The opioid epidemic has adversely affected neonates and children; but the scope and mechanisms of these affects are not well understood. Failure to understand the impact of prenatal opioid exposure on long term adverse health outcomes could lead to gaps in care for this population. The purpose of this study is to investigate the association of prenatal opioid exposure with the development of adverse respiratory health outcomes, both acute and chronic. We propose that prenatal exposure leads to increased odds of development of childhood asthma, respiratory distress, apnea, and bronchiolitis. This is a retrospective cohort study using the PearlDiver Mariner database and a simple match design. Records from preterm and full-term infants exposed to opioids in utero are analyzed separately for the development of adverse health outcomes. Our preliminary results indicate that opioid exposure in utero results in preterm birth. In full-term infant births, opioid exposure leads to increased odds for developing respiratory distress (OR = 7.54), bronchiolitis (OR = 4.12) and apnea (OR = 1.58). Lastly, diagnoses for adverse respiratory outcomes were earlier in full-term opioid exposed infants than in their unexposed controls. The significance of this study is that it will encourage closer monitoring of full-term infants who are exposed to opioids in utero for specific respiratory outcomes and provide conceptual grounding for future mechanistic studies.



Prenatal opioid exposure impacts respiratory outcomes within the first 5 years of life

Background
The Revised IDEA (R-IDEA) assessment tool, a validated instrument iterating on the IDEA tool developed by Baker et al., allows for residency programs to provide dependable feedback on clinical reasoning skills. It evaluates clinical documentation on admission notes utilizing four categories: interpretive summary, differential diagnosis, explanation of reasoning for lead, and alternative diagnoses. The R-IDEA tool provides more detailed anchors in each domain than the original, and a composite score of 6 or more (out of 10) signifies high-quality clinical reasoning. This study evaluates the pre- and post-intervention degrees of satisfaction, self-confidence, and ease of use of the R-IDEA tool among residents and interns during inpatient clinical rotations. Additionally, it assesses the degree of improvement in interns' clinical reasoning scores. By measuring these factors, the study aims to determine the tool’s effectiveness in enhancing clinical reasoning skills and the feedback process within an academic medical setting.
Methods
A single-blinded prospective cohort study with simple randomization was conducted at the ProMedica Toledo Hospital across five inpatient services (four general medicine and one ICU) over three months. The admission notes of 20 interns were evaluated by trained senior residents using the R-IDEA tool at the onset of the month-long rotation, followed by standardized feedback to the interns within the first week. A second evaluation using the R- IDEA tool at the end of the month gauged the interns' clinical reasoning improvement. A blinded faculty member reviewed residents' scoring for consistency. Satisfaction and confidence levels in delivering feedback with the R-IDEA tool were measured through pre- and post-intervention surveys of 17 senior residents and 16 interns.
Results
Using regression models for ordinal data, the R-IDEA scoring of 40 intern admission notes showed a significant increase (p<0.001) in the composite score from an average of 5 to 9, suggesting an improvement in the quality of clinical reasoning.
Using a Likert scale, results from the intern pre- and post-R-IDEA tool survey showed significant improvement (p<0.001) in median scores for confidence and knowledge in writing interpretive summaries and creating differential diagnoses. Results from the resident surveys showed significant improvement (p<0.001) in median scores for confidence in the assessment, evaluation, and feedback process.
Conclusion
These findings underscore the significant enhancement in intern clinical reasoning with the R- IDEA tool. Moreover, it bolsters residents' confidence in their feedback methods. This tool can be integrated into Internal Medicine residency programs as a structured tool to augment interns' clinical reasoning effectively.

