ≥0.9 ng/mL was associated with AKI in sepsis patients respectively.

Abstract PO4-15-05: Genomic characterization and molecular predictive biomarkers for chemotherapy in a real-world population with metastatic triple-negative breast cancer

Abstract Background: The genomic landscape of metastatic triple-negative breast cancer (mTNBC) in a real-world population is poorly defined and despite recent advances in precision oncology, molecular biomarkers for chemotherapy are largely lacking. The presence of specific genomic alterations and alterations in oncogenic pathways have the potential to provide prognostic as well as predictive information for chemotherapy, which remains the backbone treatment strategy for mTNBC. Methods: We conducted next-generation sequencing (NGS) with the FoundationOne CDx panel on tissue from the primary tumor and/or metastasis of 112 consecutive patients with mTNBC that were treated between 1998 and 2019 at 4 different Swedish hospitals. Every genomic alteration was, if applicable, subdivided into 1 of 10 canonical oncogenic pathways and noted for its involvement in the homologous recombination pathway (HRP). Frequently altered genes and pathways were then correlated with overall survival (OS) and evaluated regarding their association with progression-free survival (PFS) and response rate (RR) in patients treated with different chemotherapy agents. Tumor samples of patients with rapid progression or exceptional response to chemotherapy underwent exploratory comparison with regards to frequently altered genes and pathways and known clinical prognostic factors were compared between the two patient groups. Results: After excluding 15 patients due to insufficient quantity/quality of tumor tissue or absence of clinical data, 97 patients were analyzed. The median age at diagnosis of metastatic disease was 61 (range: 28-90), 80 % had visceral disease and 26 % received platinum-based chemotherapy in the first line setting. The most frequently altered genes were: TP53 (82 %), RAD21 (25 %), PIK3CA (23 %), MYC (22 %) and BRCA 1 or 2 (16 %). The most frequently altered pathways were TP53 (86 %), PI3K (60 %), RTK/RAS (47 %) and cell cycle (36 %). In total, 26 % of patients had an alteration in the HRP. None of the most frequently occurring genomic alterations were associated with OS. Variants of clinical significance in the HRP and BRCA1/BRCA2 genes were associated with a longer PFS in patients treated with platinum-based chemotherapy in the first line setting (HR 0.12-0.84 and 0.12-0.92). Exceptional responders to chemotherapy exhibited a more favorable clinical profile than rapid progressors (median age 51.5 vs 66.5, median Charlson comorbidity index 0.5 vs 3) whereas some numerical difference in the genomic profiling in terms of genomic alterations in MYC and RAS/RTK pathways (more often in exceptional responders) could be observed. Conclusions: We found no genomic alteration with prognostic significance in a cohort of mTNBC patients treated with chemotherapy in a real-world setting. Somatic variants of clinical significance in BRCA 1 and 2 and other HRP-related genes seem to define subgroups of patients with mTNBC that respond favorably to platinum-based chemotherapy. Further research into the genomic landscape of tumors from patients with rapid progression or exceptional response to specific treatment strategies can provide insights into mechanisms of resistance and identify new predictive biomarkers. Citation Format: Erik Olsson, Henrik Lindman, Evangelos Digkas, Viktoria Thurfjell, Haidar Mir Ali, Ute Krüger, Anna-Karin Wennstig, Marie Sundqvist, Antonis Valachis. Genomic characterization and molecular predictive biomarkers for chemotherapy in a real-world population with metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-15-05.

A Multidisciplinary Approach to End-Stage Limb Salvage in the Highly Comorbid Atraumatic Population: An Observational Study.

