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Weight Trends Among Children and Adolescents within Central Indiana 2023 data addendum
No full textThe 2024 addendum to the full report on obesity trends among children and adolescents in central Indiana presents updated data and insights, reflecting changes observed over the past year. This addendum incorporates an additional 389,000 patient encounters, enhancing the robustness of the longitudinal analysis. The updated findings reveal a continued increase in obesity prevalence, with notable demographic variations and significant impacts from the COVID-19 pandemic. This report aims to provide a deeper understanding of the evolving obesity trends and inform targeted public health strategies to mitigate this growing concern
Real‐world observations of GLP‐1 receptor agonists and SGLT‐2 inhibitors as potential treatments for Alzheimer's disease
No full textIntroduction: Glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors have potential beneficial effects in Alzheimer's disease (AD).
Methods: We conducted pharmacoepidemiologic studies using two large-scale real-world databases. We fitted covariate-adjusted Cox models to compare the risks of AD among initiators of GLP-1 receptor agonists, SGLT-2 inhibitors, and DPP-4 inhibitors.
Results: We identified GLP-1 receptor agonist initiation compared to DPP-4 inhibitors initiation was associated with a reduced risk of AD (hazard ratio [HR] ≤ 0.69 and P value < 0.001) and SGLT-2 inhibitor initiation compared to DPP-4 inhibitor initiation was associated with a reduced risk of AD (HR ≤ 0.67 and P value < 0.001).
Discussion: GLP-1 receptor agonist initiation and SGLT-2 inhibitor initiation are associated with a reduced risk of AD. Randomized clinical trials are warranted to validate the causal beneficial effects of GLP-1 receptor agonists and SGLT-2 inhibitors in AD.
Highlights: Glucagon-like peptide-1 (GLP-1) receptor agonists are significantly associated with a reduced risk of Alzheimer's disease (AD) compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are significantly associated with a reduced risk of AD compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Two GLP-1 receptor agonists (liraglutide and semaglutide) and three SGLT-2 inhibitors (dapagliflozin, canagliflozin, and empagliflozin) are associated with a reduced risk of AD in drug-specific sensitivity analyses
Correction: MHCII reduction is insufficient to protect mice from alpha-synuclein-induced degeneration and the Parkinson’s HLA locus exhibits epigenetic regulation
No full textCorrection to: Scientific Reports 10.1038/s41598-025-95679-3, published online 21 April 2025
Fredric P. Manfredsson was omitted from the author list in the original version of this Article.
Consequently, in the Author contributions section,
“E.M.K. and M.G.T. conceived the study. E.M.K. designed the study and supervised the technical staff involved in the study. E.M.K., J.J., C.D.S., J.M., S.L.H., M.K.H., R.L.W., S.D.K., J.C., K.B.M., V.J. performed the various surgeries and assays. N.R.M. provided human samples in accordance with IRB. J.M.B. and M.G.T. obtained funding support. J.M.B. and C.D.S. provided guidance and interpretation on ATAC-seq and MHCII gene expression. E.M.K., J.J., M.G.T. and V.J. wrote and edited the paper. E.M.K., J.J. and V.J. were responsible for all prepared figures. All authors reviewed and approved the final version of the manuscript.”
now reads:
“E.M.K. and M.G.T. conceived the study. E.M.K. designed the study and supervised the technical staff involved in the study. E.M.K., J.J., C.D.S., J.M., S.L.H., M.K.H., R.L.W., S.D.K., J.C., K.B.M., F.P.M., and V.J. performed the various surgeries and assays. N.R.M. provided human samples in accordance with IRB. J.M.B. and M.G.T. obtained funding support. J.M.B. and C.D.S. provided guidance and interpretation on ATAC-seq and MHCII gene expression. E.M.K., J.J., M.G.T. and V.J. wrote and edited the paper. E.M.K., J.J. and V.J. were responsible for all prepared figures. All authors reviewed and approved the final version of the manuscript.”
Furthermore, the Acknowledgements section has been updated. It now reads:
“We thank the Emory Flow Cytometry Core for their assistance with the use of the LSRII, as well as the Emory Genomics Core for completing library preparations and sequencing. We thank Haydeh Payami and the Tansey lab for thoughtful discussions. Partial funding from this work came from a pilot grant from Emory PD-CERC (MGT and JMB), a pilot grant from NIH/NINDS 1P50NS071669 Emory’s Udall Parkinson’s Disease Center/UL1RR025008 Atlanta Clinical and Translational Science Institute (ACTSI) (JMB and MGT), NIH RO1AI153102 (JMB), NIH/NINDS RF1NS128800 (MGT) and NIH/NINDS 5R01NS092122 (MGT and JMB). Support was also provided by Michael J Fox foundation MJFF-023296 (VJ and MGT), 1FL ADRC Alzstars P30AG066506 (VJ) and Alzheimer’s Association AARG-22-927012 (VJ). Figure 1 was created in BioRender. Jernigan, J. (2025) https://BioRender.com/r71q005.”
