Publications

2024

Alnuaimi, Saif, Tea Reljic, Fatima S Abdulla, Hamda Memon, Sarah Al-Ali, Teagen Smith, Fadila Serdarevic, Zelija Velija Asimi, Ambuj Kumar, and Sabina Semiz. (2024) 2024. “PPAR Agonists As Add-on Treatment With Metformin in Management of Type 2 Diabetes: A Systematic Review and Meta-Analysis.”. Scientific Reports 14 (1): 8809. https://doi.org/10.1038/s41598-024-59390-z.

The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.

R, Kunjulakshmi, Ambuj Kumar, Keerthana Vinod Kumar, Avik Sengupta, Kavita Kundal, Simran Sharma, Ankita Pawar, et al. (2024) 2024. “AagingBase: a Comprehensive Database of Anti-Aging Peptides.”. Database : The Journal of Biological Databases and Curation 2024. https://doi.org/10.1093/database/baae016.

The process of aging is an intrinsic and inevitable aspect of life that impacts every living organism. As biotechnological advancements continue to shape our understanding of medicine, peptide therapeutics have emerged as a promising strategy for anti-aging interventions. This is primarily due to their favorable attributes, such as low immunogenicity and cost-effective production. Peptide-based treatments have garnered widespread acceptance and interest in aging research, particularly in the context of age-related therapies. To effectively develop anti-aging treatments, a comprehensive understanding of the physicochemical characteristics of anti-aging peptides is essential. Factors such as amino acid composition, instability index, hydrophobic areas and other relevant properties significantly determine their efficacy as potential therapeutic agents. Consequently, the creation of 'AagingBase', a comprehensive database for anti-aging peptides, aims to facilitate research on aging by leveraging the potential of peptide therapies. AagingBase houses experimentally validated 282 anti-aging peptides collected from 54 research articles and 236 patents. Employing state-of-the-art computational techniques, the acquired sequences have undergone rigorous physicochemical calculations. Furthermore, AagingBase presents users with various informative analyses highlighting atomic compositions, secondary structure fractions, tertiary structure, amino acid compositions and frequencies. The database also offers advanced search and filtering options and similarity search, thereby aiding researchers in understanding their biological functions. Hence, the database enables efficient identification and prioritization of potential peptide candidates in geriatric medicine and holds immense potential for advancing geriatric medicine research and innovations. AagingBase can be accessed without any restriction. Database URL: https://project.iith.ac.in/cgntlab/aagingbase/.

Peterson, Erica E ElSeed, Jared T Roeckner, Taylor W Deall, Michele Karn, Jose R Duncan, Jaime Flores-Torres, Ambuj Kumar, and Tara M Randis. (2024) 2024. “Need for Gastrostomy Tube in Periviable Infants.”. American Journal of Perinatology. https://doi.org/10.1055/s-0044-1781461.

OBJECTIVE:  We sought to identify clinical and demographic factors associated with gastrostomy tube (g-tube) placement in periviable infants.

STUDY DESIGN:  We conducted a single-center retrospective cohort study of live-born infants between 22 and 25 weeks' gestation. Infants not actively resuscitated and those with congenital anomalies were excluded from analysis.

RESULTS:  Of the 243 infants included, 158 survived until discharge. Of those that survived to discharge, 35 required g-tube prior to discharge. Maternal race/ethnicity (p = 0.006), intraventricular hemorrhage (p = 0.013), periventricular leukomalacia (p = 0.003), bronchopulmonary dysplasia (BPD; p ≤ 0.001), and singleton gestation (p = 0.009) were associated with need for gastrostomy. In a multivariable logistic regression, maternal Black race (Odds Ratio [OR] 2.88; 95% confidence interval [CI] 1.11-7.47; p = 0.029), singleton gestation (OR 3.99; 95% CI 1.28-12.4; p = 0.017) and BPD (zero g-tube placement in the no BPD arm; p ≤ 0.001) were associated with need for g-tube.

CONCLUSION:  A high percentage of periviable infants surviving until discharge require g-tube at our institution. In this single-center retrospective study, we noted that maternal Black race, singleton gestation, and BPD were associated with increased risk for g-tube placement in infants born between 22 and 25 weeks' gestation. The finding of increased risk with maternal Black race is consistent with previous reports of racial/ethnic disparities in preterm morbidities. Additional studies examining factors associated with successful achievement of oral feedings in preterm infants are necessary and will inform future efforts to advance equity in newborn health.

