Hypophosphorylated pRb knock-in mice exhibit hallmarks of aging and vitamin C-preventable diabetes.

Despite extensive analysis of pRB phosphorylation in vitro, how this modification influences development and homeostasis in vivo is unclear. Here, we show that homozygous Rb∆K4 and Rb∆K7 knock-in mice, in which either four or all seven phosphorylation sites in the C-terminal region of pRb, respectively, have been abolished by Ser/Thr-to-Ala substitutions, undergo normal embryogenesis and early development, notwithstanding suppressed phosphorylation of additional upstream sites. Whereas Rb∆K4 mice exhibit telomere attrition but no other abnormalities, Rb∆K7 mice are smaller and display additional hallmarks of premature aging including infertility, kyphosis, and diabetes, indicating an accumulative effect of blocking pRb phosphorylation. Diabetes in Rb∆K7 mice is insulin-sensitive and associated with failure of quiescent pancreatic ß-cells to re-enter the cell cycle in response to mitogens, resulting in induction of DNA damage response (DDR), senescence-associated secretory phenotype (SASP), and reduced pancreatic islet mass and circulating insulin level. Pre-treatment with the epigenetic regulator vitamin C reduces DDR, increases cell cycle re-entry, improves islet morphology, and attenuates diabetes. These results have direct implications for cell cycle regulation, CDK-inhibitor therapeutics, diabetes, and longevity.

A temporal in vivo catalog of chromatin accessibility and expression profiles in pineoblastoma reveals a prevalent role for repressor elements.

Pediatric pineoblastomas (PBs) are rare and aggressive tumors of grade IV histology. Although some oncogenic drivers are characterized, including germline mutations in RB1 and DICER1, the role of epigenetic deregulation and cis-regulatory regions in PB pathogenesis and progression is largely unknown. Here, we generated genome-wide gene expression, chromatin accessibility, and H3K27ac profiles covering key time points of PB initiation and progression from pineal tissues of a mouse model of CCND1-driven PB. We identified PB-specific enhancers and super-enhancers, and found that in some cases, the accessible genome dynamics precede transcriptomic changes, a characteristic that is underexplored in tumor progression. During progression of PB, newly acquired open chromatin regions lacking H3K27ac signal become enriched for repressive state elements and harbor motifs of repressor transcription factors like HINFP, GLI2, and YY1. Copy number variant analysis identified deletion events specific to the tumorigenic stage, affecting, among others, the histone gene cluster and Gas1, the growth arrest specific gene. Gene set enrichment analysis and gene expression signatures positioned the model used here close to human PB samples, showing the potential of our findings for exploring new avenues in PB management and therapy. Overall, this study reports the first temporal and in vivo cis-regulatory, expression, and accessibility maps in PB.

Prediction of American Society of Anesthesiologists Physical Status Classification from preoperative clinical text narratives using natural language processing.

BACKGROUND: Electronic health records (EHR) contain large volumes of unstructured free-form text notes that richly describe a patient's health and medical comorbidities. It is unclear if perioperative risk stratification can be performed directly from these notes without manual data extraction. We conduct a feasibility study using natural language processing (NLP) to predict the American Society of Anesthesiologists Physical Status Classification (ASA-PS) as a surrogate measure for perioperative risk. We explore prediction performance using four different model types and compare the use of different note sections versus the whole note. We use Shapley values to explain model predictions and analyze disagreement between model and human anesthesiologist predictions. METHODS: Single-center retrospective cohort analysis of EHR notes from patients undergoing procedures with anesthesia care spanning all procedural specialties during a 5 year period who were not assigned ASA VI and also had a preoperative evaluation note filed within 90 days prior to the procedure. NLP models were trained for each combination of 4 models and 8 text snippets from notes. Model performance was compared using area under the receiver operating characteristic curve (AUROC) and area under the precision recall curve (AUPRC). Shapley values were used to explain model predictions. Error analysis and model explanation using Shapley values was conducted for the best performing model. RESULTS: Final dataset includes 38,566 patients undergoing 61,503 procedures with anesthesia care. Prevalence of ASA-PS was 8.81% for ASA I, 31.4% for ASA II, 43.25% for ASA III, and 16.54% for ASA IV-V. The best performing models were the BioClinicalBERT model on the truncated note task (macro-average AUROC 0.845) and the fastText model on the full note task (macro-average AUROC 0.865). Shapley values reveal human-interpretable model predictions. Error analysis reveals that some original ASA-PS assignments may be incorrect and the model is making a reasonable prediction in these cases. CONCLUSIONS: Text classification models can accurately predict a patient's illness severity using only free-form text descriptions of patients without any manual data extraction. They can be an additional patient safety tool in the perioperative setting and reduce manual chart review for medical billing. Shapley feature attributions produce explanations that logically support model predictions and are understandable to clinicians.

