United States

Invasive pulmonary aspergillosis (IPA) is a life-threatening fungal infection typically
associated with profound immunosuppression. However, cases are increasingly observed in patients with non-classical risk factors, such as malnutrition, diabetes, and chronic lung disease. We report the case of a 50-year-old male with significant weight loss, malnutrition, and a history of diabetes, COPD, and alcohol use, who presented with respiratory symptoms and sepsis. Imaging and laboratory findings were suggestive of invasive aspergillosis, however, antifungal treatment was initiated late in the clinical course. Diagnostic studies ultimately confirmed fungal elements, a positive Aspergillus antigen, and highly elevated β-D-glucan, but the patient deteriorated and died. This case highlights the importance of early empiric antifungal therapy in high-risk patients with imaging suggestive of fungal disease, particularly when clinical presentation is complex and diagnostic delays may lead to missed therapeutic windows. 


AMA Research Challenge 2025 

Invasive Pulmonary Aspergillosis in Multiorgan Dysfunction: A Diagnostic Challenge

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AMA Research Challenge 2022

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While considerable developments have been made in treating Immunodeficiency Virus (HIV) infection, many aspects of its interactions with host factors remain an area of considerable research interest toward the hope of developing a cure. HIV is a retrovirus that enters host immune cells via recognition of transmembrane ligands (i.e. CD4, CCR5, CXC4) by viral envelope (gp41, gp120), allowing then for membrane fusion and subsequent virion production and/or genome integration. The complexity of managing treatment of a virus integrated into immune cell genomes presents unique therapeutic and research challenges which have long stymied complete viral clearance and necessitate continued basic science research. 

Previous transcriptomic studies identified altered Annexin A5 (AnxA5) expression in T cell lines with varying susceptibility to HIV-1. AnxA5 is a member of the Ca+2-dependent, PtdSer-binding Annexin family of proteins. AnxA5 is demonstrably involved in the induction of membrane curvature, endocytic vesicle formation, shielding procoagulant enzymes from activation, and attenuating the proapoptotic innate immune response; however, its role in HIV infection remains unclear.

To study the potential interactions between AnxA5 and HIV, infections in the context of AnxA5 overexpression and stable knockdown were performed by plasmid or short-hairpin RNA (shRNA) expression, respectively. Exogenous overexpression of AnxA5 slightly increased the susceptibility of HEK293T cells to infection versus control cells. Knockdown of AnxA5 resulted in a 3-fold reduction of infection relative to scramble shRNA control cells. Combined, these data suggest that AnxA5 is a positive factor for HIV infection.

It was also found that virus production from the AnxA5 knockdown cells was reduced 2-fold. Moreover, the infectivity of virus produced from the shAnxA5 cells was reduced 3-fold compared to virus produced from control cells. These data suggest AnxA5 expression is required for virus production. Notably, reconstitution of AnxA5 expression in the knockdown HEK293T-shAnxA5 cell lines did not fully reconstitute HIV susceptibility. This suggests either the potential of off-target effects of shRNA knockdown or the potential that reconstitution of expression by exogenous ectopic plasmid was insufficient to restore the original subcellular expression profile of AnxA5.

Overall, these data identify AnxA5 as a cellular factor potentially involved in HIV replication. Further in vitro and in vivo studies are needed to elucidate the mechanism and clinical implications of this host-viral interaction.


AnnexinA5 – a host factor regulating HIV susceptibility

Objective: The increased rate of diet-related chronic conditions, such as diabetes, hypertension, and dyslipidemia, has been alarming. These conditions often co-occur, and their management has been a burden on the healthcare system and economy. If remain untreated, their combined effect can lead to more severe health outcomes. Patients with lack or limited access to healthcare are at higher risk for morbidity and mortality caused by the combined effect of these diet-related chronic conditions. The aim of this study was to assess the co-occurrence of diabetes, hypertension, and dyslipidemia among a group of uninsured adults living in South Florida.

