Abstract 144: Roles of Aging and Cellular Senescence in Intracranial Aneurysm Rupture

Background: Aging is an independent risk factor for the rupture of intracranial aneurysm. One of the hallmarks of aging is chronic tissue inflammation. Sirtuin-1 keeps inflammation in check through the deacetylation of various proteins. It is well known that the levels of Sirtuin-1 in vascular tissues decrease with aging, resulting in chronic vascular inflammation. Age-dependent decrease in Sirtuin-1 may explain the link between aging and increased risk for aneurysmal rupture. Hypothesis: Reduction of Sirtuin-1 promotes aneurysmal rupture by inducing sustained aneurysmal wall inflammation. Methods: First, we assessed the levels of Sirtuin-1 expression in intracranial aneurysm tissues from patients older than 70 y.o. and compared with those from the younger patients (40 to 50 y.o.). Second, using a mouse model, we tested effects of Sirtuin-1 specific activator SRT1720 (15mg/kg/day) and specific inhibitor EX-527 (2.5mg/kg/day) on the development of aneurysmal rupture. In addition, we assessed the mRNA expression of inflammatory cytokines (IL-6, IL-1beta, MCP-1, and MMP-9) in cerebral arteries and aneurysms in mice treated with vehicle, SRT1720, or EX-527. Results: Sirtuin-1 expression levels in intracranial aneurysm tissues from the older patients were lower than those from the younger patients. The pharmacological inhibition of Sirtuin-1 increased rupture rate in mice (vehicle vs. EX-527: 58% vs. 88%, P <0.05). Moreover, the pharmacological activation of Sirtuin-1 reduced rupture rate in mice (vehicle vs. SRT1720: 80% vs. 50%, P <0.05). Levels of IL-6, MMP-9 mRNAs in cerebral arteries were significantly higher in the inhibitor group than in the vehicle group. On the other hand, both mRNA levels were lower in the activator group than in the vehicle group. Conclusions: Our findings suggest that the reduction of Sirtuin-1 promotes aneurysmal rupture via the induction of inflammation. This may explain the increased risk for aneurysmal subarachnoid hemorrhage in the older population. Our findings may become a basis for future studies to develop new therapies that target Sirtuin-1 for the prevention of aneurysmal rupture, especially in older patients.

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Abstract P118: Inhibition of Endoplasmic Reticulum Stress Prevents Intracranial Aneurysmal Rupture in a Mouse Model

Hypertension ◽

10.1161/hyp.70.suppl_1.p118 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Daisuke Kudo ◽

Hajime Furukawa ◽

Satoru Eguchi ◽

Tomoki Hashimoto

Keyword(s):

Endoplasmic Reticulum ◽

Angiotensin Ii ◽

Mouse Model ◽

Er Stress ◽

Intracranial Aneurysms ◽

Vehicle Group ◽

Systemic Hypertension ◽

Aneurysmal Rupture ◽

Rupture Rate ◽

Salt Hypertension

Background: Aneurysmal subarachnoid hemorrhage (SAH) can cause significant mortality and morbidity. To develop a therapy for prevention of intracranial aneurysmal rupture and subsequent SAH, it is important to clarify the mechanism of intracranial aneurysmal rupture. Stimulation of the renin-angiotensin system (RAS) causes hypertension and cardiovascular remodeling. Recent evidence shows that angiotensin II enhances endoplasmic reticulum (ER) stress and inhibition of ER stress prevents angiotensin II-induced vascular remodeling but not hypertension in mice. RAS has also been implicated in intracranial aneurysms. We have previously shown that angiotensin II receptor blocker (losartan) prevented intracranial aneurysmal rupture in a mouse model without affecting systemic hypertension. To clarify the mechanism of intracranial aneurysmal rupture via RAS, we have tested our hypothesis that inhibition of ER stress prevents intracranial aneurysmal rupture in a mouse model. Method: We used a mouse model of intracranial aneurysms in which spontaneous aneurysmal rupture causes neurologic symptoms. Intracranial aneurysms were induced in wild type mice by a single stereotactic injection of elastase (35mU) into the cerebrospinal fluid at right basal cistern and deoxycorticosterone (DOCA)-salt hypertension. Vehicle or 4-phenylbutyric acid (PBA, ER stress inhibitor , 100mg/kg/day) was subcutaneously injected into all mice once a day. To detect aneurysmal rupture, we performed daily neurological examinations. Symptomatic mice were euthanized immediately when they developed neurological symptoms, and all asymptomatic mice were euthanized 21 days after aneurysm induction. The incidence of aneurysms and rupture rate were compared between vehicle group and PBA group. Results: The incidence of aneurysms was not significantly different between two groups (100% in vehicle, 20 of 20 vs. 87% in PBA, 20 of 23, p=0.09). However, rupture rate was significantly lower in the PBA group (60%, 12 of 20) than the vehicle group (95%, 19 of 20). (p=0.008). Conclusion: Inhibition of ER stress reduced aneurysmal rupture in a mouse model of intracranial aneurysm induced by combination of elastase injection and DOCA-salt hypertension.

