Prognostic Impact Of Comorbidity Research Articles

Cause-Specific Mortality and Prognostic Impact of Comorbidity in Japanese Patients With Chronic Lymphocytic Leukemia.

Due to its rarity, there are very limited data available on the cause of death (COD) and its association with comorbidities in Japanese chronic lymphocytic leukemia (CLL) patients. To investigate the prevalence of comorbidities and their impact on cause-specific mortality, we retrospectively reviewed 121 Japanese patients with CLL. The median age was 69 years, with 47.9% having at least one comorbidity listed in the Charlson Comorbidity Index (CCI), and 12.4% were multimorbid. With a median follow-up of 74 months, the 5- and 10-year overall survival rates were 80.6% and 60.1%, respectively. Among the 44 deaths observed, CLL progression was the leading COD (38.6%), which together with infections and other malignancies accounted for nearly 80%. Patients with higher CCI risk categories had significantly higher 5-year all-cause mortality (CCI 1-2: 22.9% and ≥ 3: 31.4%) and non-CLL-specific mortality (CCI 1-2: 18.8% and ≥ 3: 31.4%) compared to those without (CCI 0: 12.6%, p = 0.005; 3.5%, p < 0.001, respectively), whereas CLL-specific mortality was not influenced. On multivariate analysis, age and CCI retained a significant prognostic impact on all-cause mortality (hazard ratio [HR] 1.08, p < 0.001 and HR 1.88, p = 0.004, respectively) and non-CLL-specific mortality (HR 1.12, p < 0.001 and HR 3.81, p < 0.001, respectively). Our study showed that CLL itself was the leading COD, and comorbidity burden was associated with non-CLL-specific deaths. This highlights the importance of better disease control and effective management of comorbidities.

The prognostic impact of comorbidity, nutritional and performance status on patients with diffuse large B cell lymphoma.

The aim of the study was to investigate the impact of nutritional status, comorbidity, and performance status on patients with diffuse large B-cell lymphoma (DLBCL). A retrospective study was conducted on 112 DLBCL patients who were diagnosed at our center between 2009 and 2018. Demographic and disease characteristics and laboratory test results were recorded. Assessments were made using the age-adjusted Charlson comorbidity index (CCI-A) for comorbidity, albumin level for nutritional status, and Eastern Cooperative Oncology Group (ECOG) score for performance status. The mean age of the patients was found to be 62.63 ± 15.16 years. The ECOG score of 65 patients (69.1%) was in the range of 0-1. The mean follow-up time of the patients was determined to be 25.24 ± 25.11 months, and at the end of the follow-up period, 64 patients (57.1%) were survivors. The progression-free survival (PFS), overall survival (OS), and 5-year OS rates of those with CCI-A > 4 were found to be significantly lower than those with CCI-A score ≤4 (P < 0.05). As a result of the Cox-Regression (Backward: LR method) analysis, ECOG and albumin levels were found to be independent risk factors for both OS and PFS (P < 0.05). This study demonstrated that CCI-A, ECOG, and nutritional status are independent prognostic markers for DLBCL patients. Initial evaluation of these patients should include all these parameters, which are easily available at the time of diagnosis.

Prognostic Impact of Comorbidities on Outcomes of Patients (pts) with Relapsed or Refractory Large B-Cell Lymphoma (r/r LBCL) Treated with Chimeric Antigen Receptor T-Cell Therapy (CART)