Massive splenic cyst in pregnancy: case report.

BACKGROUND: Primary splenic cysts are very rarely diagnosed in pregnancy, with only thirteen cases described in the literature. We examine the approach towards diagnosing and managing uniquely large abdominal masses that significantly complicate obstetric care. CASE PRESENTATION: A 37-year-old primigravida woman presented with abdominal distension and discomfort, yet otherwise asymptomatic. On ultrasound, an incidental pregnancy at 25 weeks of gestation and a large pelvic lesion were discovered. MRI defined a 28 × 29 cm lobulated, complex cystic mass in the upper abdomen. The patient underwent two ascitic drainages throughout her pregnancy. At 34 weeks of gestation, she had a classical caesarean section. Then at five-weeks postpartum, she underwent a laparotomy and total splenectomy with 16 L of fluid drained. Histopathological analysis revealed an epithelial cyst of the spleen. Her recovery was complicated by complete portal vein thrombosis. CONCLUSION: This case describes the largest splenic cyst ever reported in pregnancy and explores the diagnostic dilemmas and treatment challenges associated. We introduce the utility of serial ascitic drainages in prolonging the pregnancy and emphasise the reliance on imaging for surveillance of splenic size and fetal wellbeing.

Obstetric outcomes in major vs minor placenta praevia: A retrospective cohort study.

BACKGROUND: Placenta praevia (PP) is a rare obstetric condition associated with significant maternal and perinatal morbidity. Traditionally, the degree of PP has been classified into minor and major; however, there are very few robust studies that compare the maternal outcomes of these types of PP. AIMS: To identify any significant differences in obstetric outcomes between major and minor PP, including antepartum, intraoperative and postpartum complications. MATERIALS AND METHODS: A retrospective cohort study was conducted at the Royal Brisbane & Women's Hospital between 2009 and 2018; all women were diagnosed with PP. RESULTS: Of the total of 368 women recruited, over half of the participants were diagnosed with major PP (57%), while the remaining had minor PP. Women with major PP, compared to women with minor PP, had an increased risk of antepartum haemorrhage (odds ratio (OR) 2.77, P < 0.001), delivery at an earlier gestational age (36.1 vs 37.4 weeks), general anaesthesia (OR 3.25, P < 0.001), greater proportion of emergency lower segment (51% vs 40%) and classical caesarean (7.7% vs 3.8%), increased number of uterotonics (incidence rate ratio (IRR) 1.17, P < 0.031), greater blood loss (IRR 1.32, P < 0.001) and higher frequency of blood transfusion (IRR 2.00, P < 0.027), and longer postpartum hospital stay (IRR 1.26, P < 0.001). Hysterectomy was performed for three women with major PP, compared to one with minor PP. CONCLUSIONS: The degree of PP significantly impacts obstetric outcomes, with major PP associated with worse maternal morbidity antenatally, intraoperatively and postpartum. Therefore, to optimise patient care, this study emphasises the importance of identifying and distinguishing between different types of PP.

Compliance monitoring via a Bluetooth-enabled retainer: A prospective clinical pilot study.

