Nevin Manimala

J Coll Physicians Surg Pak. 2023 Nov;33(11):1217-1222. doi: 10.29271/jcpsp.2023.11.1217.

ABSTRACT

OBJECTIVE: To investigate the anti-fibrotic effects of pirfenidone on Peyronie’s disease in an experimental rat model with intracavernosal injection of TGF-β and whether pirfenidone improves erectile function.

STUDY DESIGN: Experimental study. Place and Duration of the Study: Faculty of Medical Experimental Animals and Research Laboratory, Trakya University, from January to March 2021.

METHODOLOGY: In this study, 27 male Sprague Dawley rats were used, and three groups were randomly identified. The rats in Group 1 served as the control group. Group 2 was not treated, and Group 3 was treated with pirfenidone therapy. The rats in Group 3 were administered pirfenidone 30 mg/kg/day by oral gavage, every day for four weeks, three weeks after the start of the experiment. At the end of seven weeks, a haemodynamic study was performed with cavernosal nerve stimulation to evaluate the erectile function, the rats were sacrificed, and the penile tissues were evaluated immunohistochemically.

RESULTS: MeICP/MIBP values were found to be higher in treated rats compared to rats in the untreated group but no statistically significant difference was found in MeICP/MIBP values between the control, Peyronie model, and treatment groups (p=0.25). According to the histopathological examination, the rate of fibrosis with H&E staining was mild (100%) in the control group, severe (100%) in the Peyronie group, and severe (87.5% severe and 12.5% moderate) in the Peyronie + treatment group.

CONCLUSION: In the study, pirfenidone used in the treatment of Peyronie’s disease had a positive effect on erectile function, though not considered statistically significant. It has been shown that it has no histopathological effect on Peyronie’s plaques.

KEY WORDS: Anti-fibrotic agent, Erectile function, Experimental study, Peyronie’s disease, Pirfenidone.

PMID:37926870 | DOI:10.29271/jcpsp.2023.11.1217

Pharmacotherapy. 2023 Nov 5. doi: 10.1002/phar.2889. Online ahead of print.

ABSTRACT

PURPOSE: Acute kidney injury (AKI) commonly occurs in patients with lymphoma exposed to high-dose methotrexate (HDMTX), but our ability to reliably predict AKI is limited. This study sought to develop and validate a model for predicting AKI after HDMTX exposure.

METHODS: This multisite, retrospective study of consecutive adult lymphoma patients treated with HDMTX used the LASSO method to identify factors available at the outset of therapy that predicted incident AKI within 7 days following HDMTX. The model was then validated in an independent cohort.

RESULTS: The incidence of AKI within 7 days following HDMTX was 21.6% (95% Confidence Interval (CI) 18.4%-24.8%) in the derivation cohort (435 unique patients who received a total of 1,642 doses of HDMTX) and 15.6% (95% CI 5.3%-24.8%) in the validation cohort (55 unique patients who received a total of 247 doses of HDMTX). Factors significantly associated with AKI after HDMTX in the multivariable model included age ≥ 55 years, male sex, and lower HDMTX dose number. Other factors that were not found to be significantly associated with AKI on multivariable analysis, but were included in the final model, were body surface area, Charlson Comorbidity Index, and estimated glomerular filtration rate. The c-statistic of the model was 0.72 (95% CI 0.69-0.75) in the derivation cohort and 0.72 (95% CI 0.60-0.84) in the validation cohort.

CONCLUSION: This model utilizing identified sociodemographic and clinical factors is predictive of AKI following HDMTX administration in adult patients with lymphoma.

PMID:37926860 | DOI:10.1002/phar.2889

Acta Paediatr. 2023 Nov 5. doi: 10.1111/apa.17027. Online ahead of print.

ABSTRACT

AIM: To investigate how the aetiology of very preterm birth/very low birth weight is associated with mortality and later neurodevelopmental outcomes.

