United States

Background
Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is widely used to treat diabetic eye disease (DED), yet systemic VEGF suppression may impair peripheral wound healing. The association between anti-VEGF treatment and risk of diabetic foot ulcers (DFUs) and lower extremity amputations (LEAs) remains unclear. We seeked to evaluate the risk of DFUs and LEAs associated with intravitreal anti-VEGF injections (IVI) in patients with DED and to compare risks among ranibizumab, aflibercept, and bevacizumab.
Methods
We conducted a retrospective cohort study (April 2005 - April 2025) using a multicenter, population-based electronic health records network encompassing over 120 million individuals from 71 United States healthcare organizations. Adults (≥18 years) diagnosed with DED (diabetic retinopathy or diabetic macular edema) who received ≥3 IVI were compared to those who received ≤2 injections (control group) during the study period, since prior evidence demonstrated systemic suppression of plasma VEGF levels following three monthly intravitreal injections. The exposure was IVI (ranibizumab, aflibercept, or bevacizumab). Main outcome measures included incidence of any LEAs, above-ankle LEAs, and DFUs following incident DED diagnosis. Propensity score matching (1:1) was applied to balance baseline characteristics between groups. Cox proportional hazards analyses were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) in the full cohort and among high-risk subgroups with proliferative diabetic retinopathy (PDR), peripheral artery disease (PAD), end-stage renal disease (ESRD), or DFUs.
Results
Of 448,100 patients with DED, 35,269 received ≥3 injections and 412,831 received ≤2 injections. After matching, 34,070 patients remained in each group. IVI cohort was associated with increased risk of LEA (HR 1.54, 95% CI 1.38–1.72), above-ankle LEA (HR 1.31, 95% CI 1.08–1.59), and DFU (HR 1.36, 95% CI 1.30–1.42) compared with the control group. In high-risk subgroups, IVI was associated with increased risk of LEA in patients with PDR (HR 1.44, 95% CI 1.27-1.62), PAD (HR 1.35, 95% CI 1.12–1.56), ESRD (HR 2.06, 95% CI 1.28–3.31), and DFU (HR 1.46, 95% CI 1.22–1.75). Risks were similar across anti-VEGF agents.
Conclusion
IVI therapy for DED was associated with increased risk of LEA, particularly with comorbid PDR, PAD, ESRD, or DFUs. These findings highlight the importance of monitoring for limb complications in patients undergoing intravitreal anti-VEGF treatment.

2025 AMA Research Challenge – Member Premier Access

Intravitreal Anti-VEGF Therapy and Risk of Limb Complications in Patients with
Diabetic Eye Disease

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Title: Diagnostic and Therapeutic Benefits of POCUS in Assessing Musculoskeletal Pain in Primary Care Settings

Background: Traditionally, when patients present with musculoskeletal pain in primary care settings, they are prescribed analgesics and possibly an X-ray to diagnose and treat the pain. It is only if the pain persists that other measures are taken, such as further imaging and referrals to pain management. Point of care ultrasound (POCUS) is a cheap and effective diagnostic tool that is often used in the ER to diagnose musculoskeletal pain to efficiently treat patients in a timely manner. 

Aim (goal or objective): The goal is to examine the diagnostic and therapeutic benefits of POCUS in evaluating musculoskeletal pain within primary care settings, compared to traditional imaging or clinical-only approaches.

Methods/Intervention: We conducted a literature-based review from PubMed, analyzing current evidence from cross-sectional studies, reviews, and case series involving POCUS use for MSK conditions in general practice. We focused on outcomes including diagnostic accuracy, patient satisfaction, care efficiency, and therapeutic applications (i.e. guided injections). Key studies from both inpatient and outpatient settings were used to extrapolate potential benefits relevant to primary care.

Results: POCUS enhances both diagnostic accuracy and procedural precision in evaluating musculoskeletal pain through real-time static and dynamic assessments. It facilitates immediate interventions—such as aspirations and injections—reducing reliance on external imaging. Studies also describe a “POCUS Positive Care Effect,” where patients report greater satisfaction, trust, and understanding of their condition. In primary care, this dual benefit of clinical utility and socioemotional value supports POCUS as a powerful, patient-centered diagnostic tool.