Impact of R-IDEA Tool on Interns' Clinical Reasoning and Satisfaction During Medicine Rotation

INTRODUCTION: 
Post traumatic and chronic osteoarthritis (OA) share the underlying feature of damaged hyaline cartilage and exposure of type-II collagen (CII) in the damaged tissue due to erosive proteolytic degradation triggered by low grade ongoing inflammation. Adipose tissue derived mesenchymal stem cells (ADSC) have shown efficacy in the treatment of osteoarthritis through their ability to mitigate the host inflammatory response through paracrine signaling and possess capability for chondrogenic differentiation. However in vivo, very few ADSC bind to the damaged cartilage or differentiate in the OA lesion. Our study offers a solution to these obstacles through the creation of injectable type I collagen (Col I) microspheres loaded with ADSC and linked to an E4D4 IgG monoclonal antibody that specifically targets the type II collagen (MabCII) unmasked in osteoarthritic hyaline cartilage. Upon binding to damaged cartilage, the ADSC carried by the microsphere rapidly migrate onto the damaged cartilage surface. We propose that MabCII linked to Col I microspheres can serve as an intraarticular carrier for transport and targeting large numbers of ADSC to osteoarthritic tissue while promoting chondrogenic differentiation.

METHODS: 
Isolation and culture of ADSC: The ADSC were isolated from subcutaneous fat tissue of 3-4 months old pigs as described previously (1). All animal protocols and experimental procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Tennessee Health Science Center. The adipose tissue was digested with 200 μg/mL collagenase II solution (Sigma) to yield ADSC that were cultured in Dulbecco's Modified Eagle Medium-High Glucose (DMEM-HG) (Gibco) supplemented with fetal bovine calf serum (FBS) and antibiotics at 37°C and 5% CO2. The ADSC were characterized by flow cytometry and for multigenic differentiation before experimental use. 

Preparation of MabCII targeted Col I scaffold: 
Lyophilized purified native Col I from fetal calf skin was the gift of Dr. David Brand, Memphis VA Medical Center. The E4D4 IgG monoclonal antibody was isolated and characterized as described previously (2). The experimental group of MabCII targeted scaffolds were constructed using a two-step EDC/NHS crosslinking reaction (ThermoFischer) that bound hydroxyl groups on Col I to primary amine groups on MabCII in a 2:3 molar ratio. The efficiency of conjugation of MabCII conjugation on the Col I scaffold was measured by protein assay of the supernatant after pelleting the collagen by centrifugation at 1000g’s for 10 minutes. Cellular scaffolds were assembled in a solution of DMEM-HG + FBS using 4mg/ml homogenized MabCII-Col I and 16 million cells/ml ADSC. 

Experimental group and analysis: 
5ul droplets of the cells (80,000 cells) in a 4 mg/ml collagen suspension were plated on a non-tissue culture petri dish to form microsphere pellets and then cultured in DMEM-HG supplemented with FBS and antibiotics at 37°C and 5% CO2 for three days. At this time point, microsphere pellets were either collected for experimentation, or left on tissue culture plate and imaged under light microscopy after 4, 6, and 12 days (Figure 1). Control groups were established using pelleted ADSC (80,000 cells/ 5 microliters) without any Col I and ADSC integrated in a Col I scaffold without linked MabCII similarly cultured. To test the migration of ADSC from the scaffold onto damaged cartilage tissue, ADSC were stained with a fluorescent dye (Vivotrack680, PerkinElmer) before pellet formation. A 5ul MabCII linked scaffolded pellet was subsequently placed on to a 5 mm trypsinized cartilage explant and imaged after 6 days using a Keyence BZ-X800 microscope with a Cy5.5 filter (NIKON). To demonstrate targeting efficiency of our MabCII linked scaffolds, microspheres of fluorescent ADSC, pelleted alone or with Col I or MabCII/Col I were suspended in a 2 ml test tube on a rocker table with 5 mm damaged (trypsinized) cartilage explants. IVIS images were obtained at 4 and 24 hours and total fluorescence of ROI was calculated by Living Image 4.2 software. 

RESULTS: 
ADSC integrated in Col I microspheres and cultured demonstrated release from microsphere and growth on tissue culture plate (Figure 1). Additionally, over 6 days in culture, ADSC migrated from their microsphere attached to the cartilage explant and spread on damaged cartilage tissue as seen by the spread of fluorescence outside of the stationary ADSC/MabCII microsphere (Figure 1). This migration was again demonstrated by scanning electron photography of stationary 5ul ADSC + Col I pellets after 4 days of incubation on trypsinized cartilage explants. The images exhibited ADSC viability on day 4 by capturing active cell division on the damaged cartilage (Figure 2). Finally, IVIS imaging of quantified fluorescence showed targeting of only ADSC/Col I/ MabCII microspheres to damaged cartilage at 4 hours, while the explants incubated alone or with ADSC or ADSC/Col I exhibited no florescence at this time point (Figure 3). ADSC/Col I linked MabCII pellets remained fluorescent on damaged cartilage at 24 hours. 