KEY POINTS: · BPD, singleton birth, and Black race are associated with need for g-tube in periviable infants.. · Severe intraventricular hemorrhage is associated with increased mortality or g-tube placement in periviable infants.. · Further investigation into the relationship between maternal race and g-tube placement is warranted..

Kumar, Ambuj, Keerthana Vinod Kumar, Kavita Kundal, Avik Sengupta, Simran Sharma, Kunjulakshmi R, and Rahul Kumar. (2024) 2024. “MyeloDB: a Multi-Omics Resource for Multiple Myeloma.”. Functional & Integrative Genomics 24 (1): 17. https://doi.org/10.1007/s10142-023-01280-0.

Multiple myeloma (MM) is a common type of blood cancer affecting plasma cells originating from the lymphoid B-cell lineage. It accounts for about 10% of all hematological malignancies and can cause significant end-organ damage. The emergence of genomic technologies such as next-generation sequencing and gene expression analysis has opened new possibilities for early detection of multiple myeloma and identification of personalized treatment options. However, there remain significant challenges to overcome in MM research, including integrating multi-omics data, achieving a comprehensive understanding of the disease, and developing targeted therapies and biomarkers. The extensive data generated by these technologies presents another challenge for data analysis and interpretation. To bridge this gap, we have developed a multi-omics open-access database called MyeloDB. It includes gene expression profiling, high-throughput CRISPR-Cas9 screens, drug sensitivity resources profile, and biomarkers. MyeloDB contains 47 expression profiles, 3 methylation profiles comprising a total of 5630 patient samples and 25 biomarkers which were reported in previous studies. In addition to this, MyeloDB can provide significant insight of gene mutations in MM on drug sensitivity. Furthermore, users can download the datasets and conduct their own analyses. Utilizing this database, we have identified five novel genes, i.e., CBFB, MANF, MBNL1, SEPHS2, and UFM1 as potential drug targets for MM. We hope MyeloDB will serve as a comprehensive platform for researchers and foster novel discoveries in MM. MyeloDB Database URL: https://project.iith.ac.in/cgntlab/myelodb/ .

Wyant, Hannah N, Marc A Silva, Stephanie Agtarap, Farina A Klocksieben, Teagen Smith, Risa Nakase-Richardson, and Shannon R Miles. (2024) 2024. “Applying the PTSD Checklist-Civilian and PTSD Checklist for DSM-5 Crosswalk in a Traumatic Brain Injury Sample: A Veterans Affairs Traumatic Brain Injury Model Systems Study.”. Psychological Assessment 36 (6-7): 425-32. https://doi.org/10.1037/pas0001315.

This study evaluates the use of the crosswalk between the PTSD Checklist-Civilian (PCL-C) and PTSD Checklist for DSM-5 (PCL-5) designed by Moshier et al. (2019) in a sample of service members and veterans (SM/V; N = 298) who had sustained a traumatic brain injury (TBI) and were receiving inpatient rehabilitation. The PCL-C and PCL-5 were completed at the same time. Predicted PCL-5 scores for the sample were obtained according to the crosswalk developed by Moshier et al. We used three measures of agreement: intraclass correlation coefficient (ICC), mean difference between predicted and observed scores, and Cohen's κ to determine the performance of the crosswalk in this sample. Subgroups relevant to those who have sustained a TBI, such as TBI severity, were also examined. There was strong agreement between the predicted and observed PCL-5 scores (ICC = .95). The overall mean difference between predicted and observed PCL-5 scores was 0.07 and not statistically significant (SD = 8.29, p = .89). Significant mean differences between predicted and observed PCL-5 scores calculated between subgroups were seen in Black participants (MD = -4.09, SD = 8.41, p = .01) and those in the Year 5 follow-up group (MD = 1.77, SD = 7.14, p = .03). Cohen's κ across subgroups had a mean of κ = 0.76 (.57-1.0), suggesting that there was moderate to almost perfect diagnostic agreement. Our results suggest the crosswalk created by Moshier et al. can be applied to SM/V who have suffered a TBI. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Dayto, Denisse Camille, Wojciech Blonski, Tea Reljic, Farina Klocksieben, Jeffrey Gill, Rene D Gomez-Esquivel, Brijesh Patel, et al. (2024) 2024. “A Systematic Critical Appraisal of Clinical Practice Guidelines of Antithrombotic Agents in Gastrointestinal Endoscopy Using the AGREE II Tool.”. Journal of Gastroenterology and Hepatology 39 (5): 818-25. https://doi.org/10.1111/jgh.16485.

