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1. A mathematical model of glomerular fibrosis in diabetic kidney disease to predict therapeutic efficacy

   https://doi.org/10.3389/fphar.2024.1481768  

   Thomas, Haryana Y; Ford_Versypt, Ashlee N (October 2024, Frontiers in Pharmacology)

   BackgroundGlomerular fibrosis is a tissue damage that occurs within the kidneys of chronic and diabetic kidney disease patients. Effective treatments are lacking, and the mechanism of glomerular damage reversal is poorly understood. MethodsA mathematical model suitable for hypothesis-driven systems pharmacology of glomerular fibrosis in diabetes was developed from a previous model of interstitial fibrosis. The adapted model consists of a system of ordinary differential equations that models the complex disease etiology and progression of glomerular fibrosis in diabetes. ResultsWithin the scope of the mechanism incorporated, advanced glycation end products (AGE)—matrix proteins that are modified due to high blood glucose—were identified as major contributors to the delay in the recovery from glomerular fibrosis after glucose control. The model predicted that inhibition of AGE production is not an effective approach for accelerating the recovery from glomerular fibrosis. Further, the model predicted that treatment breaking down accumulated AGE is the most productive at reversing glomerular fibrosis. The use of the model led to the identification that glucose control and aminoguanidine are ineffective treatments for reversing advanced glomerular fibrosis because they do not remove accumulated AGE. Additionally, using the model, a potential explanation was generated for the lack of efficacy of alagebrium in treating advanced glomerular fibrosis, which is due to the inability of alagebrium to reduce TGF- $\mathrm{\beta }$. ImpactUsing the mathematical model, a mechanistic understanding of disease etiology and complexity of glomerular fibrosis in diabetes was illuminated, and then hypothesis-driven explanations for the lack of efficacy of different pharmacological agents for treating glomerular fibrosis were provided. This understanding can enable the development of more efficacious therapeutics for treating kidney damage in diabetes. 

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2. Factors Associated With Nonadherence to Lung Cancer Screening Across Multiple Screening Time Points

   https://doi.org/10.1001/jamanetworkopen.2023.15250  

   Lin, Yannan; Liang, Li-Jung; Ding, Ruiwen; Prosper, Ashley Elizabeth; Aberle, Denise R.; Hsu, William (May 2023, JAMA Network Open)

   ImportanceScreening with low-dose computed tomography (CT) has been shown to reduce mortality from lung cancer in randomized clinical trials in which the rate of adherence to follow-up recommendations was over 90%; however, adherence to Lung Computed Tomography Screening Reporting & Data System (Lung-RADS) recommendations has been low in practice. Identifying patients who are at risk of being nonadherent to screening recommendations may enable personalized outreach to improve overall screening adherence. ObjectiveTo identify factors associated with patient nonadherence to Lung-RADS recommendations across multiple screening time points. Design, Setting, and ParticipantsThis cohort study was conducted at a single US academic medical center across 10 geographically distributed sites where lung cancer screening is offered. The study enrolled individuals who underwent low-dose CT screening for lung cancer between July 31, 2013, and November 30, 2021. ExposuresLow-dose CT screening for lung cancer. Main Outcomes and MeasuresThe main outcome was nonadherence to follow-up recommendations for lung cancer screening, defined as failing to complete a recommended or more invasive follow-up examination (ie, diagnostic dose CT, positron emission tomography–CT, or tissue sampling vs low-dose CT) within 15 months (Lung-RADS score, 1 or 2), 9 months (Lung-RADS score, 3), 5 months (Lung-RADS score, 4A), or 3 months (Lung-RADS score, 4B/X). Multivariable logistic regression was used to identify factors associated with patient nonadherence to baseline Lung-RADS recommendations. A generalized estimating equations model was used to assess whether the pattern of longitudinal Lung-RADS scores was associated with patient nonadherence over time. ResultsAmong 1979 included patients, 1111 (56.1%) were aged 65 years or older at baseline screening (mean [SD] age, 65.3 [6.6] years), and 1176 (59.4%) were male. The odds of being nonadherent were lower among patients with a baseline Lung-RADS score of 1 or 2 vs 3 (adjusted odds ratio [AOR], 0.35; 95% CI, 0.25-0.50), 4A (AOR, 0.21; 95% CI, 0.13-0.33), or 4B/X, (AOR, 0.10; 95% CI, 0.05-0.19); with a postgraduate vs college degree (AOR, 0.70; 95% CI, 0.53-0.92); with a family history of lung cancer vs no family history (AOR, 0.74; 95% CI, 0.59-0.93); with a high age-adjusted Charlson Comorbidity Index score (≥4) vs a low score (0 or 1) (AOR, 0.67; 95% CI, 0.46-0.98); in the high vs low income category (AOR, 0.79; 95% CI, 0.65-0.98); and referred by physicians from pulmonary or thoracic-related departments vs another department (AOR, 0.56; 95% CI, 0.44-0.73). Among 830 eligible patients who had completed at least 2 screening examinations, the adjusted odds of being nonadherent to Lung-RADS recommendations at the following screening were increased in patients with consecutive Lung-RADS scores of 1 to 2 (AOR, 1.38; 95% CI, 1.12-1.69). Conclusions and RelevanceIn this retrospective cohort study, patients with consecutive negative lung cancer screening results were more likely to be nonadherent with follow-up recommendations. These individuals are potential candidates for tailored outreach to improve adherence to recommended annual lung cancer screening. 

