Risks of Less Common Cancers in Proven Mutation Carriers With Lynch Syndrome

Purpose Patients with Lynch syndrome are at high risk for colon and endometrial cancer, but also at an elevated risk for other less common cancers. The purpose of this retrospective cohort study was to provide risk estimates for these less common cancers in proven carriers of pathogenic mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6. Patients and Methods Data were pooled from the German and Dutch national Lynch syndrome registries. Seven different cancer types were analyzed: stomach, small bowel, urinary bladder, other urothelial, breast, ovarian, and prostate cancer. Age-, sex- and MMR gene–specific cumulative risks (CRs) were calculated using the Kaplan-Meier method. Sex-specific incidence rates were compared with general population incidence rates by calculating standardized incidence ratios (SIRs). Multivariate Cox regression analysis was used to estimate the impact of sex and mutated gene on cancer risk. Results The cohort comprised 2,118 MMR gene mutation carriers (MLH1, n = 806; MSH2, n = 1,004; MSH6, n = 308). All cancers were significantly more frequent than in the general population. The highest risks were found for male small bowel cancer (SIR, 251; 95% CI, 177 to 346; CR at 70 years, 12.0; 95% CI, 5.7 to 18.2). Breast cancer showed an SIR of 1.9 (95% CI, 1.4 to 2.4) and a CR of 14.4 (95% CI, 9.5 to 19.3). MSH2 mutation carriers had a considerably higher risk of developing urothelial cancer than MLH1 or MSH6 carriers. Conclusion The sex- and gene-specific differences of less common cancer risks should be taken into account in cancer surveillance and prevention programs for patients with Lynch syndrome.

Download Full-text

Comparison of incidence rates and risk factors of heart failure between two male cohorts born 30 years apart

Heart ◽

10.1136/heartjnl-2019-316059 ◽

2020 ◽

Vol 106 (21) ◽

pp. 1672-1678

Author(s):

Constantinos Ergatoudes ◽

Per-Olof Hansson ◽

Kurt Svärdsudd ◽

Annika Rosengren ◽

Erik Östgärd Thunström ◽

...

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

Heart Disease ◽

Ischaemic Heart Disease ◽

Physical Inactivity ◽

Cox Regression ◽

Incidence Rates ◽

Cox Regression Analysis ◽

Increased Risk ◽

The Impact

ObjectiveTo compare two cohorts of middle-aged men from the general population born 30 years apart for incidence and predictors of heart failure (HF).MethodsTwo population samples of men, born in 1913 (n=855) and in 1943 (n=797), were examined at 50 years of age and followed up for 21 years (1963–1994 and 1993–2014). Cox regression analysis was used to examine the impact of different factors on the risk of developing HF.ResultsEighty men born in 1913 (9.4%) and 42 men born in 1943 (5.3%) developed HF during follow-up; adjusted HRs comparing the two cohorts (born 1943 vs 1913) were: 0.46 (95% CI 0.28 to 0.74, p=0.002). In both cohorts, higher body mass index, higher diastolic blood pressure, treatment for hypertension, onset of either atrial fibrillation (AF), ischaemic heart disease and diabetes mellitus were associated with higher risk of HF. Higher heart rate was associated with an increased risk only in men born in 1913, whereas higher systolic blood pressure (SBP), smoking, higher glucose, higher cholesterol and physical inactivity were associated with an increased risk in men born in 1943. AF contributed higher risk of incident HF, whereas SBP and physical inactivity contributed lower risk in men born in 1943 compared with men born in 1913.ConclusionsMen born in 1943 had half the risk of HF after their 50s than those born 30 years earlier. AF, obesity, ischaemic heart disease, diabetes and hypertension remain important precursors of HF.

Download Full-text

Higher glucocorticoid replacement doses are associated with increased mortality in patients with pituitary adenoma

Acta Endocrinologica ◽

10.1530/eje-17-0340 ◽

2017 ◽

Vol 177 (3) ◽

pp. 251-256 ◽

Cited By ~ 30

Author(s):

Casper Hammarstrand ◽

Oskar Ragnarsson ◽

Tobias Hallén ◽

Eva Andersson ◽

Thomas Skoglund ◽

...