OBJECTIVES: To conduct a prospective pilot trial to test the clinical efficacy and accuracy of a newly developed Bluetooth-enabled retainer, which was synchronized with an iOS mobile application, cloud database and provider webpage. SETTING AND SAMPLE POPULATION: Five orthodontic residents in a university setting. MATERIAL AND METHODS: At the delivery of the retainers (T0), each participant was given an Bluetooth-enabled retainer, logbook and iPod Touch installed with the mobile application. Participants were instructed to wear the retainer for 12 hours per day and record in the logbook each time the retainer was inserted or removed and trained to synchronize the device daily to the mobile application. After the 5-day study period (T1), statistical analysis was performed comparing the device-reported data to the logbook data using two calculation methods. RESULTS: From T0 - T1, the participants wore their retainers for a median of 11.55 hours per day and the median difference between the self-reported (logbook) data and the device data was 35 minutes or 5.1% over the 5-day study period. Using an adjusted method to calculate the device-reported wear time, the median error was 13 minutes or 1.9%. CONCLUSION: Subjects were able to successfully wear the retainer and upload the data to the mobile application and cloud database. Patient compliance and technical issues could be monitored daily via the provider webpage, and early intervention was possible with reminder messaging. The Bluetooth-enabled retainer showed a clinically acceptable level of accuracy and usability that validates it for future clinical testing.

Novel racemosin B derivatives as new therapeutic agents for aggressive breast cancer.

Carbazole derivatives show anti-cancer activity and are of great interest for drug development. In this study, we synthesized and analyzed several new alkylamide derivatives of racemocin B, a natural indolo[3,2-a]carbazole molecule originally isolated from the green alga Caulerpa racemose. Several alkylamide derivatives were found to exhibit moderate to strong growth inhibition against human breast cancer cell lines. They induced G2/M cell cycle arrest and apoptosis in the aggressive triple-negative breast cancer cell line MDA-MB-231. Among these derivatives, compound 25 with the lowest IC50 induced cell death by suppressing autophagy. This was accompanied by inhibition of autophagic flux and accumulation of autophagy protein 1 light chain 3, LC3II, and p62. The novel alkylamide derivative offers a potential new treatment for human breast cancer.

Comparison of Adherence to the 2013 ACC/AHA Cholesterol Guideline in a Teaching Versus Nonteaching Outpatient Clinic.

BACKGROUND: Little information is available regarding prescribers' adherence rate to the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol guideline, especially that from a teaching versus a nonteaching setting. OBJECTIVES: We aim to evaluate adherence rates to the 2013 ACC/AHA cholesterol guideline in a teaching versus a nonteaching practice site. In addition, the impact of a pharmacist-led seminar on adherence rate to the guideline was assessed. METHODS: This study is a 2-part retrospective chart review. Part 1 consists of patients who were initiated on statin therapy between December 2013 and November 2014. Patients were analyzed to determine if they received concordant statin therapy as recommended by the guideline. For the second part, we evaluated the impact of a seminar on the adherence rate to the guideline. RESULTS: Of the 325 patients who received a statin prescription, 233 were included in the study. Prescriber adherence to the guideline was 42.9%, which was significantly lower than the 65.8% observed in a study previously conducted at a teaching outpatient clinic ( P < 0.0001). For the second part of our study, prescriber adherence to the guideline 3 months before the pharmacist-led seminar was 53.5%, and this adherence rate remained virtually unchanged at 54.2% at 3 months after the educational session. CONCLUSION: The overall adherence rate to the 2013 ACC/AHA cholesterol guideline from this nonteaching outpatient clinic was significantly lower than that previously observed in a teaching outpatient clinic. The single pharmacist-led seminar did not significantly affect prescribers' adherence rate to the guideline.

Customized order-entry sets can prevent antiretroviral prescribing errors: a novel opportunity for antimicrobial stewardship.