Background CAR T-cell therapy is a standard of care for patients with r/r LBL and despite promising responses, outcomes can vary depending on the condition of the patient prior to the infusion. Pre-existing comorbidities as scored by the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) (Sorror, et al. Blood. 2005) have been shown to be associated with morbidities and mortality following transplants. The impact of comorbidities on outcomes of CAR T-cell therapy is not well established. To this end, we sought to develop and validate a CAR T-cell therapy-specific comorbidity index (CT-CI) and examine its prognostic value in predicting survival and toxicity outcomes. Methods Utilizing the cellular therapy registry from the Center for International Blood and Marrow Transplant Research (CIBMTR) adult pts were identified with r/r LBCL receiving commercially available CAR T-cell therapy since FDA approval (2017 and 2018 for axi-cel and tisa-cel, respectively) until December 2020. Each reported individual comorbidity according to the HCT CI was individually assessed on its impact on outcomes after CAR T cell infusion Pts were randomly assigned to training (67% of pts) and validation (33% of pts) cohorts. In the training set, Cox proportional hazard model was used to examine risk factors associated with OS. A stepwise selection method was used to identify the significant covariates affecting OS with a significance level of 0.01. Pairwise interactions between significant factors were tested. Multivariate analysis (MVA) adjusting for the significant covariates was used to develop a weighted score for each comorbidity based on the magnitude of hazard ratios (HRs) for OS. The CT-CI score (the sum of weighted scores of individual comorbidities) was then tested in the validation cohort. Results We identified 1916 pts, median age was 63.6 years (range: 18.5-91), with 24.7% (n=473) ≥70 years of age, and 63.9% males (n=1225). A total 13.8% (n=265) and 24.1% (n=461) of pts had double∖triple hit LBCL and transformed lymphoma, respectively. Of the whole cohort 19.5% (n=373) of pts had Karnofsky performance status (KPS) less than 80, while 43.6% (n=836) had an elevated LDH prior to CT. Incidence of all grade CRS was 75.4% (8.5% grade ≥3 and all grade ICANS was 44.4% (19.5% grade ≥3), respectively. 12-month progression free survival (PFS) was 42.2% (95% CI 39.9-44.5) and 12-month OS was 61.6 (95% CI 59.4-63.9). The primary cause of death was disease progression 73.2% (n=617). Incidence of treatment related mortality (TRM) was 4.3% (95% CI 3.4-5.3). At least 1 comorbidity was recorded for 1321 (68.9%), while 558 (29.1%) had none and 37 (1.9%) did not have reported data. The most commonly reported were history of cardiac disease (11.8%), diabetes requiring non-diet treatment (13.8%), psychiatric disturbance (18.1%), pulmonary disease (moderate- 15.0%, severe- 12.2%) and hepatic disease (mild- 8.2%, moderate∖severe- 2 %). Table 1 shows comorbidities associated with overall mortality on multivariable analysis in the training cohort. Other clinical factors associated with worse OS were lower KPS (<80 vs. 90-100 (HR 1.956, 95%CI 1.577-2.424, p<0.0001, 80-90 vs. 90-100 HR 1.239, 95%CI 1.006-1.527, p=0.0442), and resistant disease or a partial response at time of infusion (resistant disease vs. CR; HR 3.891, 95%CI 1.932-7.836, p<0.0001, PR vs. CR HR 2.789, 95%CI 1.361-5.713, p=0.0051) Higher CT-CI scores were associated with worse 1-year OS in the training, validation, and entire cohorts (0 vs 1 vs 2 vs ≥3) (Table 2). The C-index was 0.56. While KPS and LDH were associated with toxicities, specific comorbidities and the CT-CI were not associated with development or incidence of CRS or ICANS. Conclusion Development of a novel CT-CI has shown that comorbidities are predictive of mortality after CAR T-cell therapy and may influence clinical decisions for treatment selection in high risk pt populations. Further analysis will be presented at the meeting. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comorbidities in unclassifiable interstitial lung disease

BackgroundComorbidities are common in interstitial lung diseases (ILD) and have an important association with survival, but the frequency and prognostic impact of comorbidities in unclassifiable interstitial lung disease (uILD) remains elusive. We aimed to describe the prevalence of comorbidities and assess the impact on survival in patients with uILD. Furthermore, we aimed to identify and characterize potential phenotypes based on clusters of comorbidities and examine their association with disease progression and survival.MethodsIncident patients diagnosed with uILD were identified at two ILD referral centers in Denmark and Germany from 2003 to 2018. The diagnosis uILD was based on multidisciplinary team meetings. Clinical characteristics and comorbidities were extracted from ILD registries and patient case files. Survival analyses were performed using Cox regression analyses, disease progression was analyzed by linear mixed effects models, and clusters of comorbidities were analyzed using self-organizing maps.ResultsA total of 249 patients with uILD were identified. The cohort was dominated by males (60%), former (49%) or current (15%) smokers, median age was 70 years, mean FVC was 75.9% predicted, and mean DLCO was 49.9% predicted. One-year survival was 89% and three-year survival was 73%. Eighty-five percent of the patients had ≥ 1 comorbidities, 33% had ≥ 3 comorbidities and 9% had ≥ 5 comorbidities. The only comorbidity associated with excess mortality was dyslipidemia. No association between survival and number of comorbidities or the Charlson comorbidity index was observed. Three clusters with different comorbidities profiles and clinical characteristics were identified. A significant annual decline in FVC and DLCO % predicted was observed in cluster 1 and 2, but not in cluster 3. No difference in mortality was observed between the clusters.ConclusionsThe comorbidity burden in uILD is lower than reported in other types of ILD and the impact of comorbidities on mortality needs further clarification. Three clusters with distinct comorbidity profiles were identified and could represent specific phenotypes. No difference in mortality was observed between clusters, but slower disease progression was observed in cluster 3. Better understanding of disease behavior and mortality will require further studies of subgroups of uILD with longer observation time.

Prognostic Value of Comorbidity for Patients with Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy.