Background: The use of free tissue transfer (FTT) is efficacious for chronic, non-healing lower extremity (LE) wounds. The four pillars of managing patient comorbidities, infection control, blood flow status, and biomechanical function are critical in achieving successful limb salvage. The authors present their multidisciplinary institutional experience with a review of 300 FTTs performed for the complex LE limb salvage of chronic LE wounds. Methods: A single-institution, retrospective review of atraumatic LE FTTs performed by a single surgeon from July 2011 to January 2023 was reviewed. Data on patient demographics, comorbidities, preoperative management, intraoperative details, flap outcomes, postoperative complications, and long-term outcomes were collected. Results: A total of 300 patients who underwent LE FTT were included in our retrospective review. Patients were on average 55.9 ± 13.6 years old with a median Charlson Comorbidity Index of 4 (IQR: 3). The majority of patients were male (70.7%). The overall hospital length of stay (LOS) was 27 days (IQR: 16), with a postoperative LOS of 14 days (IQR: 9.5). The most prevalent comorbidities were diabetes (54.7%), followed by peripheral vascular disease (PVD: 35%) and chronic kidney disease (CKD: 15.7%). The average operative LE FTT time was 416 ± 115 min. The majority of flaps were anterolateral thigh (ALT) flaps (52.7%), followed by vastus lateralis (VL) flaps (25.3%). The immediate flap success rate was 96.3%. The postoperative ipsilateral amputation rate was 12.7%. Conclusions: Successful limb salvage is possible in a highly comorbid patient population with a high prevalence of diabetes mellitus, peripheral vascular disease, and end-stage renal disease. In order to optimize patients prior to their LE FTT, extensive laboratory, arterial, and venous preoperative testing and diabetes management are needed preoperatively. Postoperative monitoring and long-term follow-up with a multidisciplinary team are also crucial for long-term limb salvage success.

Clinical effectiveness of cefiderocol for the treatment of bloodstream infections due to carbapenem-resistant Acinetobacter baumannii during the COVID-19 era: a single center, observational study.

We assessed the clinical effectiveness of cefiderocol (CFDC) in comparison with colistin (COL) for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infections (BSI). Retrospective cohort study including adults with CRAB-BSI. Outcomes were mortality, clinical cure and adverse events during therapy. The average treatment effect of CFDC compared to COL was weighted with the inverse-probability treatment weight (IPTW). Overall, 104 patients were included (50 CFDC, 54 COL), median age 66.5 years, median Charlson Comorbidity Index 5, septic shock in 33.6% of patients. Primary BSI accounted for 43.3% of cases, followed by ventilator-associated pneumonia (VAP) (26%), catheter-related BSI (20.2%) and hospital-acquired pneumonia (HAP) (9.6%). Although not significantly, mortality at all time points was lower for CFDC than COL, while clinical cure was higher in CFDC than COL (66% vs. 44.4%, p = 0.027). Adverse events were more frequent in COL than CFDC-group (38.8% vs. 10%, p < 0.0001), primarily attributed to acute kidney injury (AKI) in the COL group. Patients with bacteremic HAP/VAP treated with CFDC had a significant lower 30-d mortality and higher clinical cure than COL (p = 0.008 and p = 0.0008, respectively). Increment of CCI (p = 0.005), ICU (p = 0.025), SARS-CoV2 (p = 0.006) and ECMO (p < 0.0001) were independently associated with 30-d mortality, while receiving CFDC was not associated with survival. CFDC could represent an effective and safe treatment option for CRAB BSI, especially in patients with bacteremic HAP/VAP and frail patients where the risk of acute renal failure during therapy should be avoided.

Mortality after emergency department discharge: an analysis of 453599 cases.

