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Nevin Manimala Statistics

Prognostic Value of Preoperative Serum Carcinoembryonic Antigen for Overall Survival and Recurrence-Free Survival in Resectable Thymic Epithelial Tumors

Technol Cancer Res Treat. 2022 Jan-Dec;21:15330338221119340. doi: 10.1177/15330338221119340.

ABSTRACT

Introduction: Tumor markers have been shown to be closely related to the long-term survival of patients with cancer and the recurrence of various malignant tumors. However, their role in thymic epithelial tumors (TETs) remains to be elucidated. We aimed to investigate whether the preoperative tumor biomarkers carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) could serve as independent predictors of postoperative prognosis in patients with TETs. Materials and Methods: We retrospectively included a total of 111 patients with TETs who underwent thymectomy at our hospital. Cox regression analysis was used to evaluate the statistical significance of CEA and NSE as independent predictors of overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier curves were used to present the results of our survival analyses. Results: Cox regression analysis showed that T stage, World Health Organization (WHO) histologic type, tumor size, and CEA levels served as independent prognostic factors for OS (P < .05). Whereas for RFS, multivariate analysis showed that only T stage, WHO histologic type, and drinking history were independently associated with it (P < .05). Conclusion: Our study found that preoperative serum CEA levels and tumor size may be strong predictors of postoperative OS in patients with TETs.

PMID:36217838 | DOI:10.1177/15330338221119340

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Nevin Manimala Statistics

A flexible and efficient Bayesian implementation of point process models for spatial capture-recapture data

Ecology. 2022 Oct 11:e3887. doi: 10.1002/ecy.3887. Online ahead of print.

ABSTRACT

Spatial capture-recapture (SCR) is now routinely used for estimating abundance and density of wildlife populations. A standard SCR model includes sub-models for the distribution of individual activity centers and for individual detections conditional on the locations of these activity centers. Both sub-models can be expressed as point processes taking place in continuous space, but there is a lack of accessible and efficient tools to fit such models in a Bayesian paradigm. Here, we describe a set of custom functions and distributions to achieve this. Our work allows for more efficient model fitting with spatial covariates on population density, offers the option to fit SCR models using the semi-complete data likelihood (SCDL) approach instead of data augmentation, and better reflects the spatially continuous detection process in SCR studies that use area searches. In addition, the SCDL approach is more efficient than data augmentation for simple SCR models while losing its advantages for more complicated models that account for spatial variation in either population density or detection. We present the model formulation, test it with simulations, quantify computational efficiency gains, and conclude with a real-life example using non-invasive genetic sampling data for an elusive large carnivore, the wolverine (Gulo gulo) in Norway.

PMID:36217822 | DOI:10.1002/ecy.3887

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Nevin Manimala Statistics

Garg scoring system to predict long-term healing in cryptoglandular anal fistulas: a prospective validation study

Ann Coloproctol. 2022 Oct 11. doi: 10.3393/ac.2022.00346.0049. Online ahead of print.

ABSTRACT

PURPOSE: Complex anal fistulas can recur after clinical healing, even after a long interval which leads to significant anxiety. Also, ascertaining the efficacy of any new treatment procedure becomes difficult and takes several years. We prospectively analyzed the validity of Garg scoring system (GSS) to predict long-term fistula healing.

METHODS: In patients operated for cryptoglandular anal fistulas, preoperative magnetic resonance imaging (MRI) and postoperative MRI was done at 3 months to assess fistula healing. Scores as per the GSS were calculated for each patient at 3 months postoperatively and correlated with long-term healing to check the accuracy of the scoring system.

