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Nevin Manimala Statistics

Investigation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in vitro inflammation model at molecular level

Mol Cell Biochem. 2023 Jul 11. doi: 10.1007/s11010-023-04788-y. Online ahead of print.

ABSTRACT

In our study, we aimed to create an inflammation model in endothelial and macrophage cell lines and to examine the changes in the expression of hyperpolarization activated cyclic nucleotide gated (HCN) channels at the molecular level. HUVEC and RAW cell lines were used in our study. 1 µg/mL LPS was applied to the cells. Cell media were taken 6 h later. TNF-α, IL-1, IL-2, IL-4, IL-10 concentrations were measured by ELISA method. Cell media were cross-applied to cells for 24 h after LPS. HCN1/HCN2 protein levels were determined by Western-Blot method. HCN-1/HCN-2 gene expressions were determined by qRT-PCR method. In the inflammation model, a significant increase in TNF-α, IL-1, and IL-2 levels was observed in RAW cell media compared to the control. While no significant difference was observed in IL-4 level, a significant decrease was observed in IL-10 level. While a significant increase in TNF-α level was observed in HUVEC cell medium, no difference was observed in other cytokines. In our inflammation model, an 8.44-fold increase in HCN1 gene expression was observed in HUVEC cells compared to the control group. No significant change was observed in HCN2 gene expression. 6.71-fold increase in HCN1 gene expression was observed in RAW cells compared to the control. The change in HCN2 expression was not statistically significant. In the Western-Blot analysis, a statistically significant increase in HCN1 level was observed in the LPS group in HUVEC cells compared to the control; no significant increase in HCN2 level was observed. While a statistically significant increase in HCN1 level was observed in the LPS group in RAW cells compared to the control; no significant increase in HCN2 level was observed. In immunofluorescence examination, it was observed that the level of HCN1 and HCN2 proteins in the cell membrane of HUVEC and RAW cells increased in the LPS group compared to the control group. While HCN1 gene/protein levels were increased in RAW and HUVEC cells in the inflammation model, no significant change was observed in HCN2 gene/protein levels. Our data suggest that the HCN1 subtype is dominant in endothelium and macrophages and may play a critical role in inflammation.

PMID:37432633 | DOI:10.1007/s11010-023-04788-y

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Nevin Manimala Statistics

Vertebral body tethering for idiopathic scoliosis: a systematic review and meta-analysis

Spine Deform. 2023 Jul 11. doi: 10.1007/s43390-023-00723-9. Online ahead of print.

ABSTRACT

PURPOSE: Vertebral body tethering (VBT) is a recent procedure to correct and reduce spinal curves in skeletally immature patients with adolescent idiopathic scoliosis (AIS). The purpose of this systematic review and meta-analysis is to determine the expected curve reduction and potential complications for adolescent patients after VBT.

METHODS: PubMed, Embase, Google Scholar and Cochrane databases were searched until February 2022. Records were screened against pre-defined inclusion and exclusion criteria. Data sources were prospective and retrospective studies. Demographics, mean differences in Cobb angle, surgical details and complication rates were recorded. Meta-analysis was conducted using a random-effects model.

RESULTS: This systematic review includes 19 studies, and the meta-analysis includes 16 of these. VBT displayed a statistically significant reduction in Cobb angle from pre-operative to final (minimum 2 years) measurements. The initial mean Cobb angle was 47.8° (CI 95% 42.9-52.7°) and decreased to 22.2° (CI 95% 19.9-24.5°). The mean difference is – 25.8° (CI 95% – 28.9-22.7) (p < 0.01). The overall complication rate was 23% (CI 95% 14.4-31.6%), the most common complication was tether breakage 21.9% (CI 95% 10.6-33.1%). The spinal fusion rate was 7.2% (CI 95% 2.3-12.1%).

CONCLUSION: VBT results in a significant reduction of AIS at 2 years of follow-up. Overall complication rate was relatively high although the consequences of the complications are unknown. Further research is required to explore the reasons behind the complication rate and determine the optimal timing for the procedure. VBT remains a promising new procedure that is effective at reducing scoliotic curves and preventing spinal fusion in the majority of patients.

LEVEL OF EVIDENCE: Systematic review of Therapeutic Studies with evidence level II-IV.