Conclusions/Discussion: POCUS offers both clinical and therapeutic advantages in musculoskeletal pain management in primary care—enabling faster diagnosis, better targeted treatments, and improved patient satisfaction. Its real-time capabilities and socioemotional benefits position it as a valuable, patient-centered alternative to the delayed and fragmented approach of traditional care pathways.

Diagnostic and Therapeutic Benefits of POCUS in Assessing Musculoskeletal Pain in Primary Care Settings


Background
Hypokalemia periodic paralysis (HPP) presents with episodic flaccid muscle weakness due to severe hypokalemia, which can be hereditary ionchannelopathy or acquired via renal losses such as distal renal tubular acidosis (dRTA). dRTA stems from impaired H⁺ secretion in α-intercalated cells, causing metabolic acidosis, alkaline urine, and potassium wasting. Primary Sjögren’s syndrome (pSS) can rarely causes tubulointerstitial nephritis through autoantibody mediated, triggering dRTA, and in rare cases, dRTA-induced HPP may be the presenting feature, even before sicca symptom. Here in, we report a case of HPP as the first manifestation of primary Sjögren’s syndrome-associated dRTA in a previously undiagnosed patient

Case Presentation
A 40-year-old woman arrived at the emergency department with acute, painless limb weakness that rapidly progressed over 48 hours to near-quadriplegia. Examination revealed areflexia but intact sensation and autonomic function. He complained of mouth dryness and muscle twitching. She has no history of diuretic use, endocrine disorder, nephrolithiasis, or substance abuse.
Laboratory studies demonstrated severe hypokalemia (1.4 mEq/L), metabolic acidosis (pH 7.26, HCO₃⁻ 13 mEq/L), a normal anion gap, alkaline urine (pH 7.6), positive urinary anion gap, and renal potassium loss confirming distal (type 1) RTA. Autoimmune screening yielded high-titer anti Ro and anti La positivity and Schirmer’s test < 5 mm bilaterally, fulfilling ACR/EULAR criteria for pSS. Renal function, albumin, and proteinuria were within normal limits; ultrasound excluded structural kidney disease.
She was treated with intravenous potassium chloride and sodium bicarbonate to correct electrolyte and acid base imbalance. High dose methylprednisolone followed by prednisone taper and pilocarpine were initiated to address autoimmune activity and sicca symptoms. Limb strength improved within 48 hours, and six month follow up showed no relapse and normalized biochemical parameters. 
Discussion
This case illustrates autoimmune-mediated pSS inducing distal (type 1) RTA, via lymphocytic inflammation and impaired H⁺ ATPase or carbonic anhydrase activity resulting in metabolic acidosis, renal potassium wasting, and severe hypokalemia triggering hypokalemic periodic paralysis. Distal RTA, uncommon in adults, warrants thorough exclusion of alternative renal, glomerular, endocrine, or structural etiologies, as was systematically accomplished here. Although patients with pSS often exhibit sicca symptoms, renal involvement may precede these signs, making paralysis the initial manifestation. Recognition through combined urine pH, anion gap, and autoimmune serology enabled prompt correction with potassium, bicarbonate, corticosteroids, and pilocarpine. This reinforces the importance of considering pSS in women presenting with unexplained hypokalemic paralysis, even in the absence of overt extraglandular features







Primary Sjögren’s Syndrome Presenting with Hypokalaemia Periodic Paralysis and Distal Renal Tubular Acidosis: A Case Report

Background
Goblet cell adenocarcinomas (GCAs) are uncommon, distinctive tumors of the appendix, accounting for under 14% of all appendiceal neoplasms. Their incidence is about 0.05 per 100,000 people annually, with a median diagnostic age of around 59 years. GCAs exhibit “intermediate” aggressiveness between appendiceal neuroendocrine neoplasms and adenocarcinomas, featuring both neuroendocrine and epithelial characteristics. We describe a case of a 54-year-old woman who was diagnosed incidentally following an appendectomy for appendicitis.