RESULTS: Fifty-seven patients were enrolled, but 50 were finally included (7 were excluded). These 50 patients (age, 41.2± 12.4 years; 46 males) were followed up for 12 to 20 months (median, 17 months). Forty-seven patients (94.0%) had complex fistulas, 28 (56.0%) had recurrent fistulas, 48 (96.0%) had multiple tracts, 20 (40.0%) had horseshoe tracts, 15 (30.0%) had associated abscesses, 5 (10.0%) were suprasphincteric, and 8 (16.0%) were supralevator fistulas. The GSS could accurately predict long-term healing (specificity and high positive predictive value, 31 of 31 [100%]) but was not very accurate in predicting non-healing (negative predictive value, 15 of 19 [78.9%]). The sensitivity in predicting healing was 31 of 35 (88.6%).

CONCLUSION: GSS accurately predicts long-term fistula with a high positive predictive value (100%) but is less accurate in predicting non-healing. This scoring system can help allay anxiety in patients and facilitate the early validation of innovative procedures for anal fistulas.

PMID:36217811 | DOI:10.3393/ac.2022.00346.0049

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Nevin Manimala Statistics

International society of university colon and rectal surgeons survey of surgeons’ preference on rectal cancer treatment

Ann Coloproctol. 2022 Oct 11. doi: 10.3393/ac.2022.00255.0036. Online ahead of print.

ABSTRACT

PURPOSE: Rectal cancer treatment has a wide range of possible approaches from radical extirpative surgery to nonoperative watchful waiting following chemoradiotherapy, with or without, additional chemotherapy. Our goal was to assess the personal opinion of active practicing surgeons on rectal cancer treatment if he/she was the patient.

METHODS: A panel of the International Society of University Colon and Rectal Surgeons (ISUCRS) selected 10 questions that were included in a questionnaire that included other items including demographics. The questionnaire was distributed electronically to ISUCRS fellows and other surgeons included in our database and remained open from April 16 to 28, 2020.

RESULTS: One hundred sixty-three specialists completed the survey. The majority of surgeons (n=65, 39.9%) chose the minimally invasive (laparoscopic) surgery for their personal treatment of rectal cancer. For low-lying rectal cancer T1 and T2, the treatment choice was standard chemoradiation+local excision (n=60, 36.8%) followed by local excision±chemoradiotherapy if needed (n=55, 33.7%). In regards to locally advanced low rectal cancer T3 or greater, the preference of the responders was for laparoscopic surgery (n=65, 39.9%). We found a statistically significant relationship between surgeons’ age and their preference for minimally invasive techniques demonstrating an age-based bias on senior surgeons’ inclination toward open approach.

CONCLUSION: Our survey reveals an age-based preference by surgeons for minimally invasive surgical techniques as well as organ-preserving techniques for personal treatment of treating rectal cancer. Only 1/4 of specialists do adhere to the international guidelines for treating early rectal cancer.

PMID:36217808 | DOI:10.3393/ac.2022.00255.0036

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Nevin Manimala Statistics

Preoperative anemia and deep vein thrombosis in patients with perioperative bone trauma: a cohort study

BMC Musculoskelet Disord. 2022 Oct 10;23(1):905. doi: 10.1186/s12891-022-05869-7.

ABSTRACT

BACKGROUND: In current active prevention (including physical and drug prevention), the incidence of perioperative deep vein thrombosis (DVT) of the lower extremities remains high in patients with bone trauma. Risk factors need to be further optimized, and high-risk patients must be identified early. Preoperative comorbidities, especially preoperative anemia, and DVT in patients with perioperative bone trauma are not clear. The purpose of this study was to explore the causal relationship between preoperative anemia and DVT in patients with perioperative bone trauma, and further reduce the incidence of DVT in patients with bone trauma.

OBJECTIVES: To analyze the relationship between preoperative anemia and perioperative DVT in patients with femoral and pelvic fractures and provide a reference for the optimization of risk factors for DVT.

METHODS: The clinical data of 1049 patients with femoral and pelvic fractures who received surgical treatment from May 2018 to June 2021 were retrospectively analyzed. Propensity score matching (PSM) was performed for the covariates of DVT. Modified Poisson regression was used to analyze the relationship between preoperative anemia and DVT.