Methods: A retrospective analysis of deidentified electronic health records of 272 patients seen within a 4-week timeframe in a community care clinic in South Florida was performed. The dataset excluded all the protected health information elements and included patients` demographics, anthropometrics, laboratory results, medications, and relevant past medical history. Descriptive and binary statistical analysis were used for sample characteristics and co-occurrence assessment.

Results: Overall, 23.9% of patients had a diagnosis for diabetes, including females (n=37) and males (n=28). The mean age was 55.58±11.52 years. Bivariate analysis showed 70.8% co-occurrence of diabetes and hypertension. Co-occurrence of diabetes and dyslipidemia was 64.4%. All combined, 49.2% of patients with diabetes had both hypertension and dyslipidemia.

Conclusions: The results of this study showed a high co-occurrence rate of diet-related chronic conditions among uninsured patients. Multidisciplinary community-based interventions and improved access to healthcare services may help with prevention and management of these conditions among uninsured patients.
Keywords: Nutrition, Diet, Diabetes, Prediabetes, Chronic Conditions, Hypertension, Obesity, Dyslipidemia


Co-Occurrence of Diet-Related Chronic Conditions Among a Group of Uninsured Adults with Diabetes

Abstract Title
Exploring the Association Between Loneliness, Depression and Heart Disease Risk in a Free Medical Clinic

Background
Depression and loneliness have each been linked to cardiovascular disease (CVD), but few studies have examined their combined impact. A 2022 AHA statement identified loneliness as an independent CVD risk factor, while depression is tied to elevated 10-year and lifetime ASCVD risk, commonly assessed with the ACC ASCVD calculator and PHQ-9. This study investigated how UCLA Loneliness Scale and PHQ-9 scores relate to ASCVD risk in adults at a free clinic in Upstate South Carolina.

Methods
Thirty-one English-speaking patients ages 20–79 with a lipid panel drawn in the past year were recruited. Participants completed the PHQ-9, UCLA Loneliness Scale, and a brief health and demographic survey before or after their visit. A free pulse oximeter was offered as an incentive. Depression and loneliness scores were calculated based on the respective scoring guides. PHQ9 and UCLA loneliness scores were calculated per standard guides. Ten-year and lifetime ASCVD risks were computed using the ACC ASCVD calculator. Data were de-identified and analyzed in Excel for correlations, scatter plots, and multiple linear regressions, cross-verified using two online calculators.

Results
Data from 30 participants were analyzed after excluding one outlier. Multiple linear regression revealed a moderate, significant collective effect of PHQ-9 and UCLA scores on total cholesterol (R=0.51, p=0.017). Higher PHQ-9 scores were associated with lower total cholesterol, while higher UCLA scores correlated with higher total cholesterol. Stratification by statin use (n=13) and non-use (n=17) weakened these associations (p=0.28; p=0.24). No significant relationships emerged between PHQ-9, UCLA scores, and LDL levels overall (p=0.27), though subgroup trends suggested higher PHQ-9 scores linked to lower LDL and higher UCLA scores to higher LDL in statin users (p=0.057). Associations with HDL were weak and non-significant.
A strong correlation was found between PHQ-9 and UCLA scores (R=0.66, p<0.001). However, relationships with 10-year or lifetime ASCVD risk were weak and non-significant on both multiple and simple regressions.

Conclusion
No significant associations were observed between ASCVD risk and PHQ-9 or UCLA scores, likely due to the small sample size. Larger studies are needed to clarify these relationships. Importantly, we identified a significant link between depression and loneliness scores and total cholesterol. While these psychosocial factors are closely related, our findings suggest they may pose distinct challenges to cardiovascular health and are not interchangeable predictors of cholesterol or ASCVD risk.

