scholarly journals The Interplay between Anticholinergic Burden and Anemia in Relation to 1-Year Mortality among Older Patients Discharged from Acute Care Hospitals

2021 ◽  
Vol 10 (20) ◽  
pp. 4650
Author(s):  
Andrea Corsonello ◽  
Luca Soraci ◽  
Francesco Corica ◽  
Valeria Lago ◽  
Clementina Misuraca ◽  
...  

Anticholinergic burden (ACB) and anemia were found associated with an increased risk of death among older patients. Additionally, anticholinergic medications may contribute to the development of anemia. Therefore, we aimed at investigating the prognostic interplay of ACB and anemia among older patients discharged from hospital. Our series consisted of 783 patients enrolled in a multicenter observational study. The outcome of the study was 1 year mortality. ACB was assessed by an Anticholinergic Cognitive Burden score. Anemia was defined as hemoglobin < 13 g/dL in men and <12 g/dL in women. The association between study variables and mortality was investigated by Cox regression analysis. After adjusting for several potential confounders, ACB score = 2 or more was significantly associated with the outcome in anemic patients (HR = 1.93, 95%CI = 1.13–3.40), but not non anemic patients (HR = 1.51, 95%CI = 0.65–3.48). An additive prognostic interaction between ACB and anemia was observed (p = 0.02). Anemia may represent a relevant effect modifier in the association between ACB and mortality.

2021 ◽  
Vol 10 (8) ◽  
pp. 1680
Author(s):  
Urban Berg ◽  
Annette W-Dahl ◽  
Anna Nilsdotter ◽  
Emma Nauclér ◽  
Martin Sundberg ◽  
...  

Purpose: We aimed to study the influence of fast-track care programs in total hip and total knee replacements (THR and TKR) at Swedish hospitals on the risk of revision and mortality within 2 years after the operation. Methods: Data were collected from the Swedish Hip and Knee Arthroplasty Registers (SHAR and SKAR), including 67,913 THR and 59,268 TKR operations from 2011 to 2015 on patients with osteoarthritis. Operations from 2011 to 2015 Revision and mortality in the fast-track group were compared with non-fast-track using Kaplan–Meier survival analysis and Cox regression analysis with adjustments. Results: The hazard ratio (HR) for revision within 2 years after THR with fast-track was 1.19 (CI: 1.03–1.39), indicating increased risk, whereas no increased risk was found in TKR (HR 0.91; CI: 0.79–1.06). The risk of death within 2 years was estimated with a HR of 0.85 (CI: 0.74–0.97) for TKR and 0.96 (CI: 0.85–1.09) for THR in fast-track hospitals compared to non-fast-track. Conclusions: Fast-track programs at Swedish hospitals were associated with an increased risk of revision in THR but not in TKR, while we found the mortality to be lower (TKR) or similar (THR) as compared to non-fast track.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 210-210
Author(s):  
T. J. Huang ◽  
D. Li ◽  
Y. Li ◽  
S. P. Kar ◽  
S. Krishnan ◽  
...  

210 Background: The plasma membrane xCT cystine-specific subunit of the cystine/glutamate transporter contributes to chemotherapy resistance in pancreatic cancer by regulating intracellular glutathione levels and protecting cancer cells against oxidative stress. We previously noted that the rs7674870 single nucleotide polymorphism (SNP) of xCT correlated with overall survival in pancreatic cancer and may be predictive of platinum resistance. There are no data regarding xCT protein expression in pancreatic cancer or the functional significance of this SNP. Methods: Paraffin-embedded core and surgical biopsy tumor specimens from 49 patients with metastatic pancreatic adenocarcinoma were analyzed by immunohistochemistry (IHC) using an xCT specific antibody (Novus Biologicals). xCT protein IHC expression scores (product of intensity and percentage of staining cells) were analyzed in relation to overall survival and genotype of the patients using the one factor ANOVA test, Kaplan-Meier plot, log-rank test, and Cox regression analysis. Overall survival was measured from the date of diagnosis to the date of death or last follow-up. Results: Positive xCT expression was detected in 38 (78%) of the 49 samples, and 9 (18%) patients had high levels of expression. High xCT expression was associated with lower overall survival as compared with low expression (5.1 months versus 8.8 months; p = 0.119). In a multivariate Cox regression model with adjustment for prognostic parameters of age, sex, performance status and CA19-9 level, high xCT expression was associated with a 2.1-fold increased risk of death (p = 0.096). Performance status also correlated with overall survival (p = 0.027). Preliminary analysis on the genotype-phenotype association (n = 12) indicated that xCT expression was higher with the TT genotype than the TC/CC genotype (p = 0.115), which is consistent with the previous observation that the TT genotype was associated with reduced survival. Conclusions: These data provide supporting evidence for a possible role of cystine/glutamate transporter xCT subunit in pancreatic cancer progression and survival. Further pharmacogenomic and clinicopathologic studies are ongoing. No significant financial relationships to disclose.