RESULTS: After matching 1:1 propensity scores in 1049 patients included in this study, there were 258 patients in the anemic and non-anemic groups. Preoperative anemia was statistically significant for the formation of DVT in patients with perioperative bone trauma (P = 0.000, RR = 1.567 [95% CI 1.217-2.017]). This conclusion remained true after PSM (P = 0.009, RR = 1.500 [95% CI 1.105-2.036]). Preoperative anemia has some predictive value for perioperative DVT, with DVT-associated preoperative anemia thresholds of 125 g/L and area under the receiver operating characteristic curve of 0.5877 (95% CI 0.5345 to 0.6408). On this basis, sensitivity and specificity were 89.2 and 30.3%, respectively, with a Youden index of 0.195. In addition, we conducted an E-value determination of the propensity score; the E-value analysis showed robustness to unmeasured confounding.

CONCLUSIONS: Preoperative anemia is highly correlated with perioperative DVT in patients with bone trauma, which is the cause of perioperative DVT in these patients.

PMID:36217199 | DOI:10.1186/s12891-022-05869-7

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Biomarkers of interstitial lung disease associated with primary Sjögren’s syndrome

Eur J Med Res. 2022 Oct 10;27(1):199. doi: 10.1186/s40001-022-00828-3.

ABSTRACT

OBJECTIVES: The aim of this study was to investigate serum biomarkers linked to primary Sjögren’s syndrome (pSS)-associated interstitial lung disease (ILD).

METHODS: 69 pSS patients were consecutively enrolled and evaluated via quantitative ILD scoring based on high-resolution computed tomography (HRCT). Biomarkers of interest were assessed by multiplex enzyme-linked immunosorbent assays (ELISAs).

RESULTS: Among consecutively enrolled patients with pSS, the presence of pSS-ILD was 50% based on the presence of radiographically defined interstitial lung abnormalities (ILA) meeting specified criteria for mild/moderate (ILA 2) or severe (ILA 3) disease. Age, immunoglobulin M (IgM), C-reactive protein (CRP), and serum levels of eotaxin/CCL11, Krebs von den Lungen-6 (KL-6), TNFα, and TGFα were significantly higher in the combined pSS-ILD group (ILA 2 + ILA 3) than in the pSS-no-ILD and pSS-indeterminate ILD groups (ILA 0 and ILA 1, respectively) in unadjusted analyses (p < 0.05 for all variables). A binary logistic regression model revealed that disease duration and KL-6 levels were associated with the presence of pSS-ILD (p < 0.05). Complementary least absolute shrinkage and selection operator (LASSO) modeling showed that age, KL-6, and TNF-α effectively differentiated pSS-ILD (ILA 2 + ILA3) from pSS without ILD (ILA 0 + ILA 1), with an area under the curve (AUC) of 0.883 (p value < 0.0001).

CONCLUSIONS: Patient age, disease duration, and serum levels of both KL-6 and TNFα were the most discriminating factors associated with the presence of ILD in our pSS patients. Higher levels of CRP, IgM, eotaxin, TGFα, and TNFα should also prompt the search for occult as well as clinically evident lung involvement based on statistically significant univariate associations with pSS-ILD.

CLINICAL TRIAL REGISTRATION: None.

PMID:36217184 | DOI:10.1186/s40001-022-00828-3

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Nevin Manimala Statistics

Multiomic analysis of papillary thyroid cancers identifies BAIAP2L1-BRAF fusion and requirement of TRIM25, PDE5A and PKCδ for tumorigenesis

Mol Cancer. 2022 Oct 10;21(1):195. doi: 10.1186/s12943-022-01665-y.

ABSTRACT

BACKGROUND: Papillary thyroid carcinoma (PTC) is one of the most common forms of thyroid cancer with a cure rate of over 90% after surgery. However, aggressive forms may still occur, and personalized therapeutic strategies are increasingly required.

