Citations

Study Design. Post hoc analysis of prospectively-collected data. Objective. To identify factors predicting the most (and least) satisfaction following surgery for cervical spondylotic myelopathy (CSM). Summary of Background Data. Patient satisfaction affects long-term outcomes after surgery but the preoperative factors that influence postoperative satisfaction have not been well studied in patients with CSM. Methods. We conducted a post hoc analysis of prospectively-collected data from the Quality Outcomes Database (QOD) CSM registry cohort. Baseline and surgical characteristics were compared for patients with CSM reporting the most [North American Spine Society Satisfaction Score (NASS) 1] and least (NASS 4) satisfaction 24 months postoperatively. A multivariable logistic regression model was constructed using backward stepwise elimination to determine significant predictors of most versus least satisfaction. Twenty-four-month patient-reported outcomes (PROs) were compared. Results. Overall, 1141 patients were prospectively enrolled with 948 (83.1%) reaching 24-month follow-up. Of these, 699 met prespecified inclusion criteria: 610 (87.3%) were most satisfied and 89 (12.7%) were least satisfied. Though there were mean improvements in all 24-month PROs for the most satisfied cohort ( P <0.001), there were no significant improvements in 24-month PROs for the least satisfied cohort ( P >0.05). Using multivariable logistic regression modeling, a preoperative symptom of upper extremity weakness (OR=2.5, P =0.003), subjective myelopathy (OR=2.0, P =0.04), absence of numbness complaints (OR=2.2, P =0.003), symptom duration under 12 months (OR=1.6, P =0.047), Caucasian race (OR=2.3, P =0.001), participation in activities outside of the home (OR=2.0, P =0.04), anterior approach (OR=2.3, P <0.001), and higher baseline quality of life (OR=4.0, P =0.01) were predictive of the most satisfaction. Conclusion. Compared with the least satisfied, those most satisfied following surgery for CSM more often had a preoperative symptom of arm weakness, subjective myelopathy, the absence of numbness complaints, symptom duration under 12 months, higher baseline quality of life, and participation in activities outside of the home. Compared with a posterior approach, an anterior approach was associated with the most satisfaction. Taken together, early surgical treatment--before myelopathic symptoms significantly impact one's quality of life--may be considered to optimize patient satisfaction following CSM surgery.

Background Chlorhexidine is commonly used in prevention bundles for ventilator-associated pneumonia. Results for use of chlorhexidine in critically ill patients requiring mechanical ventilation via an endotracheal tube are mixed, and data for patients using a tracheostomy are lacking. Objectives To assess the risk for ventilator-associated pneumonia according to chlorhexidine exposure in patients requiring a new tracheostomy for mechanical ventilation. Methods This single-center, retrospective cohort study compared the development of ventilator-associated pneumonia according to chlorhexidine exposure in adult intensive care unit patients requiring new tracheostomy at a large academic medical center. Adults who received a new tracheostomy and required ventilator support for at least 48 hours were included. Patients treated for pneumonia at the time of tracheostomy or who met additional exclusion criteria were excluded. Results Of 235 patients who met the inclusion criteria, 203 received chlorhexidine and 32 did not. The cohort was predominantly White, male, and admitted to a surgical intensive care unit. Incidence of ventilator-associated pneumonia did not differ significantly between patients exposed or not to chlorhexidine (by 30 days, 32.5% vs 35.7%, P = .87). Time to development of ventilator-associated pneumonia also did not differ significantly between patients exposed or not (9 vs 12 days, respectively, P = .34). Conclusions Chlorhexidine exposure was not associated with a difference in the incidence of or time to ventilator-associated pneumonia after new tracheostomy. Further study is needed on the role of chlorhexidine in preventing ventilator-associated pneumonia after a new tracheostomy.

Abstract Provided herein are novel compounds as TREM2 agonists, pharmaceutical compositions, use of such compounds in treating Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Nasu-Hakola disease, and stroke, and processes for preparing such compounds.

A 64-year-old Asian woman diagnosed with synchronous breast ductal carcinoma in situ (DCIS) and stage IV EGFR-mutated non-small cell carcinoma of the lung (NSCLC). A decision was made to defer management of the DCIS and initiate Osimertinib for lung cancer treatment, since this was a life-limiting diagnosis. At 9 months, restaging FDG-PET CT showed an interval response in the NSCLC and complete loss of FDG avidity at the biopsy-proven DCIS site. Breast MRI confirmed complete imaging resolution of the DCIS. The clinical resolution of breast DCIS during third-generation EGFR inhibitor therapy has not been previously reported in humans and highlights a potential role for the EGFR/HER2 (ERBB) pathway in pre-invasive breast cancer.

Background: Integrating machine learning (ML) with population pharmacokinetic (PPK) modeling may improve therapeutic drug monitoring predictions. Methods: Tacrolimus trough concentrations from lung transplant patients were split into a training data set (1151 concentrations in 80 patients) and a testing data set (224 concentrations in 20 patients). A PPK model was developed using NONMEM, followed by the development of 10 ML models to fit individual pharmacokinetic parameters from the PPK model with Bayesian forecasting. The best performing ML model was selected as the final model. Both the final PPK and ML models were compared for prediction performance. A web-based dashboard was established with R-shiny to recommend dosing regimens based on patient data. Results: In the PPK model, postoperative days, hematocrit, aspartate aminotransferase, tacrolimus daily dose, coadministered voriconazole or posaconazole, and the CYP3A5*3 genotype were identified significant covariates on the clearance. The Cubist ML model outperformed the PPK model, showing lower root mean squared error for tacrolimus concentrations in the testing data set. An online web-based precision dosing dashboard was created, accessible at (https://tac-dose-ml.shinyapps.io/shiny/). Conclusions: Integrating ML with PPK modeling could yield superior tacrolimus concentration predictions for lung transplant patients, offering an efficient alternative to Bayesian forecasting. The online dashboard provides rapid, individualized dosing recommendations.