BACKGROUND: Patients with human immunodeficiency virus (HIV) infection on antiretroviral (ARV) therapy are at increased risk for medication errors during transitions of care between the outpatient and inpatient settings. This can lead to treatment failure or toxicity. Previous studies have emphasized the prevalence of medication errors in such patients, but few have reported initiatives to prevent errors from occurring. METHODS: The study was conducted in a 1,400-bed health care center with a state-designated Acquired Immunodeficiency Syndrome (AIDS) Center in the Bronx, New York. The antimicrobial stewardship team and HIV specialists developed customized order-entry sets (COES) to guide ARV prescribing and retrospectively reviewed their effect on error rates of initial ARV orders for inpatients before reconciliation. Patient records were reviewed in six-month periods before and after intervention. The student's t-test or Mann-Whitney U test was used to compare continuous variables; chi-square or Fisher's exact test was used for categorical variables. RESULTS: A total of 723 and 661 admissions were included in the pre-intervention and post-intervention periods, respectively. Overall, error rates decreased by 35% (38.0% to 24.8%, P < 0.01) with COES. Wrong doses and drug interactions decreased by more than 40% (P < 0.005). Error reductions were observed in protease inhibitor (PI)-based (43.6% versus 28.7%, P < 0.01) and non-PI-based (38.0% versus 24.4%, P = 0.02) regimens with COES. A shift in predominant drug-class errors was observed as there was a trend toward increased usage of non-PI regimens post-intervention. Admission in the pre-intervention period (adjusted odds ratio [AOR], 1.79; 95% confidence interval [CI], 1.39-2.31) and use of PI-based regimens (AOR, 2.03; 95% CI, 1.53-2.70) remained significantly associated with ARV prescribing errors after controlling for confounding factors. CONCLUSION: Detailed COES improved ARV prescribing habits, reduced the potential for prescribing incorrect regimens, and can prove useful and cost-effective where HIV-specific medication reconciliation is unavailable.

Pre-Clinical Studies of a Novel Bispecific Fusion Protein Targeting C3b and VEGF in Neovascular and Nonexudative AMD Models.

INTRODUCTION: KNP-301 is a bi-specific fragment crystallizable region (Fc) fusion protein, which inhibits both C3b and vascular endothelial growth factor (VEGF) simultaneously for patients with late-stage age-related macular degeneration (AMD). The present study evaluated in vitro potency, in vivo efficacy, intravitreal pharmacokinetics (IVT PK), and injectability of KNP-301. METHODS: C3b and VEGF binding of KNP-301 were assessed by surface plasmon resonance (SPR) and enzyme-linked immunosorbent assay (ELISA), and cellular bioassays. A laser-induced choroidal neovascularization (CNV) model and a sodium iodate-induced nonexudative AMD model were used to test the in vivo efficacy of mouse surrogate of KNP-301. Utilizing fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT) scans, the reduction in disease lesions were analyzed in a CNV mouse model. In the nonexudative AMD mouse model, outer nuclear layer (ONL) was assessed by immunofluorescence staining. Lastly, intravitreal pharmacokinetic study was conducted with New Zealand white rabbits via IVT administration of KNP-301 and injectability of KNP-301 was examined by a viscosity test at high concentrations. RESULTS: KNP-301 bound C3b selectively, which resulted in a blockade of the alternative pathway, not the classical pathway. KNP-301 also acted as a VEGF trap, impeding VEGF-mediate signaling. Our dual-blockade strategy was effective in both neovascular and nonexudative AMD models. Moreover, KNP-301 had an advantage of potentially less frequent dosing due to the long half-life in the intravitreal chamber. Our viscosity assessment confirmed that KNP-301 meets the criteria of the IVT injection. CONCLUSIONS: Unlike current therapies, KNP-301 is expected to cover patients with late-stage AMD of both neovascular and nonexudative AMD, and its long-term PK profile at the intravitreal chamber would allow convenience in the dosing interval of patients.

Large Language Model Capabilities in Perioperative Risk Prediction and Prognostication.