To quantify and analyze mortality in patients who die within 30 days of discharge home from a hospital emergency department (ED). All patients older than 14 years of age who were discharged home from the ED of a tertiary care hospital over a 5-year period were included. We collected age, sex, and other demographic variables, as well as the Charlson Comorbidity Index (CCI). The outcome variables of interest were 7-day and 30-day mortality and cause of death. Deaths were classified as expected and directly related to the emergency, expected but not directly related, unexpected and directly related, and unexpected and not directly related. A death was classified as an adverse event if it was directly related to a problem of diagnosis or management in the ED, underestimation of severity, or complications of a procedure. Of 519312 patients attended in the ED, 453 599 were discharged home. Of those discharged, 148 died at home within 7 days (32.63 deaths/100 000 discharges) and 355 died within 30 days (78.48 deaths/100 000 discharges). One hundred thirteen deaths (31.8%) were expected and related to the emergency 24.91/100 000), 169 (47.6%) were expected but unrelated 37.26/100 000), 4 (1.1%) were unexpected and related 1.10/100000), and 69 (19.4%) were unexpected and unrelated 15.21/100000). Deaths were considered adverse events related to ED care in 24.2% of the cases. Underestimation of severity was responsible for the highest proportion (10.7%) of such deaths. The median age of patients who died was 83 years, and the median Charlson comorbidity index (CCI) was 6. The most common cause of death was a malignant tumor (23.0%), followed by congestive heart failure (20.2%) and atherosclerotic cardiovascular disease (13.2%). Unexpected deaths related to ED care were significantly related to a higher proportion of adverse events related to diagnosis (P = .001), management (P = .004), and underestimation of severity (P .001). Early deaths after discharge home from a hospital ED occured in patients of advanced age with concomitant conditions. The main clinical settings were neoplastic and cardiovascular disease. Seven-day and 30-day mortality rates directly related to the emergency visit were low. Adverse events related to ED care played a role in about a quarter of the deaths after discharge.

Real-world evaluation of imipenem/cilastatin/relebactam across US medical centres

We assessed 160 patients who received imipenem/cilastatin/relebactam for ≥2 days. At treatment initiation, the median Charlson Comorbidity Index was 5, 45% were in the intensive care unit, and 19% required vasopressor support. The in-hospital mortality rate was 24%. These data advance our understanding of real-world indications and outcomes of imipenem/cilastatin/relebactam use.

The significance of monitoring respiratory sample cultures and polymerase chain reaction tests for detecting bacterial pathogens in severely and critically ill patients with COVID-19

Background. Bacterial superinfection is one of the most common and potentially lethal complications in severely and critically ill patients with COVID-19. Objectives. To determine the colonisation time frame and the spectrum of potential bacterial pathogens in respiratory samples from patients with severe and critical COVID-19, using routine culture and polymerase chain reaction (PCR) tests. Methods. A prospective observational study was conducted on patients aged ≥18 years with confirmed severe and critical COVID-19 who were admitted to or transferred to the intensive care unit (ICU). Respiratory samples were collected for microbial culture and PCR testing within the first 2 days after ICU admission/transfer, between days 3 and 6, and after 7 days of ICU stay. Results. A total of 82 patients, with a median (interquartile range) age of 74.5 (67.3 - 81.0) years and a median Charlson comorbidity index of 4 (3 - 5), were enrolled in the study. Colonisation with any pathogen was observed in 67% of patients, after a median of 4 (2 - 6) days in the ICU. On days 0 - 2 of the ICU stay, micro-organisms were detected in 18% of patients, with Klebsiella pneumoniae (without acquired antibiotic resistance) and methicillin-susceptible Staphylococcus aureus being most frequently identified. Later, Acinetobacter baumannii and carbapenem-resistant K. pneumoniae became the predominant micro-organisms, identified in nearly half of the patients. In 74% of the samples, the results of microbial culture and PCR tests were identical. In 17%, PCR revealed bacterial pathogens not identified by culture. Conclusion. Our study confirms that colonisation of the respiratory tract occurs early in the course of ICU stay. Superinfections are predominantly caused by multidrug-resistant Gram-negative bacteria.

Real-World Experience of Ceftobiprole for Community- and Hospital-Acquired Pneumonia from a Stewardship Perspective.

Ceftobiprole is a fifth-generation cephalosporin approved by European and American regulatory agencies for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). Ceftobiprole administration is useful in severe CAP as well as HAP where the potential is to save other β-lactams including carbapenems or linezolid/vancomycin in clinical practice. The aim of this study was to report the real-world evidence of ceftobiprole in patients with CAP and HAP in a single center. In this retrospective study, we included 159 patients with CAP or HAP: 105 (66%) had CAP and 54 (34%) had HAP. The median age was 70 years (IQR 60-77), the median Charlson Comorbidity Index was 5 (IQR 3-7.5) and baseline INCREMENT ESBL score was 8 (IQR 6-11). Ceftobiprole was mostly given as a combination treatment (77%) or as a carbapenem-sparing strategy (44%). There were no differences in mortality between shorter and longer duration of treatment (<7 days compared with ≥7 days (HR 1.02, C.I. 0.58-1.77, p = 0.93) or between first-line (HR 1.00, C.I. 0.46-2.17, p = 0.989) and second-line therapy. Ceftobiprole use in CAP or HAP in the real world is effective as a first- and second-line treatment as well as a carbapenem-sparing strategy. Further studies are needed to explore the full potential of ceftobiprole, including its real-world use in antimicrobial stewardship programs.