PMID:37432604 | DOI:10.1007/s43390-023-00723-9

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Nevin Manimala Statistics

Early perioperative outcomes of single-port compared to multi-port robot-assisted laparoscopic partial nephrectomy

J Robot Surg. 2023 Jul 11. doi: 10.1007/s11701-023-01617-8. Online ahead of print.

ABSTRACT

Single-port (SP) robot-assisted laparoscopic partial nephrectomy (RAPN) is a promising new technique. The aim of this study was to compare surgical and oncological outcomes of SP-RAPN to the multi-port (MP) surgical platform. This is a retrospective, cohort-based study involving patients undergoing SP-RAPN between 2019 and 2020 at a single institution. Demographic, preoperative, surgical, and postoperative outcomes data were gathered and compared to a 1-to-1 matched MP cohort. A total of 50 SP and 50 matched MP cases were included. Length of surgery and ischemia time were not statistically significant between the two cohorts; however, estimated blood loss (EBL) was significantly lower in the SP group than in the MP (IQR 25-50 vs. IQR 50-100 mL, p = 0.002). No differences were seen in regard to the 30-day readmission rate, surgical margin status, pain scores, and complications between the two approaches. We found no statistically significant differences in positive margins, pain score, length of stay, or readmission rate between matched SP and MP patients. These data support the viability of the SP technique as an alternative to MP-RAPN when in the hands of experienced surgeons.

PMID:37432590 | DOI:10.1007/s11701-023-01617-8

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Nevin Manimala Statistics

External Validation of the BRAVO Diabetes Model Using the EXSCEL Clinical Trial Data

Diabetes Ther. 2023 Jul 11. doi: 10.1007/s13300-023-01441-1. Online ahead of print.

ABSTRACT

INTRODUCTION: We have developed the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes model, an individual-level, discrete-time microsimulation model specifically designed for type 2 diabetes (T2D) management. This study aims to validate the model’s performance when populated exclusively with a fully de-identified dataset to ensure its applicability in secure settings.

METHODS: Patient-level data from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial were fully de-identified by removing all identifiable information and masking numerical values (e.g., age, body mass index) within ranges to minimize the risk of re-identification. To populate the simulation, we imputed the masked numerical values using data from the National Health and Nutrition Examination Survey (NHANES). We applied the BRAVO model to the baseline data to predict 7-year study outcomes for the EXSCEL trial and assessed its discrimination power and calibration using C-statistics and Brier scores.

RESULTS: The model demonstrated acceptable discrimination and calibration in predicting the first occurrence of non-fatal myocardial infarction, non-fatal stroke, heart failure, revascularization, and all-cause mortality. Even with the fully deidentified data from the EXSCEL trial primarily presented in ranges rather than specific values, the BRAVO model exhibited robust prediction performance for diabetes complications and mortality.

CONCLUSIONS: This study demonstrates the feasibility of using the BRAVO model in settings where only fully de-identified patient-level data are available.

PMID:37432547 | DOI:10.1007/s13300-023-01441-1

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Nevin Manimala Statistics

Angiotensin II type 1 receptor antibodies and native kidney function in pediatric liver and intestinal transplant recipients

Pediatr Nephrol. 2023 Jul 11. doi: 10.1007/s00467-023-06055-0. Online ahead of print.

ABSTRACT

BACKGROUND: Angiotensin II type-1 receptor antibody (AT1R-Ab) has been associated with vascular injury and kidney dysfunction in pediatric kidney transplant recipients. The role of AT1R-Ab in the development of chronic kidney disease in pediatric liver and intestinal transplant recipients has not been explored.

METHODS: Twenty-five pediatric intestinal transplant recipients and 79 pediatric liver transplant recipients had AT1R-Ab levels measured at varying time points in the post-transplant period. Estimated glomerular filtration rate (eGFR) was determined using creatinine based CKiD U25 equation and measured at time of AT1R-Ab measurement, at 1 year post-AT1R-Ab measurement, at 5 years post-AT1R-Ab measurement, and at the most recent routine clinic visit. The prevalence of hypertension and antihypertensive medication use were also evaluated.

RESULTS: Younger age at time of AT1R-Ab measurement was associated with AT1R-Ab positivity in liver transplant recipients. There was no association between AT1R-Ab status and change in eGFR, prevalence of hypertension, or use of antihypertensive medications at the described time points.