In addition, the affiliation “Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA” was omitted for authors Elizabeth M. Kline, Mary K. Herrick, Sean D. Kelly, Jianjun Chang, Malú Gámez Tansey, and Valerie Joers
Loss of MMP9 leads to altered inflammation and ECM interactions in a mouse model of cerebral small vessel disease
No full textBackground:
Vascular contributions to cognitive impairment and dementia (VCID) represent a major cause of dementia. Hyperhomocysteinemia (HHcy)‐driven cerebral small vessel disease (cSVD) leads to the degeneration of astrocytic end‐feet and an upregulation of matrix metalloproteinases (MMPs), which remodel the basement membrane, triggering growth factor activation and inflammation. This study explores the role of MMP9 in cSVD using MMP9‐/‐ mice subjected to a HHcy diet.
Method:
Six‐month‐old C57Bl6/J mice and MMP9‐/‐ mice were placed on a diet deficient in B vitamins and enriched in methionine or a control diet with normal levels of B vitamins and methionine for 12 weeks. The left hemibrain was fixed in PFA while the right brain was dissected for biochemistry. RNA was extracted from the frontal cortex and analyzed using NanoString's Mouse Neuroinflammation and Cardiovascular Disease panels. Microhemorrhage assessment via Prussian blue staining as well as Dp71, AQP4, and GFAP detected by immunohistochemistry were performed on the left hemisphere.
Result:
Gene expression analysis in MMP9‐/‐ mice on a control diet revealed significant reductions in inflammation‐related genes (Cd14, Slamf8, Prkcq, Lag3) and lower expression of the microglial marker P2ry12 compared to wild‐type mice. Additionally, MMP9‐/‐ mice exhibited increased expression of macrophage extracellular matrix (ECM) scavenging receptors (Cd44, Cd163, Siglec1) and enhanced regulation of the PIP3 signaling pathway across multiple cell types. Under a HHcy diet, wild‐type mice showed elevated expression of Cpa3, Reln, and the glial transcription factor EOMES, while MMP9‐/‐ mice demonstrated increased expression of PECAM1, Hira, Myd88, and Pink1. Although MMP9‐/‐ mice displayed a trend toward fewer microbleeds, the difference was not statistically significant.
Conclusion:
Our findings suggest that MMP9 plays a key role in the inflammatory response associated with HHcy‐induced cSVD. The absence of MMP9 led to reduced expression of several inflammation‐related genes as well as an increase in ECM interacting genes from macrophages, though differences in gene expression profiles between wild‐type and MMP9‐/‐ mice highlight distinct molecular pathways. Further studies are needed to fully understand MMP9's role in cSVD progression
Oral vs Intravenous Antibiotics for Fracture-Related Infections: The POvIV Randomized Clinical Trial
No full textImportance: Fracture-related infection (FRI) is a serious complication following fracture fixation surgery. Current treatment of FRIs entails debridement and 6 weeks of intravenous (IV) antibiotics. Lab data and retrospective clinical studies support use of oral antibiotics, which are less expensive and may have fewer complications than IV antibiotics.
Objective: To evaluate the effectiveness of treatment of FRI with oral vs IV antibiotics.
Design, setting, and participants: The POvIV multicenter, prospective randomized clinical trial was conducted across 24 trauma centers in the US among patients aged 18 to 84 years who had fracture repair or arthrodesis with fixation with implants and developed an FRI without radiographic evidence of osteomyelitis. Patients were enrolled between March 2013 and September 2018 and followed up for 12 months after hospitalization for treatment of their FRI.
Intervention: Oral vs IV antibiotics following FRI.
Main outcomes and measures: The primary outcome was number of surgical interventions, and the primary hypothesis was noninferiority of oral vs IV antibiotics with respect to the number of study injury-related surgical interventions by 1 year. Unadjusted modified intent-to-treat (mITT) and adjusted per-protocol (PP) analyses were prespecified. A post hoc adjusted mITT analysis was conducted to resolve discrepancies between the results of the prespecified mITT and PP analyses. Recurrence of a deep surgical site infection was a key secondary outcome.