Patient Characteristics Impacting Adherence to Serial Observation for Vestibular Schwannomas.

To examine patient characteristics that impact serial observation adherence amongvestibular schwannoma (VS) patients. Retrospective chart review. Single tertiary care center. We selected for VS patients from 201 to 2020 who elected for serial observation as initial management. Patients under 18, with previous management, bilateral or intralabyrinthine VS, and neurofibromatosis type 2 were excluded. Demographics, tumor characteristics, and follow-up status were extracted. Single and multiple logistic regression was used to identify patient characteristics impacting follow-up. We identified 507 VS patients who chose serial observation as initial management. Most were female (56.0%), white (73.0%), and married (72.8%). The mean age was 59.3 and most had private insurance (56.4%). Median Charlson Comorbidity Index was 2.00. Mean pure tone audiometry (PTA) average was 41.7 Hz. Average tumor size was 9.04 mm. Of 507 patients, 358 (70.6%) returned for at least one follow-up. On multiple logistic regression analysis, patients with private insurance (odds ratio [OR]: 0.39, confidence interval [CI]: 0.22-0.68; P = .001), racial minority background (OR: 0.54, CI: 0.35-0.83; P = .005), worse PTA averages (OR: 0.99, CI: 0.98-1.00; P = .044), and older age at diagnosis (OR: 0.97, CI: 0.95-1.00; P = .038) were less likely to follow-up. Private health insurance, racial minority background, worse PTA average, and older age were associated with decreased follow-up amongadult VS patients electing serial observation. Patients with these characteristics may require additional support to ensure serial observation adherence.

The Association between Serum Level of Vitamin D and Inflammatory Biomarkers in Hospitalized Adult Patients: A Cross-Sectional Study Based on Real-World Data.

The association between vitamin D status and inflammation remains unclear in hospitalized patients. We performed the current study based on real-world data from two teaching hospitals. Serum level of vitamin D (assessed by 25-hydroxyvitamin D) was evaluated within 2 days after admission. All the patients were further classified into three groups: deficiency (<12 ng/mL), insufficiency (12-20 ng/mL), and adequate (≥20 ng/mL). White blood cell (WBC) count, serum level of C-reactive protein (CRP), and procalcitonin were also measured and used to evaluate inflammation. Other potential covariates were abstracted from medical records. Charlson comorbidity index (CCI) was calculated to assess the severity of disease. A total number of 35,528 hospitalized adult patients (21,171 men and 14,357 women) were included. The average age and BMI were 57.5 ± 16.2 years and 23.4 ± 3.7 kg/m2, respectively, while medium vitamin D level was 16.1 ng/mL (interquartile range: 11.4 ng/mL, 21.6 ng/mL) and median CCI was one point (interquartile range: 0 point, two points). The prevalence of deficiency and insufficiency was 28.0% and 40.5%. Multivariate linear regression model showed that serum level of vitamin D was significantly associated with WBC and CRP but not associated with procalcitonin. Each standard deviation (≈7.4 ng/mL) increase in vitamin D was associated with a decrease in WBC by 0.13 × 109/mL (95% CI: 0.2 × 109/mL, 0.06 × 109/mL) and 0.62 mg/L (95% CI: 0.88 mg/L, 0.37 mg/L) for CRP. Subgroup analysis and sensitivity analysis (excluding those whose eGFR <60 ml/min/1.73 m2, those whose daily calorie intake <1,000 kcal, and those who were recruited from Xin Hua hospital) generated similar results. The deficiency and insufficiency of vitamin D in the hospitalized adult patients was very common. However, the results should be interpreted with caution for limited representation of the whole inpatients. Low level of vitamin D was associated with inflammatory biomarkers, which provide the evidences to early intervention for lower the risk of infection.