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Newly Diagnosed Myeloma Pateints Are at Risk of Venous Thrombotic Events - High Risk Patients Need To Be Identified and Recieve Thromboprophylaxis: The MRC Experience.

Blood ◽

10.1182/blood.v104.11.2395.2395 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2395-2395

Author(s):

Faith E. Davies ◽

J. Anthony Child ◽

Kim Hawkins ◽

Susan Bell ◽

Julia Brown ◽

...

Keyword(s):

High Risk ◽

Older Patients ◽

Autologous Transplantation ◽

High Dose ◽

Central Venous ◽

Thrombotic Risk ◽

Younger Patients ◽

High Risk Patients ◽

Increased Risk ◽

Risk Patients

Abstract Standard treatment for younger patients with presenting myeloma is VAD followed by high-dose melphalan with stem cell support. However this regimen requires a central venous catheter with risks of recurrent line infections and central venous thrombus. A number of oral alternatives have been used including dexamethasone (Dex), thalidomide (Thal) or combinations (Thal/Dex), although to date no randomized control trial has compared an intravenous with oral induction therapy. In older patients melphalan/prednisolone (MP) remains the standard approach. Thal combinations (MPT, CTD, DVdT) improve response rates and providing side effects can be managed effectively may also be appropriate for an elderly population. Patients with myeloma have an increased risk of venous thrombotic events (VTEs), and presenting patients receiving Thal may be at increased risk due to bulk disease. Combination with anthracyclines may also exacerbate this risk. The MRC Myeloma IX trial has been designed to address some of these issues. Younger patients are randomized to receive intravenous CVAD or an oral Thal containing regimen, CTD prior to autologous transplantation; older patients are randomized to MP or the Thal containing regimen, CTDa. At trial initiation (May 2003) physicians were advised that patients should start low-dose Thal (100mg od in the intensive and 50mg od in the non-intensive arm) and slowly dose escalate to 200mg. Patients at high risk of VTE should be considered for full anticoagulation with either warfarin or LMWH. As of Aug 2004 420 patients (239 intensive, 181 non-intensive) have been randomized and a total of 30 VTEs in 28 patients have been reported (22 intensive, 6 non-intensive). In the intensive arm there were 8 DVT, 9 PE and 7 line-related thromboses. In the non-intensive arm there were 4 DVT and 2 PE. CVAD CTD CTDa MP DVT 4.2% 2.5% 4.4% 0% PE 1.7% 5.8% 2.2% 0% Line related 5.0% 0.8% NA NA Total 10.9% 9.1% 6.6% 0% The median time from randomization to DVT/PE was 54.5 days (range 15–113). 4 patients were identified who had additional risk factors (2 immobility, 1 recent operation, 1 renal failure). Only 1 patient was receiving prophylaxis having previously suffered a DVT. There was one PE-related death. Importantly 2 PE and 5 DVT occurred in patients not receiving Thal therapy. All central thrombosis occurred in relation to the central line. In the non-intensive arm the addition of Thal increased VTE risk compared to MP. In conclusion myeloma patients have an increased incidence of VTE (5.9%–8.3%) although in this study so far patients on MP appear to have no excess thrombotic risk. Patients receiving infusional regimes are also at increased risk of line-related events (additional 5.0%). Using the combination of a slowly increasing Thal dose and thromboprophylaxis based on identification of high risk patients the addition of Thal marginally increased DVT/PE risk over and above the risk seen in patients with infusional regimens, but even in a large study such as this the number of events are too small to make firm recommendations. Currently our advice remains unchanged and ALL high risk patients should receive thromboprophylaxis.

