Nevin Manimala

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

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Aug;35(8):839-843. doi: 10.3760/cma.j.cn121430-20230407-00253.

ABSTRACT

OBJECTIVE: To investigate the prognostic value of cardiac ultrasound left ventricular ejection fraction (LVEF) on admission in patients with septic cardiomyopathy.

METHODS: A retrospective cohort study was conducted. The patients with septic cardiomyopathy hospitalized in the intensive care unit of Zhoupu Hospital Affiliated to Shanghai Health College from January 2019 to March 2023 were enrolled. The general information including gender and age, LVEF on admission, severity of illness scores within 24 hours after admission [acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score], procalcitonin (PCT), cardiac biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), and MB isoenzyme of creatine kinase (CK-MB)], mitochondria related indicators [aspartate aminotransferase (AST), AST/alanine aminotransferase (ALT) ratio], blood lactate (Lac), the usage of vasoactive drugs and mechanical ventilation, and the prognosis during hospitalization were collected. The differences in above clinical data between the two groups were compared. The variables with statistically significant differences in univariate analysis were incorporated into multivariate Logistic regression analysis to analyze the independent risk factors for death during hospitalization in patients with septic cardiomyopathy. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the prognostic value of LVEF by echocardiography on admission in patients with septic cardiomyopathy during hospitalization.

RESULTS: A total of 62 patients were enrolled, including 36 males and 26 females. Thirty-nine cases died and 23 cases survived during hospitalization, and the mortality was 62.90%. Compared with the survival group, the LVEF of patients on admission was lower in the death group [0.51 (0.40, 0.57) vs. 0.56 (0.51, 0.63), P < 0.01], APACHE II score, SOFA score, Lac, NT-proBNP, CK-MB within 24 hours after admission were higher [APACHE II score: 22.18±8.38 vs. 17.39±8.22, SOFA score: 9.90±3.87 vs. 7.09±3.27, Lac (mmol/L): 5.10 (2.63, 11.50) vs. 2.00 (1.40, 5.00), NT-proBNP (μg/L): 5.24 (2.84, 11.29) vs. 2.53 (0.35, 6.63), CK-MB (U/L): 1.88 (0.21, 5.33) vs. 0.17 (0.02, 1.62), all P < 0.05], and the proportion of vasoactive drug application was higher (82.05% vs. 47.83%, P < 0.01). Multivariate Logistic regression analysis showed that LVEF on admission was an independent risk factor for predicting the prognosis of patients with septic cardiomyopathy during hospitalization [odds ratio (OR) = 0.920, 95% confidence interval (95%CI) was 0.855-0.990, P = 0.025]. ROC curve analysis showed that the area under the ROC curve (AUC) of LVEF on admission for predicting the death of patients with septic cardiomyopathy was 0.715 (95%CI was 0.585-0.845, P = 0.005). When LVEF ≤ 0.52, the sensitivity was 73.9%, and the specificity was 61.5%.

CONCLUSIONS: The lower cardiac ultrasound LVEF on admission, the worse the prognosis of patients with septic cardiomyopathy. The cardiac ultrasound LVEF on admission can be used as a clinical index to evaluate the severity of the condition and predict the prognosis of patients with septic cardiomyopathy.

PMID:37593863 | DOI:10.3760/cma.j.cn121430-20230407-00253

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Aug;35(8):834-838. doi: 10.3760/cma.j.cn121430-20220418-00385.

ABSTRACT

OBJECTIVE: To analyze the causes of hyperdynamic left ventricular ejection fraction (LVEF) in sepsis patients in the intensive care unit (ICU) and its impact on prognosis.

METHODS: A retrospective cohort study was conducted. The clinical data of 273 sepsis patients admitted to the department of critical care medicine of the Affiliated People’s Hospital of Jiangsu University from January 2018 to October 2021 were collected including gender, age, severity score, comorbidities, source of infection, vital signs, transthoracic echocardiographic (TTE) parameters, fluid intake and output, vasoactive drug dose, therapeutic measures and prognostic indicators. The patients were divided into normal LVEF group (LVEF 0.55-0.70), low LVEF group (LVEF < 0.55) and hyperdynamic LVEF group (LVEF > 0.70) according to the TTE examination results within 7 days of ICU admission. The clinical indicators among the three groups were compared and analyzed, and multivariate Logistic regression analysis was used to screen risk factors for the development of hyperdynamic LVEF in patients with sepsis. Spearman correlation analysis was used to determine the correlation between the mortality of different types of LVEF and clinical variables.

RESULTS: Among 273 patients, 20 patients with severe valvular or cardiomyopathy at admission and those who did not completed cardiac ultrasound within 7 days of ICU admission were excluded. A total of 253 patients were finally enrolled, including 169 patients in the normal LVEF group, 40 patients in the low LVEF group, and 44 patients in the hyperdynamic LVEF group. There were statistically significant differences in age, sequential organ failure assessment (SOFA) score, central venous pressure (CVP), heart rate (HR), oxygenation index (PaO₂/FiO₂), blood lactate (Lac), urine output, vasoactive drug dose, ratio of hypertension, ischemic heart disease, chronic liver disease, cancer, invasive mechanical ventilation and renal replacement therapy (RRT), and incidence of septic shock among the different types of LVEF groups. TTE results analysis showed that the hyperdynamic LVEF group had higher stroke volume (SV) and cardiac index (CI) than those in the normal LVEF and low LVEF groups, lower systemic vascular resistance (SVR) than that in the normal LVEF and low LVEF groups, and an increased E/A ratio. The 90-day mortality in the hyperdynamic LVEF group was significantly higher than that in the normal LVEF and low LVEF groups [59.1% (26/44) vs. 24.9% (42/169), 32.5% (13/40), both P < 0.05]. Multivariate Logistic regression analysis showed that chronic liver disease [odds ratio (OR) = 1.712, 95% confidence interval (95%CI) was 0.912-3.234, P < 0.001], cancer (OR = 2.784, 95%CI was 1.296-6.151, P < 0.001), HR (OR = 1.026, 95%CI was 1.014-1.038, P < 0.001), vasoactive drug dose (OR = 1.133, 95%CI was 1.009-1.291, P < 0.001), and invasive mechanical ventilation (OR = 2.141, 95%CI was 1.285-3.651, P < 0.001) were independent factors for hyperdynamic LVEF in ICU sepsis patients. Correlation analysis showed that the mortality of hyperdynamic LVEF, normal LVEF and low LVEF patients was positively correlated with vasoactive drug dose (r value was 0.251, 0.361, 0.289, respectively, all P < 0.001). The mortality of the hyperdynamic LVEF patients was negatively correlated with SVR (r = -0.545, P < 0.001).

CONCLUSIONS: Chronic liver disease, cancer, HR, vasoactive drugs dose, and invasive mechanical ventilation are independent risk factors for hyperdynamic LVEF in patients with sepsis. Hyperdynamic LVEF is positively associated with mortality in sepsis patients, which may be due to the the decrease of SVR caused by septic vascular paralysis.

PMID:37593862 | DOI:10.3760/cma.j.cn121430-20220418-00385