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Association of urine phthalate metabolites levels with kidney function in 1610 US adolescents

Environ Sci Pollut Res Int. 2023 May 6. doi: 10.1007/s11356-023-27389-0. Online ahead of print.

ABSTRACT

Phthalates are widely used as plasticizer or fragrance ingredients in various consumer products worldwide. However, evidence for the overall effects of mixed exposure to phthalate on kidney function has not been widely investigated. The purpose of this article was to assess the association of urine phthalate metabolite levels and kidney injury parameters in adolescents. We used data from the combined 2007-2016 National Health and Nutrition Examination Survey (NHANES). We fitted weighted linear regressions and Bayesian kernel machine regressions (BKMR) models to explore the association of urinary phthalate metabolites with four parameters of kidney function after adjusting for covariates. Weighted linear regression models showed that MiBP (β = 8.057; PFDR = 0.016) was significantly positively associated with eGFR and MEP (β = -0.799; PFDR < 0.001) was significantly negatively correlated with BUN. BKMR analysis showed that the higher the concentration of phthalate metabolite mixture, the higher eGFR in adolescents. Based on the results of these two models, our findings revealed that mixed exposure to phthalates was associated with elevated eGFR in adolescents. However, as the study is cross-sectional, reverse causality is possible, and altered kidney function may impact the concentration of phthalate metabolites in urine.

PMID:37148507 | DOI:10.1007/s11356-023-27389-0

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A treatment prediction strategy for overactive bladder using a machine learning algorithm that utilized data from the FAITH study

Neurourol Urodyn. 2023 May 6. doi: 10.1002/nau.25190. Online ahead of print.

ABSTRACT

AIMS: To use machine learning algorithms to develop a model to accurately predict treatment responses to mirabegron or antimuscarinic agents in patients with overactive bladder (OAB), using real-world data from the FAITH registry (NCT03572231).

METHODS: The FAITH registry data included patients who had been diagnosed with OAB symptoms for at least 3 months and were due to initiate monotherapy with mirabegron or any antimuscarinic. For the development of the machine learning model, data from patients were included if they had completed the 183-day study period, had data for all timepoints and had completed the overactive bladder symptom scores (OABSS) at baseline and end of study. The primary outcome of the study was a composite outcome combining efficacy, persistence, and safety outcomes. Treatment was deemed “more effective” if the composite outcome criteria for “successful,” “no treatment change,” and “safe” were met, otherwise treatment was deemed “less effective.” To explore the composite algorithm, a total of 14 clinical risk factors were included in the initial data set and a 10-fold cross-validation procedure was performed. A range of machine learning models were evaluated to determine the most effective algorithm.

RESULTS: In total, data from 396 patients were included (266 [67.2%] treated with mirabegron and 130 [32.8%] treated with an antimuscarinic). Of these, 138 (34.8%) were in the “more effective” group and 258 (65.2%) were in the “less effective” group. The groups were comparable in terms of their characteristic distributions across patient age, sex, body mass index, and Charlson Comorbidity Index. Of the six models initially selected and tested, the decision tree (C5.0) model was chosen for further optimization, and the receiver operating characteristic of the final optimized model had an area under the curve result of 0.70 (95% confidence interval: 0.54-0.85) when 15 was used for the min n parameter.

CONCLUSIONS: This study successfully created a simple, rapid, and easy-to-use interface that could be further refined to produce a valuable educational or clinical decision-making aid.

PMID:37148497 | DOI:10.1002/nau.25190

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Quantitative analysis of dual-phase enhanced CT in cervical lymph node metastasis of papillary thyroid carcinoma: a comparative study along with pathological manifestations

Endocrine. 2023 May 6. doi: 10.1007/s12020-023-03386-8. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to investigate the diagnostic value of dual-phase enhanced computed tomography (CT) in the cervical lymph node metastasis (LNM) of papillary thyroid carcinoma (PTC) by analyzing the dual-phase enhanced Hounsfield units (HUs) of lymph node and sternocleidomastoid muscle, and the ratio and difference.