BACKGROUND AND AIM: The quality of clinical practice guidelines (CPGs) for the management of antithrombotic agents in patients undergoing gastrointestinal (GI) endoscopy has not been systematically appraised. The goal of this study was to evaluate the methodological quality of CPGs for the management of antithrombotic agents in periendoscopic period published within last 6 years.

METHODS: A systematic search of PubMed and Embase databases was performed to identify eligible CPGs published between January 1, 2016, and April 14, 2022, addressing the management of antithrombotic agents in the periendoscopic period. The quality of the CPG was independently assessed by six reviewers using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Domain scores were considered of sufficient quality when > 60% and of good quality when > 80%.

RESULTS: The search yielded 343 citations, of which seven CPGs published by the gastroenterology associations in Asia (n = 3), Europe (n = 2), and North America (n = 2) were included for the critical appraisal. The overall median score for the AGREE II domains was 93% (interquartile range [IQR] 11%) for scope and purpose, 79% (IQR 61%) for stakeholder involvement, 79% (IQR 36%) for rigor of development, 100% (IQR 14%) for clarity of presentation, 32% (IQR 36%) for applicability, 93% (IQR 29%) for editorial independence, and 86% (IQR 29%) for overall assessment.

CONCLUSIONS: The findings show that the overall methodological quality of the CPGs for the management of antithrombotic agents in the periendoscopic period varies across the domains. There is significant scope for improvement in the methodological rigor and applicability of CPGs.

Elsamna, Samer T, Matthew E Lin, Teagen Smith, Michael Johns, Amy Rutt, and Yael Bensoussan. (2024) 2024. “Impact of BMI on Dyspnea and Need for Surgical Intervention in Bilateral Vocal Fold Immobility.”. Otolaryngology–head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery 171 (2): 486-93. https://doi.org/10.1002/ohn.753.

OBJECTIVE: Bilateral vocal fold paralysis (BVFP) and posterior glottic stenosis (PGS) are causes of bilateral vocal fold immobility (BVFI) and may cause shortness of breath, stridor, and need for surgical intervention. Although increased body mass index (BMI) is associated with restrictive breathing patterns in patients with normal upper airways, it is unclear how BMI impacts dyspnea and need for surgical intervention in BVFI patients.

STUDY DESIGN: Retrospective cohort study.

SETTING: Three tertiary academic centers in the United States.

METHODS: Demographics, BMI, Dyspnea Index (DI), etiology, presence of tracheostomy and surgical intervention (dilation, tracheostomy, cordotomy, arytenoidectomy, open reconstruction) were collected. Primary outcomes included dyspnea measured by DI and need for surgery to improve airway. Linear regressions were performed to assess continuous outcomes. Mann-Whitney U-test was utilized to assess categorical outcomes.

RESULTS: Among 121 patients, 52 presented with BVFP and 69 with PGS. Previous neck surgery was the most common cause of BVFI (40.2%). 44.3% of patients received a tracheostomy. Through multivariate linear regression, increased BMI was significantly associated with increased DI in the entire cohort (β = .43, P = .016). Increased BMI was also associated with need for any surgical intervention (odds ratio [OR] = 1.07, 95% confidence interval [CI] = [1.01-1.13]) in the overall cohort. When stratifying our data, BMI was only significantly associated with DI in BVFP (β = .496) and need for surgical intervention in PGS (OR = 1.11, 95% CI = [1.01-1.21]), although a positive trend was seen in all analyses.

CONCLUSION: Increased BMI may correlate with worsening dyspnea symptoms and need for surgical intervention in patients with BVFI. Weight-loss-related counseling may benefit symptom management.

Wyant, Hannah N, Marc A Silva, Stephanie Agtarap, Farina A Klocksieben, Teagen Smith, Risa Nakase-Richardson, and Shannon R Miles. (2024) 2024. “Applying the PTSD Checklist-Civilian and PTSD Checklist for DSM-5 Crosswalk in a Traumatic Brain Injury Sample: A Veterans Affairs Traumatic Brain Injury Model Systems Study.”. Psychological Assessment 36 (6-7): 425-32. https://doi.org/10.1037/pas0001315.