DISCUSSION: 
Adipose tissue derived mesenchymal stem cell regenerative therapy for regrowth of damaged cartilage for osteoarthritis relies on ADSC’s ability to differentiate into chondrocytes on damaged hyaline cartilage tissue. We demonstrate in vitro that the use of a CII targeting MabCII linked to a Col I scaffold induced chondrogenesis of ADSC and increased the specificity and rapidity whereby ADSC can be delivered to osteoarthritic tissue. Our targeted pellets not only bound more rapidly to damaged cartilage, but they also remained attached after 24hrs and migrated onto the damaged cartilage. These results show promise for an in vivo study using our MabCII targeted Col I microspheres as an intra-articular injectable therapeutic treatment for osteoarthritis. 

SIGNIFICANCE: 
The creation of an injectable cellular scaffold with ability to target ADSC to type-II collagen on damaged hyaline cartilage increases the localization of mesenchymal stem cells to an osteoarthritic lesion at early stages. This increases ADSC therapeutic potential as a treatment for OA.

REFERENCES: 
1. Bhatti F, Kim SJ, Yi AK, Hasty K.A., Cho. H. “Cytoprotective Role of Vitamin E in Porcine Adipose-Tissue Derived Mesenchymal Stem Cells against Hydrogen-peroxide Induced Oxidative Stress” Cell and Tissue Research. 2018, 374(1):111-120. (PMID: 29951700). 2. Bedingfield SK, Colazo JM, Yu F, Liu DD, Jackson MA, Himmel LE, Cho H, Crofford LJ, Hasty KA, Duvall CL. Amelioration of post-traumatic osteoarthritis via nanoparticle depots delivering small interfering RNA to damaged cartilage. Nat Biomed Eng. 2021 Sep;5(9):1069-1083. (PMID: 34413494).

Mesenchymal Stem Cell Therapy Targeted to Damaged OA CartilageUsing Type I Collagen Microspheres Linked to Monoclonal Antibody to Type II Collagen

Background
Trauma patients with hemorrhagic shock (HS) accounts for 40% of preventable death. Shock-induced endotheliopathy has garnered interest recently and one aspect of this, endothelial glycocalyx shedding (EGX), has shown to promote coagulopathy following hemorrhage. Ferroptosis is an iron dependent, non-apoptotic form of controlled cell death triggered by the oxidation of membrane phospholipids. Liproxstatin-1 is an inhibitor of this process and can protect against oxidative damage to the endothelial cell membrane and subsequent shedding of glycocalyx. Our goal is to determine if administration of Liproxstatin-1, a ferroptosis inhibitor can reduce glycocalyx shedding in hemorrhaged rats providing evidence of its therapeutic value in the setting of hemorrhagic shock. 

Methods
A rat model of hemorrhagic shock and resuscitation was used to assess glycocalyx disruption in the lungs via fluorescent-labeled wheat germ agglutinin staining in frozen tissue and by syndecan-1 ELISA on plasma samples. A control group (n=5) resuscitated only with Lactated Ringer’s solution, following hemorrhage and resuscitation (H/R) was compared against an experimental group (n=1) that received Liproxstatin-1 following hemorrhage and before resuscitation.

Results
Glycocalyx shedding (assessed by an increase in plasma syndecan-1 levels) was significantly lower in the Liproxstatin-1 treated group compared to control group. Additionally, Liproxstatin-1 treated animals were able to sustain a higher mean arterial pressure (MAP), and oxygen saturation throughout the resuscitation period measured at 15- and 30-minutes following Liproxstatin-1 infusion. 

Conclusion
Ferroptosis inhibitor Liproxstatin-1 can reduce morbidity acutely during hemorrhagic shock and protect endothelial cell membrane from oxidative damage due to its ability to slow the generation of reactive oxygen species (ROS) and lipid hydroperoxides. 