METHODS: We performed integrated genomic and proteomic analysis of PTC tumor samples from patients who did not harbor BRAF or RAS mutations. We validate the analysis and present in-depth molecular analysis of the identified genetic rearrangement by employing biochemical and cell biological assays. Finally, we employ 3D spheroid models, loss of function studies and chemical inhibitors to target the hitherto upregulated factors. The data are analysed with appropriate statistical tests which are mentioned in the legends section.

RESULTS: In a 23-year-old patient with thyroiditis, we identified a novel rearrangement leading to a BAIAP2L1-BRAF fusion that transforms immortalized human thyroid cells in a kinase and CC-domain dependent manner. Moreover, quantitative proteomic analysis of the same patient samples revealed the upregulation of several proteins including the Ubiquitin E3 ligase TRIM25, PDE5A, and PKCδ. Further, in a cohort of PTC patients, we observed higher expression of TRIM25 and PKCδ in the tumor and metastatic lesions, when compared to the matched normal tissue. Inhibition of TRIM25, PDE5A and PKCδ with small molecules or RNA interference affected not only viability and proliferation of BAIAP2L1-BRAF transformed cells, but also the viability, growth and invasion of corresponding 3D spheroid cultures.

CONCLUSIONS: Apart from unveiling a novel oncogenic BRAF fusion in PTCs, our data may open a novel avenue of therapeutic targeting in human PTCs.

PMID:36217175 | DOI:10.1186/s12943-022-01665-y

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Fetal exposure to phthalates and bisphenols and DNA methylation at birth: the Generation R Study

Clin Epigenetics. 2022 Oct 10;14(1):125. doi: 10.1186/s13148-022-01345-0.

ABSTRACT

BACKGROUND: Phthalates and bisphenols are non-persistent endocrine disrupting chemicals that are ubiquitously present in our environment and may have long-lasting health effects following fetal exposure. A potential mechanism underlying these exposure-outcome relationships is differential DNA methylation. Our objective was to examine the associations of maternal phthalate and bisphenol concentrations during pregnancy with DNA methylation in cord blood using a chemical mixtures approach.

METHODS: This study was embedded in a prospective birth cohort study in the Netherlands and included 306 participants. We measured urine phthalates and bisphenols concentrations in the first, second and third trimester. Cord blood DNA methylation in their children was processed using the Illumina Infinium HumanMethylation450 BeadChip using an epigenome-wide association approach. Using quantile g-computation, we examined the association of increasing all mixture components by one quartile with cord blood DNA methylation.

RESULTS: We did not find evidence for statistically significant associations of a maternal mixture of phthalates and bisphenols during any of the trimesters of pregnancy with DNA methylation in cord blood (all p values > 4.01 * 10-8). However, we identified one suggestive association (p value < 1.0 * 10-6) of the first trimester maternal mixture of phthalates and bisphenols and three suggestive associations of the second trimester maternal mixture of phthalates and bisphenols with DNA methylation in cord blood.

CONCLUSIONS: Although we did not identify genome-wide significant results, we identified some suggestive associations of exposure to a maternal mixture of phthalates and bisphenols in the first and second trimester with DNA methylation in cord blood that need further exploration in larger study samples.

PMID:36217170 | DOI:10.1186/s13148-022-01345-0

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Effect of psychological first aid program on stress level and psychological well-being among caregivers of older adults with alzheimer’s disease

BMC Nurs. 2022 Oct 10;21(1):275. doi: 10.1186/s12912-022-01049-z.

ABSTRACT

INTRODUCTION: Older adults with Alzheimer’s disease (AD) experience drastic changes in their physical and mental abilities. AD patients became heavily dependent on their caregivers for everyday functions, which have significant implications not only for them but also for their caregivers. So, many AD caregivers experienced an increased level of depression and anxiety symptoms, lower perceived control, and higher burden compared to non-AD caregivers. Therefore, psychological first aid (PFA) and educational interventions are designed to enable those caregivers to meet the daily requirements of their patient care and to cope with its challenges.