METHODS: The CT arterial-phase and venous-phase imaging data of 143 metastasis-positive lymph nodes (MPLNs) in 88 cases and 172 metastasis-negative lymph nodes (MNLNs) in 128 cases with PTC were retrospectively analyzed. All lymph nodes were confirmed by surgical pathology. The arterial-phase HU of lymph nodes (ANHU), venous-phase HU of lymph nodes (VNHU), arterial-phase HU of the sternocleidomastoid muscle (AMHU) and venous-phase HU of the sternocleidomastoid muscle (VMHU) were measured, and their difference and ratio (ANHU-AMHU, ANHU/AMHU, VNHU-VMHU, VNHU/VMHU) were calculated. The cutoff values and corresponding diagnostic efficacy for diagnosing LNM in PTC were sought by performing the receiver operating characteristic curves. The maximum pathological diameter (MPD) measured on pathological sections of lymph nodes was compared with the maximum transverse diameter (MTD) and maximum sagittal diameter (MSD) and their average values on CT images.

RESULTS: The ANHU, and VNHU of MPLNs and MNLNs were 111.89 ± 33.26 and 66.12 (56.81-76.86) (P < 0.001), and 99.07 ± 23.27 and 75.47 ± 13.95 (P < 0.001), respectively. The area under the curve, sensitivity, and specificity of the arterial-phase three parameters (ANHU, ANHU-AMHU, ANHU/AMHU) for diagnosing LNM were (0.877-0.880), (0.755-0.769), and (0.901-0.913), respectively, and the venous-phase three parameters (VNHU, VNHU-VMHU, VNHU/VMHU) were (0.801-0.817), (0.650-0.678), and (0.826-0.901), respectively. Compared with MPD, MTD (Z = -2.686, P = 0.007) and MSD (Z = -3.539, P < 0.001) were significantly different, while (MTD + MSD)/2 was not statistically different (Z = -0.038b, P = 0.969).

CONCLUSION: In the differential diagnosis of cervical LNM of PTC by dual-phase enhanced CT angiography, the arterial phase had higher diagnostic efficacy.

PMID:37148418 | DOI:10.1007/s12020-023-03386-8

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Increased prevalence of nodular thyroid disease in patients with Klinefelter syndrome

Endocrine. 2023 May 6. doi: 10.1007/s12020-023-03387-7. Online ahead of print.

ABSTRACT

PURPOSE: Thyroid dysfunction in patients with Klinefelter syndrome (KS) remains an unresolved issue. Although low free thyroxine (FT4) levels within the normal range and normal thyroid stimulating hormone (TSH) levels have been reported, there is currently no data on nodular thyroid disease in this population. This study aims to evaluate the results of thyroid ultrasound (US) examinations in KS patients compared with healthy controls.

METHODS: A cohort of 122 KS and 85 age-matched healthy male controls underwent thyroid US screening and thyroid hormone analysis. According to US risk-stratification systems, nodules ≥1 cm were examined by fine needle aspiration (FNA).

RESULTS: Thyroid US detected nodular thyroid disease in 31% of KS compared to 13% of controls. No statistical differences in the maximum diameter of the largest nodules and in moderate and highly suspicious nodules were found between patients and the control group. Six KS patients and two controls with nodules underwent FNA and were confirmed as cytologically benign. In line with published data, FT4 levels were found significantly near the lower limit of the normal range compared to controls, with no differences in TSH values between the two groups. Hashimoto’s thyroiditis was diagnosed in 9% of patients with KS.

CONCLUSIONS: We observed a significantly higher prevalence of nodular thyroid disease in KS compared to the control group. The increase in nodular thyroid disease is likely linked to low levels of FT4, inappropriate TSH secretion, and/or genetic instability.

PMID:37148417 | DOI:10.1007/s12020-023-03387-7

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Effects of myo-inositol vs. metformin on hormonal and metabolic parameters in women with PCOS: a meta-analysis

Ir J Med Sci. 2023 May 6. doi: 10.1007/s11845-023-03388-5. Online ahead of print.