METHODS: Very preterm/very low-birth weight singletons were categorised based on the aetiology of preterm birth: spontaneous preterm birth (n = 47, 28.1%), preterm premature rupture of membranes (n = 56, 33.5%) or placental vascular pathology (n = 64, 38.3%). Mortality, cerebral palsy, severe cognitive impairment by 11 years of age (<2SD) and mean full-scale intelligence quotient at 11 years were studied in association with birth aetiology.

RESULTS: There was no difference in mortality or rate of cerebral palsy according to birth aetiologies. The rate of severe cognitive impairment was lower (4.9% vs. 15.3%) in the preterm premature rupture of the membrane group in comparison to the placental vascular pathology group (OR 0.2, 95% CI 0.03-0.9, adjusted for gestational age). At 11 years, there was no statistically significant difference in the mean full-scale intelligence quotient.

CONCLUSION: Placental vascular pathology, as the aetiology of very preterm birth/very low birth weight, is associated with a higher rate of severe cognitive impairments in comparison to preterm premature rupture of membranes, although there was no difference in the mean full-scale intelligence quotient at 11 years. The aetiology of very preterm birth/very low birth weight was not associated with mortality or the rate of cerebral palsy.

PMID:37926858 | DOI:10.1111/apa.17027

BMC Med Genomics. 2023 Nov 6;16(1):277. doi: 10.1186/s12920-023-01713-6.

ABSTRACT

BACKGROUND: The pathogenesis of rheumatoid arthritis (RA) is an immune imbalance, in which various inflammatory immune cells and pro-inflammatory factors are involved. Interleukin-17 (IL-17), a potent pro-inflammatory cytokine, has been found to have increased expression in the joints of patients with RA compared to healthy individuals. However, the causal relationship between the expression level of IL-17 or IL-17 receptor (IL-17R) and RA remained unknown. In this study, two-sample Mendelian randomization (MR) was used to investigate the causal relationship between IL-17 and RA.

METHODS: Summary statistics for RA (14,361 RA cases and 43,923 healthy controls) and IL-17 (3,301 samples) were obtained from an available meta-analysis of published genome-wide association studies (GWAS). Relevant single nucleotide polymorphisms (SNPs) were selected by executing quality control steps from the GWAS summary results. Then we used bi-directional two-sample Mendelian randomization (MR) and multi-variable MR (MVMR) analysis to examine evidence of causality. MR and MVMR analyses progressed mainly using inverse variance weighted (IVW), weighted median (WM), and MR-Egger regression methods, which were applied to the genetic instrumental variables (IVs) of IL-17A/IL-17 RA, IL-17C/IL-17 RC, and IL-17D/IL-17RD and RA. For assessing the robustness of the results, we also carried out a sensitivity analysis to assess heterogeneity and pleiotropy, such as MR-Egger, leave-one-out, and MR pleiotropy residual sum and outlier (MR-PRESSO).

RESULTS: Two-sample MR Analysis showed the causal relationship between IL-17A/IL-17RA and RA. The presence of genetically high IL-17A/IL-17RA may increase the risk of RA (IL-17A(OR = 1.095; 95% C.I., 0.990-1.210, p.adj = 0.013), IL-17RA(OR = 1.113, 95%CI = 1.006-1.231, p.adj = 0.006)). However, the results indicated that IL-17C/IL-17RC, and IL-17D/IL-17RD demonstrated no causal impact on RA (IL-17C(OR = 1.007, 95%CI = 0.890-1.139, p.adj = 0.152), IL-17RC(OR = 1.006, 95%CI = 0.904-1.119, p.adj = 0.152), IL-17D(OR = 0.979, 95%CI = 0.843-1.137, p.adj = 0.130), IL-17RD(OR = 0.983, 95%CI = 0.876-1.104, p.adj = 0.129)). Furthermore, MVMR analysis shown that IL-17RA(OR = 1.049, 95% CI: 0.997-1.102, p.adj = 0.014) was associated with increased risk of RA. Sensitivity analysis showed no heterogeneity and pleiotropy, suggesting that the above results were robust and reliable.