Optimizing periprosthetic fracture management and in-hospital outcome: insights from the PIPPAS multicentric study of 1387 cases in Spain

BackgroundThe incidence of all periprosthetic fractures (PPF), which require complex surgical treatment associated with high morbidity and mortality, is predicted to increase. The evolving surgical management has created a knowledge gap regarding its impact on immediate outcomes. This study aimed to describe current management strategies for PPF and their repercussions for in-hospital outcomes as well as to evaluate their implications for the community.MethodsPIPPAS (Peri-Implant PeriProsthetic Survival Analysis) was a prospective multicentre observational study of 1387 PPF performed during 2021. Descriptive statistics summarized the epidemiology, fracture characteristics, management, and immediate outcomes. A mixed-effects logistic regression model was employed to evaluate potential predictors of in-hospital mortality, complications, discharge status, and weight-bearing restrictions.ResultsThe study encompassed 32 (2.3%) shoulder, 4 (0.3%) elbow, 751 (54.1%) hip, 590 (42.5%) knee, and 10 (0.7%) ankle PPF. Patients were older (median 84 years, IQR 77–89), frail [median clinical frailty scale (CFS) 5, IQR 3–6], presented at least one comorbidity [median Charlson comorbidity index (CCI) 5, IQR 4–7], were community dwelling (81.8%), and had outdoor ambulation ability (65.6%). Femoral knee PPF were most frequently associated with uncemented femoral components, while femoral hip PPF occurred equally in cemented and uncemented stems. Patients were managed surgically (82%), with co-management (73.9%), through open approaches (85.9%) after almost 4 days (IQR, 51.9–153.6 h), with prosthesis revision performed in 33.8% of femoral hip PPF and 6.5% of femoral knee PPF. For half of the patients, the discharge instructions mandated weight-bearing restrictions. In-hospital mortality rates were 5.2% for all PPF and 6.2% for femoral hip PPF. Frailty, age > 84 years, mild cognitive impairment, CFS > 3, CCI > 3, and non-geriatric involvement were candidate predictors for in-hospital mortality, medical complications, and discharge to a nursing care facility. Management involving revision arthroplasty by experienced surgeons favoured full weight-bearing, while an open surgical approach favoured weight-bearing restrictions.ConclusionsCurrent arthroplasty fixation check and revision rates deviate from established guidelines, yet full weight-bearing is favoured. A surgical delay of over 100 h and a lack of geriatric co-management were related to in-hospital mortality and medical complications. This study recommends judicious hypoaggressive approaches. Addressing complications and individualizing the surgical strategy can lead to enhanced functional outcomes, alleviating the economic and social burdens upon hospital discharge.Level of Evidence Level IV case series.Trial registration: registered at ClinicalTrials.gov (NCT04663893), protocol ID: PI 20-2041.Graphical abstract

Colon cancer survival in the elderly without curative surgery.

The aim of this study was to chart the natural history of elderly patients with colon cancer who are managed nonoperatively, with the primary outcome being life expectancy from diagnosis to death. This was a retrospective analysis of patients aged 80 years and above diagnosed with colon cancer in a tertiary care referral hospital in England between 1 January 2012 and 31 December 2017. Thirty-two patients were diagnosed with non-metastatic colon cancer and managed non-operatively. The median age of patients in this study was 86 years. The group had a median Charlson Comorbidity Index of 7 (range 6-12) and the median frailty score was 6 (range 3-8). Progression to metastatic disease was identified in two patients; two further patients showed locoregional progression of cancer and therefore required palliative surgical intervention. Survival of these patients ranged from 105 to 1,782 days with a median life expectancy of 586 days. Place of death was identified in 15/31 patients: 4 (27%) died in hospital, 12 (38%) died at home and 15 (47%) died in a nursing or residential home; data were missing for 1 patient (3%). Nonoperative management of elderly patients with colon cancer yields reasonable life expectancy and a low risk of life-threatening local complications.