Simple SummaryUpper tract urothelial carcinoma (UTUC) is a rare malignancy that occurs mostly in elderly individuals with a high prevalence of comorbidities. However, the prognostic impact of comorbidities in these patients is not well evaluated. The aim of this retrospective study was to assess the significance of Adult Comorbidity Evaluation-27 (ACE-27) grade on the clinical outcomes of 409 patients with non-metastatic UTUC who underwent radical nephroureterectomy. We found that a high ACE-27 grade was an independent risk factor for UTUC progression, UTUC-specific death, and all-cause mortality in multivariate analyses. A prognostic model combining ACE-27 grade, tumor stage, and tumor grade showed good predictive performance and accuracy. Integrating the ACE-27 grade with standard pathological features can help physicians in clinical decision-making and risk stratification.Patients with upper tract urothelial carcinoma (UTUC) have a high prevalence of comorbidities. However, the prognostic impact of comorbidities in these patients is not well studied. We aimed to outline the comorbidity burden in UTUC patients and investigate its relationship with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). We retrospectively reviewed the clinicopathological data of 409 non-metastatic UTUC patients who received radical nephroureterectomy between 2000 and 2015. The comorbidity burden was evaluated using the Adult Comorbidity Evaluation-27 (ACE-27). Kaplan-Meier survival analysis showed that high ACE-27 grade was significantly associated with worse PFS, CSS, and OS. In multivariate Cox regression and competing risk analyses, we found that ACE-27 grade, tumor stage, and tumor grade were independent prognosticators of OS, CSS, and PFS. We combined these three significant factors to construct a prognostic model for predicting clinical outcomes. A receiver operating characteristic curve revealed that our prognostic model had high predictive performance. The Harrel’s concordance indices of this model for predicting OS, CSS, and PFS were 0.81, 0.85, and 0.85, respectively. The results suggest that the UTUC patient comorbidity burden (ACE-27) provides information on the risk for meaningful clinical outcomes of OS, CSS, and PFS.

The impact of comorbidities and their stacking on short- and long-term prognosis of patients over 50 with community-acquired pneumonia

BackgroundThe prognosis of patients hospitalized with community-acquired pneumonia (CAP) with regards to intensive care unit (ICU) admission, short- and long-term mortality is correlated with patient’s comorbidities. For patients hospitalized for CAP, including P-CAP, we assessed the prognostic impact of comorbidities known as at-risk (AR) or high-risk (HR) of pneumococcal CAP (P-CAP), and of the number of combined comorbidities.MethodsData on hospitalizations for CAP among the French 50+ population were extracted from the 2014 French Information Systems Medicalization Program (PMSI), an exhaustive national hospital discharge database maintained by the French Technical Agency of Information on Hospitalization (ATIH). Their admission diagnosis, comorbidities (nature, risk type and number), other characteristics, and their subsequent hospital stays within the year following their hospitalization for CAP were analyzed. Logistic regression models were used to assess the associations between ICU transfer, short- and 1-year in-hospital mortality and all covariates.ResultsFrom 182,858 patients, 149,555 patients aged ≥ 50 years (nonagenarians 17.8%) were hospitalized for CAP in 2014, including 8270 with P-CAP. Overall, 33.8% and 90.5% had ≥ 1 HR and ≥ 1 AR comorbidity, respectively. Cardiac diseases were the most frequent AR comorbidity (all CAP: 77.4%). Transfer in ICU occurred for 5.4% of CAP patients and 19.4% for P-CAP. Short-term and 1-year in-hospital mortality rates were 10.9% and 23% of CAP patients, respectively, significantly lower for P-CAP patients: 9.2% and 19.8% (HR 0.88 [95% CI 0.84–0.93], p < .0001). Both terms of mortality increased mostly with age, and with the number of comorbidities and combination of AR and HR comorbidities, in addition of specific comorbidities.ConclusionsNot only specific comorbidities, but also the number of combined comorbidities and the combination of AR and HR comorbidities may impact the outcome of hospitalized CAP and P-CAP patients.

Impact of comorbidity burden on renal cell carcinoma prognosis: A Danish nationwide cohort study.

