Category: Statistics

Breast Cancer Res Treat. 2023 Feb 11. doi: 10.1007/s10549-023-06871-w. Online ahead of print.

ABSTRACT

PURPOSE: The safety of local estrogen therapy in patients on adjuvant endocrine treatment is questioned, but evidence on the issue is scarce. This nested case-control registry-based study aimed to investigate whether estrogen therapy affects breast cancer mortality risk in women on adjuvant endocrine treatment.

METHODS: In a cohort of 15,198 women diagnosed with early hormone receptor (HR)-positive breast cancer and adjuvant endocrine treatment, 1262 women died due to breast cancer and were identified as cases. Each case was matched with 10 controls. Exposure to estrogen therapy with concurrent use of aromatase inhibitors (AIs), tamoxifen, or both sequentially, was compared between cases and controls.

RESULTS: No statistically significant difference in breast cancer mortality risk was seen in patients with exposure to estrogen therapy concurrent to endocrine treatment, neither in short-term or in long-term estrogen therapy use.

CONCLUSIONS: The study strengthens current evidence on local estrogen therapy use in breast cancer survivors, showing no increased risk for breast cancer mortality in patients on adjuvant AIs or tamoxifen.

PMID:36773184 | DOI:10.1007/s10549-023-06871-w

Eur J Epidemiol. 2023 Feb 11. doi: 10.1007/s10654-023-00969-7. Online ahead of print.

ABSTRACT

The carcinogenicity of opium consumption was recently evaluated by a Working Group convened by the International Agency for Research on Cancer (IARC). We supplement the recent IARC evaluation by conducting an extended systematic review as well as a quantitative meta-analytic assessment of the role of opium consumption and risk for selected cancers, evaluating in detail various aspects of study quality on meta-analytic findings. We searched the published literature to identify all relevant studies on opium consumption and risk of selected cancers in humans through 31 October, 2022. Meta-relative risks (mRRs) and associated 95% confidence intervals (CIs) were estimated using random-effects models for studies of cancer of the urinary bladder, larynx, lung, oesophagus, pancreas, and stomach. Heterogeneity among studies was assessed using the I² statistic. We assessed study quality and conducted sensitivity analyses to evaluate the impact of potential reverse causation, protopathic bias, selection bias, information bias, and confounding. In total, 2 prospective cohort studies and 33 case-control studies were included. The overall pooled mRR estimated for ‘ever or regular’ versus ‘never’ use of opium ranged from 1.50 (95% CI 1.13-1.99, I² = 0%, 6 studies) for oesophageal cancer to 7.97 (95% CI 4.79-13.3, I² = 62%, 7 studies) for laryngeal cancer. Analyses of cumulative opium exposure suggested greater risk of cancer associated with higher opium consumption. Findings were robust in sensitivity analyses excluding studies prone to potential methodological sources of biases and confounding. Findings support an adverse association between opium consumption and cancers of the urinary bladder, larynx, lung, oesophagus, pancreas and stomach.

PMID:36773182 | DOI:10.1007/s10654-023-00969-7

Methods Mol Biol. 2023;2637:63-73. doi: 10.1007/978-1-0716-3016-7_5.

ABSTRACT

Genome sequencing technologies have rapidly evolved in the past decades, enabling us to interpret the human genome through multiple perspectives, ranging from cross-species comparisons, naturally occurring variation in health and disease state to regulatory mechanisms.Although such perspectives are all informative to narrow down the list of genes or variants for perturbation experiments based on specific biological aims, utilizing multiple sources of information is often challenging in practice.In this chapter, we provide an overview of major large-scale functional and population genomics resources, followed by a practical example of selecting target variants for genetic perturbation experiments involving genome engineering techniques such as CRISPR/Cas.

PMID:36773138 | DOI:10.1007/978-1-0716-3016-7_5

Methods Mol Biol. 2023;2637:49-62. doi: 10.1007/978-1-0716-3016-7_4.