Further experiments will be performed to complete the Liproxstatin-1 experimental group (n=5) as well as a control group using Cyrene (n=5), a DMSO-like solvent used to dissolve Liproxstatin-1 for intravenous administration. Additionally, tissue staining of lung vasculature will be performed to evaluate the glycocalyx disruption in the vascular beds of the lungs in the Cyrene, and Liproxstatin-1 groups as well as a group resuscitated with Lactated Ringers solution (H/R) alone. 


Can Inhibiting Ferroptosis Mitigate Vascular Injury and Subsequent Glycocalyx Shedding in the Setting of Hemorrhagic Shock?

Abstract Title
The Impact of Altered Mental Status on Intensive Care Unit Outcomes: A Retrospective Cohort Study

Background
Altered Mental Status (AMS) ranges from confusion to coma and is frequently encountered in patients admitted to the Intensive Care Unit (ICU). Etiologies include metabolic disturbances, neurological insults, and systemic illnesses. The precise impact of AMS on in-ICU mortality remains an area of ongoing research, necessitating comprehensive evaluation and elucidation. The objective of our study was to identify significant patterns and outcomes associated with the presence of AMS upon initial Emergency Department (ED) presentation to better inform ICU management and enhance patient care.

Methods
A retrospective cohort study was conducted using patient data from the Northwell Health network, focusing on adult ICU admissions between July 1, 2022, and July 1, 2023. The study included 21,900 unique patients. The primary variables were AMS presence and in-ICU mortality, both recorded as binary outcomes. Descriptive statistics were analyzed for patient demographics and clinical characteristics, including gender distribution and racial composition. The association between AMS and in-ICU mortality was tested using a Chi-square test of independence, with statistical significance set at p < 0.05. The impact of AMS on ICU and hospital stays, treatments (steroids and vasopressors), and acute renal failure incidence was further assessed using Chi-square tests with relative risks and 95% confidence intervals calculated.

Results
Patients with AMS experienced longer ICU and hospital stays, averaging 144.3 hours in the ICU and 13.6 days in the hospital compared to 111.3 hours and 10.1 days for those without AMS, respectively. Patients with AMS were more likely to receive steroids, χ2(1, N = 21,900) = 40.0, p < .001, RR = 1.13, 95% CI [1.08, 1.18]. They were also more likely to be on vasopressors, χ2(1, N = 21,900) = 98.2, p < .001, RR = 1.24, 95% CI [1.18, 1.31], and to develop acute renal failure, χ2(1, N = 21,900) = 53.1, p < .001, RR = 1.15, 95% CI [1.10, 1.20]. The Chi-square test demonstrated a significant association between AMS and in-ICU mortality, χ2(1, N = 21,900) = 111, p < .001, RR = 1.13, 95% CI [1.10, 1.17]. 

Conclusion 
AMS presence was significantly associated with longer ICU and hospital length of stay, more frequent need for vasopressors and steroids, a higher occurrence of acute renal failure, and increased in-ICU mortality rates. These findings underline the importance of AMS as a prognostic indicator in ICU settings and stress the need for increased awareness and proactive management of AMS to potentially improve patient outcomes in the ICU.

The Impact of Altered Mental Status on Intensive Care Unit Outcomes: A Retrospective Cohort Study

Background: Total hip and knee arthroplasty (THA and TKA) are two of the most common joint arthroplasties performed in the United States, with the prevalence of these procedures anticipated to continue increasing with the aging population. Therefore, medical education programs must expose students to the pathology, mechanisms of surgical intervention, and variance in implant materials for THA and TKA. One of the purposes of the WMed Skeletal Teaching and Research (STaR) Series is to target this educational goal, however, considering whether the collection is representative of the surrounding population is imperative when training medical providers to care for local communities. As few formal skeletal collections exist within the United States, research pertaining to representation of orthopedic surgeries is arguably nonexistent. The WMed STaR Series aims to target this gap in research, comparing representation of THA and TKA from the series to community statistics.