Importance: General-domain large language models may be able to perform risk stratification and predict postoperative outcome measures using a description of the procedure and a patient's electronic health record notes. Objective: To examine predictive performance on 8 different tasks: prediction of American Society of Anesthesiologists Physical Status (ASA-PS), hospital admission, intensive care unit (ICU) admission, unplanned admission, hospital mortality, postanesthesia care unit (PACU) phase 1 duration, hospital duration, and ICU duration. Design, Setting, and Participants: This prognostic study included task-specific datasets constructed from 2 years of retrospective electronic health records data collected during routine clinical care. Case and note data were formatted into prompts and given to the large language model GPT-4 Turbo (OpenAI) to generate a prediction and explanation. The setting included a quaternary care center comprising 3 academic hospitals and affiliated clinics in a single metropolitan area. Patients who had a surgery or procedure with anesthesia and at least 1 clinician-written note filed in the electronic health record before surgery were included in the study. Data were analyzed from November to December 2023. Exposures: Compared original notes, note summaries, few-shot prompting, and chain-of-thought prompting strategies. Main Outcomes and Measures: F1 score for binary and categorical outcomes. Mean absolute error for numerical duration outcomes. Results: Study results were measured on task-specific datasets, each with 1000 cases with the exception of unplanned admission, which had 949 cases, and hospital mortality, which had 576 cases. The best results for each task included an F1 score of 0.50 (95% CI, 0.47-0.53) for ASA-PS, 0.64 (95% CI, 0.61-0.67) for hospital admission, 0.81 (95% CI, 0.78-0.83) for ICU admission, 0.61 (95% CI, 0.58-0.64) for unplanned admission, and 0.86 (95% CI, 0.83-0.89) for hospital mortality prediction. Performance on duration prediction tasks was universally poor across all prompt strategies for which the large language model achieved a mean absolute error of 49 minutes (95% CI, 46-51 minutes) for PACU phase 1 duration, 4.5 days (95% CI, 4.2-5.0 days) for hospital duration, and 1.1 days (95% CI, 0.9-1.3 days) for ICU duration prediction. Conclusions and Relevance: Current general-domain large language models may assist clinicians in perioperative risk stratification on classification tasks but are inadequate for numerical duration predictions. Their ability to produce high-quality natural language explanations for the predictions may make them useful tools in clinical workflows and may be complementary to traditional risk prediction models.

Comprehensive overview of the anesthesiology research landscape: A machine Learning Analysis of 737 NIH-funded anesthesiology primary Investigator's publication trends.

Background: Anesthesiology plays a crucial role in perioperative care, critical care, and pain management, impacting patient experiences and clinical outcomes. However, our understanding of the anesthesiology research landscape is limited. Accordingly, we initiated a data-driven analysis through topic modeling to uncover research trends, enabling informed decision-making and fostering progress within the field. Methods: The easyPubMed R package was used to collect 32,300 PubMed abstracts spanning from 2000 to 2022. These abstracts were authored by 737 Anesthesiology Principal Investigators (PIs) who were recipients of National Institute of Health (NIH) funding from 2010 to 2022. Abstracts were preprocessed, vectorized, and analyzed with the state-of-the-art BERTopic algorithm to identify pillar topics and trending subtopics within anesthesiology research. Temporal trends were assessed using the Mann-Kendall test. Results: The publishing journals with most abstracts in this dataset were Anesthesia & Analgesia 1133, Anesthesiology 992, and Pain 671. Eight pillar topics were identified and categorized as basic or clinical sciences based on a hierarchical clustering analysis. Amongst the pillar topics, "Cells & Proteomics" had both the highest annual and total number of abstracts. Interestingly, there was an overall upward trend for all topics spanning the years 2000-2022. However, when focusing on the period from 2015 to 2022, topics "Cells & Proteomics" and "Pulmonology" exhibit a downward trajectory. Additionally, various subtopics were identified, with notable increasing trends in "Aneurysms", "Covid 19 Pandemic", and "Artificial intelligence & Machine Learning". Conclusion: Our work offers a comprehensive analysis of the anesthesiology research landscape by providing insights into pillar topics, and trending subtopics. These findings contribute to a better understanding of anesthesiology research and can guide future directions.

Single-cell peripheral immunoprofiling of lewy body and Parkinson's disease in a multi-site cohort.

BACKGROUND: Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson's Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans. METHODS: In a case-control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer's disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating. RESULTS: The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes. CONCLUSIONS AND RELEVANCE: Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease.

Thinking (Metastasis) outside the (Primary Tumor) Box.