ABSTRACT

A wide range of diseases, including cancer, autoimmune diseases, or neurodegenerative diseases, have been associated with single nucleotide mutations in their causative genes. Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system is a flexible and efficient genome engineering technology widely used for researches and therapeutic applications which offers immense opportunity to treat genetic diseases. The complex of Cas9 and the guide RNA acts as an RNA-guided endonuclease. Cas9 recognizes a sequence motif known as a protospacer adjacent motif (PAM), and then the guide RNA base pairs with its proximal target region of 20 nucleotides with sequence complementarity. Here we describe the procedure named single nucleotide polymorphism-distinguishable (SNPD)-CRISPR system which can suppress or enhance the expression of disease-causative gene with single nucleotide mutation distinguished from its wild-type. In this study, we used HRAS, one of most famous cancer-causative genes, as an example of a target gene.

PMID:36773137 | DOI:10.1007/978-1-0716-3016-7_4

Clin Oral Investig. 2023 Feb 11. doi: 10.1007/s00784-023-04911-9. Online ahead of print.

ABSTRACT

OBJECTIVES: The study aimed to compare the two local anesthetic techniques: inferior alveolar nerve block (IANB) and intraligamentary anesthesia (ILA) during the restorative treatment of mandibular first permanent molars in pediatric patients.

MATERIALS AND METHODS: In this randomized, controlled, cross-over, single-blind, split-mouth study, participants were divided into two groups: group 1, ILA in the first session and IANB in the second session, and group 2, IANB in the first session and ILA in the second session. The pain perception was analyzed using the visual analog scale (VAS) and Wong-Baker FACES pain rating scale (WBFPRS). Heart rate, arterial oxygen saturation (SpO₂), and postoperative complications were recorded. The data were analyzed with the Brunner-Langer model, Spearman correlation analysis, Fisher’s exact t-test, chi-square, and McNemar tests.

RESULTS: Seventy-eight patients aged between 6 and 12 years were included. The session effect was not statistically significant in ILA (p = 0.762 and p = 0.411) for pain scores while it was significant in IANB (p < 0.001 for each score). There was no significant difference in the VAS, WBFPRS, heart rate, and SpO₂ between the anesthesia techniques (p = 0.454, p = 0.436, p = 0.406, p = 0.285, respectively). Postoperative complications increased in the IANB technique in the first session.

CONCLUSIONS: Intraligamentary anesthesia may be an alternative technique to IANB for the restorative treatment of mandibular first permanent molars in pediatric patients. In the first session, clinicians may choose the ILA instead of IANB.

CLINICAL RELEVANCE: In clinical procedures, administering anesthesia, which is effective, is less painful, and poses relatively low complication risk, has significant importance in sustaining children’s cooperation with dental treatment.

PMID:36773129 | DOI:10.1007/s00784-023-04911-9

Langenbecks Arch Surg. 2023 Feb 11;408(1):83. doi: 10.1007/s00423-023-02831-6.

ABSTRACT

PURPOSE: This study aimed to assess the prevalence and progression of lower urinary tract symptoms following laparoscopic surgery for deep-infiltrating endometriosis of the rectosigmoid and identify preoperative factors associated with worse postoperative outcomes.

METHODS: Prospective, observational study.

SETTINGS: single-center, referral hospital for endometriosis. Patients undergoing laparoscopic surgery for deep-infiltrating endometriosis of the rectosigmoid colon between October 2016 and October 2018.

MAIN OUTCOME MEASURES: urinary function was assessed with the validated Portuguese language version of the International Prostate Symptom Score, which is also used in women. The score was collected before and after surgery. The Wilcoxon signed-rank test was used to compare pre and postoperative scores and the chi-square test compared symptoms categorized by severity.

RESULTS: Fifty-three patients were assessed and 44 were included. Concerning urinary symptoms after surgery, the irritative symptoms prevailed over the obstructive ones. Additionally, 58.8% and 54.5% of the women reported moderate or severe symptoms at pre and postoperative, respectively. In at least one questionnaire category, the postoperative questionnaire scores increased in ten (22.7%) participants. A statistically significant difference was found comparing the changes from absent/mild to moderate/severe IPSS categories (P = 0.039). No significant changes were identified in any of the International Prostate Symptom Score pre and postoperatively (P = 0.876).