Case Presentation
A 54-year-old woman with well-managed hypertension was referred to our service, following an appendectomy on 08/04/2022 for suspected appendicitis. Histopathology unexpectedly revealed a 3.5–4.5 cm, grade 2 goblet cell adenocarcinoma involving the proximal two-thirds of the appendix. There was
transmural, lymphovascular, and perineural involvement, and positive margins. She had experienced mild, intermittent rectal bleeding over the previous six months but was otherwise asymptomatic. To rule out synchronous lesions, a colonoscopy was done on 08/25/2022. It was limited to 30 cm due to colonic narrowing, showing internal hemorrhoids. A follow-up CT scan on 09/15/2022 confirmed no polyps,
masses, or metastases. Due to positive margins at the appendiceal base, a right hemicolectomy was performed on 10/03/2022. Pathology revealed residual goblet cell adenocarcinoma invading the cecal muscularis propria (pT4b), with 0/22 regional lymph nodes involved (pN0), and no distant metastases
(pMx). KRAS mutation and microsatellite instability testing were negative. Postoperative surveillance with CEA monitoring every three months remained within normal limits. Laboratory tests showed iron
deficiency and low vitamin B12, which were treated successfully with intravenous iron and oral vitamin B12 supplementation following a loading intramuscular injection. She continues to be in remission.

Discussion
Most appendiceal GCAs are diagnosed incidentally upon histopathological examination of appendectomy specimens. This case underlines the necessity of routine pathology for all removed appendices, as tumors
may present solely with luminal obstruction. In resource-limited settings, where histopathology is performed inconsistently, such diagnoses may be missed, highlighting the need for increased support from
healthcare bodies. For cases with deeper invasion or positive margins, a right hemicolectomy confers a survival advantage in stages II and III of the disease. However, early detection remains challenging, underscoring the need for continuity of care to identify recurrence or metastasis. In women, the risk of transcoelomic spread to the ovaries suggests a possible role for gynecologic surveillance. Systematic reviews and meta-analyses are needed to develop evidence-based surveillance guidelines. Molecularly targeted therapies should also be explored for patients who are not surgical candidates.

Unveiling the disguise behind Appendicitis: A Case Study of Appendiceal Goblet Cell Adenocarcinoma


Background:
Rheumatoid arthritis (RA) is a systemic autoimmune disease that primarily presents as inflammatory polyarthritis. Extra-articular manifestations, including pleural and pericardial effusions can occur years after onset. Symptomatic unilateral pleural effusions are seen in ~3–5% of RA patients, while pericardial involvement is much rarer.

Case Presentation:
74-year-old transgender female with hypertension, chronic hepatitis B, and renal cell carcinoma in remission presented with subacute progressive dyspnea and unintentional weight loss. She had been hospitalized two months prior for an exudative pericardial effusion with signs of early tamponade, managed with pericardial drainage.

Upon re-admission, she was hypoxic at 88% on RA which improved with 4L oxygen. Imaging revealed a new moderate left-sided pleural effusion and a small recurrent pericardial effusion. Thoracentesis confirmed exudative effusion per Light’s criteria: pleural-to-serum protein ratio of 0.6, LDH ratio of 1.63, and pleural LDH of 262 U/L (>2/3 upper limit of normal). Glucose was normal (87 mg/dL). CT chest showed a mildly enlarged perivascular mediastinal lymph node and a stable right middle
lobe nodule, with no interstitial lung disease.

Autoimmune workup revealed RF of 32 IU/mL (normal <14) and anti-CCP >250 U/mL (normal <20). Infectious studies, cytology, and AFP cultures from both fluid compartments were negative. The effusions were attributed to RA-associated serositis, despite the absence of joint symptoms.
Her course was complicated by worsening hypoxemia requiring temporary pigtail catheter placement. After stabilization, she was started on prednisone, with plans to initiate methotrexate outpatient. Biologic therapy was deferred due to the risk of hepatitis B reactivation. Now, stable on lefunominode without recurrent serositis.