CONCLUSION: The MR analysis provides evidence that IL-17A/IL-17RA are risk factors for RA. This emphasizes the importance of intervention on IL-17A/IL-17RA in patients with RA. Developing drugs that limit IL-17A may reduce the risk of RA.

PMID:37926850 | DOI:10.1186/s12920-023-01713-6

BMC Public Health. 2023 Nov 6;23(1):2162. doi: 10.1186/s12889-023-17025-4.

ABSTRACT

BACKGROUND: Depression is increasingly recognized as a worldwide serious, public health concern. A better understanding of depression is important for advancing its management and learning the difference between major depressive disorder (MDD) and dysthymia. Our aim is to conduct a concurrent analysis of the trends of both MDD and dysthymia in China.

METHODS: The data on depression from 1990 to 2019 were collected from the Global Burden of Disease Study 2019 (GBD 2019). To determine the average annual percent changes (AAPC) and relative risks (RRs), joinpoint regression and the age-period-cohort models were employed, respectively.

RESULTS: The incidence number of MDD and dysthymia continuously increased in China from 1990 to 2019, however, the age-standardized rates (ASR) had a decreasing trend in both men and women. The results from joinpoint regression showed that a declining trend was presented in young people (< 50 years) but an increased trend in the elderly (≥ 50 years) both in men and women, during 1990-2019. Age is the most influential factor for MDD and dysthymia. Age RRs for MDD incidence had an overall increasing trend with age. Period RR in MDD presented a U-shaped pattern, while Cohort RRs presented an inverted U-shaped pattern. On the other hand, RRs in dysthymia for period and cohort effects had no statistical significance, only the age effect presented an inverted U-shaped pattern.

CONCLUSIONS: The disparities in trends observed between MDD and dysthymia during the period of 1990-2019 indicated the significance of distinguishing between these two disorders. The age, period and cohort effects all had a greater impact on MDD than on dysthymia, and age effects presented different influential patterns in these two. To alleviate the burden of depressive disorders in China, proactive measures need to be implemented, with particular attention to the elderly population.

PMID:37926849 | DOI:10.1186/s12889-023-17025-4

BMC Res Notes. 2023 Nov 5;16(1):313. doi: 10.1186/s13104-023-06596-5.

ABSTRACT

INTRODUCTION: This study investigates the effectiveness of incorporating simulated interactive guidelines in nursing students’ performance during disaster situations, compared to routine training.

METHOD: This study was a crossover design with pre-and post-tests for two groups. Each group consisted of 60 students selected using the census method. SIG and routine (Face-to-Face) training sessions were conducted as a crossover design. Triage knowledge questionnaires were used in the pretest to assess triage knowledge. An OSCE test was administered in the posttest to assess student performance, followed by a triage skills questionnaire. Both questionnaires were highly reliable, as indicated by Cronbach’s alpha coefficients (0.9 and 0.95, respectively). Statistical analysis was performed using SPSS version 26 software at a significance level 0.05.

RESULT: The chi-square test showed that the two groups were homogeneous regarding age. Regarding knowledge level, both groups were homogeneous before the intervention (P = 0.99). Nevertheless, the results of the OSCE test showed that the students in Group A had a higher level of skill than the students in Group B (93% versus 70%). Also, 18% of the students in group B had low skills.

DISCUSSION: The study found that student outcomes improved in both groups receiving SIG, suggesting that interaction and simulation improve learning. However, gamification is an ideal precursor to learning and not a substitute for education. Therefore, gamification should not be used as a stand-alone teaching method.

CONCLUSIONS: The crossover study found that simulators and games should not be considered stand-alone teaching methods but can contribute to learning sustainability when used alongside instruction.

PMID:37926836 | DOI:10.1186/s13104-023-06596-5

BMC Geriatr. 2023 Nov 6;23(1):717. doi: 10.1186/s12877-023-04399-8.

ABSTRACT

BACKGROUND: Little is known about how physical activity influences the relationship between neuroticism and cognitive function and cognitive decline.