The metastasis of tumor cells into vital organs is a major cause of death from diverse types of malignancies [...].

Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer.

Metastatic breast-cancer is a major cause of death in women worldwide, yet the relationship between oncogenic drivers that promote metastatic versus primary cancer is still contentious. To elucidate this relationship in treatment-naive animals, we hereby describe mammary-specific transposon-mutagenesis screens in female mice together with loss-of-function Rb, which is frequently inactivated in breast-cancer. We report gene-centric common insertion-sites (gCIS) that are enriched in primary-tumors, in metastases or shared by both compartments. Shared-gCIS comprise a major MET-RAS network, whereas metastasis-gCIS form three additional hubs: Rho-signaling, Ubiquitination and RNA-processing. Pathway analysis of four clinical cohorts with paired primary-tumors and metastases reveals similar organization in human breast-cancer with subtype-specific shared-drivers (e.g. RB1-loss, TP53-loss, high MET, RAS, ER), primary-enriched (EGFR, TGFß and STAT3) and metastasis-enriched (RHO, PI3K) oncogenic signaling. Inhibitors of RB1-deficiency or MET plus RHO-signaling cooperate to block cell migration and drive tumor cell-death. Thus, targeting shared- and metastasis- but not primary-enriched derivers offers a rational avenue to prevent metastatic breast-cancer.

Transcriptional profiling of mouse projection neurons with VECTORseq.

Existing techniques for transcriptional profiling of projection neurons could be applied to only one neuronal population per experiment. To increase throughput, we developed VECTORseq, which repurposes retrogradely infecting viruses to deliver multiplexable RNA barcodes, enabling projection anatomy to be read out in single-cell datasets. In this protocol, we describe the delivery of viral barcodes to mouse brain to label different projection neurons. We then detail single-cell or nuclei isolation for sequencing, followed by the analysis of single-cell sequencing data. For complete details on the use and execution of this protocol, please refer to Cheung et al. (2021).

A racemosin B derivative, C25, suppresses breast cancer growth via lysosomal membrane permeabilization and inhibition of autophagic flux.

Breast cancer is the most common malignancy among women worldwide. As conventional therapies are only partially successful in eradicating breast cancer, the development of novel strategies is a top priority. We previously showed that C25, a new racemosin B derivative, exerts its anti-cancer activity through inhibition of autophagy, but the underlying mechanism remained unknown. Here we show that C25 inhibits the growth of diverse breast cancer cell subtypes and effectively suppresses tumor progression in a xenotransplantation model of triple negative breast cancer. C25 acts as a lysosomotropic agent to induce lysosomal membrane permeabilization and inhibit autophagic flux, resulting in cathepsin release and cell death. In accordance, RNA sequencing and gene set enrichment analysis revealed that C25 induces pathways consistent with autophagy inhibition, cell cycle arrest and senescence. Interestingly, knockdown of TFEB or SQSTM1 reduced cell death induced by C25 treatment. Finally, we show that C25 synergizes with the chemo-therapeutics etoposide and paclitaxel to further limit breast cancer cell growth. Thus, C25 alone or in combination with other anti-neoplastic agents offers a novel therapeutic strategy for aggressive forms of breast cancer and possibly other malignancies.

Improving antibiotic prescribing for acute bronchitis in the ambulatory setting using a multifaceted approach.

Antibiotics are frequently prescribed inappropriately for acute respiratory infections in the outpatient setting. We report the implementation of a multifaceted outpatient antimicrobial stewardship initiative resulting in a 12.3% absolute reduction of antibiotic prescribing for acute bronchitis in primary care clinics receiving active interventions.

Case Report: Radiographic Identification of Intrapleural Misplacement of Epidural Catheter in an Intubated Post-Lung Transplant Patient.

Intrapleural misplacement of epidural catheter is a rare complication of thoracic epidural placement, which can be difficult to detect in intubated patients with unreliable pain reports and hemodynamic response to the test dose. We describe a case of intrapleural misplacement of thoracic epidural in a 50-year-old man status-post bilateral lung transplant and highlight the use of radiographic techniques to identify the misplacement.