ABSTRACT

OBJECTIVE: Polycystic Ovary Syndrome is the most prevalent hormonal disorder in females. Over the years, metformin (MET) has become the first-line choice of treatment; however, due to its gastrointestinal side effects, a more recent drug, myo-inositol (MI), has been introduced. We aim to conduct a systematic review and meta-analysis to compare the effects of MET and MI on hormonal and metabolic parameters.

MATERIALS AND METHODS: Authors extensively searched PubMed, Scopus, Cochrane Library, Google Scholar, and Web of Science for randomized clinical trials (RCTs) until August 2021. Eight (n = 8) articles were included, with a total sample size of 1088, of which 460 patients received MET, 436 received MI, and 192 received a combination of both. Standard mean differences (SMDs) and Confidence Intervals (CIs) were used for data synthesis, and forest plots were made using Review Manager 5.4 for Statistical Analysis using the random-effect model.

RESULTS: The meta-analysis indicates that there is no significant difference between MET and MI in terms of their effects on BMI (SMD = 0.16, 95% CI: – 0.11 to 0.43, p = 0.24), fasting insulin (SMD = 0.00, 95% CI: – 0.26 to 0.27, p = 0.97), fasting blood sugar (SMD = 0.11, 95% CI: – 0.31to 0.53, p = 0.60), HOMA index (SMD = 0.09, 95% CI: – 0.20 to 0.39, p = 0.50), and LH/FSH (SMD = 0.20, 95% CI: – 0.24 to 0.64, p = 0.37). BMI, fasting blood sugar, and LH/FSH ratio reported moderate heterogeneity because of the varying number of study participants.

CONCLUSION: Our meta-analysis comparing hormonal and metabolic parameters between MET and MI did not show much significant difference, indicating both drugs are equally beneficial in improving metabolic and hormonal parameters in patients with PCOS.

PMID:37148410 | DOI:10.1007/s11845-023-03388-5

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Chemotherapy alone vs. chemotherapy plus radiotherapy in female adolescent and young adults with Hodgkin’s lymphoma: reproductive health outcomes

J Cancer Surviv. 2023 May 6. doi: 10.1007/s11764-023-01388-z. Online ahead of print.

ABSTRACT

PURPOSE: To examine the effects of Hodgkin’s lymphoma and its treatment on reproductive health in female adolescent and young adults (AYA).

METHODS: We conducted a retrospective, population-based, matched-cohort study of female patients with Hodgkin’s lymphoma diagnosed at 15-39 years of age from 1995 to 2014 in Ontario, Canada. Three female individuals with no history of cancer (unexposed) were matched by birth year and census subdivision to each patient with cancer (exposed). In a subset of the cohort (2005 onwards), the Hodgkin’s lymphoma patients were further classified into two groups for analysis based on treatment exposure: (1) chemotherapy alone or (2) combined chemotherapy and radiation. Reproductive health outcomes were infertility, childbirth, and premature ovarian insufficiency (POI). Relative risks (RR) were calculated using modified Poisson regression adjusted for income quintile, immigration status, and parity.

RESULTS: A total of 1443 exposed and 4329 unexposed individuals formed our cohort. Hodgkin’s lymphoma patients were at an increased risk of infertility (aRR 1.86; 95% CI 1.57 to 2.20) and POI (aRR 2.81; 95% CI 2.16 to 3.65). While the risk of infertility persisted in both treatment groups (chemotherapy alone, combined chemotherapy plus radiotherapy), the increased risk of POI was only statistically significant in the chemotherapy plus radiotherapy group. No differences in childbirth rates were observed, overall or by treatment exposure compared with unexposed individuals.

CONCLUSIONS: Female AYA survivors of Hodgkin’s lymphoma face an increased risk of infertility, independent of exposure to chemotherapy alone, or chemotherapy plus radiotherapy. The risk of POI is higher in those requiring radiotherapy vs. chemotherapy alone.