CONCLUSIONS: There was a high prevalence of pre and postoperative urinary symptoms. Patients with preoperative moderate/severe International Prostate Symptom Score are at risk of persisting urinary dysfunction after surgery for rectosigmoid deep endometriosis.

PMID:36773124 | DOI:10.1007/s00423-023-02831-6

J Cancer Res Clin Oncol. 2023 Feb 11. doi: 10.1007/s00432-023-04594-5. Online ahead of print.

ABSTRACT

PURPOSE: Uterine carcinosarcomas (UCSs) are aggressive biphasic malignancies, with a carcinomatous/epithelial component and a sarcomatous/mesenchymal counterpart. The aim of this study was to evaluate the impact of the sarcomatous component (homologous vs heterologous) on the overall survival (OS) and progression-free survival (PFS).

METHODS: This is a multicenter observational retrospective study conducted in patients with stage I and II UCSs.

RESULTS: Ninety-five women with histological diagnosis of early-stage UCSs were retrieved: 60 (63.2%) had tumors with homologous sarcomatous components, and 35 (36.8%) with heterologous. At univariate analysis, a stromal invasion ≥ 50%, the presence of clear cell, serous or undifferentiated carcinomatous component, the heterologous sarcomatous component and FIGO stage IB and II were shown to be variables with a statistically significant negative impact on PFS. Similarly, a depth of invasion ≥ 50%, the heterologous sarcomatous component and FIGO stage IB and II were statistically negative prognostic factors also concerning OS. At multivariate analysis, only the heterologous sarcomatous component was confirmed to be a statistically significant negative prognostic factor both on PFS (HR 2.362, 95% CI 1.207-4.623, p value = 0.012) and on OS (HR 1.950, 95% CI 1.032-3.684, p = 0.040).

CONCLUSION: Carcinomatous and sarcomatous components both played a role in tumor progression and patients’ survival. However, only the sarcomatous component retained a statistical significance at the multivariable model suggesting its preeminent prognostic role in early-stage UCSs.

PMID:36773091 | DOI:10.1007/s00432-023-04594-5

Adv Ther. 2023 Feb 11. doi: 10.1007/s12325-022-02419-4. Online ahead of print.

ABSTRACT

BACKGROUND: The expression of signaling molecules downstream of the mammalian target of rapamycin (mTOR) is dysregulated in patients with rheumatic fever (RF), but the causality of mTOR on RF remains unknown. This study aimed to investigate the causal effects of the mTOR-dependent proteins in RF.

METHODS: The summary data for targets of the mTOR signaling were acquired from the publicly available INTERVAL study GWAS data. Data on RF have been obtained from the Integrated Epidemiology Unit GWAS database (38,209 cases and 156,711 healthy controls). A two-sample Mendelian randomization (MR) study was conducted to examine the association of RF risk and mTOR-dependent proteins (EIF4EBP2, EIF-4E, EIF-4G, EIF-4A, RP-S6K, and ATG7), including the inverse-variance weighted (IVW) method, MR-Egger, and weighted median, which was followed by sensitivity analyses.

RESULTS: RP-S6K is associated with a lowered risk of RF with an odds ratio (OR) of 0.97, 95% confidence interval (95% CI) of 0.94-0.99 (p = 0.027). In contrast, ATG7 accounts for higher risk of RF with an OR of 1.05 (95% CI = 1.00-1.12, p = 0.047). No apparent heterogeneity and no horizontal pleiotropy were observed in the sensitivity analysis (p > 0.05). No statistical significance was identified for levels of EIF4A, EIF4G, EIF4E-BP2, and RP-S6K with RF risk (p > 0.05).