CONCLUSIONS: AT1R-Ab positivity was not associated with a decline in eGFR or hypertension in pediatric liver and intestinal transplant recipients. Further studies are needed using other markers of kidney function, such as cystatin C, to validate this finding. A higher resolution version of the Graphical abstract is available as Supplementary information.

PMID:37432534 | DOI:10.1007/s00467-023-06055-0

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Nevin Manimala Statistics

Identifying predictive factors for bowel control in patients with spina bifida and spinal cord injuries

Pediatr Surg Int. 2023 Jul 11;39(1):231. doi: 10.1007/s00383-023-05509-8.

ABSTRACT

PURPOSE: This study aimed to assess our bowel management program (BMP) and identify predictive factors for bowel control in patients with Spina Bifida (SB) and Spinal Cord Injuries (SCI). Additionally, in patients with SB, we examined the impact of fetal repair (FRG) on bowel control.

METHODS: We included all patients with SB and SCI seen in the Multidisciplinary Spinal Defects Clinic at Children’s Hospital Colorado from 2020 to 2023.

RESULTS: 336 patients included. Fecal incontinence was present in 70% and bowel control in 30%. All patients with urinary control also had bowel control. Fecal incontinence prevalence was higher in patients with ventriculoperitoneal (VP) shunt (84%), urinary incontinence (82%), and wheelchair users (79%) compared to those who did not need a VP shunt (56%), had urinary continence (0%) and non-wheelchair users (52%), respectively (p = < 0.001 in all three scenarios). After completing BMP, 90% remained clean for stool. There was no statistical significance when comparing bowel control in FRG with non-fetal repair group.

CONCLUSIONS: Urinary continence predicts bowel control in patients with SB and SCI. Risk factors for fecal incontinence were the need for a VP shunt, urinary incontinence, and wheelchair usage. We did not find any positive impact of fetal repair on bowel and urinary control.

PMID:37432519 | DOI:10.1007/s00383-023-05509-8

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Nevin Manimala Statistics

Risk factors for developing calcinosis in juvenile dermatomyositis: subcutaneous and myofascial edema in initial magnetic resonance imaging

Rheumatol Int. 2023 Jul 11. doi: 10.1007/s00296-023-05385-4. Online ahead of print.

ABSTRACT

Calcinosis is a sequela of Juvenile Dermatomyositis (JDM) with significant morbidity. A retrospective study observing risk factors for JDM calcinosis, including a possible association between higher intensity of subcutaneous and myofascial edema in initial magnetic resonance imaging (MRI) and development of calcinosis was performed at a tertiary pediatric medical center. Data from the past 20 years on JDM patients with MRIs at the time of JDM diagnosis were obtained. MRIs were individually evaluated by two pediatric musculoskeletal radiologists who blindly graded the intensity of edema on a 0-4 Likert scale. Clinical data and edema scores were compared between patients who developed calcinosis and who did not. Forty-three patients (14 with calcinosis and 29 without calcinosis) were identified. The calcinosis group contained more racial and ethnic minorities, younger ages of JDM onset and longer time to reach JDM diagnosis. Muscle enzyme levels at JDM diagnosis were lower in the calcinosis group, especially Creatinine Kinase (CK) (p = 0.047) and Alanine Aminotransferase (ALT) (p = 0.015). The median score for edema in both groups was 3 (p = 0.39) with an inter-rater reliability of 95%. There was no association between increased subcutaneous and myofascial edema in MRIs at the time of JDM diagnosis and development of calcinosis. Earlier age of JDM onset, racial and ethnic minority, and delay in JDM diagnosis could be risks for developing calcinosis. The calcinosis group presented with lower muscle enzyme levels at the time of JDM diagnosis, especially CK and ALT with statistical significance. This could reflect delay in diagnosis and treatment.

PMID:37432516 | DOI:10.1007/s00296-023-05385-4

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Examining the Association Between Digital Stress Components and Psychological Wellbeing: A Meta-Analysis

Clin Child Fam Psychol Rev. 2023 Jul 11. doi: 10.1007/s10567-023-00440-9. Online ahead of print.