IMPLICATIONS FOR CANCER SURVIVORS: These results emphasize the importance of pre-treatment fertility counseling and reproductive health surveillance for AYAs diagnosed with Hodgkin’s lymphoma.

PMID:37148406 | DOI:10.1007/s11764-023-01388-z

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What does degeneration at the cervicothoracic junction tell us? A kinematic MRI study of 93 individuals

Eur Spine J. 2023 May 6. doi: 10.1007/s00586-023-07743-z. Online ahead of print.

ABSTRACT

PURPOSE: Current decision-making in multilevel cervical fusion weighs the potential to protect adjacent levels and reduce reoperation risk by crossing the cervicothoracic junction (C7/T1) against increased operative time and risk of complication. Careful planning is required, and the planned distal and adjacent levels should be assessed for degenerative disc disease (DDD). This study assessed whether DDD at the cervicothoracic junction was associated with DDD, disc height, translational motion, or angular variation in the adjacent superior (C6/C7) or inferior (T1/T2) levels.

METHODS: This study retrospectively analyzed 93 cases with kinematic MRI. Cases were randomly selected from a database with inclusion criteria being no prior spine surgery and images having sufficient quality for analysis. DDD was assessed using Pfirrmann classification. Vertebral body bone marrow lesions were assessed using Modic changes. Disc height was measured at the mid-disc in neutral and extension. Translational motion and angular variation were calculated by assessing translational or angular motion segment integrity respectively in flexion and extension. Statistical associations were assessed with scatterplots and Kendall’s tau.

RESULTS: DDD at C7/T1 was positively associated with DDD at C6/C7 (tau = 0.53, p < 0.01) and T1/T2 (tau = 0.58, p < 0.01), with greater disc height in neutral position at T1/T2 (tau = 0.22, p < 0.01), and with greater disc height in extended position at C7/T1 (tau = 0.17, p = 0.04) and at T1/T2 (tau = 0.21, p < 0.01). DDD at C7/T1 was negatively associated with angular variation at C6/C7 (tau = – 0.23, p < 0.01). No association was appreciated between DDD at C7/T1 and translational motion.

CONCLUSION: The association of DDD at the cervicothoracic junction with DDD at the adjacent levels emphasizes the necessity for careful selection of the distal level in multilevel fusion in the distal cervical spine.

PMID:37148392 | DOI:10.1007/s00586-023-07743-z

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A prospective randomised controlled trial evaluating prophylactic Floseal, a gelatin and thrombin-based haemostatic matrix, in postoperative drain output and blood transfusion in transforaminal lumbar interbody fusion surgery

Eur Spine J. 2023 May 6. doi: 10.1007/s00586-023-07748-8. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the prophylactic use of Floseal in reducing postoperative blood loss in patients undergoing Transforaminal Lumbar Interbody Fusion (TLIF). TLIF is a lumbar spine decompression and fusion procedure with potential for postoperative blood loss. Prophylactic application of Floseal, a gelatin and thrombin-based haemostatic matrix to the surgical wound before closure was shown to be effective in reducing postoperative drain output in anterior cervical discectomy and fusion. This study postulated that prophylactic use of Floseal before wound closure would reduce postoperative blood loss in patients who underwent TLIF.

METHODS: Randomised controlled trial comparing prophylactic use of Floseal and control in patients undergoing single level or two-level TLIF. Primary outcomes included postoperative drain output within 24 h and postoperative transfusion rate. Secondary outcomes included days of drain placement, length of stay and haemoglobin level.

RESULTS: A total of 50 patients was recruited. Twenty six patients were allocated to the Floseal group and 24 were allocated to the control group. There were no baseline characteristic differences between the groups. There were no statistically significant differences in primary outcomes which included postoperative drain output within 24 h and postoperative transfusion rate between patients who received prophylactic Floseal and control. There were no statistically significant differences in secondary outcomes which included haemoglobin level, days of drain placement and length of stay between the two groups.