2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Annlia Paganini-Hill ◽  
Stuart C. White ◽  
Kathryn A. Atchison

In the last decade the effect of oral health on the general health and mortality of elderly people has attracted attention. We explored the association of dental health behaviors and dentition on all-cause mortality in 5611 older adults followed from 1992 to 2009 (median=9years) and calculated risk estimates using Cox regression analysis in men and women separately. Toothbrushing at night before bed, using dental floss everyday, and visiting the dentist were significant risk factors for longevity. Never brushing at night increased risk 20–35% compared with brushing everyday. Never flossing increased risk 30% compared with flossing everyday. Not seeing a dentist within the last 12 months increased risk 30–50% compared with seeing a dentist two or more times. Mortality also increased with increasing number of missing teeth. Edentulous individuals (even with dentures) had a 30% higher risk of death compared with those with 20+ teeth. Oral health behaviors help maintain natural, healthy and functional teeth but also appear to promote survival in older adults.


2010 ◽  
Vol 112 (5) ◽  
pp. 1116-1127 ◽  
Author(s):  
Miklos D. Kertai ◽  
Nirvik Pal ◽  
Ben J. A. Palanca ◽  
Nan Lin ◽  
Sylvia A. Searleman ◽  
...  

Background Current data suggest that mortality after noncardiac surgery may be associated with persistent hypotension and the cumulative duration of low processed electroencephalogram-based bispectral index (BIS). This study assessed the relationships among cumulative duration of low BIS (BIS &lt; 45), intermediate-term mortality, and anesthetic dose after cardiac surgery. Methods The authors studied 460 patients (mean age, 63.0 +/- 13.1 yr; 287 men) who underwent cardiac surgery between September 2005 and October 2006 at Washington University Medical Center, St Louis, Missouri. By using multivariable Cox regression analysis, perioperative factors were evaluated for their potential association with intermediate-term all-cause mortality. Results A total of 82 patients (17.8%) died during a median follow-up of 3 yr (interquartile range, 2.7-3.3 yr). Comparing patients who died with those who survived, there was no statistically significant difference in the relationship between end-tidal anesthetic gas concentrations during the anesthetic maintenance phase and the BIS. Cumulative duration of low BIS was independently associated with intermediate-term mortality. The 1.29 adjusted hazard ratio (95% CI, 1.12-1.49) for intermediate-term mortality with cumulative duration of low BIS translated into a 29% increased risk of death for every cumulative hour spent with a BIS less than 45. The final multivariable Cox regression model showed a good discriminative ability (c-index of 0.78). Conclusions This study found an association between cumulative duration of low BIS and mortality in the setting of cardiac surgery. Notably, this association was independent of both volatile anesthetic concentration and duration of anesthesia, suggesting that intermediate-term mortality after cardiac surgery was not causally related to excessive anesthetic dose.


Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3735
Author(s):  
Hara Polioudaki ◽  
Anastasia Mala ◽  
Eleni Gkimprixi ◽  
Maria A. Papadaki ◽  
Amanda Chantziou ◽  
...  

