Role of RET genetic variants in MEN2-associated pheochromocytoma

Background: RET polymorphisms have been involved in the clinical presentation and prognosis of multiple endocrine neoplasia type 2 (MEN2)-associated medullary thyroid carcinoma.ObjectiveTo investigate the effect of RET variants on the penetrance of pheochromocytoma (PHEO) in MEN2 patients. Methods: The RET variants L769L, S836S, and G691S/S904S were evaluated in a cohort of 153 MEN2 patients attending a tertiary teaching hospital. A comparison of RET variant frequencies between patients with and without PHEO was performed. Kaplan–Meier curves and Cox regression analysis were used to estimate the effect of RET variants on the age-dependent penetrance.ResultsA total of 48 (31.4%) patients presented with MEN2-associated PHEOs. The mean age at diagnosis was 35.5±13.4 years, 60.4% of patients were women, and 92.8% had RET mutations at codon 634. The frequencies of RET polymorphisms were as follows: 20.1% L769L, 4.75% S836S, and 17.3% S904S/G691S. We did not observe any association between the frequencies of L769L, S836S, or S904S/G691S variants and PHEO development (all P>0.05). However, individuals carrying two RET polymorphic alleles had an increased estimated risk of PHEO (2.63; 95% CI, 1.4–5.0; P=0.004) and were younger at diagnosis when compared with those with one or no polymorphism (29.6±6.3 and 39.3±14.4 years respectively; P=0.006). Accordingly, additional analysis using Cox proportional hazard models demonstrated that the presence of two RET variants was associated with an increased risk for early PHEO development (hazard ratio, 5.99 (95% CI, 2.24–16.03); P<0.001).ConclusionsRET polymorphic alleles have an additive effect on the estimated risk of age-related PHEO penetrance in MEN2 patients.

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Fast-Track Programs in Total Hip and Knee Replacement at Swedish Hospitals—Influence on 2-Year Risk of Revision and Mortality

Journal of Clinical Medicine ◽

10.3390/jcm10081680 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1680

Author(s):

Urban Berg ◽

Annette W-Dahl ◽

Anna Nilsdotter ◽

Emma Nauclér ◽

Martin Sundberg ◽

...

Keyword(s):

Fast Track ◽

Cox Regression ◽

Cox Regression Analysis ◽

Total Hip ◽

Total Knee Replacements ◽

Risk Of Death ◽

Kaplan Meier ◽

Increased Risk ◽

Hip And Knee Arthroplasty ◽

Total Knee

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.

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Varicella zoster virus infections increase the risk of disease flares in patients with SLE: a matched cohort study

Lupus Science & Medicine ◽

10.1136/lupus-2019-000339 ◽

2019 ◽

Vol 6 (1) ◽

pp. e000339 ◽

Cited By ~ 3

Author(s):

Fangfang Sun ◽

Yi Chen ◽

Wanlong Wu ◽

Li Guo ◽

Wenwen Xu ◽

...

Keyword(s):