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TLR4 (Toll-Like Receptor 4) Mediates the Development of Intracranial Aneurysm Rupture

Hypertension ◽

10.1161/hypertensionaha.118.12595 ◽

2020 ◽

Vol 75 (2) ◽

pp. 468-476

Author(s):

Kazuha Mitsui ◽

Taichi Ikedo ◽

Yoshinobu Kamio ◽

Hajime Furukawa ◽

Michael T. Lawton ◽

...

Keyword(s):

Intracranial Aneurysm ◽

Knockout Mice ◽

Critical Factor ◽

Inflammatory Cells ◽

Aneurysm Rupture ◽

Primary Response ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Aneurysmal Rupture ◽

Rupture Rate

Inflammation is emerging as a critical factor in the pathophysiology of intracranial aneurysm. TLR4 (toll-like receptor 4) contributes not only to the innate immune responses but also to the inflammatory processes associated with vascular disease. Therefore, we examined the contribution of the TLR4 pathway to the development of the rupture of intracranial aneurysm. We used a mouse model of intracranial aneurysm. TLR4 inhibition significantly reduced the development of aneurysmal rupture. In addition, the rupture rate and levels of proinflammatory cytokines were lower in TLR4 knockout mice than the control littermates. Macrophage/monocyte-specific TLR4 knockout mice had a lower rupture rate than the control littermate mice. Moreover, the deficiency of MyD88 (myeloid differentiation primary-response protein 88), a key mediator of TLR4, reduced the rupture rate. These findings suggest that the TLR4 pathway promotes the development of intracranial aneurysmal rupture by accelerating inflammation in aneurysmal walls. Inhibition of the TLR4 pathway in inflammatory cells may be a promising approach for the prevention of aneurysmal rupture and subsequent subarachnoid hemorrhage.

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Real-world outcomes in older adults treated with immunotherapy: A United Kingdom multicenter series of 2,049 patients.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.12026 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 12026-12026

Author(s):

Anna Claire Olsson-Brown ◽

Mark Baxter ◽

Caroline Dobeson ◽

Laura Feeney ◽

Rebecca Lee ◽

...

Keyword(s):