Keyword(s):

Pituitary Adenoma ◽

General Population ◽

Excess Mortality ◽

Cox Regression ◽

Standardized Mortality Ratio ◽

Secondary Adrenal Insufficiency ◽

Cox Regression Analysis ◽

Mortality Ratio ◽

The Impact

Objective Patients with secondary adrenal insufficiency (AI) have an excess mortality. The objective was to investigate the impact of the daily glucocorticoid replacement dose on mortality in patients with hypopituitarism due to non-functioning pituitary adenoma (NFPA). Methods Patients with NFPA were followed between years 1997 and 2014 and cross-referenced with the National Swedish Death Register. Standardized mortality ratio (SMR) was calculated with the general population as reference and Cox-regression was used to analyse the mortality. Results The analysis included 392 patients (140 women) with NFPA. Mean ± s.d. age at diagnosis was 58.7 ± 14.6 years and mean follow-up was 12.7 ± 7.2 years. AI was present in 193 patients, receiving a mean daily hydrocortisone equivalent (HCeq) dose of 20 ± 6 mg. SMR (95% confidence interval (CI)) for patients with AI was similar to that for patients without, 0.88 (0.68–1.12) and 0.87 (0.63–1.18) respectively. SMR was higher for patients with a daily HCeq dose of >20 mg (1.42 (0.88–2.17)) than that in patients with a daily HCeq dose of 20 mg (0.71 (0.49–0.99)), P = 0.017. In a Cox-regression analysis, a daily HCeq dose of >20 mg was independently associated with a higher mortality (HR: 1.88 (1.06–3.33)). Patients with daily HCeq doses of ≤20 mg had a mortality risk comparable to patients without glucocorticoid replacement and to the general population. Conclusion Patients with NFPA and AI receiving more than 20 mg HCeq per day have an increased mortality. Our data also show that mortality in patients substituted with 20 mg HCeq per day or less is not increased.

Download Full-text

Long-Term Clinical Outcome in Elderly Patients Undergoing Mitral Valve Repair

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0040-1716324 ◽

2020 ◽

Author(s):

Julia Götte ◽

Armin Zittermann ◽

Kavous Hakim-Meibodi ◽

Masatoshi Hata ◽

Rene Schramm ◽

...

Keyword(s):

Mitral Valve ◽

General Population ◽

Elderly Patients ◽

Cox Regression ◽

Functional Class ◽

Tricuspid Valve Repair ◽

Valve Repair ◽

Cox Regression Analysis

Abstract Background Long-term data on patients over 75 years undergoing mitral valve (MV) repair are scarce. At our high-volume institution, we, therefore, aimed to evaluate mortality, stroke risk, and reoperation rates in these patients. Methods We investigated clinical outcomes in 372 patients undergoing MV repair with (n = 115) or without (n = 257) tricuspid valve repair. The primary endpoint was the probability of survival up to a maximum follow-up of 9 years. Secondary clinical endpoints were stroke and reoperation of the MV during follow-up. Univariate and multivariable Cox regression analysis was performed to assess independent predictors of mortality. Mortality was also compared with the age- and sex-adjusted general population. Results During a median follow-up period of 37 months (range: 0.1–108 months), 90 patients died. The following parameters were independently associated with mortality: double valve repair (hazard ratio, confidence interval [HR, 95% CI]: 2.15, 1.37–3.36), advanced age (HR: 1.07, CI: 1.01–1.14 per year), diabetes (HR: 1.97, CI: 1.13–3.43), preoperative New York Heart Association (NYHA) functional class (HR: 1.41, CI: 1.01–1.97 per class), and operative creatininemax levels (HR: 1.32, CI: 1.13–1.55 per mg/dL). The risk of stroke in the isolated MV and double valve repair groups at postoperative year 5 was 5.0 and 4.1%, respectively (p = 0.65). The corresponding values for the risk of reoperation were 4.0 and 7.0%, respectively (p = 0.36). Nine-year survival was comparable with the general population (53.2 vs. 53.1%). Conclusion Various independent risk factors for mortality in elderly MV repair patients could be identified, but overall survival rates were similar to those of the general population. Consequently, our data indicates that repairing the MV in elderly patients represents a suitable and safe surgical approach.