We aimed to evaluate the co-expression of PD-L1 and epithelial-mesenchymal markers in CTCs from metastatic breast cancer (MBC) patients and to determine if there is any relationship with patients’ outcome after eribulin treatment. Using cytospin preparations of peripheral blood mononuclear cells (PBMCs) from MBC patients treated with eribulin and a combination of immunocytochemistry and immunofluorescence, we quantified PD-L1, keratins and vimentin in single and cluster CTCs on days 1 and 8 of the first-treatment cycle. CTCs (n = 173) were found in 31 out of 38 patients. At baseline, the presence of cluster CTCs (p = 0.048), cluster mesenchymal CTCs (mCTCs) (p = 0.0003) or cluster PD-L1+mCTCs (p = 0.006) was associated with shorter overall survival (OS). In multivariate cox regression analysis, the detection of cluster mCTCs was the only parameter associated with increased risk of death (p = 0.024). On day 8 post-eribulin administration, PD-L1+mCTCs and especially single PD-L1+mCTCs decreased in 75% and 89% of patients, respectively. The detection of single PD-L1+mCTCs after eribulin treatment was correlated with shorter PFS (p = 0.047) and OS (p = 0.020). In conclusion, our study identified for the first time that cluster and single PD-L1+mCTCs subpopulations are of clinical significance in patients with MBC and highlighted the importance of CTC phenotyping during treatment with eribulin.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 3-3
Author(s):  
Grace Lee ◽  
Daniel W. Kim ◽  
Vinayak Muralidhar ◽  
Devarati Mitra ◽  
Nora Horick ◽  
...  

3 Background: While treatment-related lymphopenia (TRL) is common and associated with poorer survival in multiple solid malignancies, little data exists for anal cancer. We evaluated TRL and its association with survival in anal cancer patients treated with chemoradiation (CRT). Methods: A retrospective analysis of 140 patients with non-metastatic anal squamous cell carcinoma (SCC) treated with definitive CRT was performed. Total lymphocyte counts (TLC) at baseline and monthly intervals up to 12 months after initiating CRT were analyzed. Multivariable Cox regression analysis was performed to evaluate the association between overall survival (OS) and TRL, dichotomized by G4 TRL ( < 0.2k/μl) two months after initiating CRT. Kaplan-Meier and log-rank tests were used to compare OS between patients with versus without G4 TRL. Results: Median time of follow-up was 55 months. Prior to CRT, 95% of patients had a normal TLC ( > 1k/μl). Two months after initiating CRT, there was a median of 71% reduction in TLC from baseline and 84% of patients had TRL: 11% G1, 31% G2, 34% G3, and 8% G4. On multivariable Cox model, G4 TRL at two months was associated with a 3.7-fold increased risk of death (p = 0.013). On log-rank test, the 5-year OS rate was shorter in the cohort with versus without G4 TRL at two months (32% vs. 86%, p < 0.001). Conclusions: TRL is common and may be another prognostic marker of OS in anal cancer patients treated with CRT. The association between TRL and OS supports the hypothesis that host immunity plays an important role in survival among patients with anal cancer. These results support ongoing efforts of randomized trials underway to evaluate the potential role of immunotherapy in localized anal cancer.


2013 ◽  
Vol 169 (3) ◽  
pp. 367-376 ◽  
Author(s):  
Fausto Bogazzi ◽  
Annamaria Colao ◽  
Giuseppe Rossi ◽  
Martina Lombardi ◽  
Claudio Urbani ◽  
...  