Discussion:
Pleural effusions are a recognized extra-articular feature of RA, though typically asymptomatic and discovered incidentally. While RA is more prevalent in biological females, RA-related lung disease is more common in males (annual incidence: 0.34% in females vs. 1.54% in males) (1). These effusions are typically unilateral, exudative, and left-sided. However, this case was atypical due to the absence of classically low glucose (<60 mg/dL) and high LDH (>700 U/L). Pericardial effusions are less common, seen in 3.6% of females and 1.7% of males with RA (2). Elevated RF and anti-CCP are associated with increased risk of extra-articular complications. This patient’s initial RA presentation as serositis, without joint involvement, is exceedingly rare. Extra-articular RA can precede joint symptoms. This case highlights the need to consider RA in patients with unexplained exudative pleural or pericardial effusions, even in the absence of joint involvement.


Silent Seropositive RA: Exudative Pleural and Pericardial Effusions as Initial Presentation of Rheumatoid Arthritis​

Ring Enhancements and Ringing Alarms: A Rare Case of Neurocysticercosis 



Background 

Neurocysticercosis (NCC), caused by the larval form of Taenia solium, is a leading cause of acquired epilepsy worldwide, particularly in endemic regions such as South Asia and Latin America. In non-endemic areas, NCC is often underrecognized, especially in immigrants or travelers. Clinical manifestations vary depending on the number, location, and stage of the cysts, and may include seizures, focal neurological deficits, or neuropsychiatric symptoms. 


Case Presentation 

A 37-year-old South Asian male with a history of ulcerative colitis and hypothyroidism presented to the emergency department following a witnessed syncopal episode accompanied by convulsive activity. Two days prior, he experienced a transient, involuntary leftward neck deviation while driving, lasting approximately 10 seconds without associated symptoms. The following day, while eating, he experienced a similar urge, followed by upward eye deviation, loss of consciousness, and generalized tonic-clonic movements of the upper extremities. Post-ictal confusion was noted. Initial evaluation revealed stable vital signs, mild leukocytosis, and hypokalemia. A CT scan of the head showed two small calcific foci in the right frontal and temporal lobes with associated vasogenic edema. MRI of the brain revealed two ring-enhancing lesions with surrounding edema, consistent with neurocysticercosis. Upon further questioning, the patient reported recent ingestion of undercooked pork, a potential source of Taenia solium infection. He was discharged on albendazole, praziquantel, prednisone, and levetiracetam. However, he returned to the ED two weeks later with mood swings, depression, and aggression. Levetiracetam was subsequently replaced with zonisamide. 



Discussion 

Neurocysticercosis is considered rare in the United States, with an estimated incidence ranging from 0.2 to 0.6 cases per 100,000 people per year. This case highlights the importance of considering neurocysticercosis in patients presenting with new-onset seizures and relevant epidemiologic exposure. While the patient’s neuropsychiatric symptoms were most likely due to levetiracetam, such symptoms can also occur in neurocysticercosis. These may include depression, psychosis, visual hallucinations, mood disturbances, and behavioral changes such as aggression or irritability.

Ring Enhancements and Ringing Alarms: A Rare Case of Neurocysticercosis

Background:
Septic arthritis is a serious and potentially life-threatening infection of the joint space that demands timely diagnosis and intervention. While the knee and hip joints are most common, the shoulder accounts for only 5–12% of septic arthritis cases, making it a relatively rare site. This case report presents the clinical course of a 70-year-old man with metastatic non-small cell lung cancer who developed MRSA septic arthritis of the left shoulder, complicated by progression to osteomyelitis requiring surgical resection of the humeral head and placement of an antibiotic spacer. This case highlights the challenges of diagnosing and managing MRSA joint infections in medically complex oncology patients and contributes to the limited literature on chronic shoulder sepsis in older adults.

