Category: Nevin Manimala

Indian J Gastroenterol. 2023 Aug 18. doi: 10.1007/s12664-023-01426-9. Online ahead of print.

ABSTRACT

Least absolute shrinkage and selection operator (Lasso) regression is a statistical technique that can be used to study the effects of clinical variables in outcome prediction. In this study, we aimed at systematically reviewing the application of Lasso regression in gastroenterology for developing predictive models and providing a method of performing Lasso regression. A comprehensive search strategy was conducted in PubMed, Embase and Cochrane CENTRAL databases (Keywords: lasso regression; gastrointestinal tract/diseases) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were screened for eligibility based on pre-defined selection criteria and the data was extracted using a standardized form. Total 16 studies were included, comprising a diverse range of gastroenterological disease-related outcomes. Sample sizes ranged from 134 to 8861 subjects. Eleven studies reported liver disease-related prediction models, while five focused on non-hepatic etiology models. Lasso regression was applied for variable selection, risk prediction and model development, with various validation methods and performance metrics used. Model performance metrics included Area Under the Receiver Operating Characteristics (AUROC), C-index and calibration plots. In gastroenterology, Lasso regression has been used in various diseases such as inflammatory bowel disease, liver disease and esophageal cancer. It is valuable for complex scenarios with many predictors. However, its effectiveness depends on high-quality and complete data. While it identifies important variables, it doesn’t provide causal interpretations. Therefore, cautious interpretation is necessary considering the study design and data quality.

PMID:37594652 | DOI:10.1007/s12664-023-01426-9

Biochem Genet. 2023 Aug 18. doi: 10.1007/s10528-023-10481-y. Online ahead of print.

ABSTRACT

The kidney lost a lot of protein in the urine when you have nephrotic syndrome (NS). Clinical manifestations mostly common in NS include massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Idiopathic nephrotic syndrome is currently classified into steroid-dependent (SDNS) and steroid-resistant (SRNS) based on the initial response to corticosteroid therapy at presentation. Several reports examined the association of the MYH9 gene (rs3752462, C > T) variant and ELMO1 gene (rs741301 G > A) variant as risk factors for Nephrotic Syndrome. This study aimed to determine the potential effect of the MYH9 gene (rs3752462, C > T) and ELMO1 gene (rs741301) variant on the risk of (NS) among Egyptian Children. This study included two hundred participants involving 100 nephrotic syndrome (NS) cases and 100 healthy controls free from nephrotic syndrome (NS). The MYH9 gene (rs3752462, C > T) variant and ELMO1 gene (rs G > A741301) variant were analyzed by ARMS-PCR technique. Nephrotic syndrome cases include 74% SRNS and 26% SDNS. Higher frequencies of the heterozygous carrier (CT) and homozygous variant (TT) genotypes of the MYH9 (rs3752462, C > T) variant were observed in NS patients compared to the controls with p-value < 0.001. The frequencies of the MYH9 (rs3752462, C > T variant indicated a statistically significant elevated risk of NS under various genetic models, including allelic model (OR 2.85, p < 0.001), dominant (OR 3.97, p < 0.001) models, and the recessive model OR 5.94, p < 0.001). Higher frequencies of the heterozygous carrier (GA) and homozygous variant (AA) genotypes of ELMO1gene (rs G > A741301) variant were observed in NS patients compared to the controls with p-value < 0.001. The frequencies of the ELMO1 (rs G > A741301) variant indicated a statistically significant elevated risk of NS under various genetic models, including allelic model (OR 2.15, p < 0.001), dominant models (OR 2.8, p < 0.001), and the recessive model (OR 4.17, p = 0.001). Both MYH9 and ELMO1 gene variants are significantly different in NS in comparison with the control group (p < 0.001). The MYH9 gene (rs3752462, C > T) and ELMO1gene (rs G > A741301) variants were considered independent risk factors for NS among Egyptian Children.

PMID:37594641 | DOI:10.1007/s10528-023-10481-y

J Autism Dev Disord. 2023 Aug 18. doi: 10.1007/s10803-023-06094-4. Online ahead of print.