Download Full-text

Cumulative risks of colorectal cancer in Han Chinese patients with Lynch syndrome in Taiwan

Scientific Reports ◽

10.1038/s41598-021-88289-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Abram Bunya Kamiza ◽

Wen-Chang Wang ◽

Jeng-Fu You ◽

Reiping Tang ◽

Huei-Tzu Chien ◽

...

Keyword(s):

Colorectal Cancer ◽

Lynch Syndrome ◽

Cumulative Risk ◽

Germline Mutations ◽

Han Chinese ◽

Chinese Patients ◽

Mutation Carriers ◽

Amsterdam Criteria ◽

Cumulative Risks ◽

Age And Sex

AbstractPatients with Lynch syndrome have a high risk of colorectal cancer (CRC). In this study, we estimated the age- and sex-specific cumulative risks of CRC in Han Chinese patients with Lynch syndrome caused by the pathogenic germline mutations in MLH1 or MSH2 in Taiwan. Based on 321 mutation carriers and 419 non-mutation carriers from 75 pedigrees collected in an Amsterdam criteria family registry in Taiwan, the age- and sex-specific cumulative risks of CRC in male carriers of mutation in MLH1 and MSH2 at the age of 70 years were 60.3% (95% confidence interval (CI) = 31.1%–89.9%) and 76.7% (95% CI = 37.2%–99.0%), respectively. For females, the cumulative risks of CRC at the age of 70 were estimated to be 30.6% (95% CI = 14.3%–57.7%) and 49.3% (95% CI = 21.9%–84.5%) in the carriers of MLH1 and MSH2 germline mutations, respectively. In conclusion, the cumulative risks of CRC at the age of 70 in the Han Chinese patients is higher in mutation carriers than non-mutation carriers and male mutation carriers have a higher cumulative risk of developing CRC than the female mutation carriers.

Download Full-text

Impact of Hybrid Operating Rooms on Long-Term Clinical Outcomes Following Fenestrated and Branched Endovascular Aortic Repair

Journal of Endovascular Therapy ◽

10.1177/1526602821996725 ◽

2021 ◽

pp. 152660282199672

Author(s):

Giovanni Tinelli ◽

Marie Bonnet ◽

Adrien Hertault ◽

Simona Sica ◽

Gian Luca Di Tanna ◽

...

Keyword(s):

Operating Room ◽

Clinical Outcomes ◽

Cox Regression ◽

Statistical Significance ◽

Aortic Aneurysms ◽

Study Patient ◽

Cox Regression Analysis ◽

Significant Difference ◽

The Impact

Purpose: Evaluate the impact of hybrid operating room (HOR) guidance on the long-term clinical outcomes following fenestrated and branched endovascular repair (F-BEVAR) for complex aortic aneurysms. Materials and Methods: Prospectively collected registry data were retrospectively analyzed to compare the procedural, short- and long-term outcomes of consecutive F-BEVAR performed from January 2010 to December 2014 under standard mobile C-arm versus hybrid room guidance in a high-volume aortic center. Results: A total of 262 consecutive patients, including 133 patients treated with a mobile C-arm equipped operating room and 129 with a HOR guidance, were enrolled in this study. Patient radiation exposure and contrast media volume were significantly reduced in the HOR group. Short-term clinical outcomes were improved despite higher case complexity in the HOR group, with no statistical significance. At a median follow-up of 63.3 months (Q1 33.4, Q3 75.9) in the C-arm group, and 44.9 months (Q1 25.1, Q3 53.5, p=0.53) in the HOR group, there was no statistically significant difference in terms of target vessel occlusion and limb occlusion. When the endograft involved 3 or more fenestrations and/or branches (complex F-BEVAR), graft instability (36% vs 25%, p=0.035), reintervention on target vessels (20% vs 11%, p=0.019) and total reintervention rates (24% vs 15%, p=0.032) were significantly reduced in the HOR group. The multivariable Cox regression analysis did not show statistically significant differences for long-term death and aortic-related death between the 2 groups. Conclusion: Our study suggests that better long-term clinical outcomes could be observed when performing complex F-BEVAR in the latest generation HOR.