Methods: Donors from the WMed STaR Series were thoroughly evaluated for the presence of THAs and TKAs, as well as associated musculoskeletal pathology. The type and material of implant, laterality of intervention, donor medical history, and donor demographics were documented. Preliminary data collected from the series was evaluated in comparison to national statistics, and will plan to be compared to analogous data from orthopedic patients seen at the WMed Health clinic.

Results: The American College of Rheumatology cites about 1.2 million TKA and THA procedures in the U.S. annually with approximately 36.3% being THA and 63.7% being TKA. Upon evaluation of the STaR series, there were six THA (83% with a metal femoral head and a polymer socket, and the remaining 17% with a ceramic femoral head and a polymer socket) and seven TKA (all with metal tibial and femoral components and plastic spacers). This results in a relative frequency of 46.2% THA and 53.8% TKA in the WMed STaR Series, showing that while WMed has a similar proportion of THA and TKA to the national statistic, the STaR Series shows slightly higher prevalence of THA. 

Conclusion: The development of the WMed STaR Series will provide educators with a reference for orthopedic implants available for medical education, and will offer a unique perspective for further understanding of musculoskeletal pathology and mechanism for surgical intervention. Medical education resources that reflect the surrounding populations, such as the WMed STaR series, are imperative to prepare medical trainees to deliver comprehensive care to their communities. 


An Examination of Orthopedic Implants in the WMed Skeletal Teaching and Research Series: Presenting a Resource for Medical Education and Research

Varying Cortical Involvement of Periacetabular Metastatic Lesions Affects Bone Strain in the Pelvis 

Background
Metastatic bone disease, common in advanced cancer, significantly impacts survival and quality of life. As cancer survivorship improves, the incidence of skeletal metastases rises. Effective orthopedic constructs are crucial for enhancing patient outcomes. Currently, there is no validated method for biomechanical modeling or optimal surgical treatment of metastatic acetabular defects. Tumors near the acetabulum can weaken the pelvis, but the effect of different defects on fracture risk is unclear. This study aims to develop anatomic models of metastatic pelvic defects to predict fracture risk zones using finite element analysis.

Methods 
A short fiber-filled epoxy artificial bone was laser-scanned to create a 3D hemipelvic model, including cortical and trabecular regions. Lesions were defined by their cortical bone intersection area, based on binary subtraction. An orthopedic surgeon determined average lesion size and location, following the modified Harrington Classification System. Acetabular defect models were converted into finite element models via volumetric meshing. Analysis compared defect models' volumetric size, cortical bone loss, and stress/strain magnitudes. Peak stresses were evaluated at the medial wall, superior acetabular dome, acetabular rim, anterior, and posterior columns. Margin of safety quantified fracture risk, mapping weakened acetabular areas.

Results
Simulated tumors' average length and cortical bone loss were 6.3 cm and 5.5 cm3, respectively. The hemipelvis with the anterior column defect had the lowest margin of safety and highest change in peak stress compared to no defect. The anterior defect and the anterior defect involving the medial wall had similar margin of safety results.

Conclusion
Anterior column and anterior column with medial wall defects were more severe than defects involving posterior & medial wall of the hemipelvis, posing greater fracture risks than posterior and medial wall defects. This study enhances our understanding of fracture risk in metastatic pelvic lesions, guiding surgical decision-making and improving patient care by decreasing unnecessary procedures.


Varying Cortical Involvement of Periacetabular Metastatic Lesions Affects 
Bone Strain in the Pelvis

Abstract Title
Analyzing Recruitment Methods to Increase Diversity in Biobank Collections

Background
Biospecimen collection has played an integral role in research by storing valuable data and tissue samples from both patients with diseases, such as cancer and HIV, as well as healthy control specimens for comparison. The results of these studies shed light on the pathogenic processes of diseases, provide risk stratification, validate new diagnostic tools, and develop targeted pharmacotherapies. Including diverse samples from various races, ethnicities, and backgrounds is essential to increase the generalizability of the results of these studies. Traditional university research participants are typically recruited from the student body and surrounding area, which may not accurately represent the demographics of the local population. Our objective was to create a tissue bank from healthy individual blood samples that is representative of the San Antonio, Texas population for use in future research and analyze traditional university research recruitment methods.