ABSTRACT

Caregivers of children with autism spectrum disorder (ASD) often report higher rates of depression and the related negative thought patterns that may precede a clinical diagnosis. These negative thought patterns are referred to as depressive cognitions. Depressive cognitions are exacerbated by child problem behaviors (CPB) but may be impacted by parental resilience. The current study examines relations between CPB and depressive cognitions and the role of resilience as a moderator among caregivers of children with ASD (n = 287) and a sample of caregivers of children who are typically developing (n = 207). Significant positive associations were found between CPB and depressive cognitions for caregivers of children with ASD and who are typically developing. A moderation analysis revealed that, among the ASD sample, the model accounted for 33% of the variance in caregiver depressive cognitions (R2 = 0.33, SE = 35.52, p < 0.001). The interaction of child problem behaviors and caregiver resilience on caregiver depressive cognitions was statistically significant (B = – 0.016, SE = 0.007, p = 0.037), thus resilience was a significant moderator, for caregivers of children with ASD. Resilience serves as a protective factor in the relationship between child problem behavior and caregiver depressive cognitions for caregivers of children with ASD only. This finding highlights the importance of assessing and supporting resilience among caregivers of children with ASD. Interventions addressing child behavior would benefit from additional components to bolster caregiver resilience to enhance caregiver mental health and protect against depressive cognitions.

PMID:37594631 | DOI:10.1007/s10803-023-06094-4

J Fluoresc. 2023 Aug 18. doi: 10.1007/s10895-023-03392-z. Online ahead of print.

ABSTRACT

The aim of this study was to synthesize highly fluorescent carbon dots (CDs) from glucose using a microwave hydrothermal method. It explored the impact of glucose concentration, process time, molar ratio of KH₂PO₄ to glucose, and homogenization time on the resulting CDs, employing a fractional plan 3^(k-1) with four independent parameters for twenty-seven synthesis. Results showed that longer process times at 200°C increased the fluorescence intensity of the CDs. The molar ratio of KH₂PO₄ to glucose, glucose concentration, and process time significantly influenced fluorescence. Homogenization was crucial for obtaining small particles, though an anti-aggregation agent might still be needed. UV-vis spectroscopy, spectrofluorimetry, and DLS were used to analyze the synthesized CDs. The UV-vis absorption maxima were observed around 230 nm and 282 nm, with peak shifts at different excitation wavelengths. Out of the twenty-seven samples, six CDs samples were identified to be below 10 nm and a total of twelve below 50 nm. Analyzing the results, the study concluded that the CDs possess strong fluorescence and are suitable for diverse applications. For enhanced fluorescence, longer process times at 200°C and the use of KH₂PO₄ were recommended, while shorter processes were preferred for obtaining smaller particles. Hierarchical clustering, the k-means method, Pareto charts, and profiles for predicted values and desirability were used to analyze the results. It was confirmed that higher fluorescence is favored by longer process time at 200°C and the use of KH₂PO₄. In order to obtain smaller particles, shorter processes should be used.

PMID:37594585 | DOI:10.1007/s10895-023-03392-z

J Gastroenterol. 2023 Aug 18. doi: 10.1007/s00535-023-02034-2. Online ahead of print.

ABSTRACT

BACKGROUND: Abnormal phosphate levels are associated with adverse outcomes in critical illness. However, there is scarce evidence on phosphate’s impact on acute pancreatitis outcomes, and the few studies examining this subject are relatively small and show conflicting data. We sought to determine the association between phosphate level at admission and the clinical course and outcomes of acute pancreatitis.

METHODS: In this retrospective single-center observational study, we included all adult patients admitted with a primary diagnosis of acute pancreatitis between January 2008 and June 2021. Phosphate levels at admission were classified as normal (2.8-4.5 mg/dl), low (below 2.8 mg/dl), or high (above 4.5 mg/dl).