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3. Impact of Obesity on Timing of Tracheotomy: A Multi‐institutional Retrospective Study

   https://doi.org/10.1002/lary.31586  

   Yousef, Andrew; Soliman, Shady I; Solomon, Isaac; Panuganti, Bharat A; Francis, David O; Pang, John; Klebaner, Dasha; Asturias, Alicia; Alattar, Ali; Wood, Samuel; et al (November 2024, The Laryngoscope)

   ObjectiveTo examine the impact of increased body mass index (BMI) on (1) tracheotomy timing and (2) short‐term surgical complications requiring a return to the operating room and 30‐day mortality utilizing data from the Multi‐Institutional Study on Tracheotomy (MIST). MethodsA retrospective analysis of patients from the MIST database who underwent surgical or percutaneous tracheotomy between 2013 and 2016 at eight institutions was completed. Unadjusted and adjusted logistic regression analyses were used to assess the impact of obesity on tracheotomy timing and complications. ResultsAmong the 3369 patients who underwent tracheotomy, 41.0% were obese and 21.6% were morbidly obese. BMI was associated with higher rates of prolonged intubation prior to tracheotomy accounting for comorbidities, indication for tracheotomy, institution, and type of tracheostomy (p = 0.001). Morbidly obese patients (BMI ≥35 kg/m²) experienced a longer duration of intubation compared with patients with a normal BMI (median days intubated [IQR 25%–75%]: 11.0 days [7–17 days] versus 9.0 days [5–14 days];p < 0.001) but did not have statistically higher rates of return to the operating room within 30 days (p = 0.12) or mortality (p = 0.90) on multivariable analysis. This same finding of prolonged intubation was not seen in overweight, nonobese patients when compared with normal BMI patients (median days intubated [IQR 25%–75%]: 10.0 days [6–15 days] versus 10.0 days [6–15 days];p = 0.36). ConclusionBMI was associated with increased duration of intubation prior to tracheotomy. Although morbidly obese patients had a longer duration of intubation, there were no differences in return to the operating room or mortality within 30 days. Level of Evidence3Laryngoscope, 134:4674–4681, 2024 

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4. Patient-specific 3D in vitro modeling and fluid dynamic analysis of primary pulmonary vein stenosis

   https://doi.org/10.3389/fcvm.2024.1432784  

   Devlin, Christian; Tomov, Martin L; Chen, Huang; Nama, Sindhu; Ali, Siraj; Neelakantan, Sunder; Avazmohammadi, Reza; Dasi, Lakshmi Prasad; Bauser-Heaton, Holly D; Serpooshan, Vahid (July 2024, Frontiers in Cardiovascular Medicine)

   IntroductionPrimary pulmonary vein stenosis (PVS) is a rare congenital heart disease that proves to be a clinical challenge due to the rapidly progressive disease course and high rates of treatment complications. PVS intervention is frequently faced with in-stent restenosis and persistent disease progression despite initial venous recanalization with balloon angioplasty or stenting. Alterations in wall shear stress (WSS) have been previously associated with neointimal hyperplasia and venous stenosis underlying PVS progression. Thus, the development of patient-specific three-dimensional (3D)in vitromodels is needed to further investigate the biomechanical outcomes of endovascular and surgical interventions. MethodsIn this study, deidentified computed tomography images from three patients were segmented to generate perfusable phantom models of pulmonary veins before and after catheterization. These 3D reconstructions were 3D printed using a clear resin ink and used in a benchtop experimental setup. Computational fluid dynamic (CFD) analysis was performed on modelsin silicoutilizing Doppler echocardiography data to represent thein vivoflow conditions at the inlets. Particle image velocimetry was conducted using the benchtop perfusion setup to analyze WSS and velocity profiles and the results were compared with those predicted by the CFD model. ResultsOur findings indicated areas of undesirable alterations in WSS before and after catheterization, in comparison with the published baseline levels in the healthyin vivotissues that may lead to regional disease progression. DiscussionThe established patient-specific 3Din vitromodels and the developedin vitro–in silicoplatform demonstrate great promise to refine interventional approaches and mitigate complications in treating patients with primary PVS. 

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5. Modeling relaxed policies for discontinuation of methicillin-resistant Staphylococcus aureus contact precautions

   https://doi.org/10.1017/ice.2024.23  

   Cui, Jiaming; Heavey, Jack; Lin, Leo; Klein, Eili Y; Madden, Gregory R; Sifri, Costi D; Lewis, Bryan; Vullikanti, Anil K; Prakash, B Aditya (February 2024, Infection Control & Hospital Epidemiology)

   Abstract Objective:To evaluate the economic costs of reducing the University of Virginia Hospital’s present “3-negative” policy, which continues methicillin-resistantStaphylococcus aureus(MRSA) contact precautions until patients receive 3 consecutive negative test results, to either 2 or 1 negative. Design:Cost-effective analysis. Settings:The University of Virginia Hospital. Patients:The study included data from 41,216 patients from 2015 to 2019. Methods:We developed a model for MRSA transmission in the University of Virginia Hospital, accounting for both environmental contamination and interactions between patients and providers, which were derived from electronic health record (EHR) data. The model was fit to MRSA incidence over the study period under the current 3-negative clearance policy. A counterfactual simulation was used to estimate outcomes and costs for 2- and 1-negative policies compared with the current 3-negative policy. Results:Our findings suggest that 2-negative and 1-negative policies would have led to 6 (95% CI, −30 to 44;P< .001) and 17 (95% CI, −23 to 59; −10.1% to 25.8%;P< .001) more MRSA cases, respectively, at the hospital over the study period. Overall, the 1-negative policy has statistically significantly lower costs ($628,452; 95% CI, $513,592–$752,148) annually (P< .001) in US dollars, inflation-adjusted for 2023) than the 2-negative policy ($687,946; 95% CI, $562,522–$812,662) and 3-negative ($702,823; 95% CI, $577,277–$846,605). Conclusions:A single negative MRSA nares PCR test may provide sufficient evidence to discontinue MRSA contact precautions, and it may be the most cost-effective option. 

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