Results: Among 233 total patients, mean (SD) age was 46.0 (13.9) years, and 53 patients were female (22.7%). The mean number of surgical interventions within 1 year was 1.3 and 1.1 for the oral and IV groups, respectively. The upper bound of the 95% confidence interval of the mean difference with unadjusted mITT analysis was 0.59, which was lower than the prespecified noninferiority margin of 0.67, indicating noninferiority of oral to IV antibiotics. Adjusted PP analysis did not support noninferiority of the number of reoperations. A post hoc adjusted mITT analysis also showed noninferiority. The treatment effects estimates for the key secondary outcome of reinfection showed a similar pattern as those for the primary outcome.
Conclusions and relevance: In this prospective randomized clinical trial, oral antibiotic treatment was noninferior to IV treatment with respect to the primary outcome of number of surgical interventions based on mITT analysis. However, there is some uncertainty in these findings based on preplanned and post hoc secondary analyses. A similar pattern of treatment effect estimates was observed for the secondary outcome of recurrence of infection
Delusional Parasitosis vs. Morgellons Disease: Diagnostic Challenges, Overlaps, and Clinical Implications
No full textTitle: Delusional Parasitosis vs. Morgellons Disease: Diagnostic Challenges, Overlaps, and Clinical Implications.
Author Names: Katheryn Bell1, Jennifer Beckman1, Suki Sasic1, Josey Mckinley, and Mushashra Raza M.D., MPH2
Indiana University School of Medicine.
Department of Psychiatry, Indiana University School of Medicine.
Background: Delusional parasitosis (DP) is a delusional disorder where patients believe they are infested with a parasite/bug [1]. In contrast, Morgellons disease (MD) is a psycho-dermatologic condition where a patient has the sensation of fibers in/on their skin, often with associated itching and ulcerative lesions [2]. Both conditions can either be primary or secondary to psychiatric/medical conditions. The diagnostic criteria for both is complicated by commonly associated psychiatric disorders and substance abuse, as well as the need to completely rule out underlying pathologies causing the delusions [3,4].
Case: 42 y.o. female with a history of Major Depressive Disorder (MDD), unspecified psychosis/schizophrenia, anxiety disorder, and substance use disorders involving cocaine, amphetamines, cannabis, and tobacco admitted due to suicidal ideation with plan. The patient reported a several-year history of feeling her body was infested with small bugs, insisting a bag of black fibers were those bugs. She also noted several symptoms of depression, but denied auditory hallucinations or any other symptoms of psychosis. Drug screen was positive for cocaine and cannabis. Physical exam found rashes and erosions on the face, arms, and hands. She was started on 2mg risperidone with improvement and discharged on day 7 with follow up.
Clinical Significance: The unique overlap of etiologies in this patient makes this an interesting case. The patient presented with a variety of confounding factors- substance abuse, depression, delusions of bug infestation, and presence of fibers- which make distinguishing between diagnoses such as DP, MD, psychosis, and substance-induced formication difficult. However, the patient improved with conventional treatment, calling into question whether this diagnostic parsing is even necessary.
Conclusion: Patient presented with suicidal ideation and feeling of bugs inside her body, suggestive of an MD or PD etiology, thus raising the question of whether distinguishing the two is critical for treatment
Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia
No full textPurpose: This randomized phase-II trial (ClinicalTrials.gov identifier: NCT02767557) compared efficacy of gemcitabine/nab-paclitaxel (Gem/Nab) with or without the anti-interleukin-6 (IL-6) receptor antibody tocilizumab (Toc) for advanced pancreatic cancer (PC).
Methods: A safety cohort received Gem 1,000 mg/m2 and Nab 125 mg/m2 on days 1, 8, and 15, and Toc 8 mg/kg on day 1 for each 28-day cycle. Participants with modified Glasgow prognostic scores of 1 or 2 were randomly assigned 1:1 to receive Gem/Nab/Toc or Gem/Nab. The primary end point was the overall survival (OS) rate at 6 months (OS6). Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. Exploratory end points were cachexia, quality of life, and biomarkers, including the cachexia-promoting protein, growth differentiation factor 15 (GDF15).
Results: Overall, 147 patients were treated, including six safety cohort participants. The median follow-up period was 8.1 months (IQR, 4.2-13.9). OS6 was 68.6% (95% CI, 56.3 to 78.1) for the Gem/Nab/Toc group and 62.0% (49.6-72.1) for the Gem/Nab group (P = .409). OS for Gem/Nab/Toc versus Gem/Nab improved at 18 months (27.1% v 7.0%, P = .001). No differences in median OS, PFS, or ORR were observed. Incidence of grade-3+ treatment-related adverse events (TrAEs) was 88.1% for Gem/Nab/Toc and 63.4% for Gem/Nab (P < .001). Gem/Nab/Toc decreased muscle loss versus Gem/Nab, with median change +0.1013% versus -3.430% (P = .0012) at 2 months and +0.7044 versus -3.353% (P = .036) at 4 months. Incidence of muscle loss was 43.48% on Gem/Nab/Toc versus 73.52% on Gem/Nab at 2 months (P = .0045) and 41.82% versus 68.75% (P = .0062) at 4 months. GDF15 was not changed by Gem/Nab or Gem/Nab/Toc.