Exploring the Association Between Loneliness, Depression, and Heart Disease Risk in a Free Medical Clinic

Background: Psoriasis treatments have been historically used to maintain relapsing and remitting symptoms of psoriasis, notably through corticosteroids, vitamin D analogs, calcineurin inhibitors, and coal tar, salicylic acid and retinoid therapies. Newer monoclonal antibodies risankizumab, an IL-23 inhibitor, and bimekizumab, an IL-17A and IL-17F inhibitor, have recently been FDA approved as treatment modalities in Phase 3 clinical trials. In terms of efficacy, the UltMMa-1 and UltMMa-2, IMMhance, and IMMvent clinical trials found 75-80% of patients with Psoriasis Area and Severity Index 90 (PASI 90) with Risankizumab use after 16 weeks, correlated with a 90% reduction in symptoms. Bimekizumab showed similar results in the BE VIVID, BE READY, BE SURE, and BE RADIANT trials showing 85% of patients achieving PASI90.3, 4This systematic review and meta-analysis aims to evaluate efficacy and safety of risankizumab and bimekizumab in comparison to standard of care to evaluate more recent treatments for psoriasis and elucidate their potential role in clinical practice.

Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and registered to PROSPERO(CRD420251053258). A total of 10,336 articles utilizing monoclonal antibodies were retrieved from Scopus, Embase, and PubMed databases. Articles were included if patients were receiving either bimekizumab or risankizumab for the treatment of psoriasis or psoriasis subtype and 22 articles were abstracted, using Cochrane Risk of Bias 2 tool to assess quality.

Results: Twenty-two studies with a total of 6,237 patients were included. Eleven studies analyzed 2,148 patients treated with bimekizumab and a separate eleven studies analyzed 1,919 patients treated with risankizumab. Bimekizumab and risankizumab were similarly effective in treating psoriasis as measured by the PASI 90, the Dermatology Life Quality Index (DLQI), and the Investigator’s Global Assessment (IGA). However, bimekizumab was found to have a significantly higher risk of any adverse event compared to the control. Risankizumab was found to have a significantly decreased risk of severe adverse events compared to the control. All other endpoints of this meta-analysis regarding adverse events were not found to be significant (p >0.05).

Conclusion: Based on systematic review and meta-analysis of risankizumab and bimekizumab’s efficacy and safety compared to standard of care, bimekizumab’s significantly higher rate of any adverse event and risankizumab’s significantly decreased risk of severe adverse events may serve as crucial pieces of information to guide clinicians choosing potential therapeutics for psoriasis treatment.

Safety and Efficacy of Risankizumab and Bimekizumab in the Treatment of Psoriasis: A Systematic Review and Meta-Analysis

Background: Neurointerventional procedures require rapid decision-making and continuous device manipulation under high cognitive load. Intraoperative distraction and poor visualization can delay recognition of unintentional device movement, leading to procedural errors or complications. Real-time artificial intelligence (AI) systems may mitigate these risks by enhancing situational awareness and alerting operators to potentially unsafe device behavior. This study presents the first clinical implementation of a real-time AI-based tracking platform in the United States for neurointervention.

Methods: A prospective single-center study was conducted at a tertiary neuroscience hospital from May to July 2025. Twenty-one adult patients undergoing neuroendovascular procedures were enrolled. A real-time AI system was integrated with the biplane fluoroscopy suite to track procedural devices including guidewires, microcatheters, coils, filters, and stents. The system issued audiovisual alerts when a tracked device entered or exited user-defined anatomical regions. Each notification was reviewed and categorized as true positive (TP), false positive (FP), or false negative (FN). Operator actions within 10 seconds of a TP were logged as clinically relevant responses.

Results: The AI system operated successfully in all 21 cases without technical failure or delay to clinical workflow. Across all cases, 245 notifications were recorded: 232 TPs, 13 FPs, and 17 FNs. The system achieved an overall precision of 94.7% and recall of 93.2%. Clinically relevant responses occurred in 25 of 59 evaluated TPs (42.4%), demonstrating real-time impact on operator behavior. Mean notifications per case were 11.7 ± 8.3. Alerts were most often triggered by guidewire advancement or filter migration.