CONCLUSION: Prophylactic use of Floseal was not shown to reduce postoperative bleeding in single level or two-level TLIF.

PMID:37148391 | DOI:10.1007/s00586-023-07748-8

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Expression, purification, characterization, and cytotoxic evaluation of the ML1-STxB fusion protein

Arch Microbiol. 2023 May 6;205(6):220. doi: 10.1007/s00203-023-03563-3.

ABSTRACT

Targeted delivery of a toxin substance to cancer cells is one of the most recent cancer treatment options. Mistletoe Lectin-1 (ML1) in Viscum album L. is a Ribosome-inactivating proteins with anticancer properties. Therefore, it appears that a recombinant protein with selective permeability can be generated by fusing ML1 protein with Shiga toxin B, which can bind to Gb3 receptor that is abundantly expressed on cancer cells. In this study, we sought to produce and purify a fusion protein containing ML1 fused to STxB and evaluate its cytotoxic activities. The ML1-STxB fusion protein coding sequence was cloned into the pET28a plasmid, then was transformed into E. coli BL21-DE3 cells. Following induction of protein expression, Ni-NTA affinity chromatography was used to purify the protein. Using SDS-PAGE and western blotting, the expression and purification processes were validated. On the SkBr3 cell line, the cytotoxic effects of the recombinant proteins were evaluated. On SDS-PAGE and western blotting membrane, analysis of purified proteins revealed a band of approximately 41 kDa for rML1-STxB. Ultimately, statistical analysis demonstrated that rML1-STxB exerted significant cytotoxic effects on SkBr3 cells at 18.09 and 22.52 ng/L. The production, purification, and encapsulation of rML1-STxB fusion protein with potential cancer cell-specific toxicity were successful. However, additional research must be conducted on the cytotoxic effects of this fusion protein on other malignant cell lines and in vivo cancer models.

PMID:37148384 | DOI:10.1007/s00203-023-03563-3

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The role of inflammatory biomarkers in the association between rheumatoid arthritis and depression: a Mendelian randomization study

Inflammopharmacology. 2023 May 6. doi: 10.1007/s10787-023-01241-w. Online ahead of print.

ABSTRACT

BACKGROUND: Inflammation may mediate the co-pathogenesis of rheumatoid arthritis (RA) and depression because inflammatory cytokines are associated with RA and depression. However, traditional observational research was not able to address problems with residual confusion and reverse causality.

METHODS: We summarized and retrieved 28 inflammatory cytokines associated with RA, depression, or RA with depression through a literature search. The summary statistics from genome-wide association studies for RA, inflammatory biomarkers, broad depression, and major depression disease phenotypes were used. Mendelian randomization was performed to assess the causal association between RA and inflammatory biomarkers, as well as the effects of inflammatory biomarkers on depression. Bonferroni correction was used to reduce the possibility of false positive results.

RESULTS: The study found that evidence for associations of genetically predicted RA was associated with higher levels of interleukin (IL)-9 (OR = 1.035, 95%CI = 1.002-1.068, P = 0.027), IL-12 (OR = 1.045, 95%CI = 1.045-1.014, P = 0.004), IL-13 (OR = 1.060, 95%CI = 1.028-1.092, P = 0.0001), IL-20 (OR = 1.037, 95%CI = 1.001-1.074, P = 0.047), and IL-27 (OR = 1.017, 95%CI = 1.003-1.032, P = 0.021). The level of IL-7 (OR = 1.029, 95%CI = 1.018-1.436, P = 0.030) was significantly related to RA. Only the analysis results between RA and IL-13 were satisfied with the statistical significance threshold corrected by Bonferroni (P < 0.002). However, a causal effect was not found between inflammatory biomarkers and depression.

CONCLUSIONS: In the current study the inflammatory cytokines associated with RA comorbid depression may not be the mediators that directly lead to the co-pathogenesis of RA and depression.

PMID:37148383 | DOI:10.1007/s10787-023-01241-w