Conclusion: Although the primary end point was not met and TrAEs were increased by Toc, increased survival at 18 months and reduced muscle wasting support an anticachexia effect of IL-6 blockade independent of GDF15. Further studies could leverage these findings for precision anticachexia therapy
Older injured adults reported sleep disturbances: a cross-sectional study
No full textBackground: Sleep disturbances are common among older adults recovering from traumatic injury and are associated with delayed psychological and functional recovery. Despite their prevalence, few studies have examined sleep disturbances early after injury in this population. This study evaluated the prevalence of self-reported sleep disturbances among older trauma survivors using PROMIS-based assessments within the Trauma Medical Home (TMH) care model to identify modifiable factors that may inform early, patient-centered interventions.
Methodology: In this cross-sectional study, we conducted a secondary analysis of data from the Collaborative Care for Injured Older Adults: The Trauma Medical Home Randomized Clinical Trial (TMH) study. 144 patients 50 years of age and older admitted for traumatic injury into four trauma centers reported their sleep quality using Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 4a (PROMIS-SF). Symptoms of depression and anxiety were assessed using the Hospital Anxiety and Depression Scale (HADS), of post-traumatic stress using Post Traumatic Stress Disorder (PTSD) Checklist-Civilian Version (PCL-C), and pain intensity using Pain, Enjoyment of Life, and General Activity Scale (PEG) scale. Comorbidities were quantifiedusing the Charlson Comorbidity Index (CCI), and trauma severity using the Injury Severity Score (ISS). Logistic regression was used to examine associations between sleep disturbances and psychological and clinical factors.
Results: Approximately 22% of patients reported sleep disturbances. Patients with PTSD or pain symptoms had significantly higher odds of reporting sleep disturbances (OR for PTSD = 13.21, 95% CI = [2.90, 61.17], p = 0.001; OR for pain = 1.33, 95% CI = [1.11, 1.60], p = 0.002).
Conclusion: This study extends prior research by focusing on older adult trauma survivors and assessing sleep disturbances during the immediate post-injury period using PROMIS-based patient-reported outcomes within the Trauma Medical Home (TMH) care model. This approach provides new insight into early, multidimensional symptom patterns and identifies modifiable factors that can inform timely, patient-centered interventions to improve recovery
Socioeconomic and ethnic disparities in breast cancer-related lymphedema and quality-of-life after immediate lymphatic reconstruction
No full textPurpose: Breast cancer-related lymphedema (BCRL) disproportionately impacts patients facing socioeconomic challenges. The influence of socioeconomic disparities on preventive procedures such as immediate lymphatic reconstruction (ILR) is unclear. We sought to determine the impact of area deprivation index (ADI) on BCRL incidence and patient-reported outcomes (PROs) following ILR.
Methods: We retrospectively studied consecutive patients who underwent ILR following ALND between 2017 and 2024 across multiple hospitals within a hospital network. Patients were stratified into quartiles based on ADI (Q1 = least deprived, Q4 = most deprived). BCRL prevalence and condition-specific (LYMPH-Q) quality-of-life performance was compared and correlated across quartiles via multivariable regression, including subgroup analysis by ethnicity.
Results: We identified 172 patients with follow-up time of 23.1 ± 15.2 months. Patients residing in the most deprived neighborhoods (ADI Q4) demonstrated significantly higher BCRL rates compared to those from less deprived neighborhoods (Q1-3) (16.3% vs. 3.9%; p = 0.006). In multivariable regression, residence in the most deprived neighborhoods remained independently associated with a significantly higher risk of BCRL (OR 5.10, 95% CI 1.30-20.30; p = 0.021). Subgroup analysis revealed that Black patients in the highest ADI quartile reported significantly worse LYMPH-Q function scores (median 62.0 vs 100.0; p = 0.020), compared to Black patients residing in less deprived areas. ADI was not significantly associated with surgical complications or unplanned reoperations.
Conclusions: Neighborhood socioeconomic disadvantage significantly increases BCRL risk following ILR and is associated with significantly worse patient-reported functional outcomes among Black patients. Targeted interventions addressing neighborhood-level factors are critical to mitigate these disparities and ensure equitable outcomes
2025 Physician License Renewal Information Fields
No full textThe document contains the information fields and survey tool for the 2025 Indiana physician license renewal period