Validation of the Oswestry Disability Index in Adult Spinal Deformity.

Retrospective cohort. To examine the validity of the Oswestry Disability Index (ODI) in patients with adult spinal deformity (ASD) treated with surgery. The ODI is a patient-reported outcome measure of low back pain and disability. Although nearly ubiquitous in ASD research, the measure has not been validated in this patient population. A registry of patients with ASD was queried for baseline and 1-year PROM data, including the ODI, the Scoliosis Research Society-22r (SRS-22r), and the Patient Reported Outcomes Measurement Information System-Pain Interference (PI) and Physical Function (PF) CATs. Internal reliability was assessed with Cronbach alpha, where values ≥0.7 are considered reliable. Validity was assessed with Spearman correlation coefficients calculated for the ODI against validated Patient-Reported Outcomes Measurement Information System (PROMIS)-PI and PF, and legacy measures SRS-Pain and SRS-Activity. Responsiveness to change was measured with the adjusted effect size. A total of 325 patients were enrolled, with 208 completing baseline and 1-year patient-reported outcome measures. The majority (149, 72%) were females and White (193, 93%), median Charlson Comorbidity Index 0 (interquartile range: 0-2). The majority of cases included sagittal plane deformity [mean T1PA: 24.2° (13.9)]. Cronbach alpha showed excellent internal reliability (baseline = 0.89, 1 yr = 0.90). ODI was valid, with strong correlations between PROMIS-PI, PROMIS-PF, SRS-Pain, and SRS-Activity at baseline and 1-year follow-up. All measures were responsive to change, with the ODI showing greater responsiveness than PROMIS-PI, PROMIS-PF, and SRS-Activity. The ODI is a valid measure of disability as measured by pain and function in patients with ASD. It is responsive to change in a manner not different from validated PROMIS-CAT or the SRS-22r legacy measure. It is multidimensional, however, as it assesses both pain and function simultaneously. It does not measure disability related to self-image and may not account for all disease-related disability in patients with ASD.

Evolution of Clinical Characteristics and Outcomes of Critically Ill Patients 90 Years Old or Older Over a 12-Year Period: A Retrospective Cohort Study.

The global population is aging, and the proportion of very elderly patients 90 years old or older in the ICU is expected to increase. The changes in the comorbidities and outcomes of very elderly patients hospitalized in the ICU that have occurred over time are unknown. Retrospective observational cohort study. ICUs at a single academic hospital in Germany. Ninety years old or older and admitted to the ICU between January 1, 2008, and April 30, 2019. None. Of the 92,958 critically ill patients, 1,108 were 90 years old or older. The study period was divided into two halves: January 1, 2008-August 30, 2013, and September 1, 2013-April 30, 2019. The number of patients 90 years old or older increased from the first period ( n = 391; 0.90% of total admissions) to the second period ( n = 717; 1.44%). The patients' demographic characteristics were similar between the both time periods. The median Charlson Comorbidity Index was higher during the first period (1 [interquartile range, 1-3]) than compared with the second time period (1 [0-2]; p = 0.052). The Simplified Acute Physiology Score (SAPS) II was higher during the first time period (38 [29-49]) than during the second period (35 [27-45]; p = 0.005). Vasopressor therapy was necessary in 40% ( n = 158) and 43% ( n = 310) of patients in each time period, respectively ( p = 0.363). Invasive mechanical ventilation was administered in 37% ( n = 146) and 34% ( n = 243) of patients in each time period, respectively ( p = 0.250). The median length of the ICU stay was significantly lower in the first time period than in the second time period (1.4 vs. 1.7 d; p = 0.002). The ICU (18% vs. 18%; p = 0.861) and hospital (31% vs. 29%; p = 0.395) mortality rates were comparable between the two groups. The 1-year mortality was significantly lower during the second time period than during the first time period (61% vs. 56%; p = 0.029). Cox regression analysis revealed that the SAPS II, medical cause of admission, mechanical ventilation requirement, and vasopressor use were associated with 1-year mortality. The number of patients 90 years old or older who were treated in the ICU has increased in recent years. While the patients' clinical characteristics and short-term outcomes have not changed significantly, the long-term mortality of these patients has improved in recent years.