Conclusion: This first-in-U.S. clinical study of real-time AI assistance in neurointervention demonstrated high technical accuracy, smooth integration into clinical workflow, and clinically actionable alerts in nearly half of evaluated events. AI-based intraoperative support tools may reduce cognitive burden, enhance detection of device migration, and improve procedural safety. These systems also show promise as future adjuncts in neurointerventional training, particularly in high-risk or mentor-limited settings.


Implementation and Performance of a Real-Time AI System for Device Tracking in Neurointervention

Background
Strict glycemic control for management of diabetes can result in hypoglycemic episodes and the long-term, deleterious impacts of these episodes on health are unclear. Acute hypoglycemia causes a drop in microvascular density and perfusion of the retinal superficial capillary plexus. Additionally, severe hypoglycemia is associated with a higher incidence of retinopathy in patients with type 2 diabetes and proliferative disease in patients with type 1 diabetes. Understanding the influence of hypoglycemia on diabetes progression is an important question in guiding blood glucose control regimens to manage morbidity and mortality of this disease.

Methods
We performed a retrospective cohort study using the TriNetX platform including up to 200k patients per cohort across 70 US health care organizations, selected by blood glucose value or ICD-10 code. We evaluated the impact of hypoglycemia on the risk and progression of diabetic retinopathy, relative to both hyperglycemia and normoglycemia, in participants with type 1 and type 2 diabetes. We simultaneously assessed the effect of hypoglycemia on another microvascular complication, diabetic nephropathy.

Results
Participants with hypoglycemia were at an elevated risk for both non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) compared to both glycemic-controlled and hyperglycemic participants. Hypoglycemia increased risk by up to 3.56 (3.14, 4.05) for NPDR, 4.83 (4.53, 5.15) for PDR in persons with type 2 diabetes and comparably in those with type 1 diabetes, relative to normoglycemia. Relative to hyperglycemia, hypoglycemia increased risk by up to 1.68 (1.53, 1.85) for NPDR, 2.05 (1.96, 2.15) for PDR in participants with type 2 diabetes and comparably in those with type 1 diabetes. Additionally, hypoglycemia elevated risk of progression from NPDR to PDR to a similar degree as hyperglycemia, up to 1.99 (1.56, 2.54) in persons with type 2 diabetes, relative to normoglycemia.

In the kidney, hypoglycemia increased risk of chronic kidney disease (CKD) [2.11 (2.07, 2.14); 1.42 (1.40, 1.44)], end stage renal disease (ESRD) [6.64 (6.38, 6.91); 2.48 (2.41, 2.55)], and progression from CKD to ESRD [3.74 (3.61, 3.87); 1.53 (1.51, 1.58)], relative to both normoglycemia and hyperglycemia, respectively.

Conclusion
Hypoglycemia is associated with increased risk of diabetic retinopathy and comparable risk of retinopathy progression, compared with hyperglycemia. Additionally, both elevated risk and risk of progression for diabetic nephropathy are associated with hypoglycemia. This study underscores the significant role of hypoglycemia on ocular and renal morbidity and highlights the importance of appropriately cognizant blood glucose control strategies to mitigate these outcomes.

Hypoglycemia Enhances Risk and Progression of Diabetic Retinopathy and Nephropathy

Introduction:
We compare the effects primary care and polytrauma care have on health care utilization and cost among veterans diagnosed with traumatic brain injury (TBI). Cohorts of veterans spanning from 2003 to 2023 were analyzed based on their usage of primary care, polytrauma care, both, or neither over three or more years.
Methods:
This study is a retrospective cohort analysis of LIMBIC Phenotype Study dataset linked with data from Veterans Health Administration (VHA). The cohorts were classified based on the presence or absence of a TBI diagnosis and whether veterans had no primary or polytrauma care, primary care for 3+ years, polytrauma care for 3+ years, or both primary care and polytrauma care for 3+ years. Care both within and outside of the VA system including total health care cost was documented as well. We used Propensity Score estimation method with augmented IPTW to compare utilization and cost across the groups. 
Results:
Veterans who did not use primary care or polytrauma care had an average year 1 utilization score of 3.22, which increased to a score of 22.8 by year 4. Similarly, healthcare costs for these individuals also rose from an average of $3505 to $10519. Veterans who used both primary care and polytrauma care experienced the opposite pattern: Utilization scores fell from an average of 73.66 to 39.34, and costs fell from $43092 to $16283. Veterans who only used primary care saw mild decreases in both utilization scores and costs, and those who only used polytrauma care saw little change in utilization and a large decrease in cost between Year 1 and 2 followed by minor changes across Years 2-4.
Conclusions:
When controlling for medical complexity, individuals with TBI who received regular combination of primary and polytrauma care for 3+ years continued to have lower health care utilization in subsequent years. Further analyses include identifying “surrogate” measures to identify the impact of care type and intensity on the quality and outcome of treatment. 