Older Adults ◽

Health Service ◽

Adverse Events ◽

Real World ◽

Older Patients ◽

Single Agent ◽

Receive Combination Therapy ◽

Younger Patients ◽

Increased Risk ◽

The Impact

12026 Background: Immune checkpoint inhibitor (ICI) therapy is now commonly used in a range of tumours and settings. Most data relating to outcomes and rates of immune-related adverse events (irAE) is derived from clinical trial or registry populations and small case series. Limited data exist for patients aged > 75 years. Here we present a multi-centre, real-world analysis of the outcomes and incidence of irAEs in older adults managed within a single comprehensive public health service. We also compare these outcomes to younger patients in the same cohort. Methods: A retrospective analysis of 2049 patients treated with ICIs was undertaken across 12 centres. All patients were managed within the UK National Health Service outside of a trial setting between June 2016 and September 2018. Patients received either ICI monotherapy (MT) or duel combination ICI therapy (CT) for malignant melanoma (MM), non-small cell lung cancer (NSCLC) or renal cell cancer (RCC). Data were collected using a standardised, collection tool. IrAEs ≥ grade 2 or all-grade endocrinopathies were recorded as per the Common Terminology Criteria for Adverse Events (V5) (CTCAE). Statistical analyses were performed using T-tests, Mann-Whitney and Chi-squared. Kaplan-Meier analysis and log-rank test were used for overall survival (OS) analysis. Results: 409 (20%) of patients were aged > 75 years(a), 1413 (69%) aged 50-75(b) and 227 (11.1%) aged < 50(c). There was no difference in sex, ethnicity or PD-L1 status (in the NSCLC cohort) between groups. Older patients were less likely to receive combination therapy (3%(a) v 13%(b) v 34%(c), p < 0.001). There was no difference in median OS across age groups in the cohort as a whole (p = 0.822) or for the individual tumour groups when treated with single agent ICI. Across the total cohort patients aged > 75 had no increased risk of any irAE (35%(a) v 33%(b) v 41%(c),p = 0.074). However there was an increase in irAEs in older patients treated with MT (36%(a) v 26(b) v 25%(c), p = 0.011) However there was no difference in the > 75s with regard to severe (G3/4) toxicity, toxicity type, admission or discontinuation due to toxicity in the aPD-1 group. In the overall cohort younger patients were more likely to develop irAEs and be admitted. Conclusions: Patients aged > 75 years treated with anti-PD1 therapy in the standard of care setting derive similar survival benefit to younger patients. There was no increase in ≥G3 toxicity. Our data support the safety of single agent aPD-1 ICI therapy in older adults and provide reassurance relating to the impact of toxicity.[Table: see text]

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Prevention of hemorrhage-induced renal vasoconstriction and hypoxia by angiotensin II type 1 receptor antagonism in pigs

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00073.2021 ◽

2021 ◽

Author(s):

Stephanie Franzén ◽

Erik Näslund ◽

Helen Wang ◽

Robert Frithiof

Keyword(s):

Angiotensin Ii ◽

Oxygen Delivery ◽

Kidney Injury ◽

Large Animal Model ◽

Vehicle Group ◽

Large Animal ◽

Mrna Levels ◽

Renal Vasoconstriction ◽

Arterial Blood ◽

Increased Risk

Angiotensin II (AngII) is a potent vasoconstrictor and may reduce renal blood flow (RBF), causing renal hypoxia. Hypotensive hemorrhage elevates plasma AngII levels and is associated with increased risk of acute kidney injury. We hypothesized that AngII antagonism prevents renal vasoconstriction and hypoxia caused by hemorrhage. Pigs were anaesthetized, surgically prepared and randomized to intravenous losartan (1.5 mg kg-1 h-1, n=8) or an equal volume of intravenous Ringer's acetate (vehicle-treated, n=8). Hemorrhage was induced by continuous aspiration of blood to reach and sustain mean arterial blood pressure of <50 mmHg for 30 minutes. Plasma AngII levels, hemodynamics and oxygenation were assessed 60 minutes pre-hemorrhage, 30-minutes after the start of hemorrhage and 60 minutes post-hemorrhage. Erythropoietin mRNA was analyzed in cortical and medullary tissue sampled at the end of the experiment. Hypotensive hemorrhage increased plasma AngII levels and decreased RBF and oxygen delivery in both groups. Losartan-treated animals recovered in RBF and oxygen delivery, whereas vehicle-treated animals had persistently reduced RBF and oxygen delivery. In accordance, renal vascular resistance increased over time post hemorrhage in vehicle-treated animals but was unchanged in losartan-treated animals. Renal oxygen extraction rate and cortical erythropoietin mRNA levels increased in the vehicle group but not in the losartan group. In conclusion, AngII antagonism alleviates prolonged renal vasoconstriction and renal hypoxia in a large animal model of hypotensive hemorrhage.