ABSTRACT

Extant research suggests that digital stress (DS) and its various components (Hall et al. in Psychol Assess 33(3):230-242, 2021) may mediate the association between social media use and psychosocial distress among adolescents and young adults. Yet no systematic review and meta-analysis has been conducted to examine the direct associations among DS components (i.e., approval anxiety, availability stress, fear of missing out [FOMO], connection overload, and online vigilance) and psychological outcomes. Thus, we aimed to comprehensively synthesize and quantify the association between these five DS components and psychosocial distress, and to examine whether these associations were statistically different from one another. Our search of PubMed, PsycINFO, and Communication and Mass Media Complete yielded a wide range of article abstracts across the five DS components. After reviewing inclusion and exclusion criteria, 7, 73, 60, 19, and 16 studies were included for availability stress, approval anxiety, FOMO, connection overload, and online vigilance, respectively. The results suggested that all five digital stress components had significant medium association with psychosocial distress (r = .26 to .34; p < .001). Age and sex did not significantly moderate the association between most digital stress components and psychosocial distress. However, age moderated the association between connection overload and psychosocial distress. Our findings further suggested no statistical differences among the associations between the five digital stress components and psychosocial distress. Notwithstanding its limitations, our outcomes help integrate the disparate effect sizes in the literature, indicate the strength of associations, and suggest directions for clinical intervention and future research.

PMID:37432506 | DOI:10.1007/s10567-023-00440-9

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Outcome comparison of femoral nerve block and adductor canal block during anterior cruciate ligament reconstruction: adductor canal block may cause an unexpected decrease in knee flexor strength at 6 months postoperatively

Arch Orthop Trauma Surg. 2023 Jul 11. doi: 10.1007/s00402-023-04980-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Peripheral nerve blocks are frequently used in anterior cruciate ligament (ACL) reconstruction. While femoral nerve block (FNB) has been associated with knee extensor strength reduction in the early postoperative period, no consistent view of knee extensor strength several months after ACL reconstruction exists. This study aimed to compare the impact of intraoperative FNB and adductor canal block (ACB) during ACL reconstruction on knee extensor strength at 3 and 6 months postoperatively.

MATERIALS AND METHODS: This retrospective study included 108 patients divided into FNB (70 patients) and ACB (38 patients) groups based on their postoperative pain management methods. Knee joint extensor and flexor strength were measured at 3 and 6 months postoperatively, using BIODEX at angular velocities of 60°/s and 180°/s. From these results, peak torque, limb symmetry index (LSI), peak knee extensor torque (time to peak torque and angle of peak torque), hamstrings-to-quadriceps (HQ) ratio, and amount of work were computed for two-group comparison.

RESULTS: There were no statistically significant differences in peak torque, LSI of knee extensor strength, HQ ratio, and amount of work between the two groups. However, maximum knee extension torque at 60°/s occurred significantly later in the FNB than in the ACB group at 3 months postoperatively. Additionally, the LSI of the knee flexor at 6 months postoperatively was significantly lower in the ACB group.

CONCLUSIONS: In ACL reconstruction, FNB may delay the time to peak torque for knee extension at 3 months postoperatively, which is likely to improve over the treatment course. In contrast, ACB may result in unexpected loss of knee flexor strength at 6 months postoperatively and should be considered with caution.

LEVEL OF EVIDENCE: Level III.

PMID:37432497 | DOI:10.1007/s00402-023-04980-1

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Nevin Manimala Statistics

Wilcoxon rank-sum tests to detect one-sided mixture alternatives in group sequential clinical trials

Stat Methods Med Res. 2023 Jul 11:9622802231184634. doi: 10.1177/09622802231184634. Online ahead of print.

ABSTRACT

Traditional methods based on the assumption that the treatment distribution is a pure shift of the control distribution may not always hold. The possibility that an individual from the treatment group may not respond to the treatment motivates the use of a mixture distribution for the treatment group. This paper considers two test procedures based on the Wilcoxon rank-sum statistic for a group sequential design to detect the one-sided mixture alternative. Error spending functions are used for the allocation of error rates at each stage. The two tests are evaluated individually in determination of critical values and arm sizes and asymptotic multivariate normality is shown to hold for both. Upon comparison, the tests are presented to be asymptotically equivalent. Both test statistics maintain the Type I error rate even if F is misspecified in the design alternative. A more general definition of the treatment effect is used with the mixture distribution. Method of moments estimators and constrained k-means estimators for the treatment effect are evaluated.

PMID:37431736 | DOI:10.1177/09622802231184634