Propensity Score ◽

Varicella Zoster Virus ◽

Cox Regression ◽

Control Period ◽

Cox Regression Analysis ◽

Varicella Zoster ◽

Propensity Score Weighting ◽

Kaplan Meier ◽

Increased Risk ◽

Risk Of Disease

ObjectiveTo explore whether varicella zoster virus (VZV) infection could increase the risk of disease flares in patients with SLE.MethodsPatients who had VZV reactivations between January 2013 and April 2018 were included from the SLE database (n=1901) of Shanghai Ren Ji Hospital, South Campus. Matched patients with SLE were selected as background controls with a 3:1 ratio. Patients with SLE with symptomatic bacterial infections of the lower urinary tract (UTI) were identified as infection controls. Baseline period and index period were defined as 3 months before and after infection event, respectively. Control period was the following 3 months after the index period. Flare was defined by SELENA SLEDAI Flare Index. Kaplan-Meier analysis, Cox regression model and propensity score weighting were applied.ResultsPatients with VZV infections (n=47), UTI controls (n=28) and matched SLE background controls (n=141) were included. 16 flares (34%) in the VZV group within the index period were observed, as opposed to only 7.1% in UTI controls and 9.9% in background controls. Kaplan-Meier curve revealed that patients with a VZV infection had a much lower flare-free survival within the index period compared with the controls (p=0.0003). Furthermore, after adjusting for relevant confounders including baseline disease activity and intensity of immunosuppressive therapy, Cox regression analysis and propensity score weighting confirmed that VZV infection within 3 months was an independent risk factor for SLE flares (HR 3.70 and HR 4.16, respectively).ConclusionsIn patients with SLE, recent VZV infection within 3 months was associated with increased risk of disease flares.

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Colorectal cancer survival among Ministry of National Guard-Health Affairs (MNG-HA) population 2009–2017: retrospective study

BMC Cancer ◽

10.1186/s12885-021-08705-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mesnad Alyabsi ◽

Fouad Sabatin ◽

Majed Ramadan ◽

Abdul Rahman Jazieh

Keyword(s):

Colorectal Cancer ◽

Distant Metastasis ◽

Cancer Survival ◽

National Guard ◽

Population Based ◽

Risk Of Death ◽

Cox Proportional Hazard ◽

Kaplan Meier ◽

Increased Risk ◽

Cox Proportional Hazard Models

Abstract Background Colorectal cancer (CRC) is the most diagnosed cancer among males and third among females in Saudi Arabia, with up to two-third diagnosed at advanced stage. The objective of our study was to estimate CRC survival and determine prognostic factors. Methods Ministry of National Guard- Health Affairs (MNG-HA) registry data was utilized to identify patients diagnosed with CRC between 2009 and 2017. Cases were followed until December 30th, 2017 to assess their one-, three-, and five-year CRC-specific survivals. Kaplan-Meier method and Cox proportional hazard models were used to assess survival from CRC. Results A total of 1012 CRC patients were diagnosed during 2009–2017. Nearly, one-fourth of the patients presented with rectal tumor, 42.89% with left colon and 33.41% of the cases were diagnosed at distant metastasis stage. The overall one-, three-, and five-year survival were 83, 65 and 52.0%, respectively. The five-year survival was 79.85% for localized stage, 63.25% for regional stage and 20.31% for distant metastasis. Multivariate analyses showed that age, diagnosis period, stage, nationality, basis of diagnosis, morphology and location of tumor were associated with survival. Conclusions Findings reveal poor survival compared to Surveillance, Epidemiology, and End Results (SEER) population. Diagnoses at late stage and no surgical and/or perioperative chemotherapy were associated with increased risk of death. Population-based screening in this population should be considered.

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Increased risk of Parkinson’s disease among patients with age-related macular degeneration

BMC Ophthalmology ◽

10.1186/s12886-021-02196-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Po-Yu Jay Chen ◽

Lei Wan ◽

Jung-Nien Lai ◽

Chih Sheng Chen ◽

Jamie Jiin-Yi Chen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Macular Degeneration ◽