A217 EVALUATING PREDICTIVE SCORING AND OUTCOMES OF PATIENTS DISCHARGED HOME FROM THE EMERGENCY DEPARTMENT WITH UPPER GASTROINTESTINGAL BLEEDING

Abstract Background Upper gastrointestinal bleed (UGIB) is a common emergency department (ED) presentation. The Glasgow-Blatchford Bleeding Score (GBS) is a validated tool for predicting UGIBs requiring admission for endoscopic evaluation. Utilization of GBS in Northern Ontario EDs may help risk stratify UGIB to decrease return to care. Aims This study aimed to evaluate factors and outcomes of patients discharged from the ED with suspected UGIB. Methods A total of 1,139 charts were identified with an ICD-10 ED diagnosis of gastrointestinal hemorrhage from 2016-2022. Of these, 92 charts met inclusion criteria. Patients admitted to hospital from the index ED visit, who were below the age of 18 years at the time of presentation, or with clinically suspected lower gastrointestinal hemorrhage were excluded. Patient were further grouped by place of residence if their primary address was within Thunder Bay city limits or not. Results There were 48 males (52%) with a median age of 58.7 (IQR 32.2) at presentation with UGIB to ED. The median (IQR) Charlson Comorbidity Index (CCI) and GBS were 3 (5) and 3 (6), respectively. The odds ratio for returning to the ED and being admitted for UGIB within sixty days was 4.07 times greater for patients from the region compared to Thunder Bay residents (95% CI 1.28–12.97). GBS was found to be significantly greater (p=0.048, Mann-Whitney U-Test) among seven patients who underwent emergent endoscopy from the ED and were discharged home. In univariate K-M survival analysis, the mean survival time to hospital admission at sixty days was 45 days among those with a presenting GBS score of ampersand:003E3, compared to 57 days when GBS was 3 or less (pampersand:003C0.005, log rank Mantel-Cox). After adjustment for age, sex, place of residence, and CCI, there was a 17% increase in the expected hazard for hospital admission at sixty days for each point increase in GBS (95% CI 1.03–1.34). Similarly, the expected hazard for follow-up hospital admission was 2.95 times higher (95% CI 1.11–7.85) in patients living outside Thunder Bay travelling to seek care. There were no statistically significant hazards identified between age, sex, or CCI and hospital admission (Cox proportional hazards model, p=0.001). Of patients admitted to hospital within sixty days of ED discharge (n=17), the median length of stay was five days with 56% requiring blood transfusion and 83% receiving endoscopy. Conclusions Higher GBS scores and residence outside of Thunder Bay increase the likelihood of revisit and admission to hospital for UGIB following ED discharge. Future research will aim to compare outcomes among larger urban centers. Funding Agencies NOAMA

Number of prescription medications and overall survival in veterans with metastatic hormone-sensitive prostate cancer.