CONCLUSION: MR found robust evidence of a causal association between RF and mTOR. RP-S6K and ATG7 may be targeted for intervention by repurposing existing therapeutics to reduce the risk of RF.

PMID:36773079 | DOI:10.1007/s12325-022-02419-4

Hum Genet. 2023 Feb 11. doi: 10.1007/s00439-023-02525-5. Online ahead of print.

ABSTRACT

Leveraging genome-wide association statistics generated from a large study of amyotrophic lateral sclerosis (ALS; 29,612 cases and 122,656 controls) and UK Biobank (UKB; 4,024 phenotypes, up to 361,194 participants), we conducted a phenome-wide analysis of ALS genetic liability and identified 46 genetically correlated traits, such as fluid intelligence score (r_g = – 0.21, p = 1.74 × 10^-6), “spending time in pub or social club” (r_g = 0.24, p = 2.77 × 10^-6), non-work related walking (r_g = – 0.25, p = 1.95 × 10^-6), college education (r_g = – 0.15, p = 7.08 × 10^-5), “ever diagnosed with panic attacks (r_g = 0.39, p = 4.24 × 10^-5), and “self-reported other gastritis including duodenitis” (r_g = 0.28, p = 1.4 × 10^-3). To assess the putative directionality of these genetic correlations, we conducted a latent causal variable analysis, identifying significant genetic causality proportions (gĉp) linking ALS genetic liability to seven traits. While the genetic component of “self-reported other gastritis including duodenitis” showed a causal effect on ALS (gĉp = 0.50, p = 1.26 × 10^-29), the genetic liability to ALS is potentially causal for multiple traits, also including an effect on “ever being diagnosed with panic attacks” (gĉp = 0.79, p = 5.011 × 10^-15) and inverse effects on “other leisure/social group activities” (gĉp = 0.66, p = 1 × 10^-4) and prospective memory result (gĉp = 0.35, p = 0.005). Our subsequent Mendelian randomization analysis indicated that some of these associations may be due to bidirectional effects. In conclusion, this phenome-wide investigation of ALS polygenic architecture highlights the widespread pleiotropy linking this disorder with several health domains.

PMID:36773064 | DOI:10.1007/s00439-023-02525-5

J Neurol. 2023 Feb 11. doi: 10.1007/s00415-023-11607-3. Online ahead of print.

ABSTRACT

OBJECTIVES: This paper aimed to identify white matter (WM) and gray matter (GM) abnormalities in a sample of early PD patients, and their correlations with motor and non-motor symptom severity.

METHODS: We enrolled 62 de novo PD patients and 31 healthy subjects. Disease severity and non-motor symptom burden were assessed by the Unified Parkinson’s Disease Rating Scale part III and the Non-Motor Symptoms Scale, respectively. Cognitive performance was assessed using Montreal Cognitive Assessment and Frontal Assessment Battery. All subjects underwent a 3-Tesla MRI protocol. MRI analyses included tract-based spatial statistics, cortical thickness, and subcortical and cerebellar volumetry.

RESULTS: In comparison to control subjects, PD patients exhibited lower fractional anisotropy and higher mean, axial, and radial diffusivity in most WM bundles, including corticospinal tracts, the internal and external capsule, the anterior and posterior thalamic radiations, the genu and body of the corpus callosum, cerebellar peduncles, and superior and inferior longitudinal and fronto-occipital fasciculi. Correlations between Montreal Cognitive Assessment scores and fractional anisotropy values in the right posterior thalamic radiation, left superior corona radiata, right inferior-fronto-occipital fasciculus, left inferior longitudinal fasciculus, bilateral anterior thalamic radiations, and bilateral superior longitudinal fasciculi were found. Smaller cerebellar volumes in early PD patients in the left and right crus I were also found. No GM changes were present in subcortical or cortical regions.

CONCLUSION: The combined evaluation of WM and GM in the same patient sample demonstrates that WM microstructural abnormalities precede GM structural changes in early PD patients.

PMID:36773059 | DOI:10.1007/s00415-023-11607-3