360 Background: The incidence of renal cell carcinoma is increasing worldwide and have a 5-year relative survival rates of around 75%. Comorbidity has been found to be associated with complications and mortality after renal cancer surgery. No studies have focused on comorbidity as a prognostic factor in a nationwide cohort of patients with renal cell carcinoma with long-term follow-up. Purpose: The primary aim was to evaluate the prognostic impact of comorbidity on survival in older (≥70 years) and younger (&lt;70 years) patients diagnosed with renal cell carcinoma. Methods: We established a nationwide register-based cohort of 7,894 patients aged 18 or more diagnosed with renal cell carcinoma in Denmark between 2006 and 2017, and followed their vital status for up to 13 years. We computed 1- and 5-year overall survival and hazard ratios (HRs) of death according to comorbidity status using Charlson Comorbidity Index (CCI) among patients aged &lt; 70 years and ≥ 70 years. Results: In all, 36% of the patients had registered comorbidity at the time of diagnosis. Survival decreased with increasing CCI score. It did though increase for all groups of CCI scores (0, 1-2 and 3+) over time. For patients without comorbidity diagnosed in 2006-2008 and 2015-2017, 5-year survival rate increased from 57% to 69%. For patients with a CCI score of 1-2 vs 3, the 5-year survival rate increased from 46% to 62% vs 39% to 44%. In age- and gender-stratified analyses, patients with a CCI score of 1-2 and 3+ had increased mortality compared to patients without registered comorbidity (HR 1.15, 95 % CI 1.06-1.24) and (HR 1.56, 95 % CI 1.40-1.73). Patterns were similar for older (≥70 years) and younger (&lt;70 years) patients. Particularly, diagnoses of congestive heart failure, peripheral vascular and cerebrovascular disease, dementia, chronic pulmonary disease, preexisting renal and liver disease, diabetes and lymphoma led to increased mortality. Conclusions: Comorbidity leads to inferior survival outcomes in patients with renal cell carcinoma, irrespective of age, despite an overall increasing survival. These data may guide patient counseling and prompt initiatives for controlling comorbidity.

The Impact of Comorbidity on Survival in Patients With Head and Neck Squamous Cell Carcinoma: A Nationwide Case-Control Study Spanning 35 Years

BackgroundComorbidity is presumed to impact survival of head and neck squamous cell cancer (HNSCC) patients. However, the prevalence and prognostic impact of comorbidity in these patients is not yet well established. The aim of this study is to outline the comorbidity burden of HNSCC patients and investigate the relation to overall survival and cancer-specific mortality.MethodsThe comorbidity burden of patients registered with HNSCC in the Danish Cancer Registry between 1980 and 2014 was evaluated based on the Charlson Comorbidity Index (CCI). Patients’ risks of comorbid conditions compared to age- and gender-matched controls were estimated by odds ratios (OR). The impact of comorbidity on overall survival and cancer-specific mortality was evaluated by Cox regression and Kaplan-Meier survival analysis.ResultsA total of 25,388 HNSCC patients were included (72.5% male; mean age 63.2 years at diagnosis; median follow-up 3.0 years). CCI at diagnosis was significantly higher in patients compared to controls (p < 0.001). The most common comorbid conditions among the patients were additional non-metastatic malignancy (10.9%) and cerebrovascular disease (7.7%). Compared to controls, patients had higher odds of metastatic malignancy (OR: 4.65; 95% CI: 4.21–5.15; p < 0.001), mild liver disease (OR: 6.95; 95% CI: 6.42–7.53; p < 0.001), and moderate-severe liver disease (OR: 7.28; 95% CI: 6.14–8.65; p < 0.001). The multivariate Cox analysis revealed increasing hazard ratios with increasing CCI and in coherence the Kaplan-Meier curves showed poorer overall survival and increased cancer-specific mortality in patients with higher CCI.ConclusionHNSCC patients’ comorbidity burden was significantly greater compared to the general population and increased comorbidity was correlated with increased cancer-related mortality.

One-year mortality risk after new onset comorbidity and worsening heart failure in patients with chronic heart failure

Abstract Background Heart failure (HF) is a progressive disease characterized by risk of congestion and often accompanied by a significant burden of comorbidities. At the time of HF diagnosis, these are associated with a poor outcome, but it is relatively unknown whether hospitalization due to new-onset comorbidities carries the same subsequent mortality risk as hospitalization for worsening HF. Purpose To assess one-year mortality risk after hospitalization due to new-onset chronic comorbidity compared to a hospitalization with worsening HF in a nationwide cohort of patients with HF. Methods In Danish administrative registers, we identified all patients, aged 40–95 years with a first-time HF diagnosis from 2000 through 2016. Patients were included if they survived the initial 120 days and collected prescribed renin-angiotensin system inhibitor and beta-blocker. In analyses stratified on age and baseline burden of comorbidity (based on Charlson Comorbidity Index (CCI) excluding myocardial infarction and HF, we estimated absolute one-year mortality risk continuously during follow-up, using landmarking and flexible semi-parametric methods. If a patient had a comorbidity hospitalization equivalent to an increase in his/ her CCI or a HF hospitalization, one-year mortality risk was estimated immediately hereafter. In analyses assuming constant risks during follow-up, we calculated absolute risks and risk ratios for new comorbidity- or HF hospitalizations compared to patients without events. Results We included 81,788 patients, median age 72 (Q1-Q3:63–80), 36% women. At baseline, 57% had CCI=0, 22% CCI=1, 9% CCI=2 and 12% CCI≥3. High age and baseline CCI were associated with increased mortality risk throughout follow-up. Both new comorbidity- and HF hospitalizations at any time during follow-up were associated with increased mortality risk (p&amp;lt;0.001) (Figure), and the risk was approximately constant over time. Among patients with baseline CCI=0, new-onset comorbidity (incident increase in CCI) was associated with a higher mortality risk than a HF hospitalization in all age groups, risk ratios with “no event” as reference: Age 40–64: 5.4 (95%-CI: 4.5–6.4) vs 2.5 (95%-CI: 2.1–2.9); age 65–74: 4.2 (95%-CI: 3.7–4.7) vs 2.2 (95%-CI: 1.9–2.5); age 75–84: 3.4 (95%-CI: 3.2–3.7) vs 2.3 (95%-CI: 2.1–2.5) and age 85–95: 2.6 (95%-CI: 2.4–2.8) vs 2.2 (95%-CI: 2.0–2.4) (figure). Across all strata, new-onset comorbidity was associated with at least similar risk as a HF hospitalization at any time during follow-up. Conclusions For patients with HF, hospitalization for new-onset chronic comorbidity was associated with at least the same mortality risk as worsening HF, independently of age. This finding highlights the prognostic impact of comorbidity for patients with HF and warrants further investigations in the mechanisms underlying the mortality. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Danish Heart Foundation

