Nevin Manimala

Cancer Imaging. 2023 Aug 14;23(1):76. doi: 10.1186/s40644-023-00594-3.

ABSTRACT

BACKGROUND: The aim of this work is to evaluate the performance of radiomics predictions for a range of molecular, genomic and clinical targets in patients with clear cell renal cell carcinoma (ccRCC) and demonstrate the impact of novel feature selection strategies and sub-segmentations on model interpretability.

METHODS: Contrast-enhanced CT scans from the first 101 patients recruited to the TRACERx Renal Cancer study (NCT03226886) were used to derive radiomics classification models to predict 20 molecular, histopathology and clinical target variables. Manual 3D segmentation was used in conjunction with automatic sub-segmentation to generate radiomics features from the core, rim, high and low enhancing sub-regions, and the whole tumour. Comparisons were made between two classification model pipelines: a Conventional pipeline reflecting common radiomics practice, and a Proposed pipeline including two novel feature selection steps designed to improve model interpretability. For both pipelines nested cross-validation was used to estimate prediction performance and tune model hyper-parameters, and permutation testing was used to evaluate the statistical significance of the estimated performance measures. Further model robustness assessments were conducted by evaluating model variability across the cross-validation folds.

RESULTS: Classification performance was significant (p < 0.05, H₀:AUROC = 0.5) for 11 of 20 targets using either pipeline and for these targets the AUROCs were within ± 0.05 for the two pipelines, except for one target where the Proposed pipeline performance increased by > 0.1. Five of these targets (necrosis on histology, presence of renal vein invasion, overall histological stage, linear evolutionary subtype and loss of 9p21.3 somatic alteration marker) had AUROC > 0.8. Models derived using the Proposed pipeline contained fewer feature groups than the Conventional pipeline, leading to more straightforward model interpretations without loss of performance. Sub-segmentations lead to improved performance and/or improved interpretability when predicting the presence of sarcomatoid differentiation and tumour stage.

CONCLUSIONS: Use of the Proposed pipeline, which includes the novel feature selection methods, leads to more interpretable models without compromising prediction performance.

TRIAL REGISTRATION: NCT03226886 (TRACERx Renal).

PMID:37580840 | DOI:10.1186/s40644-023-00594-3

Eye Vis (Lond). 2023 Aug 14;10(1):38. doi: 10.1186/s40662-023-00355-0.

ABSTRACT

BACKGROUND: Age-related macular degeneration (AMD) is a multifactorial degenerative disease of the macula. Different factors, environmental, genetic and lifestyle, contribute to its onset and progression. However, how they interconnect to promote the disease, or its progression, is still unclear. With this work, we aim to assess the interaction of the genetic risk for AMD and the adherence to the Mediterranean diet in the Coimbra Eye Study.

METHODS: Enrolled subjects (n = 612) underwent ophthalmological exams and answered a food questionnaire. Adherence to the Mediterranean diet was assessed with mediSCORE. An overall value was calculated for each participant, ranging from 0 to 9, using the sum of 9 food groups, and a cut off value of ≥ 6 was considered high adherence. Rotterdam Classification was used for grading. Participants’ genotyping was performed in collaboration with The European Eye Epidemiology Consortium. The genetic risk score (GRS) was calculated for each participant considering the number of alleles at each variant and their effect size. Interaction was assessed with additive and multiplicative models, adjusted for age, sex, physical exercise, and smoking.

RESULTS: The AMD risk was reduced by 60% in subjects with high adherence to the Mediterranean diet compared to subjects with low adherence to the Mediterranean diet. Combined effects of having low adherence to the Mediterranean diet and high GRS led to almost a 5-fold increase in the risk for AMD, compared to low GRS and high adherence to the Mediterranean diet. The multiplicative scale suggested a multiplicative interaction, although not statistically significant [odds ratio (OR) = 1.111, 95% CI 0.346-3.569, P = 0.859]. The additive model showed a causal positive effect of the interaction of GRS and adherence to the Mediterranean diet: relative excess risk due to interaction (RERI) = 150.9%, (95% CI: – 0.414 to 3.432, P = 0.062), attributable proportion due to interaction (AP) = 0.326 (95% CI: – 0.074 to 0.726, P = 0.055) and synergy index (SI) = 1.713 (95% CI: 0.098-3.329, P = 0.019). High GRS people benefited from adhering to the Mediterranean diet with a 60% risk reduction. For low-GRS subjects, a risk reduction was also seen, but not significantly.