Methods
Traditional methods of university recruitment at UT Health San Antonio using campus fliers, posters, emails, and class announcements were implemented. 311 individuals were screened and a total of 101 participants were enrolled. Participants self-reported a medical history without significant health conditions and provided basic demographic information. Tissue samples were acquired from blood draws and then allocated for storage in the repository. Participant demographic data was compared to the 2020 U.S. Census San Antonio population using the chi-squared test. 

Results
There was a statistically significant difference (p < 0.05) from the expected San Antonio demographics and the recruited participants of racial groups (“White/Caucasian”, “Black or African American”, “Asian”, “Native Hawaiian and Other Pacific Islander”, and “Other”) and ethnic groups (“Hispanic/Latino” and “Not Hispanic or Latino”) except for “American Indian/Alaskan Native” (Expected: 2, Actual 2). There was an overrepresentation of participants who identified as “White/Caucasian” (Expected: 61, Enrolled: 78), “Asian” (Expected: 5, Enrolled: 14), and “Not Hispanic or Latino” (Expected: 37, Enrolled: 58). There was an underrepresentation of those who identified as “Black or African American” (Expected: 10, Enrolled: 3) and “Hispanic/Latino” (Expected: 64, Actual 42). Most participants reported “White/Caucasian” (83%).

Conclusion
Advertising research opportunities in universities is an effective way of increasing enrollment at the cost of diversity. The consequences of utilizing tissue samples from a limited demographic could have significant impacts for minorities. To increase the recruitment of the underrepresented, researchers suggest the use of social media, radio advertisements, health fairs, flea markets, churches, community centers, and translated fliers.


Analyzing Recruitment Methods to Increase Diversity in Biobank Collections

Background
Malaria is a parasitic infection transmitted by the Anopheles mosquito, with Plasmodium falciparum being the most severe species. Initial symptoms include fever, headaches, and nausea, often leading to a robust immune response. Diagnostic challenges arise in non-endemic regions, and cross-reactivity with other tests may occur.
Case Presentation
A 49-year-old woman traveling from Yemen via Djibouti presented in the Midwest with irregular fluctuating fevers, cough, headache with behavioral changes, and abdominal pain with emesis. Initial workup showed pancytopenia, hemolysis, and significant splenomegaly on CT scan. Blood smear confirmed Plasmodium falciparum malaria, classified as severe due to cerebral involvement and hyperparasitemia. Despite a positive fourth-generation HIV test, confirmatory HIV differentiation test and HIV nucleic acid amplification were negative, indicating a false positive likely due to severe malaria. The patient was successfully treated with three days of artemether-lumefantrine, and symptoms subsided.

Discussion
This case highlights the potential for false positive fourth-generation HIV tests in the context of severe malaria. The high sensitivity (99.8%) and specificity (99.5%) of these tests are generally reliable, but cross-reactivity can occur, necessitating confirmatory testing to avoid misdiagnosis. Previous cases have reported similar findings. For instance, a 2019 case report described a tourist returning from West Africa with severe P. falciparum malaria who tested false positive on the fourth-generation HIV test, but confirmatory testing was negative. Another case in 2023 documented a woman with P. malariae presenting a false positive HIV test, which was subsequently negated by differentiation testing. These false positives are thought to occur due to the immune system's response to malaria, which can produce antibodies or immune complexes that cross-react with HIV test antigens. Studies have shown that younger patients with malaria might produce more nonspecific antibodies, leading to higher rates of false positives. Historical enzyme immunoassay tests also reported similar issues, with significant rates of false positives in malaria patients. The unique presentation of our patient shows the necessity of considering false positives in regions where malaria is rare but HIV testing is common. This case reinforces the need for thorough diagnostic evaluations and the importance of reflexive confirmatory testing to prevent misdiagnosis and unnecessary treatment.


False Positive Fourth Generation HIV Test in a Woman with Severe Malaria

Background:

Lung adenocarcinoma is the most common lung cancer and has variable biology that affects outcomes and treatment. Numerous prognostic factors can be obtained from resected tumors, but a tool that could predict lung adenocarcinoma biology pre-operatively would help tailor decision-making. 