Download Full-text

Diabetes mellitus was not associated with lower amputation-free survival after open revascularization for chronic limb-threatening ischemia – A nationwide propensity score adjusted analysis

Vascular Medicine ◽

10.1177/1358863x211008249 ◽

2021 ◽

pp. 1358863X2110082

Author(s):

Erika Lilja ◽

Anders Gottsäter ◽

Mervete Miftaraj ◽

Jan Ekelund ◽

Björn Eliasson ◽

...

Keyword(s):

Diabetes Mellitus ◽

Propensity Score ◽

Vascular Surgery ◽

Incidence Rate ◽

Cox Regression ◽

Major Amputation ◽

Incidence Rates ◽

Major Adverse Cardiovascular Events ◽

Cox Regression Analysis ◽

Number Of Patients

The risk of major amputation is higher after urgently planned endovascular therapy for chronic limb-threatening ischemia (CLTI) in patients with diabetes mellitus (DM). The aim of this nationwide cohort study was to compare outcomes between patients with and without DM following urgently planned open revascularization for CLTI from 2010 to 2014. Out of 1537 individuals registered in the Swedish Vascular Registry, 569 were registered in the National Diabetes Register. A propensity score adjusted Cox regression analysis was conducted to compare outcome between the groups with and without DM. Median follow-up was 4.3 years and 4.5 years for patients with and without DM, respectively. Patients with DM more often had foot ulcers ( p = 0.034) and had undergone more previous amputations ( p = 0.001) at baseline. No differences in mortality, cardiovascular death, major adverse cardiovascular events (MACE), or major amputation were observed between groups. The incidence rate of stroke was 70% higher (95% CI: 1.11–2.59; p = 0.0137) and the incidence rate of acute myocardial infarction (AMI) 39% higher (95% CI: 1.00–1.92; p = 0.0472) among patients with DM in comparison to those without. Open vascular surgery remains a first-line option for a substantial number of patients with CLTI, especially for limb salvage in patients with DM. The higher incidence rates of stroke and AMI among patients with DM following open vascular surgery for infrainguinal CLTI require specific consideration preoperatively with the aim of optimizing medical treatment to improve cardiovascular outcome postoperatively.

Download Full-text

Impact of Cardiovascular Failure in Intensive CareUnit-Acquired Pneumonia: A Single-Center, Prospective Study

Antibiotics ◽

10.3390/antibiotics10070798 ◽

2021 ◽

Vol 10 (7) ◽

pp. 798

Author(s):

Ignacio Martin-Loeches ◽

Adrian Ceccato ◽

Marco Carbonara ◽

Gianluigi li Bassi ◽

Pierluigi di Natale ◽

...

Keyword(s):

Cox Regression ◽

University Hospital ◽

Single Center ◽

Cox Regression Analysis ◽

Cardiovascular Failure ◽

Icu Length Of Stay ◽

Patients At Risk ◽

Surgical Icus ◽

Pulmonary Superinfection ◽

The Impact

Background: Cardiovascular failure (CVF) may complicate intensive care unit-acquired pneumonia (ICUAP) and radically alters the empirical treatment of this condition. The aim of this study was to determine the impact of CVF on outcome in patients with ICUAP. Methods: A prospective, single-center, observational study was conducted in six medical and surgical ICUs at a University Hospital. CVS was defined as a score of 3 or more on the cardiovascular component of the Sequential Organ Failure Assessment (SOFA) score. At the onset of ICUAP, CVF was reported as absent, transient (if lasting ≤ 3 days) or persistent (>3 days). The primary outcome was 90-day mortality modelled through a Cox regression analysis. Secondary outcomes were 28-day mortality, hospital mortality, ICU length of stay (LOS) and hospital LOS. Results: 358 patients were enrolled: 203 (57%) without CVF, 82 (23%) with transient CVF, and 73 (20%) with persistent CVF. Patients with transient and persistent CVF were more severely ill and presented higher inflammatory response than those without CVF. Despite having similar severity and aetiology, the persistent CVF group more frequently received inadequate initial antibiotic treatment and presented more treatment failures than the transient CVF group. In the persistent CVF group, at day 3, a bacterial superinfection was more frequently detected. The 90-day mortality was significantly higher in the persistent CVF group (62%). The 28-day mortality rates for patients without CVF, with transient and with persistent CVF were 19, 35 and 41% respectively and ICU mortality was 60, 38 and 19% respectively. In the multivariate analysis chronic pulmonary conditions, lack of Pa02/FiO2 improvement at day 3, pulmonary superinfection at day 3 and persistent CVF were independently associated with 90-day mortality in ICUAP patients. Conclusions: Persistent CVF has a significant impact on the outcome of patients with ICUAP. Patients at risk from persistent CVF should be promptly recognized to optimize treatment and outcomes.