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An International Comparison Of Survival Disparities In Patients With Lymphoma and Myeloma

Blood ◽

10.1182/blood.v122.21.2925.2925 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2925-2925

Author(s):

Dianne Pulte ◽

Theresa Redaniel ◽

Mona Jeffreys

Keyword(s):

Older Patients ◽

Excess Mortality ◽

Conflicts Of Interest ◽

Relative Survival ◽

The United States ◽

Life Tables ◽

Younger Patients ◽

Increased Risk ◽

The Us ◽

The Uk

Abstract Background Relative survival in older patients with lymphomas is significantly lower than in younger patients. Possible reasons for the discrepancy may include increased aggressiveness of the disease in older patients, increased frailty and co-morbidities complicating treatment in older patients, and under-treatment of older patients due to concern about increased risk of intolerance to treatment. Distinguishing between these problems on a population basis can be difficult as clinical trial data often provides data only on the “ideal” patient and may not be applicable to the general population. Here, we determine 5-year relative survival and excess mortality by age for patients diagnosed with Hodgkin's lymphoma (HL), non-Hodgkin lymphoma (NHL) and multiple myeloma. Methods Data was obtained from the Surveillance, Epidemiology, and End Results (SEER) database in the United States (US) and Cancer Registry data covering the whole of England (UK) for all patients diagnosed with HL, NHL and myeloma between 1996 and 2010. Five year relative survival was calculated by categories of age (15-24; 25-44; 45-64; 65-74 and 75+ years) using period analysis. Relative survival was calculated using age, race, gender, and country specific life tables. In addition, region specific life tables were used in the UK. Excess mortality modellingwas used to determine excess risk for older compared to younger patients, using patients age 25-44 for the reference group. Results Five year relative survival was lower for older patients diagnosed with HL, NHL, and myeloma in the US and UK. The most dramatic difference in survival by age was observed for patients with HL among whom survival for 15-24 year olds was 96.2% and 92.5% in 2006-10 in the US and UK, respectively but only 51.0% and 22.8%, respectively, for patients age 75+, representing an excess mortality of 14.02 (95% CI 12.22-16.09) and 15.69 (14.21-17.33), respectively, for the US and UK for patients age 75+ compared to 25-44. Similar, although less extreme, differences were observed for NHL and myeloma (see Table). Excess mortality ratios of 1.91 (1.84-1.99) and 3.81 (3.67-3.96) was observed for patients with NHL at age 75+ as compared to 25-44 in the US and UK, respectively. For patients with myeloma, excess mortality ratios of 2.79 (2.52-3.09) and 3.60 (3.27-3.962) for patients age 75+ compared to 25-44 were observed, respectively, for the US and UK. Adjustment for gender, ethnicity, period of diagnosis, and income (UK data only) did not significantly affect excess mortality ratios. Conclusions Survival of patients with lymphoma, especially patients with HL, is dramatically lower for older patients in both the US and UK. Older patients with lymphoma had a higher survival in the US as compared to the UK. This finding suggests that older patients in the UK may experience under-treatment. Physicians should be encouraged to evaluate patients' frailty and co-morbidities as well as their age when considering treatment options for patients with lymphoma and myeloma. Disclosures: No relevant conflicts of interest to declare.

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LO62: Systolic blood pressure is a strong predictive marker for TIA and mild stroke in younger patients

CJEM ◽

10.1017/cem.2017.124 ◽

2017 ◽

Vol 19 (S1) ◽

pp. S49

Author(s):

C. Sedgwick ◽

M. Bibok ◽

N.S. Croteau ◽

M.L. Lesperance ◽

R. Balshaw ◽

...

Keyword(s):