Impact of Primary & Polytrauma Care Services on Health Care Utilization of Veterans with All-Severity TBI

Background
Addison’s disease is a rare endocrine disorder caused by failure of the adrenal cortex, most commonly due to autoimmune destruction of the adrenal gland. It presents with nonspecific symptoms such as fatigue, weight loss, hypotension, and hyperpigmentation, often delaying diagnosis. Acute adrenal crisis is a life-threatening complication requiring urgent treatment. Diagnosis is confirmed through ACTH stimulation testing and hormonal assays. Lifelong hormone replacement, follow up, and patient education are essential for management. When Addison’s disease coexists with diabetes mellitus and stroke, the clinical complexity increases significantly due to compounded cardiovascular and metabolic risks. This underscores the need for vigilant, individualized care to prevent complications and optimize outcomes.
Case Presentation
We present a 51-year-old female with a history of hypertension, multiple strokes, seizures, type 2 diabetes mellitus, and Addison’s disease who arrived at the ED with 10 days of weakness, dysphagia, and poor oral intake. Initial labs showed elevated BUN, creatinine, hyperchloremia, and hypoalbuminemia. She was admitted for management of severe dehydration and electrolyte disturbances. The family reported recurrent hospitalizations for dysphagia, dehydration, and hypoglycemia. On day one of hospitalization, she developed hypotension, hyperglycemia, and altered mental status, raising concern for adrenal crisis. MRI revealed severe basal ganglia atrophy with iron deposition; EEG showed left frontal seizure activity. By day two, she developed hyponatremia, hypokalemia, metabolic acidosis, and acute kidney injury. Echocardiogram showed preserved ejection fraction and mild valvular regurgitation. Treatment included IV hydrocortisone, insulin, levothyroxine, fluids, and nasogastric feeding.
Despite treatment, a code blue was triggered for severe hypoglycemia. She then required intubation, vasopressors, anticonvulsants, and broad-spectrum antibiotics for sepsis. The patient suffered three cardiopulmonary arrests but achieved return of spontaneous circulation.
Discussion
This case underscores the need for early recognition, aggressive management, and proactive cardiovascular risk reduction in complex endocrine-neurological patients. The patient presented with hypoglycemia, hypotension, and metabolic acidosis—hallmarks of adrenal crisis. Adrenal crisis represents a life‐threatening emergency, particularly in individuals with a known history of diabetes and cerebrovascular accidents. Cortisol deficiency disrupts cardiovascular and metabolic stability. Furthermore, stroke‐related autonomic dysfunction weakens the body’s cardiopulmonary reserve. Together, these factors significantly increase susceptibility to hypotension, hypoglycemia, and circulatory collapse, as exemplified by this patient. Additionally, precipitating events such as infection, dehydration, and inadequate oral intake may rapidly trigger decompensation. Despite timely and appropriate intervention, patients with Addison’s disease remain at increased risk of cardiovascular morbidity and mortality, particularly when concomitant comorbidities are present.