Cox Regression ◽

Age Related Macular Degeneration ◽

Rank Test ◽

Cox Regression Analysis ◽

Age Related ◽

Increased Risk

Abstract Background This study aimed to investigate the risk of Parkinson’s disease (PD) among patients with age-related macular degeneration (AMD) and its association with confounding comorbidities. Methods A population-based retrospective cohort study was conducted using Longitudinal Health Insurance Database 2000 (LHID2000). We established AMD and non-AMD cohorts from January 1, 2000 to December 31, 2012 to determine the diagnosis of PD. A total of 20,848 patients were enrolled, with 10,424 AMD patients and 10,424 controls matched for age, sex, and index year at a 1:1 ratio. The follow-up period was from the index date of AMD diagnosis to the diagnosis of PD, death, withdrawal from the insurance program, or end of 2013. Multivariable Cox regression analysis was performed to examine the hazard ratio (HR) and 95% confidence interval (CI) for the risk of PD between the AMD and non-AMD cohorts. Result After adjusting for potential confounders, there was a higher risk of developing PD in the AMD cohort than in the non-AMD cohort (adjusted HR = 1.35, 95% CI = 1.16–1.58). A significant association could be observed in both female (aHR = 1.42, 95% CI = 1.13–1.80) and male (aHR = 1.28, 95% CI = 1.05–1.57) patients, aged more than 60 years (60–69: aHR = 1.51, 95% CI = 1.09–2.09, 70–79: aHR = 1.30, 95% CI = 1.05–1.60; 80–100: aHR = 1.40, 95% CI = 1.01–1.95), and with more than one comorbidity (aHR = 1.40, 95% CI = 1.20–1.64). A significant association between increased risk of PD and AMD was observed among patients with comorbidities of osteoporosis (aHR = 1.68, 95% CI = 1.22–2.33), diabetes (aHR = 1.41, 95% CI = 1.12–1.78) and hypertension (aHR = 1.36, 95% CI = 1.15–1.62) and medications of statin (aHR = 1.42, 95% CI = 1.19–1.69) and calcium channel blocker (CCB) (aHR = 1.32, 95% CI = 1.11–1.58). The cumulative incidence of PD was significantly higher over the 12-year follow-up period in AMD cohort (log-rank test, p < 0.001). Conclusions Patients with AMD may exhibit a higher risk of PD than those without AMD.

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Radioactive Iodine Treatment and the Risk of Long-Term Cardiovascular Morbidity and Mortality in Thyroid Cancer Patients: A Nationwide Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm10174032 ◽

2021 ◽

Vol 10 (17) ◽

pp. 4032

Author(s):

Chun-Hao Kao ◽

Chi-Hsiang Chung ◽

Wu-Chien Chien ◽

Daniel Hueng-Yuan Shen ◽

Li-Fan Lin ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Patients ◽

Radioactive Iodine ◽

Cox Regression ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Cardiovascular Morbidity And Mortality ◽

Increased Risk ◽

Cumulative Risks

(1) Background: This study aimed to investigate the association between radioactive iodine (RAI) and long-term cardiovascular disease (CVD) morbidity/mortality in thyroid cancer. (2) Methods: The study was conducted using data from the Taiwan National Health Insurance Database during 2000–2015. Thyroid cancer patients aged ≥20 years were categorized into RAI (thyroidectomy with RAI) and non-RAI (thyroidectomy only) groups. The Cox proportional hazard regression model and Kaplan–Meier method were used for analysis. (3) Results: A total of 13,310 patients were included. Kaplan–Meier analysis demonstrated that the two groups had similar cumulative risks of CVD (log-rank p = 0.72) and CVD-specific mortality (log-rank p = 0.62). On Cox regression analysis of different RAI doses, the risk of CVD was higher in the cumulative dosage >3.7 GBq (hazard ratio = 1.69, 95% confidence interval = 1.24–2.40, p < 0.001). (4) Conclusions: RAI was not associated with an increased risk of CVD in thyroid cancer. However, CVD surveillance is indicated in the patients receiving the cumulative RAI dosage above 3.7 GBq.

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The Association Between Serum Leptin Levels and Cardiovascular Events in Patients with Rheumatoid Arthritis

Laboratory Medicine ◽

10.1093/labmed/lmaa037 ◽

2020 ◽

Vol 52 (1) ◽

pp. 86-92 ◽

Cited By ~ 1

Author(s):

Jiliang Chen ◽

Zhiping Xie ◽

Zou Bin

Keyword(s):