68 Background: Robustassessment of comorbid conditions is essential to clinical care and the risk-stratification of patients for adverse events and death. Prescription medications may be a simple and readily available tool to estimate patient risk independent of established comorbidity indices, such as the Charlson Comorbidity Index (CCI). Clinicians have access to medication lists, facilitating assessment of comorbidities. We sought to examine the relationship between prescription medications and long-term outcomes in veterans treated for metastatic hormone-sensitive prostate cancer (mHSPC). Methods: We conducted a nationwide retrospective observational study of United States Veterans diagnosed with mHSPC in the Veterans Health Administration from 2010-2021. We determined the number of unique drugs and their respective Anatomic Therapeutic Chemical (ATC) Level One classes prescribed in the year prior to the initiation of treatment. Multivariable logistic regression and Cox proportional hazard modeling was used to assess the association between number of drugs with all-cause 90-day mortality and overall survival (OS) while accounting for covariates including age, CCI, body mass index, prostate specific antigen, and race. Results: Among 8,434 Veterans, a median (IQR) of 9 (5-14) unique medications and 5 (3-7) unique ATC medication classes were filled in the year prior to treatment. The mean age was 74.2 (SD 10.1) years, and 2,126 Veterans were black (25.2%). The median CCI was 3 (2.75-6). Increasing age was associated with increased CCI across age strata with mean CCI of 3.16 in age &lt;60, 3.76 in 60-70, 4.43 in 70-80, and 5.25 in 80+ (p&lt;0.001). Increasing age was associated with an increased number of unique medicines with mean 8.59 in age &lt;60, 9.53 in 60-70, 10.1 in 70-80, and 10.4 in 80+ (p&lt;0.001). There was no significant difference in the number of medications prescribed based on race. Veterans with 1-4 medicines had the longest average survival at 38.2 months compared to 5-9 medicines (33.1 months), 10-14 medicines (27.1 months), and 15+ medicines (22.0 months) (p&lt;0.001). After adjusting for relevant patient, tumor, and treatment factors, the number of medications and drug classes were each independently associated with increased mortality with adjusted HR (95% CI) of 1.03 (1.02-1.03) and 1.05 (1.04-1.07), respectively. Veterans treated with 5-9, 10-14, and 15+ medicines had an increased risk of death compared to Veterans on 1-4 medicines [aHR 1.11 (1.03-1.19); 1.29 (1.19-1.39); and 1.51 (1.39-1.65) respectively]. Conclusions: The number of prescription medications and drug classes are independently associated with OS in patients diagnosed with mHSPC, even after accounting for important covariates including age and CCI. Assessment of patient medications may provide a simple, yet reliable tool to assess comorbidities, risk of adverse events, and death.

Cardiovascular medications and overall survival in metastatic hormone-sensitive prostate cancer.

75 Background: The assessment of comorbid cardiovascular disease can predict health outcomes and may risk-stratify patients for adverse events and death. Current methods used to estimate patient risk, such as the Charlson Comorbidity Index (CCI), are based on International Classification of Diseases (ICD) codes, which are a poor indicator of severity and complexity of comorbid disease. Alternatively, the number of cardiovascular drugs could be an efficient tool for estimating patient risk. In this study, we examined the relationship between cardiovascular medications and survival in patients being treated for metastatic hormone-sensitive prostate cancer (mHSPC). Methods: A nationwide retrospective observational study of US Veterans with de novo mHSPC in the Veterans Health Administration between 2011-2021 with at least 1 prescription medicine of any class. We determined the number of cardiovascular drugs from Anatomic Therapeutic Chemical (ATC) drug class C prescribed in the year prior up to 14 days before initiation of treatment. Multivariable logistic regression and Cox proportional hazard modeling was used to assess the association between number of drugs with overall survival (OS) while accounting for important covariates including age, body-mass index (BMI), prostate specific antigen (PSA), CCI, race, and weight change. Results: Among 7,875 veterans, a median (IQR) of 2 (1-4) unique cardiovascular medications were filled in the year prior to treatment. The mean age was 74.3 years (SD 10.0) with a median CCI of 3 (3-6). Age was associated with increased number of cardiac medicines with a mean of 1.6 drugs in &lt;60 years, 2.2 drugs in 60-69, 2.5 drugs in 70-80, and 2.5 drugs in 80+ years (p&lt;0.001). Increased number of medications was associated with decreased OS using the Kaplan-Meier method (p&lt;0.001, see table). After adjusting for age, race, BMI, weight change, PSA, and CCI, the number of medications was independently associated with increased mortality with an adjusted hazard ratio (aHR) of 1.05 (1.03-1.06) for each additional cardiac drug. Increased mortality was observed in patients treated with 2 or more cardiac drugs (see table). Conclusions: The number of cardiovascular medications is associated with decreased survival in veterans undergoing treatment for mHSPC, even after accounting for important covariates including age, BMI, PSA, and CCI. The assessment of cardiovascular medications may provide a simple and reliable tool to estimate comorbid disease and survival in patients with cancer. [Table: see text]