CONCLUSIONS: Genetics and Mediterranean diet interact to protect against AMD, proving there is an interplay between genetics and environmental factors.

TRIAL REGISTRATION: The AMD Incidence (NCT02748824) and Lifestyle and Food Habits Questionnaire in the Portuguese Population Aged 55 or More (NCT01715870) studies are registered at www.

CLINICALTRIALS: gov . Five-year Incidence of Age-related Macular Degeneration in the Central Region of Portugal (AMD IncidencePT); NCT02748824: date of registration: 22/04/16. Lifestyle and Food Habits Questionnaire in the Portuguese Population Aged 55 or More; NCT01715870: date of registration: 29/10/12.

PMID:37580831 | DOI:10.1186/s40662-023-00355-0

Health Qual Life Outcomes. 2023 Aug 15;21(1):90. doi: 10.1186/s12955-023-02177-z.

ABSTRACT

BACKGROUND: The EQ-5D-5 L is a commonly used generic measure of health. This study aimed to evaluate the psychometric properties of the EQ-5D-5 L in patients with Graves’ disease (GD).

METHODS: A prospective cohort of patients with GD recruited at three public hospitals in Hong Kong completed the EQ-5D-5 L and ThyPRO-39 questionnaires at baseline, 1-month, and 6-month follow-ups. Convergent validity was tested by examining the Spearman correlation between EQ-5D-5 L and ThyPRO-39 scores at baseline. 1-month test-retest reliability was assessed by Intraclass Correlation Coefficient (ICC), Gwet’s Agreement Coefficient 2 (AC2), and percentage agreement. Responsiveness of EQ-5D-5 L index and EQ-VAS scores was assessed using effect size statistics (standardized effect size [SES] and standardized response mean [SRM]).

RESULTS: Of 125 recruited patients, 101 (80.8%) and 100 (80.0%) patients were followed up at 1- and 6-month, respectively. For convergent validity, there was a moderate negative correlation between EQ-5D-5 L index or EQ-VAS score and ThyPRO-39 overall QoL-impact score (-0.350, -0.451), between EQ-VAS score and composite score (-0.483), and strong negative correlation between EQ-5D-5 L index score and composite score (-0.567). The Gwet’s AC2 and percentage agreement were the highest in self-care (0.964 and 0.967), followed by mobility (0.952 and 0.962), usual activities (0.934 and 0.948), pain/discomfort (0.801 and 0.887), and anxiety/depression (0.788 and 0.882). The ICC for the EQ-5D-5 L index and the EQ-VAS was 0.707 and 0.700. For patients who reported having ‘worsened’ health at 6-month follow-up, the SES and SRM were – 0.66 and – 0.42 for EQ-5D-5 L index and – 1.15 and – 1.00 for EQ-VAS, respectively.

CONCLUSIONS: The EQ-5D-5 L demonstrated convergent validity, test-retest reliability, and responsiveness to worsened health status among patients with GD.

PMID:37580816 | DOI:10.1186/s12955-023-02177-z

Trop Dis Travel Med Vaccines. 2023 Aug 15;9(1):11. doi: 10.1186/s40794-023-00193-x.

ABSTRACT

BACKGROUND: Prompt administration of post-exposure prophylaxis (PEP) is crucial to prevent a fatal rabies infection after an animal associated injury (AAI), preferably within 24 h. PEP, especially in case of a type III injury for which rabies immune globulin (RIG) is needed, is difficult to obtain abroad. This, along with the fear of potentially having contracted a lethal disease, might be an important source for anxiety and distress. We investigated the occurrence and extent of self-reported anxiety and distress at different timepoints among Dutch travellers after encountering an AAI, and the involved factors.

METHODS: A retrospective quantitative observational study was conducted including insured Dutch travellers who actively contacted Eurocross Assistance after encountering an AAI abroad. An online questionnaire was designed to measure anxiety and distress levels, using the HADS (Hospital Anxiety and Depression Scale) and distress thermometer at three time points: departure from home (T1), post-AAI (T2), and treatment administration (T3). Statistical analyses included T-tests, Chi-square tests, and ANCOVA analyses.

RESULTS: We showed a significant increase in mean anxiety and distress scores at T2, and a significant decrease at T3. Women were more often anxious and distressed. Between T1 and T2, PrEP, and being aware of the risks were positively associated with anxiety levels, and PrEP and WHO region Africa with distress levels. Between T2 and T3, anxiety levels remained higher for monkey-induced injury, thoracic injuries, and WHO region Southeast Asia. PEP-delay between 24-48 h resulted in decreased distress levels at this time period, while type II injury elevated distress levels.