METHODS: Data from the Chicago Health and Aging Project (CHAP) was utilized to conduct this study. CHAP is a population-based cohort study of chronic conditions in older adults. Participants completed in-home interviews cycles of three years from 1993-2012. Mixed effects regression models were conducted to test the associations between physical activity, neuroticism, and the interaction between neuroticism and physical activity on outcomes: global cognitive function, global cognitive decline, episodic memory, decline in episodic memory, perceptual speed, and decline in perceptual speed. Stratified mixed effects regression models by physical activity level were conducted to test the associations between neuroticism and global cognitive function and global cognitive decline.

RESULTS: A total of 7,685 participants were eligible for this study. Participants were 62% female and 64% African American. We found statistically significant associations for the interaction of high physical activity and neuroticism on baseline global cognitive function (β = 0.017 (SE = 0.007), p = .010) and on the interaction of neuroticism and high physical activity on baseline episodic memory (β = 0.020 (SE = .009), p = .021) and on decline in episodic memory over time (β = -0.003 (SE = .001), p = .039).

CONCLUSION: Higher physical activity lessened the association between higher neuroticism and poor cognitive outcomes.

PMID:37926833 | DOI:10.1186/s12877-023-04399-8

Cancer Chemother Pharmacol. 2023 Nov 5. doi: 10.1007/s00280-023-04608-6. Online ahead of print.

ABSTRACT

BACKGROUND: The association of chemotherapy-induced myelosuppression with tumor response and overall survival remained controversial. The study was conducted to investigate the association between them in small cell lung cancer (SCLC).

METHODS: 204 eligible patients with SCLC were respectively included and categorized into three groups (no, mild, and severe myelosuppression) based on myelosuppression degree after the first chemotherapy. Curative efficacy of 2-cycle chemotherapy was evaluated by the objective response rate (ORR) and disease control rate (DCR). Univariate and multivariate logistic regression analyses were conducted to investigate their association. Receiver operator characteristic (ROC) curves, net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to assess the predictive ability of myelosuppression.

RESULTS: In the fully-adjusted model, mild (OR, 4.61; 95% CI, 1.35 to 18.27; P = 0.020) and severe (OR, 7.22; 95% CI, 1.30 to 72.44; P = 0.046) myelosuppression were positively associated with DCR. However, only mild myelosuppression was significantly associated with ORR (OR, 2.78; 95% CI, 1.30 to 6.14; P = 0.010). Although we observed evidence of increased ORR in severe myelosuppression, the difference was not statistically significant. Furthermore, based on the results of the ROC curve, NRI and IDI, chemotherapy-induced myelosuppression cannot be used as a accurate and independent predictor for curative efficacy, but it can improve overall prediction accuracy.

CONCLUSION: Chemotherapy-induced myelosuppression was significantly associated with curative efficacy of 2-cycle chemotherapy in SCLC, which could help predict treatment efficacy and guide chemotherapy dosage.

PMID:37926753 | DOI:10.1007/s00280-023-04608-6

Eur Radiol. 2023 Nov 6. doi: 10.1007/s00330-023-10389-6. Online ahead of print.

ABSTRACT

OBJECTIVES: Sinonasal squamous cell carcinoma (SCC) follows a poor prognosis with high tendency for local recurrence. We aimed to evaluate whether MRI radiomics can predict early local failure in sinonasal SCC.

METHODS: Sixty-eight consecutive patients with node-negative sinonasal SCC (January 2005-December 2020) were enrolled, allocated to the training (n = 47) and test sets (n = 21). Early local failure, which occurred within 12 months of completion of initial treatment, was the primary endpoint. For clinical features (age, location, treatment modality, and clinical T stage), binary logistic regression analysis was performed. For 186 extracted radiomic features, different feature selections and classifiers were combined to create two prediction models: (1) a pure radiomics model; and (2) a combined model with clinical features and radiomics. The areas under the receiver operating characteristic curves (AUCs) were calculated and compared using DeLong’s method.