The prognostic impact of comorbidity, nutritional and performance status on patients with diffuse large B cell lymphoma

The prognostic impact of comorbidity, nutritional and performance status on patients with diffuse large B cell lymphoma

AML-355: The Prognostic Validity of the Acute Myeloid Leukemia Composite Model in Predicting Risks of One-Year Mortality among Patients in Atlantic Canada: A Multi-Centre Experience

Background Intensive chemotherapy is the standard of care for remission induction for fit patients with newly diagnosed acute myeloid leukemia (AML). However, assessing the prognostic impact of comorbidities on outcomes when counselling patients remains a challenge. To this end, we sought to validate the prognostic validity of a newly proposed AML composite model (AML-CM) which incorporates both comorbidities and leukemia-specific features to predict overall mortality following administration of intensive induction chemotherapy. Methods We retrospectively collected data on patients with newly diagnosed AML who received their first induction chemotherapy in Halifax, NS and St. John's, NL, Canada. The AML-CM scores were calculated as per previously published guidelines (Sorror et al in 2017). Logistic regression models were performed to analyze 8-week and 1-year mortality and competing risk regression with Fine and Grey model to model overall survival after adjusting for known variables. Results 194 patients treated January 1, 2009 to December 31, 2017 were identified. Fifty-six percent were males. Median age at induction was 54 years with an age range from 18 to 75 years. Thirty-eight percent of patients were 60 years or older. Molecular/cytogenetic risk per ELN classification was as follows: 23% favourable risk, 37% intermediate risk, 34% high risk, and 6% unknown. The most frequently used regimen was the standard 3+7 regimen (daunorubicin and cytarabine). The AML-CM was predictive of 8-week, odds ratio 2.39 (95%CI 1.09-5.239) AML-CM 7-9 vs AML-CM 1-4, (p-value 0.0284) and 1-year mortality, odds ratio 11.76 (95% CI 2.45-56.51) AML-CM 10+ vs AML-CM 1-4 (p-value 0.0021). Overall survival was inversely proportional to increasing AML-CM scores (p Conclusions The AML-CM is a valid prognosticator for early and late mortality in our patient population. Our findings emphasize the significance of comorbidities assessment prior to induction therapy for AML and the potential use in tailoring targeted interventions to mitigate their risks alongside leukemia treatments. Additionally, the AML-CM could be utilized to adjust for the impact of comorbidities in clinical trials investigating newer intensive AML therapies.

Prognostic effect of comorbidities in patients with chronic myeloid leukemia treated with a tyrosine kinase inhibitor.

Comorbidities at diagnosis among patients with chronic myeloid leukemia in chronic phase (CML‐CP) may affect their overall survival (OS) rate even in the tyrosine kinase inhibitor (TKI) era. However, the prognostic impact of comorbidities in patients with CML‐CP treated with a second‐generation TKI (2GTKI) has not been elucidated. We evaluated the effect of comorbidities on survival using the Charlson Comorbidity Index (CCI) in patients with CML‐CP treated with imatinib or a 2GTKI (nilotinib and dasatinib). From April 2010 to March 2013, 506 patients with CML‐CP were registered for the population‐based cohort study, and 452 with a median age of 56 y were assessable. Treatment groups included 139 patients receiving imatinib, 169 receiving nilotinib, and 144 receiving dasatinib. Comorbidities were diagnosed in 99 patients. CCI scores were stratified as follows: 2, 353 patients; 3, 72 patients; and ≥4, 27 patients. Treatment response did not vary relative to CCI scores. However, across the entire cohort, the OS rate was significantly lower among patients with higher CCI scores than in those with a CCI score of 2 (94.4% in score 2, 89.0% in score 3, and 72.8% in score ≥4; P < .001). Multivariate analysis identified a CCI score of ≥4 as a strong adverse prognostic factor for OS rather than the disease‐specific risk factor, older age, performance status, or selection of TKI (Wald test, P < .01). Our results demonstrated that comorbidities at diagnosis were the most important predictive factor for successful treatment, regardless of the TKI type used in CML‐CP. This trial was registered at UMIN‐CTR as 00003581.