Rheumatoid Arthritis ◽

Prognostic Factor ◽

Cox Regression ◽

Univariate Analysis ◽

Elevated Serum ◽

Confounding Factors ◽

Serum Leptin ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Increased Risk

Abstract Objective Cardiovascular diseases (CVDs) are important complications for patients with rheumatoid arthritis (RA). The study aimed to explore whether serum leptin is associated with a increased risk of cardiovascular (CV) events in patients with RA. Methods Two hundred twenty-three patients with RA were followed for a mean of 40 (range = 8-42) months. Serum leptin levels were measured at baseline. Cox regression analysis was performed to assess the association between leptin levels and the risk of CV events. Results The univariate analysis showed that patients with RA with higher serum leptin levels had higher rates of CV events and CV mortality, respectively (P <.001). The logistic regression model showed that leptin was independently related to CVD history (odds ratio = 1.603, 95% confidence interval [CI], 1.329–2.195; P =.005) after adjusting for confounding factors in patients with RA at baseline. The multivariate Cox proportional hazard model suggested that leptin was an independent prognostic factor for CV events in patients with RA after adjustments were made for clinical confounding factors (hazard ratio = 2.467, 95% CI, 2.019–4.495; P <.001). The Kaplan-Meier analysis showed that compared with patients with RA with leptin levels below the median value (≤15.4 mg/L), patients with leptin above the median value (>15.4 μg/L) had a higher rate of CV events (P <.001). Conclusion Leptin was significantly associated with CV events in patients with RA. Elevated serum leptin levels may be a reliable prognostic factor for predicting CV complications in patients with RA.

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Chemoradiation-related lymphopenia and its association with survival in patients with anal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.3 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 3-3

Author(s):

Grace Lee ◽

Daniel W. Kim ◽

Vinayak Muralidhar ◽

Devarati Mitra ◽

Nora Horick ◽

...

Keyword(s):

Cancer Patients ◽

Anal Cancer ◽

Cox Regression ◽

Cox Model ◽

Rank Test ◽

Anal Squamous Cell Carcinoma ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Kaplan Meier ◽

Increased Risk

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.

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The Importance of Early Carotid Endarterectomy in Symptomatic Patients

Annals of The Royal College of Surgeons of England ◽

10.1308/003588409x359312 ◽

2009 ◽

Vol 91 (3) ◽

pp. 210-213 ◽

Cited By ~ 5

Author(s):

SR Kulkarni ◽

MS Gohel ◽

RA Bulbulia ◽

MR Whyman ◽

KR Poskitt

Keyword(s):

Carotid Endarterectomy ◽

Cox Regression ◽

The Elderly ◽

Cox Regression Analysis ◽

Symptomatic Carotid ◽

Kaplan Meier ◽

Symptomatic Carotid Stenosis ◽

Chi Squared ◽

Estimated Risk ◽

Repeat Events

INTRODUCTION Early carotid endarterectomy (CEA) in symptomatic patients may prevent repeat cerebral events. This study investigates the relationship between waiting time for CEA and the incidence of repeat cerebral events prior to surgery in symptomatic patients. PATIENTS AND METHODS A prospective database of consecutive patients undergoing CEA between January 2002 and December 2006 was reviewed. Repeat event rates prior to surgery were calculated using Kaplan–Meier analysis and predictive factors identified using Cox regression analysis. RESULTS A total of 118 patients underwent CEA for non-disabling stroke, TIA and amaurosis fugax. Repeat cerebral events occurred in 34 of 118 (29%) patients at a median 51 days (range, 2–360 days) after the first event. The estimated risk of repeat events was 2% at 7 days and 9% at 1 month after first event (Kaplan–Meier survival analysis). Age (HR 1.059; 95% CI 1.014–1.106; P = 0.009] was identified as a predictor of repeat events. Patients underwent surgery at median 97 days (range, 7–621 days) after the first event. Eleven of 60 (18%) patients waiting ≤?97 days for surgery and 23 of 58 (40%) patients waiting >?97 days had repeat events. (P = 0.011, chi-squared test). CONCLUSIONS Delays in surgery should be reduced in order to minimise repeat cerebral events in patients with symptomatic carotid stenosis, particularly in the elderly population.