AIM: Determine the effect of psychological first aid program on stress level and psychological well-being among caregivers of older adults with Alzheimer’s disease.

DESIGN: One group pre-test post-test was followed.

SUBJECTS: A convenience sample of one hundred (100) caregivers of older adults with AD.

SETTING: All online groups concerned with the care of Alzheimer’s disease patients on Facebook.

TOOLS: Socio-demographic and clinical data of older adults with Alzheimer’s disease and their caregivers’ questionnaire, Alzheimer’s disease knowledge scale, Kingston caregiver stress scale, and authentic identity measures (AIM) scale of psychological well-being RESULTS: The psychological first aid program has highly statistically significant effect on the AD caregivers’ knowledge, stress level and psychological well-being as (t=-30.707, P = 0.000, t = 8.500, P = 0.000 & t= -4.763, P = 0.000 respectively).

CONCLUSION: Psychological first aid program is considered an effective intervention in decreasing the AD caregivers’ stress and increasing their psychological wellbeing and knowledge regarding delivering care for AD patients.

PMID:36217138 | DOI:10.1186/s12912-022-01049-z

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Empirical evidence of study design biases in nutrition randomised controlled trials: a meta-epidemiological study

BMC Med. 2022 Oct 11;20(1):330. doi: 10.1186/s12916-022-02540-9.

ABSTRACT

BACKGROUND: Instruments to critically appraise randomised controlled trials (RCTs) are based on evidence from meta-epidemiological studies. We aim to conduct a meta-epidemiological study on the average bias associated with reported methodological trial characteristics such as random sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and compliance of RCTs in nutrition research.

METHODS: We searched the Cochrane Database of Systematic Reviews, for systematic reviews of RCTs, published between 01 January 2010 and 31 December 2019. We combined the estimates of the average bias (e.g. ratio of risk ratios [RRR] or differences in standardised mean differences) in meta-analyses using the random-effects model. Subgroup analyses were conducted to investigate the potential differences among the RCTs with low versus high/unclear risk of bias with respect to the different types of interventions (e.g. micronutrients, fatty acids, dietary approach), outcomes (e.g. mortality, pregnancy outcomes), and type of outcome (objective, subjective). Heterogeneity was assessed through I2 and τ2, and prediction intervals were calculated.

RESULTS: We included 27 Cochrane nutrition reviews with 77 meta-analyses (n = 927 RCTs). The available evidence suggests that intervention effect estimates may not be exaggerated in RCTs with high/unclear risk of bias (versus low) judgement for sequence generation (RRR 0.97, 95% CI 0.93 to 1.02; I2 = 28%; τ2 = 0.002), allocation concealment (RRR 1.00, 95% CI 0.96 to 1.04; I2 = 27%; τ2 = 0.001), blinding of participants and personnel (RRR 0.95, 95% CI 0.91 to 1.00; I2 = 23%; τ2 = 0), selective reporting (RRR 0.97, 95% CI 0.92 to 1.02; I2 = 24%; τ2 = 0), and compliance (RRR 0.95, 95% CI 0.89 to 1.02; I2 = 0%; τ2 = 0). Intervention effect estimates seemed to be exaggerated in RCTs with a high/unclear risk of bias judgement for blinding of outcome assessment (RRR 0.81, 95% CI 0.70 to 0.94; I2 = 26%; τ2 = 0.03), which was predominately driven by subjective outcomes, and incomplete outcome data (RRR 0.92, 95% CI 0.88 to 0.97; I2 = 22%; τ2 = 0.001). For continuous outcomes, no differences were observed, except for selective reporting.

CONCLUSIONS: On average, most characteristics of nutrition RCTs may not exaggerate intervention effect estimates, but the average bias appears to be greatest in trials of subjective outcomes. Replication of this study is suggested in this field to keep this conclusion updated.

PMID:36217133 | DOI:10.1186/s12916-022-02540-9