Noncardiac comorbidity clustering in heart failure: an overlooked aspect with potential therapeutic door.

Heart failure is associated with a range of comorbidities that have the potential to impair both quality of life and clinical outcome. Unfortunately, noncardiac diseases are underrepresented in large randomized clinical trials, and their management remains poorly understood. In clinical practice, the prevalence of comorbidities in heart failure is high. Although the prognostic impact of comorbidities is well known, their prevalence and impact in specific heart failure settings have been overlooked. Many studies have described specific single noncardiac conditions, but few have examined their overall burden and grading in patients with multiple comorbidities. The risk of comorbidities in patients with heart failure rises with more advanced disease, older age, and increased frailty-three conditions that are poorly represented in clinical trials. The pathogenic links between comorbidities and heart failure involve many pathways and include neurohormonal overdrive, inflammatory activation, oxidative stress, and endothelial dysfunction. Such interactions may worsen prognoses, but details of these relationships are still under investigation. We propose a shift from cardiac-focused care to a more systemic approach that considers all noncardiac diseases and related medications. Some new drugs class such as ARNI or SGLT2 inhibitors could change prognosis by acting directly or indirectly on metabolic disorders and related vascular consequences.

The Prognostic Impact of Comorbidities in Patients with De-Novo Diffuse Large B-Cell Lymphoma Treated with R-CHOP Immunochemotherapy in Curative Intent.

Background: Patient-related factors, namely comorbidities, impact the clinical outcome of patients with diffuse large B-cell lymphoma (DLBCL). Methods: The prevalence and prognostic impact of comorbidities were examined using the validated scores Charlson Comorbidity Index (CCI) and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) in 181 patients with DLBCL at initial diagnosis before treatment with rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone (R-CHOP). Results: Pronounced comorbidities as defined by CCI and HCT-CI scoring of ≥2 were detected in 9.9% and 28.2% of patients, respectively, and occurred more frequently at advanced age (p < 0.001). Higher CCI scoring was associated with lower complete response rate (p = 0.020). Both advanced CCI and HCT-CI were significantly associated with shortened overall survival (3-year OS: CCI ≥2 vs. 0–1, 38.9% vs. 81.3%, p < 0.001; HCT-CI ≥2 vs. 0–1, 56.9% vs. 84.9%, p < 0.001). Both comorbidity scores remained independent risk factors in the multivariate analysis (HCT-CI ≥2 HR: 2.6, p = 0.004; CCI ≥2 HR: 3.6, p = 0.001). Conclusion: This study demonstrates the prognostic relevance of comorbidities classified by CCI and HCT-CI in patients with DLBCL undergoing curative treatment with R-CHOP. A structured evaluation of comorbidities might refine prognostication alongside currently used prognostic parameters, namely age, and should be evaluated in prospective trials.

5938Mortality risk stratification in patients with severe tricuspid regurgitation - Insights from the Tricuspid Regurgitation REgistry (TRuE)

Abstract Background/Introduction Severe tricuspid regurgitation (TR) is associated with progressive right atrial (RA) and ventricular (RV) dilation, dysfunction and increased mortality. Risk factors impacting the long-term prognosis in patients with severe TR are largely undetermined. Purpose Herein, we aimed to identify risk factors associated with long-term mortality in patients with severe TR and implement a novel risk stratification strategy based on an individual five-year mortality prediction score. Methods From January 2013 to December 2017, 1238 patients with severe functional TR were enrolled in the TRuE-registry, of which 914 with a complete dataset were included in the present study. Echocardiographic quantification of RV-function and size included measurements of tricuspid annular plane systolic excursion (TAPSE), the end-diastolic basal (RVDbasal) and longitudinal diameters (RVDlong) and the RA-volume index (RAVI). The cohort was randomly divided into a development (n=610) and validation (n=304) sample. A risk stratification model was developed using a multivariable Cox regression. Results The variables statistically significant to predict five-year-mortality, included in the final model and used as score parameters were: age, COPD, dialysis, pulmonary artery systolic pressure, RAVI, TAPSE RVDbasal, RVDlong and systolic hepatic vein flow reversal (sHVFR). Progressive enlargement of RV and RA and concomitant sHVFR was associated with higher values of hazard ratios (HR, Figure A). Based on the HR values, a risk score with 3 categories was developed (Figure B): low (0–2), intermediate (3–5), high (6–16). Among the risk groups, Kaplan Meier estimates of all-cause mortality at 5 years were 18%, 52% and 84% respectively (p&lt;0.001; https://thetruerisk.com). The score showed good discrimination, with a concordance index of 0.75. At internal validation, a good agreement between the derivation and validation datasets indicated a good calibration of the survival curves. Implementation of a long term risk score Conclusion The present study demonstrates the prognostic impact of comorbidities and right heart remodeling on long-term mortality in patients with severe TR. The presented risk score provides an easy and accurate estimation of long-term mortality and may thus help to guide therapeutic decision-making in this difficult group of patients.