CONCLUSIONS: This study showed significant anxiety and distress levels after an AAI among the vast majority of travellers, which is detrimental to their health-related quality of life (HR-QOL). This highlights the importance of proper pre-travel information. In the context of rabies prevention, these results suggest that pre-travel advice and policy makers should also take aspects of HR-QOL into consideration.

PMID:37580813 | DOI:10.1186/s40794-023-00193-x

Vet Dermatol. 2023 Aug 14. doi: 10.1111/vde.13197. Online ahead of print.

ABSTRACT

BACKGROUND: In canine otitis externa (OE), biofilm-producing bacteria are frequently present but biofilm may be underdiagnosed clinically.

HYPOTHESIS/OBJECTIVES: The study aimed to investigate an association between clinical and cytological findings with bacteriological data from dogs with OE, to establish, through Environmental Scanning Electron Microscope (ESEM) examination, whether the presence of biofilm in vivo can be predicted and to evaluate the impact of biofilm on antimicrobial susceptibility tests.

MATERIALS AND METHODS: Fifty-six dogs showing clinical signs of OE were enrolled. One cotton swab each was collected for ESEM, bacterial culture and susceptibility testing and for cytology. Staphylococcus pseudintermedius (n = 42, 48.8%) and Pseudomonas aeruginosa (n = 26, 30.2%) were tested for their ability to form biofilm. Minimum Inhibitory Concentrations (MIC), Minimal Biofilm Inhibitory Concentrations (MBIC) and Minimal Biofilm Eradication Concentrations (MBEC) towards enrofloxacin, gentamicin, polymyxin B and rifampicin were determined.

RESULTS: Pseudomonas aeruginosa was positively associated with the biofilm clinical evaluation (p < 0.01) and neutrophils (p < 0.05), nuclear streaks (p < 0.01) and rods bacteria (p < 0.01) on cytology. S. pseudintermedius was associated with a low presence of neutrophils. There was a statistical correlation between clinical and cytological biofilm presence (p ≤ 0.01), but none with the biofilm production assay nor ESEM biofilm detection. No differences were found comparing the results of MIC and MBIC. MBEC results showed higher values than MIC and MBIC for all antimicrobials tested (p ≤ 0.001).

CONCLUSIONS AND CLINICAL RELEVANCE: Biofilm presence in OE was often underdiagnosed. Even if there is no specific clinical or cytological pattern related to biofilm, its presence should always be suspected.

PMID:37580811 | DOI:10.1111/vde.13197

Arthritis Res Ther. 2023 Aug 14;25(1):148. doi: 10.1186/s13075-023-03122-7.

ABSTRACT

BACKGROUND: In addition to decreasing the level of cholesterol, proprotein convertase subtilis kexin 9 (PCSK9) inhibitor has pleiotropic effects, including immune regulation. However, the impact of PCSK9 on autoimmune diseases is controversial. Therefore, we used drug target Mendelian randomization (MR) analysis to investigate the effect of PCSK9 inhibitor on different autoimmune diseases.

METHODS: We collected single nucleotide polymorphisms (SNPs) of PCSK9 from published genome-wide association studies statistics and conducted drug target MR analysis to detect the causal relationship between PCSK9 inhibitor and the risk of autoimmune diseases. 3-Hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitor, the drug target of statin, was used to compare the effect with that of PCSK9 inhibitor. With the risk of coronary heart disease as a positive control, primary outcomes included the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), myasthenia gravis (MG), multiple sclerosis (MS), asthma, Crohn’s disease (CD), ulcerative colitis (UC), and type 1 diabetes (T1D).

RESULTS: PCSK9 inhibitor significantly reduced the risk of SLE (OR [95%CI] = 0.47 [0.30 to 0.76], p = 1.74 × 10^-3) but increased the risk of asthma (OR [95%CI] = 1.15 [1.03 to 1.29], p = 1.68 × 10^-2) and CD (OR [95%CI] = 1.38 [1.05 to 1.83], p = 2.28 × 10^-2). In contrast, HMGCR inhibitor increased the risk of RA (OR [95%CI] = 1.58 [1.19 to 2.11], p = 1.67 × 10^-3), asthma (OR [95%CI] = 1.21 [1.04 to 1.40], p = 1.17 × 10^-2), and CD (OR [95%CI] = 1.60 [1.08 to 2.39], p = 2.04 × 10^-2).