ObjectiveAcromegalic patients have an increased risk of mortality. The objective of this study was to compare the effect of different therapies for acromegaly on mortality.Design and methodsThe mortality rate of 438 consecutive acromegalic patients was compared with that of the general population using the standardized mortality ratio (SMR); the effect of different therapies on survival was evaluated using Cox regression analysis.ResultsTwenty patients (4.5%) died between 1999 and 2009. Age- and sex-adjusted SMR was 0.70 (95% CI 0.43–1.08). The Cox regression analysis revealed that, in the whole population, both general risk factors (age and physical status) and specific factors for acromegaly (macroadenoma, hypopituitarism and uncontrolled disease) were associated with death. The most compromised patients at diagnosis had a higher mortality rate (P=0.001), which also occurred in patients with controlled acromegaly. Death occurred in 2.4% (adenomectomy), 2.6% (adenomectomy followed by somatostatin analogue (SSA) therapy) and 11.4% (SSA therapy as the primary therapy) of the patients. The risk of death was higher in patients receiving SSA therapy as the primary therapy (hazard ratio (HR) 5.52, 95% CI 1.06–28.77,P=0.043) than in all patients submitted to adenomectomy; however, a higher risk of death occurred only in diabetic patients treated with SSAs alone (HR 21.94, 95% CI 1.56–309.04,P=0.022). Radiotherapy was associated with an increased risk of mortality, which occurred in patients with the more locally advanced disease.ConclusionsTherapies for acromegaly and comorbidities have lowered the risk of mortality to the level of the general population; the effect of SSA therapy alone or that following pituitary adenomectomy was comparable to that of curative neurosurgery on survival in non-diabetic patients; on the contrary, SSA therapy as the primary therapy may be less effective than adenomectomy in reducing mortality rate in diabetic patients.


2021 ◽  
Author(s):  
Anca Balintescu ◽  
Marcus Lind ◽  
Mikael Andersson Franko ◽  
Anders Oldner ◽  
Maria Cronhjort ◽  
...  

<b>Objective</b> <p>To investigate the nature of<b> </b>the relationship between HbA1c and sepsis among individuals with type 2 diabetes and to assess the association of sepsis and all-cause mortality in such patients.<b></b></p> <p><b>Research design and methods</b></p> <p>We included 502,871 individuals with type 2 diabetes recorded in the Swedish National Diabetes Register and used multivariable Cox regression and restricted cubic spline analyses to assess the association between time-updated HbA1c values and sepsis occurrence between January 1, 2005 and December 31, 2015. The association between sepsis and death was examined using multivariable Cox regression analysis.</p> <p><b>Result</b></p> <p>Overall, 14,534 (2.9%) patients developed sepsis during the study period. On multivariable Cox regression analysis, compared with an HbA1c of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was 1.15 (95% CI 1.07-1.24) for HbA1c <43 mmol/mol (6.1%); 0.93 (0.87-0.99) for HbA1c 53-62 mmol/mol (7.0-7.8%); 1.05 (0.97-1.13) for HbA1c 63-72 mmol/mol (7.9-8.7%); 1.14 (1.04-1.25) for HbA1c 73-82 mmol/mol (8.8-9.7%); and 1.52 (1.37-1.68) for HbA1c >82 mmol/mol (9.7%). In the cubic spline model, a reduction of the adjusted risk was observed within the lower HbA1c range until 53 mmol/mol (7.0%), with a hazard ratio of 0.78 (0.73-0.82) per standard deviation, and increased thereafter (P for non-linearity <0.001). As compared to patients without sepsis, the adjusted hazard ratio for death among patients with sepsis was 4.16 (4.03-4.30).</p> <p><b>Conclusions</b></p> <p>In a nationwide cohort of individuals with type 2 diabetes, we found a U-shaped association between HbA1c and sepsis and a four-fold increased risk of death among those developing sepsis. </p>


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21595-e21595
Author(s):  
A. Reza Djavid ◽  
Benjamin T. Fullerton ◽  
Samuel W. Wang ◽  
Meghan S. Drastal ◽  
Luke W. Barker ◽  
...  