RESULTS: Early local failure occurred in 38.3% (18/47) and 23.8% (5/21) in the training and test sets, respectively. We identified several radiomic features which were strongly associated with early local failure. In the test set, both the best-performing radiomics model and the combined model (clinical + radiomic features) yielded higher AUCs compared to the clinical model (AUC, 0.838 vs. 0.438, p = 0.020; 0.850 vs. 0.438, p = 0.016, respectively). The performances of the best-performing radiomics model and the combined model did not differ significantly (AUC, 0.838 vs. 0.850, p = 0.904).

CONCLUSION: MRI radiomics integrated with a machine learning classifier may predict early local failure in patients with sinonasal SCC.

CLINICAL RELEVANCE STATEMENT: MRI radiomics intergrated with machine learning classifiers may predict early local failure in sinonasal squamous cell carcinomas more accurately than the clinical model.

KEY POINTS: • A subset of radiomic features which showed significant association with early local failure in patients with sinonasal squamous cell carcinomas was identified. • MRI radiomics integrated with machine learning classifiers can predict early local failure with high accuracy, which was validated in the test set (area under the curve = 0.838). • The combined clinical and radiomics model yielded superior performance for early local failure prediction compared to that of the radiomics (area under the curve 0.850 vs. 0.838 in the test set), without a statistically significant difference.

PMID:37926740 | DOI:10.1007/s00330-023-10389-6

Arch Gynecol Obstet. 2023 Nov 6. doi: 10.1007/s00404-023-07253-9. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the association of minimal levator ani hiatus area with age in female adults without pelvic floor dysfunction.

METHODS: 532 female subjects aged 18 ~ 90 years without pelvic floor dysfunction, divided into four groups (Group A, 18 ~ 29 years old; Group B, 30 ~ 39 years old; Group C, 40 ~ 49 years old; Group D, ≥ 50 years old) based on age, underwent traditional pelvic two-dimensional (2D) T2-weighted imaging (T2WI) axial to the body (AxB) for measuring the minimal levator ani hiatus area. 39 female volunteers were re-recruited to undergo both traditional pelvic 2D T2WI AxB and three-dimensional (3D) T2WI. An axial plane parallel to the direction of the puborectalis muscle (AxPRM) was acquired based on 3D T2WI. The difference of levator ani hiatus area measured on AxB and AxPRM images in 39 female volunteers was compared by one-sample t test, to verify if minimal levator ani hiatus area can be acquired on the traditional pelvic 2D T2WI AxB images. Spearman analysis evaluated the association of minimal levator ani hiatus area with age and the rank-sum test analyzed the area differences among four age groups.

RESULTS: Female age was positively correlated with minimal levator ani hiatus area (r = 0.23; p < 0.001). The minimal levator ani hiatus areas of 532 subjects were: 15.17 ± 1.77 cm² in Group A, 15.52 ± 2.21 cm² in Group B, 16.03 ± 2.16 cm² in Group C, and 16.40 ± 2.10 cm² in Group D. ANOVA showed significant statistical differences among four age groups (F = 7.519, p < 0.0001). Significant differences in minimal levator ani hiatus areas were found between Group A and Group C (p = 0.0491), Group A and Group D (p = 0.0007), and Group B and Group D (p < 0.001). There was no statistical difference in minimal levator ani hiatus areas measured on AxB and AxPRM images in 39 female volunteers (p = 0.1000). There were no statistical difference in minimal levator ani hiatus areas between nulliparous and multiparous group for each age group (all p > 0.05).

CONCLUSIONS: Based on a large sample, this study summarized the minimum levator ani hiatus area of female adults without pelvic floor dysfunction in different age groups. We found significant differences among different age groups. In addition, a positive correlation was found between age and the minimum levator ani hiatus area. These findings can provide reference criteria for diagnosing pelvic organ prolapse in female adults of different age groups.

PMID:37926730 | DOI:10.1007/s00404-023-07253-9