SILA is a radiomic tool that assigns scores to 9 groups of CT features which are collectively used to calculate a risk that a tumor recurs. While SILA recurrence risks have been validated, it is not yet known how the 9 groups of features themselves might relate to lung adenocarcinoma characteristics.

In this study, our aim was to elucidate novel associations between the 9 scores and known prognostic factors in lung adenocarcinoma. 

Methods:

We retrospectively reviewed resected lung adenocarcinoma cases with available preoperative CT images at our hospital between August 2016 and August 2022.

SILA analysis involved manual segmentation of lung lesions on CT scans. The software then generated scores for each of the 9 groups of features. The 9 features are referred to by color names, such as violet (V), indigo (I), etc. We reviewed the charts to record pertinent clinical-pathologic variables. 
Statistical tests used included chi square, Kruskal-Wallis to Dunn-Bonferroni-Tests post-hoc analysis, and Mann-Whitney U-Test.

Results:
Study cohort included 276 patients with a median age of 69. There were 176 (63.4%) female patients and 197 (71.4%) stage I. There were 54 (19.6%) recurrences.

Our results showed positive and negative associations between certain color scores and markers of tumor aggression, including standardized reuptake value (SUV) on T1 scans (p-values ranging from <0.001 to 0.009) and tumor size on CT (p-values from <0.001 to 0.009). In addition, color scores had associations with known prognostic factors that can only be determined after resection, including visceral pleural invasion (p-values from <0.001 to .045) and lymphovascular invasion (p values from <0.001 to .037).

Color scores were also significantly different between certain pathologic stages. For example, violet values were significantly different between stage IB and IA2 tumors (adjusted p=0.001) and between stage IA2 and IIB tumors (adjusted p<0.001). 

Conclusion:

The associations between SILA color scores and validated markers of tumor aggression point to the exciting possibility that color scores may provide information about lung adenocarcinoma biology pre-operatively. Future work will explore additional correlations between color scores and other pre- and post-operative clinicopathologic data.


Score Indicative of Lung Cancer Aggression (SILA) color scores are correlated with aggressive features in lung adenocarcinoma


Air Pollution Induces Atrial Fibrosis via CARD9-Mediated Immune Response

Background
Exposure to ambient fine particulate matter (PM) triggers systemic inflammation and is associated with atrial fibrosis (AF) and cardiac arrhythmia. The cytosolic adaptor caspase recruitment domain 9 (CARD9) is crucial for macrophage function and innate immune response. This study aimed to investigate the role of CARD9-dependent immune response in PM-induced macrophage-mediated inflammation and the detrimental effects of PM on the heart atrium, exploring the underlying mechanisms.

Methods
Male C57BL/6 wild type (WT) mice (4-6 months old, n=8-12) and age- and sex-matched CARD9 knockout (CARD9-/-) mice (n=8-12) were intranasally exposed to PM for 1, 2, 7, 14, and 28 days. Serum levels of TNF-α, IL-1β, IL-6, and IL-10 were measured using ELISA. Total macrophage populations and M1/M2 subpopulations in bone marrow (BM) and blood were analyzed in mice with and without PM exposure. BM macrophages were cultured for 48 hours in M0, M1, or M2 medium to analyze their populations and cytokine production with or without PM exposure. Phosphorylated Akt (p-Akt), p-Erk, and Ankyrin-B levels were determined in atrial cardiomyocytes using immunoblotting. AF area was measured with Masson’s trichrome staining.

Results
PM exposure significantly elevated serum levels of TNF-α, IL-1β, and IL-6 in WT mice within 24 hours, but not in CARD9-/- mice. In CARD9-/- mice, PM exposure increased the M2 macrophage population and IL-10 levels compared to WT mice, with similar findings observed in vitro using BM cells cultured in M0, M1, and M2 media. PM-induced AF was linked to reduced atrial p-Akt and Ankyrin-B levels, effects that were mitigated in CARD9-/- mice compared to WT mice.

Conclusion
PM exposure-induced AF may be linked to an enhanced macrophage inflammatory response through CARD9-mediated reduction in IL-10 secretion, resulting in a decreased M2 macrophage polarization from M0 macrophage.