CONCLUSIONS: PCSK9 inhibitor significantly reduced the risk of SLE but increased the risk of asthma and CD. In contrast, HMGCR inhibitor may be a risk factor for RA, asthma, and CD.

PMID:37580807 | DOI:10.1186/s13075-023-03122-7

BMC Sports Sci Med Rehabil. 2023 Aug 14;15(1):102. doi: 10.1186/s13102-023-00715-2.

ABSTRACT

BACKGROUND: Low back pain is one of the most common complaints affecting many individuals. The McGill Pain Questionnaire is used in various clinical settings to assess different types of pain and one of the most extensively used outcomes measures for pain in the world. The purpose of this study was to translate and validate the original English version of the SF-MPQ-2 into Urdu (SF-MPQ-2-U).

METHODS: For this study, Mapi Research Trust protocols were followed for the forward and backward translation. Test-retest reliability was used to assess the reliability. Cronbach’s alpha and Omega was used to determine internal consistency. Pearson’s correlation was used to evaluate convergent validity. Confirmatory factor analysis was also conducted.

RESULTS: The Cronbach’s alpha for SF-MPQ-2-U was 0.73 to 0.79, indicating acceptable internal consistency. Omega score for the SF-MPQ-U were 0.918. The ICC varied from 0.799 to 0.878 for domains of SF-MPQ-2-U. The CFA of the SF-MPQ-2-U met model fit indices with GFI and NFI > 0.90. The inter-scale correlation between baseline and re-test data was from 0.63 to 0.71, indicating a positive and strong correlation. The SF-MPQ-2-U and ODI-U had a baseline correlation of 0.547. The correlation of SF-MPQ-2-U & VAS at baseline data was 0.558. Pearson’s correlation between subscales was r = 0.253 with p 0.01, which was statistically significant.

CONCLUSION: The SF-MPQ-2-U is considered to have good convergent validity at inter scale and between two scale levels. Reliability was checked by test-retest reliability, Internal consistency was checked using Cronbach’s alpha and Omega that showed good internal consistency for measuring different types of pain in patients with low back pain who speak Urdu. To make the questionnaire more valid and reliable, it is recommended for the researchers to do in-depth research on larger sample size.

PMID:37580806 | DOI:10.1186/s13102-023-00715-2

Breast Cancer Res. 2023 Aug 14;25(1):95. doi: 10.1186/s13058-023-01693-6.

ABSTRACT

BACKGROUND: Laboratory studies have indicated that a cholesterol metabolite and selective estrogen receptor modulator, 27-hydroxycholesterol (27HC), may be important in breast cancer etiology and explain associations between obesity and postmenopausal breast cancer risk. Epidemiologic evidence for 27HC in breast cancer risk is limited, particularly in multiethnic populations.

METHODS: In a nested case-control study of 1470 breast cancer cases and 1470 matched controls within the Multiethnic Cohort Study, we examined associations of pre-diagnostic circulating 27HC with breast cancer risk among African American, Japanese American, Native Hawaiian, Latino, and non-Latino White postmenopausal females. We used multivariable logistic regression adjusted for age, education, parity, body mass index, and smoking status. Stratified analyses were conducted across racial and ethnic groups, hormone receptor (HR) status, and use of lipid-lowering drugs. We assessed interactions of 27HC with steroid hormones.

RESULTS: 27HC levels were inversely related to breast cancer risk (odds ratio [OR] 0.80; 95% confidence interval [CI] 0.58, 1.12), but the association was not statistically significant in the full model. Directions of associations differed by racial and ethnic group. Results suggested an inverse association with HR-negative breast cancer (OR 0.46; 95% CI 0.20, 1.06). 27HC interacted with testosterone, but not estrone, on risk of breast cancer; 27HC was only inversely associated with risk among those with the highest levels of testosterone (OR 0.46; 95% CI 0.24, 0.86).

CONCLUSION: This is the first US study to examine circulating 27HC and breast cancer risk and reports a weak inverse association that varies across racial and ethnic groups and testosterone level.

PMID:37580793 | DOI:10.1186/s13058-023-01693-6

Syst Rev. 2023 Aug 14;12(1):141. doi: 10.1186/s13643-023-02305-2.