Download Full-text

Possible unrecognised liver injury is associated with mortality in critically ill COVID-19 patients

Therapeutic Advances in Gastroenterology ◽

10.1177/17562848211023410 ◽

2021 ◽

Vol 14 ◽

pp. 175628482110234

Author(s):

Mario Romero-Cristóbal ◽

Ana Clemente-Sánchez ◽

Patricia Piñeiro ◽

Jamil Cedeño ◽

Laura Rayón ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Liver Injury ◽

Chronic Liver Disease ◽

Critically Ill ◽

Cox Regression ◽

Chronic Liver ◽

Cox Regression Analysis ◽

Risk Of Death ◽

The Impact

Background: Coronavirus disease (COVID-19) with acute respiratory distress syndrome is a life-threatening condition. A previous diagnosis of chronic liver disease is associated with poorer outcomes. Nevertheless, the impact of silent liver injury has not been investigated. We aimed to explore the association of pre-admission liver fibrosis indices with the prognosis of critically ill COVID-19 patients. Methods: The work presented was an observational study in 214 patients with COVID-19 consecutively admitted to the intensive care unit (ICU). Pre-admission liver fibrosis indices were calculated. In-hospital mortality and predictive factors were explored with Kaplan–Meier and Cox regression analysis. Results: The mean age was 59.58 (13.79) years; 16 patients (7.48%) had previously recognised chronic liver disease. Up to 78.84% of patients according to Forns, and 45.76% according to FIB-4, had more than minimal fibrosis. Fibrosis indices were higher in non-survivors [Forns: 6.04 (1.42) versus 4.99 (1.58), p < 0.001; FIB-4: 1.77 (1.17) versus 1.41 (0.91), p = 0.020)], but no differences were found in liver biochemistry parameters. Patients with any degree of fibrosis either by Forns or FIB-4 had a higher mortality, which increased according to the severity of fibrosis ( p < 0.05 for both indexes). Both Forns [HR 1.41 (1.11–1.81); p = 0.006] and FIB-4 [HR 1.31 (0.99–1.72); p = 0.051] were independently related to survival after adjusting for the Charlson comorbidity index, APACHE II, and ferritin. Conclusion: Unrecognised liver fibrosis, assessed by serological tests prior to admission, is independently associated with a higher risk of death in patients with severe COVID-19 admitted to the ICU.

Download Full-text

NLRP3 is a Novel Prognostic Biomarker and Correlates With Immune Infiltrates in Lung Adenocarcinoma and Skin Cutaneous Melanoma

10.21203/rs.3.rs-880002/v1 ◽

2021 ◽

Author(s):