Air Pollution Induces Atrial Fibrosis via CARD9-Mediated Immune Response

Fitz-Hugh-Curtis syndrome is a rare but clinically significant complication of pelvic inflammatory disease. Patients characteristically present with pleuritic right upper quadrant pain secondary to the spread of pelvic inflammatory disease to the liver capsule. Additional clinical manifestations include cervicovaginal discharge, pelvic pain, cervical motion tenderness, and adnexal tenderness. This syndrome primarily affects women in their reproductive years and is classically linked to sexually transmitted infection with Chlamydia trachomatis and Neisseria gonorrhoeae. Long-standing disease may not manifest clinically; thus, diagnosis typically involves a combination of clinical evaluation and imaging modalities. When the diagnosis is not yet clear and complications of pelvic inflammatory disease are present (i.e., hydrosalpinx), diagnostic laparoscopy is indicated for direct visualization. The classic “violin-string” adhesions visualized on laparoscopy connecting the anterior hepatic surface to the abdominal wall are pathognomonic of the disease.

We present an atypical case of Fitz-Hugh-Curtis syndrome with a 26-year-old female who presented with long-standing dysmenorrhea, bilateral hydrosalpinx, and no prior history of sexually transmitted infection or pelvic inflammatory disease. She also lacked the characteristic right upper quadrant pain, which can sometimes be the only clinical manifestation of the disease. The diagnosis of Fitz-Hugh-Curtis syndrome was made based on laparoscopic visualization of extensive “violin-string” adhesions involving the liver, left fallopian tube, uterus, and peritoneum. Laparoscopic adhesiolysis and bilateral salpingectomy was performed, and the patient had an uncomplicated postoperative course.

Fitz-Hugh-Curtis syndrome can pose a diagnostic challenge as it has a spectrum of possible clinical manifestations. As seen in this case, laparoscopy revealed extensive adhesive disease and tubal inflammation yet, the patient did not meet the minimum criteria for pelvic inflammatory disease or complain of right upper quadrant pain at any time during the disease course. Obtaining imaging of the abdomen and pelvis via ultrasound and computed tomography can be particularly valuable in establishing the diagnosis and ruling out other pathology; however, laparoscopy is the gold-standard of diagnosis. Young, sexually active women presenting to the hospital with pelvic pain and bilateral hydrosalpinx should raise high clinical suspicion for Fitz-Hugh-Curtis syndrome, regardless of sexual history or clinical manifestation of perihepatitis. Early diagnosis and treatment with laparoscopy can help patients avoid the pain and suffering that can persist for years, as seen in this case. This case also stresses the importance of treating sexually transmitted infection and pelvic inflammatory disease early on before it progresses to chronic pelvic pain and infertility.

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Prenatal opioid exposure impacts respiratory outcomes within the first 5 years of life

Impact of R-IDEA Tool on Interns' Clinical Reasoning and Satisfaction During Medicine Rotation

Mesenchymal Stem Cell Therapy Targeted to Damaged OA CartilageUsing Type I Collagen Microspheres Linked to Monoclonal Antibody to Type II Collagen

Can Inhibiting Ferroptosis Mitigate Vascular Injury and Subsequent Glycocalyx Shedding in the Setting of Hemorrhagic Shock?

The Impact of Altered Mental Status on Intensive Care Unit Outcomes: A Retrospective Cohort Study

An Examination of Orthopedic Implants in the WMed Skeletal Teaching and Research Series: Presenting a Resource for Medical Education and Research

Varying Cortical Involvement of Periacetabular Metastatic Lesions Affects Bone Strain in the Pelvis

Analyzing Recruitment Methods to Increase Diversity in Biobank Collections

False Positive Fourth Generation HIV Test in a Woman with Severe Malaria

Score Indicative of Lung Cancer Aggression (SILA) color scores are correlated with aggressive features in lung adenocarcinoma

Air Pollution Induces Atrial Fibrosis via CARD9-Mediated Immune Response

Fitz-Hugh-Curtis Syndrome and Bilateral Hydrosalpinx in the Absence of Sexually Transmitted Infection: A Case Report

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