Evaluation of the prognostic role of co-morbidities on disease outcome in renal cell carcinoma patients.

Co-morbidities may induce local and systemic tumor progression of renal cell carcinoma (RCC); however, the prognostic impact of co-morbidities has not yet been well characterized. RCC patients (n = 2206) surgically treated at three academic institutions in the US and Europe were included in the analysis. Presence of diabetes mellitus, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, coronary heart disease, and hypothyroidism were investigated for their association with clinicopathological features and cancer-specific survival. Hypertension was associated with less advanced T stages (p = 0.025), a lower risk of lymph-node (p = 0.026) and distant metastases (p = 0.001), and improved cancer specific survival in univariable analysis (HR 0.81 95% CI 0.69-0.96, p = 0.013). However, hypertension was not an independent prognostic factor after adjustment for TNM stages, grading, and ECOG performance status (HR 0.95, 95% CI 0.80-1.12; p = 0.530). A correlation between the use of concomitant anti-hypertensive medications and improved survival outcome was not identified. All other investigated co-morbidities did not show significant associations with clinicopathological features or cancer-specific survival. Although the investigated co-morbidities are capable or inducing pathophysiological changes that are predisposing factors for tumor progression, none is an independent prognostic factor in patients with RCC.

Delay in surgery, risk of hospital-treated infections and the prognostic impact of comorbidity in hip fracture patients. A Danish nationwide cohort study, 2005-2016.

Purpose: We examined the association between delay in surgery and hospital-treated infections in hip fracture patients with and without known comorbidities.Patients and methods: All hip fracture patients aged ≥65 years registered in the Danish Multidisciplinary Hip Fracture Registry from 2005 to 2016 were included (n=72,520). Delay in surgery was defined as the time in hours from admission to surgery and was divided into 3 groups (12, 24 and 48 hrs). The outcomes were hospital-treated pneumonia, urinary tract infection and reoperation due to infection 0–30 days after surgery. As a measure of comorbidity, we used the Charlson Comorbidity Index (CCI): none (no registered comorbidities prior to the fracture), medium (1–2 points) and high (≥3 points).Results: Overall, there was an association between a delay of 12 hrs and pneumonia. A delay of 12 hrs was associated with an increased risk of pneumonia in patients with no comorbidities (adjusted hazard ratio (HR) 1.20, confidence interval (CI) 1.03–1.40) and a delay of 24 hrs was associated with an increased risk of pneumonia in patients with a medium level of comorbidity (HR 1.12, CI (1.02–1.23)). Overall, delay was associated with reoperation due to infection, particularly among patients with comorbidities, although the confidence intervals of some of the estimates were wide. A delay of 48 hrs was associated with an increased risk of reoperation due to infection in patients with a high level of comorbidity (HR 2.36, CI 1.19–4.69).Conclusion: Delay in surgery was associated with an increased risk of hospital-treated pneumonia and reoperations due to infection within 30 days of surgery. The number of postoperative hospital-treated infections within 30 days may be reduced by continuously targeting pre-, per- and postoperative optimization not only for patients with high level of comorbidity but also for hip fracture patients without known comorbidities prior to surgery.

The impact of comorbidities on mortality among men and women with COPD: report from the OLIN COPD study.