RESULTS: Out of 2308 cases, 1868 patients had documented phosphate levels at admission and were thus included in our final analysis. 1096 (59%) had normal phosphate levels, 686 (37%) had hypophosphatemia, and 86 (4.6%) had hyperphosphatemia on admission. 30-day mortality rates were 3.4%, 3.8%, and 19% in normal, low, and high phosphate levels, respectively. In univariate analysis, hyperphosphatemia was significantly associated with 30-day mortality, with an OR of 6.54 (95% CI 3.39-12.2, p < 0.001; AUC = 0.58). In a multivariate analysis adjusting for age, MAP, GFR, BUN, and pH, hyperphosphatemia remained a statistically significant independent predictor of early mortality (OR-2.93, 95% CI 1.28-6.51, p = 0.009). Hypophosphatemia was not significantly associated with 30-day mortality in univariate analysis, OR of 1.13 (95% CI 0.67-1.87, p = 0.6).

CONCLUSION: Hyperphosphatemia at admission was independently associated with increased 30-day mortality in patients with acute pancreatitis. Hypophosphatemia at admission was not significantly associated with 30-day mortality.

PMID:37594581 | DOI:10.1007/s00535-023-02034-2

Eur Arch Otorhinolaryngol. 2023 Aug 18. doi: 10.1007/s00405-023-08184-6. Online ahead of print.

ABSTRACT

BACKGROUND: Recovery of olfactory function plays a prominent role in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). While rates and timing of such recovery vary, monoclonal antibodies might yield better results which we aimed at evaluating with this study.

METHODOLOGY: A prospective controlled study was conducted at our tertiary otolaryngological center from April 1, 2021, to October 1, 2022, in CRSwNP patients. We included an active group (n = 60 patients) performing dupilumab treatment and a control group (n = 60 patients) treated with intranasal and oral corticosteroids. Primary endpoints were changes in smell visual analogical scale (VAS) and SS-I (Sniffin’ Sticks-identification) scores, and olfactory recovery rate. The secondary efficacy endpoints were nasal obstruction, rhinorrhea, headache, SNOT-22, and nasal congestion score (NCS).

RESULTS: At 6 months, the active group demonstrated better outcomes than control in SS-I scores (10.23 ± 4.21 vs.3.68 ± 3.08; p < 0.001). No significant differences were found in blood eosinophil count, SNOT-22, and NPS (p > 0.05 for all). Olfactory function in the treatment arm improved in 86.66% (52/60 cases), with normal scores in 48.33% (29/60), while the control group reported a lower recovery rate (3/60; 5%), with no normal olfaction cases. Log-rank comparison for Kaplan-Meier functions was statistically significant (p < 0.001), but no differences were found in subanalysis in the active group based on blood eosinophil count at baseline, SNOT-22, and NPS scores.

CONCLUSIONS: Patients who receive dupilumab treatment may experience a faster recovery of olfactory function compared to those receiving corticosteroid therapy. This result would be maintained regardless of the severity of type 2 CRSwNP inflammation, the volume of the polyps, or the patient’s subjective symptomatology.

PMID:37594543 | DOI:10.1007/s00405-023-08184-6

J Cancer Res Clin Oncol. 2023 Aug 18. doi: 10.1007/s00432-023-05276-y. Online ahead of print.

ABSTRACT

BACKGROUND: We evaluated the outcomes, and risk factors for recurrence in patients with early stage node-negative breast cancer in this study.

METHOD: Retrospective data analysis was done on patient treatment records from 1988 to 2018. The patient’s demographic, clinical, pathological, and therapeutic characteristics were noted. To evaluate survival analysis and predictors of recurrence, we employed Kaplan-Meier analysis with the log-rank test.

RESULTS: A total of 357 patients in all were enrolled in the research. At the time of diagnosis, the median age was 50 (with a range of 18-81). A total of 85.5% of patients had undergone a lumpectomy, while 14.5% had a mastectomy. 78.7% of patients had sentinel lymph node biopsy, and 21.3% had axillary lymph node dissection. In addition, the patients received adjuvant radiotherapy (88.7%), adjuvant endocrine therapy (82.1%), and adjuvant chemotherapy (48.5%). Recurrence of the tumor occurred in 31 (8.7%) patients (local recurrence 45.2% and metastatic disease 54.8%). Ten- and twenty-year recurrence-free survival rates were 92% and 77%. 19 (5.3%) patients had also developed contralateral breast cancer. Ten-year survival rates were 91.6%, and 20-year survival rates were 76.6%, respectively. Aged over 65 years (p = 0.004), necrosis (p = 0.002), mitosis (p = 0.003), and nuclear pleomorphism (p = 0.049) were found as statistically significant factors for recurrence in univariate analysis. In the ROC analysis, the largest size of the tumor (over 1.45 cm, p = 0.07) remained outside the statistical significance limit in terms of recurrence.