Blood Pressure ◽

Logistic Regression ◽

Systolic Blood Pressure ◽

Regression Model ◽

Older Patients ◽

Significant Risk ◽

Younger Patients ◽

Increased Risk ◽

Age And Sex

Introduction: Age and systolic blood pressure (SBP) are important predictors of Acute Cerebrovascular Syndrome (ACVS). Yet, the effect of SBP is confounded by age, making its independent contribution to ACVS risk difficult to quantify. Here we use logistic regression to explore the role of SBP in younger and older ED patients. Methods: Data comprised 1019 ED patients (ACVS 70%, 30% non-ACVS) enrolled during a 28-month period of an ongoing prospective, observational, multi-site stroke biomarker study (SpecTRA). We used logistic regression to examine the effects of age, sex, and the age:SBP interaction as predictive markers of the diagnosis of ACVS. Results: Participants (53% male) ranged in age from 18 to 97 years (Q1=58, median=70, Q3=80). SBP ranged from 84 to 248 mmHg (Q1=137, median=154, Q3=174). In our initial regression model, age, sex, SBP and the age:SBP interaction were all significant (p<0.01). Using cubic regression splines for age, sbp and their interaction yields the same conclusion (p<0.01). To better understand the role of SBP in younger vs. older patients, we stratified the sample at the median age (70 years of age). In the younger group (n=510), participants were 55% male, 60% ACVS, and had SBP ranging from 91 to 236 mmHg (Q1=133, median=148, Q3=165). In the older group (n=509), participants were 51% male, 82% ACVS and had SBP ranging from 84 to 248 mmHg (Q1=143, median=159, Q3=179), a shift of approximately 10 mmHg between the groups. The logistic regression model was then fit separately to each group without the age:SBP interaction term. In the younger group, we found SBP to be highly significant (p<0.001), with an odds-ratio (OR) of 1.18 per 10 mmHg (95% CI: 1.10-1.29). In the older group, we found that SBP was not significant (p=0.91), with an OR of 1.00 per 10 mmHg (95% CI: 0.91-1.08). Age and sex were also significant risk factors in the younger group (each p<0.01), though not in the older group (both p>0.07). Conclusion: Our findings suggest that for ED patients suspected of ACVS, SBP is a clinically relevant predictor for younger patients, with higher SBP associated with an increased risk of ACVS, regardless of patient age and sex. SBP does not appear to be a strong predictor for patients over 70. ED physicians can leverage this finding by attributing greater importance to elevated SBP in younger patients than older patients when working toward a clinical suspicion of ACVS.

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P070 Tele-consultations from the patient’s perspective: during the pandemic and beyond

Rheumatology ◽

10.1093/rheumatology/keab247.068 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Natasha Cleaton ◽

Sabrina Raizada

Keyword(s):

Older Patients ◽

Significant Proportion ◽

Clinical Excellence ◽

Vulnerable Groups ◽

British Society ◽

Younger Patients ◽

Telephone Consultation ◽

Face To Face ◽

Increased Risk

Abstract Background/Aims The current COVID-19 pandemic has challenged healthcare systems worldwide stimulating a transformation of NHS services to cope with increased acute demand, while aiming to minimise viral transmission. A significant proportion of rheumatology patients are considered ‘clinically extremely vulnerable’ and are at increased risk of COVID-19. With this in mind, alongside national guidance from the British Society for Rheumatology and the National Institute of Clinical Excellence we adapted our services in response to COVID by mostly suspending face-to-face appointments for follow up patients, instead relying on telephone or virtual consultations with a face-to-face appointment if necessary in order to minimise risk to our patients. We aimed to evaluate our use of telephone consultations during the pandemic and gain understanding of our patients views of telephone consultations longer term. Methods We retrospectively surveyed rheumatology patients under active follow-up at the royal Wolverhampton trust who had a telephone consultation with a rheumatology consultant over a 4-week period (11/5/20- 4/6/20). Patients were invited to participate via a SMS text message containing an embedded web-link to the survey. Results were analysed using SPSS version 26. Results Surveys were sent to 1,213 patients; 306 (25.2%) patients completed the survey. Responders were mostly female; the predominant diagnosis was inflammatory arthritis. Ages included: 1 (0.3%) patient 16-29 years, 46 (15.0%) 30-49, 180 (58.8%) 50-69, and 79 (25.8%) aged >70 years. Regarding their telephone consultation, 86.6% of responders were satisfied with the consultation. During the current pandemic 81.4% of responders were pleased to have a telephone consult rather than face-to-face; 57.2% of responders would be happy for their next routine appointment to be a telephone clinic. A significantly higher proportion of patients <50 years preferred telephone consultations when compared to older patients (Chi2 [DF = 3]= 10.075, P = 0.018) and more younger patients had access to a smartphone than those in the older cohort (Chi2 [DF 3]= 20.919, P = <0.001). Conclusion Overall, the short-term switch to telephone consultation was well received by our cohort. The majority of patients were satisfied with their telephone consultation and most were pleased to have a telephone consult rather than a face-to-face appointment in the current pandemic. Just over half would be happy for their next routine appointment to be a telephone consultation, however, a significantly higher proportion of younger patients prefer telephone consultations compared to older patients and a greater number of younger patients have access to a smartphone compared to older patients. Further planning is required to ensure patients in older and other vulnerable groups are not excluded should telephone clinics become a more permanent fixture. Disclosure N. Cleaton: None. S. Raizada: None.