ABSTRACT Background Eosinophilic esophagitis is associated with epithelial barrier dysfunction. Epidemiologic studies suggest environmental factors promote disease pathogenesis. The common household detergent sodium dodecyl sulfate (SDS) induces epithelial barrier dysfunction and eosinophilic inflammation in mice. We hypothesized that acute SDS exposure would compromise the esophageal mucosal barrier in humans. Methods Healthy adults brushed with 2 g of an SDS‐containing toothpaste. Esophageal impedance was measured continuously pre‐/post‐toothbrushing to assess the effect of toothpaste on epithelial barrier function. SDS was measured in saliva using a methylene blue anionic substances assay. Participants completed 1‐h esophageal string tests (ESTs) pre‐/post‐toothbrushing and protein isolates from EST eluates from the proximal and distal esophagus were analyzed by tandem mass tag mass spectrometry. Results Ten of twelve subjects completed the clinical study. SDS in the initial expectorate measured immediately after toothbrushing varied markedly (median: 321.40 μg/mL; range: 169.90–1243.00 μg/mL) and was detectable in saliva in 80% of subjects (median: 9.55 μg/mL; range: 0–123.40 μg/mL) at 60 min post toothbrushing. Esophageal mucosal impedance decreased within 30 min of toothbrushing ( p < 0.01). Toothbrushing increased salivary viscosity and proteins associated with mucosal defense in EST eluates. The tight junction pathway was downregulated while the salivary secretion and complement and coagulation cascades pathways were upregulated in the proximal esophagus. Conclusion In healthy individuals, SDS remained detectable in saliva for a prolonged period after toothbrushing at concentrations previously shown to disrupt esophageal epithelial barrier function in vitro. Toothbrushing with an SDS‐containing toothpaste was associated with reduced esophageal mucosal impedance, altered salivary properties, and activated mucosal immune responses.

Abstract Unvetted scientific claims about vaccines can spread rapidly and undermine decades of progress in immunization and public trust. A recent non-peer-reviewed analysis, promoted at political hearings, in the documentary “An Inconvenient Study,” and on social media, has been used to suggest that vaccinated children experience higher rates of chronic illness than unvaccinated peers. Despite standard regression models, critical flaws - uncontrolled confounding, exposure misclassification, unequal follow-up, and outcome multiplicity, invalidate causal inference. An independent group of international experts critically appraises this analysis and contrast its claims with the consistent evidence confirming vaccine safety and effectiveness. We also show how poorly designed studies can distort public discourse, amplify misinformation, and fuel vaccine hesitancy. We outline actions to strengthen research integrity, such as transparent data sharing, labeling of non-peer-reviewed content, and evidence-based communication. Safeguarding public health demands that vaccine evidence be methodologically sound, reviewed, and interpreted by qualified experts.

ABSTRACT Collection of hematopoietic progenitor cells and mononuclear cells by leukocytapheresis is a critical step of procuring cellular starting materials for future therapeutic use. Leukocytapheresis requires use of anticoagulant to prevent blood clotting in the extracorporeal circuit during collection. A commonly used anticoagulant is Acid Citrate Dextrose Solution A (ACD‐A). ACD‐A primarily prevents blood clotting by reversibly chelating free ionized calcium, which is essential for the clotting cascade. Electrolytes frequently affected by ACD‐A include calcium, magnesium, potassium, phosphate, and bicarbonate. Risks for development of electrolyte derangements include procedure‐related parameters as well as patient comorbidities. Symptoms range from mild paresthesias to life‐threatening cardiac arrhythmias. Recognition of related signs and symptoms is important for prompt intervention with procedure modification and electrolyte replacement to optimize patient safety. This paper will provide an enhanced understanding of the underlying pathophysiology and assist in timely identification and management of electrolyte abnormalities associated with cellular therapy collections.

Renal dysfunction is highly prevalent among patients with cirrhosis and has major implications for management, prognostication, and liver transplant decision-making. Both acute kidney injury (AKI) and chronic kidney disease (CKD) occur frequently in this population and are driven by a complex interplay of hemodynamic derangements, systemic inflammation, and intrinsic or functional renal injury. Accurate assessment of kidney function is essential, as serum creatinine and estimated glomerular filtration rate (eGFR) calculations directly influence MELD-based transplant allocation, eligibility for simultaneous liver–kidney transplantation (SLKT), and clinical decisions such as drug dosing and peri-transplant immunosuppression strategies. However, creatinine-based assessments are fundamentally limited in cirrhosis due to reduced creatinine production, sarcopenia, expanded volume of distribution, increased tubular secretion, and assay interference from hyperbilirubinemia, resulting in frequent overestimation of true GFR. Alternative methods, including cystatin C-based equations, combined creatinine–cystatin C equations, timed urine clearances, and direct GFR measurement using exogenous filtration markers (iohexol, iothalamate), offer potential advantages but also carry important limitations, particularly in decompensated disease with ascites or inflammation. Newer cirrhosis-specific eGFR equations such as the GRAIL and Royal Free Hospital formulas attempt to address these shortcomings, yet validation studies demonstrate inconsistent accuracy across patient cohorts. This review summarizes the pathophysiologic contributors to renal dysfunction in cirrhosis, evaluates the performance and pitfalls of existing kidney function assessment tools, and highlights the ongoing need for reliable, validated methods tailored to this unique population. Until improved approaches are widely accessible, serum creatinine remains the most practical—albeit imperfect—marker guiding clinical decision-making in cirrhotic patients.