ABSTRACT

BACKGROUND: Bacterial sexually transmitted infections (STIs) including Neisseria gonorrhoeae and Chlamydia trachomatis are common in men who have sex with men (MSM). These infections increase the risk of acquiring and transmitting human immunodeficiency virus (HIV) in this key population. Access to MSM in many countries in sub-Saharan Africa remains generally difficult due to discrimination or criminalization of their sexual orientation which could lead to depression and risky sexual practices associated with prevalence. This protocol therefore proposes to undertake a systematic review and meta-analysis of literature on the prevalence of gonococcal and chlamydial infections among MSM in Sub-Saharan Africa.

METHODS: This review which aims to ascertain the pooled prevalence and risk factors of these infections in sub-Saharan Africa’s MSM population will follow the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. The search strategy will review relevant articles from the following databases: PubMed, Scopus, ISI Web of Science and the Directory of Open Access Journals (DOAJ). Articles screening for eligibility and data extraction will be conducted by two independent reviewers. All discrepancies will be resolved by the third and fourth reviewers. Heterogeneity in studies will be evaluated using the I² statistic and where heterogeneity is high and significant, a random effect model will be used to estimate the pooled prevalence. Publication bias will be assessed using the Doi plot. Extracted data will be analysed using MetaXL add-on for Microsoft excel. Data will be presented in tables and graphically presented in forest plots.

DISCUSSION: In this study, we anticipate being able to systematically determine the prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis among MSM as well as explore possible risk factors associated with prevalence. The outcomes of the systematic review and meta-analyses will serve to support researchers and public health stakeholders in identifying healthcare priorities and in addressing issues pertaining to the overall wellbeing of the MSM community.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022327095.

PMID:37580787 | DOI:10.1186/s13643-023-02305-2

Cardiovasc Ultrasound. 2023 Aug 14;21(1):15. doi: 10.1186/s12947-023-00313-9.

ABSTRACT

BACKGROUND: In addition to proatherogenic properties, lipoprotein (a) (Lp(a)) has also pro-inflammatory, antifibrinolytic and prothrombogenic features. The aim of the current study was to identify the predictors of functional and morphological properties of the arterial wall in patients after myocardial infarction and increased Lp(a) levels at the beginning and after treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors.

METHODS: Seventy-six post-myocardial infarction patients with high Lp(a) levels were included in the study. Ultrasound measurements of flow-mediated dilation of brachial artery (FMD), carotid intima-media thickness (c-IMT) and pulse wave velocity (PWV) were performed initially and after 6 months of treatment. At the same time points lipids, Lp(a), inflammatory and hemostasis markers were measured in blood samples.

RESULTS: In linear regression model FMD significantly correlated with age at first myocardial infarction (β = 0.689; p = 0.022), high-sensitivity C-reactive protein (β = -1.200; p = 0.009), vascular cell adhesion protein 1 (VCAM-1) (β = -0.992; p = 0.006), overall coagulation potential (β = 1.428; p = 0.014) and overall hemostasis potential (β = -1.473; p = 0.008). c-IMT significantly correlated with age at first myocardial infarction (β = 0.574; p = 0.033) and Lp(a) (β = 0.524; p = 0.040). PWV significantly correlated with systolic blood pressure (β = 0.332; p = 0.002), tumor necrosis factor alpha (β = 0.406; p = 0.002), interleukin-8 (β = -0.315; p = 0.015) and plasminogen activator inhibitor 1 (β = 0.229; p = 0.031). After treatment FMD reached statistical significance only in univariant analysis with systolic blood pressure (r = -0.286; p = 0.004) and VCAM-1 (r = -0.229; p = 0.024). PWV and c-IMT correlated with age (r = 0.334; p = 0.001 and r = 0.486; p < 0.0001, respectively) and systolic blood pressure (r = 0.556; p < 0.0001 and r = 0.233; p = 0.021, respectively).

CONCLUSIONS: Our results suggest that age, systolic blood pressure, Lp(a) levels and other biochemical markers associated with Lp(a) are predictors of functional and morphological properties of the arterial vessel wall in post-myocardial patients with high Lp(a) levels initially. However, after 6 months of treatment with PCSK9 inhibitors only age and systolic blood pressure seem to be predictors of these properties.

TRIAL REGISTRATION: The protocol for this study was registered with clinicaltrials.gov on November, 3 2020 under registration number NCT04613167.

PMID:37580777 | DOI:10.1186/s12947-023-00313-9