CONCLUSIONS: Thirty-year outcomes in individuals with early stage, node-negative breast cancer were shown in this study. We found that the recurrence ratios between 10 and 20 years were more frequent than the first 10 years during the follow-up. Despite the small number of patients who experienced a recurrence, we demonstrated that, in univariate analysis, being older than 65 and having some pathological characteristics (nuclear pleomorphism, mitosis, and necrosis) were statistically significant factors for disease recurrence.

PMID:37594533 | DOI:10.1007/s00432-023-05276-y

AAPS PharmSciTech. 2023 Aug 18;24(7):174. doi: 10.1208/s12249-023-02599-4.

ABSTRACT

It is hypothesized that meta-iodobenzylguanidine (MIBG) complexation with etoposide (VP-16) will improve drug solubility and specificity towards BE(2)C neuroblastoma (NB) cells, 90% of which are known to be MIBG avid. After MIBG and VP-16 interaction, the dry complex was analyzed for crystalline structure, surface morphology, solubility, and size distribution by X-ray powder diffraction (P-XRD), scanning electron microscopy (SEM), infrared (FTIR) and UV spectroscopy, and dynamic light scattering. After exposure to the complex, the cell viability and decay rates were assessed by the MTS assay and estimated using exponential decay models (EDM). Multi-factorial ANOVA and an independent t-test were used to assess for cell viability and solubility data, respectively. The resulting (1: 3 w/w) VP-16: MIBG complex had a mean diameter and zeta potential of 458.5 nm and 0.951 mV, respectively. It dramatically increased the drug apparent water solubility (~ 12-folds). This was ascribed to the formation of a VP-16/MIBG nanocrystalline state mainly governed by cation-π interactions, evidenced by FTIR, SEM, and P-XRD data following the complexation. The EDM relating percent cell viability to drug concentration yielded an excellent fit (r² > 0.95) and enabled to estimate the IC₅₀ values of both native drug and its complex: 6.2 μM and 5.23 μM, respectively (indicating a conservation of drug anticancer activity). The statistical results were consistent with those of the exponential decay models, indicating that MIBG does not inhibit the anticancer activity of VP-16. This study indicates that the VP-16/MIBG complexation improves VP-16 solubility without antagonizing its anticancer activity. Moreover, the efficiency of the EDM for drug IC₅₀ estimation provides alternative mathematical method for such in vitro cytotoxicity studies.

PMID:37594527 | DOI:10.1208/s12249-023-02599-4

Epilepsia Open. 2023 Aug 18. doi: 10.1002/epi4.12817. Online ahead of print.

ABSTRACT

OBJECTIVE: Observational studies have suggested a link between telomere length (TL) and epilepsy, but the direction of the effect and whether it is causal or not is still being debated. The objective of this study was to investigate the causal relationship between TL and epilepsy using Mendelian randomization (MR) analysis.

METHODS: We performed a bidirectional two-sample MR analysis using pooled statistics from genome-wide association studies (GWAS) of TL and epilepsy. Additionally, we conducted a replication analysis using data from another GWAS study on epilepsy to validate our findings. The final results were analyzed using five MR methods, with the inverse-variance weighted (IVW) method as the primary outcome. We applied methods such as radial MR, MR pleiotropy residual and outlier test and MR Steiger filters to exclude outliers. Sensitivity analyses were also conducted to assess heterogeneity and pleiotropy.

RESULTS: Our analysis found no evidence of a causal relationship between epilepsy and TL (all P-values > 0.05). The sensitivity analysis confirms the robustness of these results.

SIGNIFICANCE: In summary, our study contradicts existing observational reports by not finding any evidence to support a causal relationship between epilepsy and TL. Further research is necessary to determine the underlying mechanism behind the association observed in observational studies.