This study evaluates the use of the crosswalk between the PTSD Checklist-Civilian (PCL-C) and PTSD Checklist for DSM-5 (PCL-5) designed by Moshier et al. (2019) in a sample of service members and veterans (SM/V; N = 298) who had sustained a traumatic brain injury (TBI) and were receiving inpatient rehabilitation. The PCL-C and PCL-5 were completed at the same time. Predicted PCL-5 scores for the sample were obtained according to the crosswalk developed by Moshier et al. We used three measures of agreement: intraclass correlation coefficient (ICC), mean difference between predicted and observed scores, and Cohen's κ to determine the performance of the crosswalk in this sample. Subgroups relevant to those who have sustained a TBI, such as TBI severity, were also examined. There was strong agreement between the predicted and observed PCL-5 scores (ICC = .95). The overall mean difference between predicted and observed PCL-5 scores was 0.07 and not statistically significant (SD = 8.29, p = .89). Significant mean differences between predicted and observed PCL-5 scores calculated between subgroups were seen in Black participants (MD = -4.09, SD = 8.41, p = .01) and those in the Year 5 follow-up group (MD = 1.77, SD = 7.14, p = .03). Cohen's κ across subgroups had a mean of κ = 0.76 (.57-1.0), suggesting that there was moderate to almost perfect diagnostic agreement. Our results suggest the crosswalk created by Moshier et al. can be applied to SM/V who have suffered a TBI. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Piper, Keaton, Teagen Smith, Miguel Saez-Alegre, Walter Jean, Yarema Bezchlibnyk, and Harry Van Loveren. (2024) 2024. “Does Head Positioning After Percutaneous Glycerol Rhizotomy for Trigeminal Neuralgia Matter?”. World Neurosurgery 181: e447-e452. https://doi.org/10.1016/j.wneu.2023.10.078.

BACKGROUND: Percutaneous glycerol rhizotomy (PGR) is a minimally invasive procedure for patients with trigeminal neuralgia who are not candidates for microvascular decompression. PGR has widely varying success rates. It has been postulated that differences in post-injection head positioning might account for the various success rates.

METHODS: By comparing glycerol dispersion after injection at various head positions, we provide the first evidence supporting post-injection head flexion positioning. Furthermore, we study the clival-Meckel cave (CMC) angle as a predictor of beneficial glycerol flow, measured on computed tomography images. Twenty-two dissected cadaveric specimens were injected with dyed glycerol through the Hartel approach. The glycerol dispersion was measured at prespecified intervals for 1 hour. The Mann-Whitney U and χ2 tests were used to determine the most ideal angle of head flexion to avoid posterior glycerol dispersion and ensure V1-V3 branch glycerol submersion.

RESULTS: We found that 30° of anterior head flexion provided optimal trigeminal nerve glycerol submersion (81.82%) in comparison to neutral (27.27%) and 15° (68.18%), P < 0.001. There was minimal unfavorable dispersion beyond 30 minutes at all angles. More obtuse CMC angles were associated with higher rates of unfavorable BC dispersion (U = 6.0; P = 0.001). For specimens with CMC angles >75°, unfavorable BC dispersion was prevented by head flexion (U = 4.5; P = 0.021). We show that 30° of lateral head tilt achieves V1 submersion in all specimens by 30 minutes [X2(1,N = 44) = 22.759; P < 0.001].

CONCLUSIONS: We found that 30° anterior head flexion for >30 minutes provides ideal conditions for PGR to avoid BC dispersion and ensure V1-V3 branches achieve glycerol submersion. For patients with V1 symptoms, contralateral head flexion might help optimize treatment effects.

Englander, Katherine, Kaitlyn Cox, Teagen Smith, Adbul Diab, Samer Ganam, Joseph Sujka, and Christopher DuCoin. (2024) 2024. “The Financial Implications of a Single-Use Device Reprocessing Program at a Tertiary Referral Center Surgical Department.”. The American Surgeon, 31348241241679. https://doi.org/10.1177/00031348241241679.

The operating room has been identified as one of the primary contributors to waste and energy expenditure in the health care system. The primary objective of our study was to evaluate the efficacy of single-use device reprocessing and report the cost savings, waste diversion, and reduction in carbon emissions. Data was collected from January 2021 to April 2023. Medline collected the data for analysis and converted it from an Excel file format to SPSS (Version 27) for analysis. Descriptive frequencies were used for data analysis. We found a mean monthly cost savings of $16,051.68 and a mean 700.68 pounds of waste a month diverted, resulting in an estimated yearly saving of $2354.29 in disposal costs and a reduction of 1112.65 CO2e emissions per month. This program has made significant contributions to cost savings and environmental efforts.