Addison’s Disease in a Patient with Stroke and Diabetes – A Fatal Lesson in Diagnostic Delay

Background
The U.S. healthcare system leads the world in per capita spending, yet outcomes often fall short. In response, value-based care (VBC) models have emerged to enhance quality, performance, and patient experience while reducing costs. Recently, private equity and corporate consolidation efforts have adopted VBC as a marketing tool. However, mergers and acquisitions (M&A) in healthcare have prompted scrutiny by federal regulators like the FTC, who argue that such consolidations may raise costs and reduce incentives for quality improvement and innovation. This study evaluates whether M&A activity in Florida hospitals aligns with the principles of value-based care. 
Methods
We used publicly available data from the Centers for Medicare and Medicaid Services (CMS) to identify hospitals in Florida that underwent M&A activity between 2015 and 2023. Thirteen hospitals were selected for analysis, focusing on one year pre- and three years post-acquisition. Quality metrics included 30-day inpatient pneumonia mortality, pressure ulcers, and serious complications. Cost indicators included the average cost of pneumonia care, total inpatient revenue, and Medicaid charges. National benchmarks from CMS were used for comparison. The value of care was assessed using the equation: Value = Quality / Cost. 
Results
Of the nine matched hospital pairs with complete CMS data from 2023 to 2025, merger hospitals outperformed their non-merger controls in six of nine pairs. However, these differences were not statistically significant based on paired t-tests and Wilcoxon signed-rank tests (p > 0.05 for all comparisons). When evaluating overall value trends, 10 of 18 hospitals (55%) demonstrated a decline in scaled value score over the three-year period. Both merger and control groups had an identical average value score of 0.59, which fell below the Florida state average (0.85) but matched the national benchmark (0.59). Trend analysis revealed a predominance of negative value slopes, suggesting a systemic decline in value across institutions, regardless of merger status.
Conclusion
This study found no significant improvement in value-based care performance among hospitals that underwent mergers in Florida when compared to matched controls. While a slight majority of merger hospitals outperformed their counterparts, the observed differences were not statistically meaningful. More broadly, the trend toward declining value scores across both groups highlights potential systemic contributors such as rising costs and stagnant clinical outcomes. These findings support growing national concerns that structural consolidation alone may not improve healthcare value, and underscore the need for more comprehensive strategies to address both cost containment and outcome improvement.

Private Equity and its impact on Value Based Care in the State of Florida

Abstract Title
Clinical Outcomes and Healthcare Utilization in Xylazine-Associated Skin and Soft Tissue Infections Among People Who Inject Drugs: A Retrospective Cohort Study
Background
Xylazine, a veterinary sedative increasingly found in the illicit drug supply, is associated with severe SSTIs that exhibit necrosis and impaired healing. These infections contribute to increased morbidity and healthcare burden. Understanding the healthcare needs of patients with xylazinerelated SSTIs is critical for optimizing treatment strategies.
Methods
A retrospective cohort study was conducted on 68 patients admitted with SSTIs at a large health system in western Pennsylvania. Patients were stratified into xylazine-positive (n=32) and nonexposed (n=36) groups based on urine drug screens, wound characteristics, or documented withdrawal management. Data extracted from electronic health records included demographics, substance use patterns, infection characteristics, hospital length of stay, readmission rates, and specialty consultations.
Results
Xylazine-positive patients had higher rates of opioid and stimulant use compared to nonexposed individuals. They exhibited a higher prevalence of bacteremia and necrotizing fasciitis. Despite comparable hospital lengths of stay, xylazine-positive patients had lower 30-day and 90-day readmission rates. They also required more multidisciplinary care, with higher rates of surgery, infectious disease, and addiction medicine consultations, though these services were inconsistently provided.
Conclusion
Xylazine-associated SSTIs present unique clinical challenges due to vasoconstrictive and cytotoxic effects that impair healing. Lower hospital readmission rates among xylazine-positive patients may reflect barriers to care rather than improved outcomes. The inconsistency in multidisciplinary care highlights gaps in care coordination. Standardized, multidisciplinary management strategies are needed to optimize treatment and improve outcomes in this high-risk population.

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AnnexinA5 – a host factor regulating HIV susceptibility

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