PMID:37593897 | DOI:10.1002/epi4.12817

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Aug;35(8):856-859. doi: 10.3760/cma.j.cn121430-20221108-00974.

ABSTRACT

OBJECTIVE: To compare the effects of citrate and heparin anticoagulation on coagulation function and efficacy in children with septic shock undergoing continuous blood purification (CBP), and to provide guidance for CBP anticoagulation in children with septic shock.

METHODS: A case control study was conducted. Thirty-seven children with septic shock admitted to the pediatric intensive care unit (PICU) of the First Affiliated Hospital of Gannan Medical University from July 2019 to September 2022 were enrolled as the research subjects. The patients were divided into citrate local anticoagulation group and heparin systemic anticoagulation group according to different anticoagulation methods. The baseline data, the level of coagulation indicators [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib), D-dimer] before treatment and 1 day after weaning from CBP, serum inflammatory mediators [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypersensitivity C-reactive protein (hs-CRP), procalcitonin (PCT)], bleeding complications during CBP and 7-day mortality were collected.

RESULTS: A total of 37 cases were enrolled finally, including 17 cases with citric acid local anticoagulation and 20 cases with heparin systemic anticoagulation. There was no statistically significant difference in general data such as gender, age, and body weight of children between the two groups. There were no statistically significant differences in baseline levels of coagulation indicators and inflammatory mediators before treatment of children between the two groups. One day after weaning from CBP, both groups showed varying degrees of improvement in coagulation indicators compared with those before treatment. Compared with before treatment, the PT of the heparin systemic anticoagulation group was significantly shortened after 1 day of weaning (s: 11.82±2.05 vs. 13.64±2.54), APTT and TT were significantly prolonged [APTT (s): 51.54±12.69 vs. 35.53±10.79, TT (s): 21.95±4.74 vs. 19.30±3.33], D-dimer level was significantly reduced (mg/L: 1.92±1.58 vs. 4.94±3.94), with statistically significant differences (all P < 0.05). While in the citrate local anticoagulation group, only APTT was significantly prolonged after treatment compared with that before treatment (s: 49.28±10.32 vs. 34.34±10.32, P < 0.05). There were no statistically significant differences in other coagulation indicators compared with before treatment. Compared with the citric acid local anticoagulation group, the PT of the heparin systemic anticoagulation group was significantly shortened after treatment (s: 11.82±2.05 vs. 13.61±3.05, P < 0.05), and the D-dimer level was significantly reduced (mg/L: 1.92±1.58 vs. 3.77±2.38, P < 0.01). The levels of inflammatory mediators in both groups were significantly reduced 1 day after CBP weaning compared with those before treatment [citric acid local anticoagulation group: hs-CRP (mg/L) was 12.53±5.44 vs. 22.65±7.27, PCT (μg/L) was 1.86±1.20 vs. 3.30±2.34, IL-6 (ng/L) was 148.48±34.83 vs. 202.32±48.62, TNF-α (ng/L) was 21.38±7.71 vs. 55.14±15.07; heparin systemic anticoagulation group: hs-CRP (mg/L) was 11.82±4.93 vs. 21.62±8.35, PCT (μg/L) was 1.90±1.08 vs. 3.18±1.97, IL-6 (ng/L) was 143.81±33.41 vs. 194.02±46.89, TNF-α (ng/L) was 22.44±8.17 vs. 56.17±16.92, all P < 0.05]. However, there was no statistically significant difference between the two groups (all P > 0.05). There was no statistically significant difference in bleeding complication during CBP and 7-day mortality in children between the citrate local anticoagulation group and the heparin systemic anticoagulation group (5.9% vs. 30.0%, 17.6% vs. 20.0%, both P > 0.05).

CONCLUSIONS: Heparin for systemic anticoagulation and regional citrate anticoagulation can significantly reduce the levels of IL-6, TNF-α, hs-CRP and PCT in children with septic shock, and relieve inflammatory storm. Compared with citric acid local anticoagulation, heparin systemic anticoagulation can shorten the PT and reduce the level of D-dimer in children with septic shock, which may benefit in the prevention and treatment of disseminated intravascular coagulation (DIC).

PMID:37593866 | DOI:10.3760/cma.j.cn121430-20221108-00974