Background:Comorbidities probably contribute to the increased mortality observed among subjects with chronic obstructive pulmonary disease (COPD), but sex differences in the prognostic impact of comorbidities have rarely been evaluated in population-based studies. The aim of this study was to evaluate the impact of common comorbidities, cardiovascular disease (CVD), diabetes mellitus (DM), and anxiety/depression (A/D), on mortality among men and women with and without airway obstruction in a population-based study.Methods:All subjects with airway obstruction [forced expiratory volume in 1 second (FEV1)/(forced) vital capacity ((F)VC) <0.70, n = 993] were, together with age- and sex-matched referents, identified after examinations of population-based cohorts in 2002–2004. Spirometric groups: normal lung function (NLF) and COPD (post-bronchodilator FEV1/(F)VC <0.70) and additionally, LLN-COPD (FEV1/(F)VC <lower limit of normal). Mortality data was collected until December 2015.Results:In COPD, the prevalence of CVD and DM was higher in men, whereas the prevalence of A/D was higher in women. The cumulative mortality was significantly higher in COPD than NLF, and higher in men than women in both groups. Among women with COPD, CVD and A/D but not DM increased the risk of death independent of age, body mass index, smoking habits, and disease severity, whereas among men DM and A/D but not CVD increased the risk for death. When the LLN criterion was applied, the pattern was similar.Conclusion:There were sex-dependent differences regarding the impact of comorbidities on prognosis in COPD. Even though the prevalence of CVD was higher in men, the impact of CVD on mortality was higher in women, and despite higher prevalence of A/D in women, the impact on mortality was similar in both sexes. The reviews of this paper are available via the supplemental material section.

Comorbidity indexing for prediction of the clinical outcome after stereotactic body radiation therapy in non-small cell lung cancer

PurposeTo determine the prognostic impact of comorbidity and age in medically inoperable early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) using the age-adjusted Charlson Comorbidity Index (aCCI).Patients and methodsBetween November 2008 and January 2015, 196 consecutive patients with medically inoperable NSCLC were treated with SBRT at a single institution. The prescribed isocenter dose was either 60.0 Gray (Gy) in six fractions for central lung cancer or 56.25 Gy in three fractions for peripheral lung cancer. Baseline comorbidities were retrospectively retrieved according to available outclinic medical records as well as the hospital information system. The aCCI was scored for each patient and subjected according to outcome and toxicity as well as all of the single items of the aCCI and other clinical parameters using univariate and multivariate analysis.ResultsThirty-one point 6 % (62/196) of patients were deceased, of whom 17.3% (34/196) died due to lung cancer and 14.3% (28/196) due to comorbidities. The median overall survival (OS) was 15.0 months (95% CI [11.9–18.1]), whereas the median cancer-specific survival (CSS) was not reached. An aCCI ≥7 compared with an aCCI ≤6 was significantly associated with an increased risk of death (HR 1.79, 95% CI [1.02–2.80], p = 0.04) and cancer-specific death (HR 9.26, 95% CI [4.83–24.39], p < 0.001), respectively. Neither OS nor CCS were significantly associated with age, sex, side (left vs. right), lobe, localization (central vs. peripheral), packyears, TNM, or any item of the aCCI. Considering the 14.3% (28/196) of deceased patients who died due to comorbidities, aCCI ≥9 was significantly associated with non-cancer-related death (HR 3.12, 95% CI [1.22–8.33], p = 0.02). The observed cumulative rate of radiation pneumonitis (RP) ≥2 was 12.7% (25/196). The aCCI had no statistical association with RP.ConclusionAdvanced age and numerous comorbidities characterizing this patient population were successfully assessed using the aCCI in terms of survival. Therefore, we recommend that age and comorbidity be indexed using the aCCI as a simple scoring system for all patients treated with SBRT for lung cancer.

Associations between comorbidities, their treatment and survival in patients with interstitial lung diseases \u2013 a claims data analysis

BackgroundInterstitial lung diseases (ILDs) are associated with a high burden of disease. However, data on the prognostic impact of comorbidities and comorbidity-related pharmaceutical treatments in patients with various ILDs remain sparse.MethodsUsing longitudinal claims data from a German Statutory Health Insurance Fund, we assessed comorbidity in ILD subtypes and associated drug treatments. Baseline comorbidity was assessed via the Elixhauser Comorbidity Index that was amended by ILD-relevant conditions. Drug treatment was assessed on the substance level using the ATC-codes of drugs prescribed at the time of ILD diagnosis. Subsequently, the comorbid conditions (main analysis) and pharmaceutical substances (secondary analysis) with a meaningful association to survival were identified for the complete ILD cohort and within the subtype strata. For this, we applied multivariate Cox models using a LASSO selection process and visualized the findings within comorbidomes.ResultsIn the 36,821 patients with ILDs, chronic obstructive pulmonary disease (COPD), arterial hypertension, and ischaemic heart disease (IHD) were the most prevalent comorbidities. The majority of patients with cardiovascular diseases received pharmaceutical treatment, while, in other relevant comorbidities, treatment quotas were low (COPD 46%, gastro-oesophageal reflux disease 65%). Comorbidities had a clinically meaningful detrimental effect on survival that tended to be more pronounced in the case of untreated conditions (e.g. hazard ratios for treated IHD 0.97 vs. 1.33 for untreated IHD). Moreover, comorbidity impact varied substantially between distinct subtypes.ConclusionsOur analyses suggest that comorbid conditions and their treatment profile significantly affect mortality in various ILDs. Therefore, comprehensive comorbidity assessment and management remains important in any ILD.