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Pre- and Perioperative Inflammatory Biomarkers in Older Patients Resected for Localized Colorectal Cancer: Associations with Complications and Prognosis

Cancers ◽

10.3390/cancers14010161 ◽

2021 ◽

Vol 14 (1) ◽

pp. 161

Author(s):

Troels Gammeltoft Dolin ◽

Ib Jarle Christensen ◽

Astrid Zedlitz Johansen ◽

Hans Jørgen Nielsen ◽

Henrik Loft Jakobsen ◽

...

Keyword(s):

Colorectal Cancer ◽

Older Patients ◽

Proportional Hazards ◽

Survival Rates ◽

Cox Proportional Hazards ◽

Inflammatory Biomarkers ◽

Younger Patients ◽

Proportional Hazards Regression ◽

Increased Risk ◽

Serum Crp

The association between pre- and perioperative inflammatory biomarkers, major complications, and survival rates after resection of colorectal cancer (CRC) in older patients is largely unknown. The aim was to investigate age-dependent differences in these associations. Serum CRP, IL-6, and YKL-40 were measured preoperatively and on the first and second day after resection of CRC (stages I–III) in 210 older (≥70 years) and 191 younger patients (<70 years). The results from the complications was presented as an odds ratio (OR, with a 95% confidence interval (CI)) with logistic regression. Results from the mortality rates were presented as a hazard ratio (HR, with a 95% CI) using Cox proportional hazards regression. The preoperative inflammatory biomarkers were higher in the older vs. the younger patients. The risk of complications was increased in older patients with a high preoperative CRP (OR = 1.25, 95% CI 1.03–1.53), IL-6 (OR = 1.57, 95% CI 1.18–2.08), and YKL-40 (OR = 1.66, 95% CI 1.20–2.28), but not in younger patients. Mortality was higher in younger patients with high preoperative YKL-40 (HR = 1.66, 95% CI 1.06–2.60). This was not found in older patients. Elevated preoperative inflammatory biomarkers among older patients were associated with an increased risk of complications, but not mortality. Preoperative inflammatory biomarkers may be useful in assessing the risk of a complicated surgical course in older patients with CRC.

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Lung cancer in older patients

Innovative medicine of Kuban ◽

10.35401/2500-0268-2021-22-2-65-71 ◽

2021 ◽

pp. 65-71

Author(s):

D. A. Kharagezov ◽

Yu. N. Lazutin ◽

S. P. Pyltsin ◽

A. G. Milakin ◽

O. N. Stateshny ◽

...

Keyword(s):

Lung Cancer ◽

Older Patients ◽

The Elderly ◽

Tumor Stage ◽

Social Programs ◽

Cancer Therapies ◽

Younger Patients ◽

Aggressive Cancer ◽

Increased Risk ◽

The Russian Federation

Increasing life expectancy is the goal of social programs in the Russian Federation as a reflection of the success of public health. Globally, there is a trend for aging of the population, contributing to an increased risk for lung cancer developing which is primarily a disease of the elderly. Chronologic age or performance scores alone are not accurate predictors of patients’ capacity for tolerating aggressive cancer therapies. Use of a comprehensive geriatric assessment to determine treatment strategy is able to reduce toxicities and treatment failures. Safe elderly patients are often able to tolerate surgical resection, radiation, and/or chemotherapy appropriate for their tumor stage, with outcomes similar to those of younger patients, albeit with higher rates of treatment-related toxicity.

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