Case Presentation:
A 70-year-old male with a complex medical history including metastatic non-small cell lung cancer, prior thyroid cancer, Parkinson’s disease, diabetes, and chronic kidney disease, presented with 3-month history of left shoulder pain, recurrent falls and generalized weakness. Radiographic imaging was unremarkable, but aspiration of the deltoid bursa yielded 41 cc of fluid, which cultured MRSA. He underwent left shoulder irrigation and debridement with intravenous (IV) vancomycin initiated. During subsequent admission for left shoulder pain, a second debridement was required. Intraoperative cultures were negative, but bone biopsy confirmed chronic osteomyelitis. Two months after initial admission, he returned to the hospital and underwent left humeral head resection arthroplasty with antibiotic spacer placement. He remained on IV vancomycin for an additional 2 months. His orthopedic recovery was complicated by rotator cuff insufficiency, glenoid wear, and humeral necrosis.

Discussion:
Over the course of six months from his initial presentation, he required coordination between orthopedics, infectious disease, and oncology. He had recently discontinued palliative pembrolizumab and showed signs of oncologic disease progression; radiation oncology deferred further radiation treatments. He was last seen by infectious disease seven months following initial diagnosis of septic arthritis. He was free of any shoulder complaints, while continuing to receive daily oral doxycycline.

Shouldering the Burden: A Case of MRSA Septic Arthritis in an Oncologic Patient

Background
Desmoid tumors are rare, benign but locally aggressive connective tissue tumors that primarily occur in young and middle-aged adults. Although nonmetastasizing, desmoid tumors can compress organs, nerves, and vasculature, which can be life-threatening, and cause pain and functional deficits. Due to the rarity and unpredictability of tumor progression, patients experience treatment challenges as no current standard of care exists. Regular imaging surveillance with multidisciplinary team management is required, and treatment options include surgical resection, systemic chemotherapy, or radiation therapy. 

Case Presentation
A 29-year-old male presented for re-evaluation of a right axillary desmoid tumor six years after his initial diagnosis due to concern for tumor expansion into the right clavicle. At the time of his diagnosis, the tumor was determined unresectable due to involvement of local critical structures, and the patient opted for surveillance to monitor tumor progression. Due to the emergence of new symptoms, a repeat MRI and needle biopsy were urgently performed, confirming new infraclavicular involvement. Subsequent genetic testing was negative for pathologic variants, suggesting a non-FAP-associated desmoid tumor. The patient was started on nirogacestat, a new therapeutic agent that has demonstrated efficacy for progression-free survival. Side effects, including transient gonadal toxicity, were discussed before initiating treatment. Following fertility preservation, the patient tolerated nirogacestat well and reported improvement in his pain.

Discussion
Despite desmoid tumors’ low incidence and overall good prognosis, this case demonstrates the significant physical and emotional burden desmoid tumors pose to patients. The uncertainty of tumor progression can be a source of concern to patients. A study by Husson et al found patients with desmoid tumors scored low on physical, social, and emotional functioning scales. Themes contributing to these scores include delayed or wrong diagnoses, confusing and complex treatments with significant side effects, the impact of physical limitations on societal, familial, and personal identities, and lack of knowledge of desmoid tumors and support from healthcare professionals. Similarly, this patient encountered significant hurdles managing his care across several specialties and hospital systems. The rarity of this case, need for a multidisciplinary team, and lack of standard of care contributed to delays in treatment and heavy emotional burden. Desmoid tumors present a significant disease burden over a lifetime and necessitate quality of life considerations such as family planning. Future management should consider the long-term effects of treatment, risk-benefit analyses, and patient support, including evaluation and management of health-related quality of life, anxiety, and depression.

Navigating the Challenges of Inoperable Desmoid Tumors: A Case Study on Multidisciplinary Management and Quality of Life Considerations

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. 


Invasive Pulmonary Aspergillosis in Multiorgan Dysfunction: A Diagnostic Challenge

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.

Next from 2025 AMA Research Challenge – Member Premier Access

Diagnostic and Therapeutic Benefits of POCUS in Assessing Musculoskeletal Pain in Primary Care Settings