e21595 Background: Cutaneous melanoma is an aggressive dermatologic malignancy with stage II-III recurrence rates ranging from 27-46%. Analysis of the tumor microenvironment (TME) is a promising mechanism to identify the patients who would benefit most from adjuvant immunotherapy given the risk for potential immune-related adverse events. Previous research by our group established the potential of utilizing CD3+CD8+ cytotoxic lymphocyte (CTL) and CD68+ macrophage densities, as well as the CTL/macrophage ratio in the TME, as prognostic biomarkers for metastatic progression and disease-specific survival (DSS). We sought to test the prognostic accuracy of the CTL/macrophage ratio in a second cohort of stage II-III melanoma patients from the Geisinger Health System. Methods: We utilized quantitative multiplex immunofluorescence (qmIF) to analyze 43 patient samples with stage II-III melanoma to validate the prospective biomarkers established in our previous CUIMC cohort. TME cell phenotype and cell density data were acquired for both the stroma as well as the combined tumor + stroma (“total TME”) via utilization of a trainable machine learning program. Cell densities and ratios were subsequently analyzed to determine associations with clinical outcomes including both disease recurrence and DSS. Results: In patients without distant metastatic recurrence (DMR), the density of CTLs and activated HLA-DR+ CTLs was higher in both the stroma ( p= 0.0003, p= 0.0152, respectively), as well as total TME ( p< 0.0001, p= 0.0165, respectively), when compared to those with DMR. The CTL/macrophage ratio in the total TME was greater in those without recurrence ( p= 0.0031). The ratio of CTLs to MPO+ neutrophils was higher in both the stroma ( p= 0.0015) and the total TME ( p= 0.0016) in those without recurrence. Survival analysis of 38 patients with known cause of death indicated a higher CTL/macrophage ratio in the total TME was associated with improved survival ( p= 0.0005). Improved survival was also associated with high CTL/neutrophil ratios in both the stroma ( p< 0.0001) and the total TME ( p< 0.0001). Cox regression analysis demonstrated a strong association between low CTL/macrophage and CTL/neutrophil ratios in the total TME and an increased risk of death ( p= 0.003, HR: 7.24, CI: 1.99-26.31; p= 0.003, HR: 22.35, CI: 2.87-173.97, respectively). Conclusions: Patients without disease recurrence display an increased infiltration of CTLs and activated HLA-DR+ CTLs, in addition to higher ratios of CTLs to macrophages and neutrophils, in the TME. High CTL/macrophage and CTL/neutrophil ratios in the total TME were also independently associated with improved DSS. Validation is underway with an additional cohort to further explore the use of these prospective biomarkers as clinical decision-making support tools to help guide the determination of patient risk and the use of adjuvant immunotherapy in melanoma.


2005 ◽  
Vol 23 (7) ◽  
pp. 1473-1482 ◽  
Author(s):  
Derek L. Dai ◽  
Magdalena Martinka ◽  
Gang Li

Purpose Akt is a serine/threonine kinase that leads to stimulation of cell cycle progression, cell proliferation, and inhibition of apoptosis. To investigate the role of Akt in melanoma pathogenesis, we examined the expression of phospho-Akt (p-Akt; Ser-473) in melanocytic lesions at different stages and analyzed the correlations between the p-Akt expression level and clinicopathologic factors and patient survival. Patients and Methods We evaluated the p-Akt expression in 12 cases of normal nevi, 58 cases of dysplastic nevi, 170 cases of primary melanomas, and 52 cases of melanoma metastases using tissue microarray and immunohistochemistry. Results Strong p-Akt expression was observed in 17%, 43%, 49%, and 77% of the biopsies in normal nevi, dysplastic nevi, primary melanoma, and melanoma metastases, respectively. Significant differences for p-Akt staining pattern were observed between normal nevi and primary melanomas (P < .05), and between primary melanomas and melanoma metastases (P < .001). Furthermore, our Kaplan-Meier survival curves showed that strong p-Akt expression is inversely correlated with both overall and disease-specific 5-year survival of patients with primary melanoma (P < .05 for both). Strikingly, our multivariate Cox regression analysis revealed that p-Akt is an independent prognostic factor in low-risk melanomas (thickness ≤ 1.5 mm; relative risk, 6.44; 95% CI, 1.28 to 32.55; P = .018). Conclusion The expression of p-Akt increases dramatically with melanoma invasion and progression and is inversely correlated with patient survival. In addition, p-Akt may serve as an independent prognostic marker and help to identify those patients with low-risk melanomas who are at increased risk of death.


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