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The Complex Association Between Bariatric Surgery and Depression: a National Nested-Control Study

Obesity Surgery ◽

10.1007/s11695-020-05201-z ◽

2021 ◽

Author(s):

Chanpreet Singh Arhi ◽

Roise Dudley ◽

Osama Moussa ◽

Maddalena Ardissino ◽

Samantha Scholtz ◽

...

Keyword(s):

Bariatric Surgery ◽

Cox Regression ◽

De Novo ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Cox Regression Analysis ◽

Cox Proportional Hazard ◽

Kaplan Meier ◽

Reduce Weight Loss ◽

History Of

Abstract Background Although bariatric surgery has been shown to reduce weight loss and obesity-related conditions, an improvement in depression remains unclear. The aim of this study was to determine whether bariatric surgery is associated with a resolution of depression, and the prevention of its onset. Method Patients with a BMI ≥ 30 kg/m2 who had undergone bariatric surgery were identified from the Clinical Practice Research Datalink (CPRD), matched 5:1 to controls. Cox regression analysis was used to determine the risk of developing de novo depression. Kaplan-Meier analysis compared the proportion of patients with no further consultations related to depression between the two groups. Results In total, 3534 patients who underwent surgery, of which 2018 (57%) had pre-existing depression, were matched to 15,480 controls. Cox proportional hazard modelling demonstrated surgery was associated with a HR of 1.50 (95% CI 1.32–1.71, p < 0.005) for developing de novo depression. For those with pre-existing depression, by 5 years, just over 20% of post-surgical patients had no further depression episodes compared with 17% of controls. Conclusion In individuals with a history of depression, bariatric surgery is associated with an improvement in mental health. On the contrary, the finding of increased de novo diagnoses of depression following surgery indicates the need for further study of the mechanisms by which bariatric surgery is associated with depression in this subset of patients.

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Intraocular Pressure Trend Following Myopic Photorefractive Keratectomy

10.21203/rs.3.rs-891473/v1 ◽

2021 ◽

Author(s):

Ghasem Fakhraie ◽

Zakieh Vahedian ◽

Reza Zarei ◽

Yadollah Eslami ◽

seyed mehdi tabatabaei ◽

...

Keyword(s):

Risk Factors ◽

Intraocular Pressure ◽

Central Corneal Thickness ◽

Cox Regression ◽

Corneal Thickness ◽

Photorefractive Keratectomy ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Lower Baseline ◽

Increased Risk

Abstract PurposeTo evaluate the intraocular pressure (IOP) trend and risk factors for IOP rise after myopic photorefractive keratectomy (PRK).Patients and MethodsOne eye of each patient undergone PRK for myopia was randomly assigned to this study. All eyes underwent tonometry by CorVis Scheimpflug Technology (CST) tonometer (Oculus Optikgeräte GmbH, Wetzlar, Germany) 1 week, 2 weeks, 1 month, 2 months, 3 months and 4 months after surgery. The eyes with IOP rise more than 5 mmHg and the risk factors were evaluated by Kaplan-Meier graph and multiple Cox regression analysis.Results348 eyes of 348 patients were enrolled in this study. Forty-three eyes (12.35%) experienced an IOP rise of more than 5 mmHg. Eyes with IOP rise had higher baseline IOP (Median 19 mmHg (IQR 18 – 22) versus. Median 15 mmHg (IQR 14 – 16); p< 0.001). Baseline central corneal thickness (CCT) was higher in eyes without IOP rise (Median 520 µm (IQR 509 – 541) versus. Median 535 µm (IQR 518 – 547); p= 0.009). in multivariate Cox regression analysis higher baseline IOP was a risk factor for IOP rise (Hazard Ratio (HR) 1.59 (95% CI 1.43 – 1.77); p< 0.001) while higher baseline CCT was protective (HR 0.97 (95% CI 0.95 – 0.98); p< 0.001).ConclusionEyes with higher baseline IOP and lower baseline CCT are at increased risk of IOP rise after PRK and should be monitored more frequently.

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