Chenxi Yuan ◽

Qingwei Wang ◽

Xueting Dai ◽

Yipeng Song ◽

Jinming Yu

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Lung Adenocarcinoma ◽

Immune Cells ◽

Cutaneous Melanoma ◽

Cox Regression ◽

Cox Regression Analysis ◽

Potential Biomarker ◽

The Impact ◽

Nlrp3 Expression

Abstract Background: Lung adenocarcinoma (LUAD) and skin cutaneous melanoma (SKCM) are common tumors around the world. However, the prognosis in advanced patients is poor. Because NLRP3 was not extensively studied in cancers, so that we aimed to identify the impact of NLRP3 on LUAD and SKCM through bioinformatics analyses. Methods: TCGA and TIMER database were utilized in this study. We compared the expression of NLRP3 in different cancers and evaluated its influence on survival of LUAD and SKCM patients. The correlations between clinical information and NLRP3 expression were analyzed using logistic regression. Clinicopathologic characteristics associated with overall survival in were analyzed by Cox regression. In addition, we explored the correlation between NLRP3 and immune infiltrates. GSEA and co-expressed gene with NLRP3 were also done in this study. Results: NLRP3 expressed disparately in tumor tissues and normal tissues. Cox regression analysis indicated that up-regulated NLRP3 was an independent prognostic factor for good prognosis in LUAD and SKCM. Logistic regression analysis showed increased NLRP3 expression was significantly correlated with favorable clinicopathologic parameters such as no lymph node invasion and no distant metastasis. Specifically, a positive correlation between increased NLRP3 expression and immune infiltrating level of various immune cells was observed. Conclusion: Together with all these findings, increased NLRP3 expression correlates with favorable prognosis and increased proportion of immune cells in LUAD and SKCM. These conclusions indicate that NLRP3 can serve as a potential biomarker for evaluating prognosis and immune infiltration level.

Download Full-text

Abstract 18639: Implantable Cardioverter-defibrillator Use is Associated With Improved Survival on the Waitlist for Heart Transplantation: A UNOS/ OPTN Registry Analysis of 36,397 Patients

Circulation ◽

10.1161/circ.132.suppl_3.18639 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Kairav Vakil ◽

Rebecca Cogswell ◽

Sue Duval ◽

Wayne Levy ◽

Peter Eckman ◽

...

Keyword(s):

Heart Transplantation ◽

Cox Regression ◽

Left Ventricular ◽

Total Artificial Heart ◽

Ventricular Assist Devices ◽

Left Ventricular Assist Devices ◽

Cox Regression Analysis ◽

End Stage ◽

The Impact ◽

Waitlist Mortality

Background: Current guidelines do not support routine use of implantable cardioverter-defibrillators (ICDs) in patients (pts) with end-stage heart failure (HF), unless these pts are awaiting advanced HF therapies such as left ventricular assist devices (LVADs) or a heart transplantation (HT). Whether ICDs improve survival in end-stage HF pts awaiting HT has not been previously examined in a large, multicenter cohort. Hypothesis: Presence of ICDs at time of listing for HT is associated with lower waitlist mortality. Methods: The United Network for Organ Sharing registry was used to identify adults (≥18 years) listed for HT between January 4, 1999 & September 30, 2014. Pts with congenital heart disease, total artificial heart, restrictive cardiomyopathy, prior HT, or missing covariates were excluded. Cox regression analysis was used to assess the impact of an ICD at the time of listing on waitlist mortality. Results: The analysis included 36,397 pts (mean age 53±12; 77% males) listed for HT. The prevalence of ICDs at listing has steadily increased over time before reaching a plateau in 2006 (27% in 1999, and range 76-82% between 2006-2014). In the unadjusted model, ICD use was associated with a 36% reduction in waitlist mortality (HR 0.64, 95% CI 0.60-0.68, p<0.001). After adjustment for covariates such as age, sex, race, creatinine, ischemic cardiomyopathy, and listing status, this association was nearly unchanged (HR 0.67, 95% CI 0.62-0.72, p<0.001). Test for interaction by listing era (pre- and post-2006) was non-significant (p=0.28). In the final adjusted model, that included listing era and LVAD status in addition to the above listed covariates, ICD use continued to remain associated with a mortality benefit on the waitlist for HT (HR 0.84, 95% CI 0.78-0.91, p<0.001). Conclusion: ICDs are increasingly prevalent in pts listed for HT; however many pts are still listed for HT without these devices. The presence of an ICD at the time of listing is associated with lower mortality on the waitlist. Although the magnitude of ICD efficacy diminishes slightly, its benefit continues to remain significant even after adjustment for listing era and LVAD use. Further analyses are required to identify specific sub-groups of pts where ICD use is most beneficial and appropriate.

Download Full-text