United States

Background: Glioblastoma multiforme (GBM) is an aggressive grade IV glioma with poor prognosis.1 The PI3K/AKT/mTOR signaling pathway is frequently dysregulated in GBM, contributing to tumor growth, stem cell survival, and immune evasion.2,3,4 This review examines the potential of this pathway to induce apoptosis and improve therapeutic outcomes.

Methods: A literature search was conducted using PubMed to identify articles published between 2018 and 2025. Search terms included “glioblastoma,” “PI3K/AKT/mTOR,” “PI3K therapy,” and “GBM tumor progression.”

Results: Mechanistic studies identify SLC25A32, β2-microglobulin (B2M), and PDIA4 as key regulators of the PI3K pathway in glioblastoma stem cell (GSC) survival. In GSCs, PI3Kα inhibitor, Alpelisib, and mTOR inhibitor, OSI-027, reduced proliferation, underscoring the pathway’s importance.4 SLC25A32, a mitochondrial folate transporter, was elevated in glioma tissue and associated with increased AKT/mTOR phosphorylation.5 B2M, upregulated in GSCs, activated the pathway by increasing PIP2 levels and promoted M2-like tumor-associated macrophage polarization, contributing to immune suppression.6 PDIA4, an ER chaperone, enhanced glycolysis and suppressed pro-apoptotic proteins, supporting GBM progression.7 A Phase I trial of Perifosine (AKT inhibitor) and Temsirolimus (mTOR inhibitor) showed synergistic tumor reduction in GBM patients, though lack of pharmacokinetic data limits mechanistic insights.8

Conclusion: Targeting the PI3K/AKT/mTOR pathway through regulators like SLC25A32, B2M, and PDIA4 shows promise in disrupting GBM survival mechanisms. Dual inhibition strategies may enhance treatment efficacy, but further mechanistic and clinical studies are needed to optimize therapeutic approaches.


Works Cited:
Wu W, Klockow JL, Zhang M, et al. Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance. Pharmacol Res. 2021;171:105780. doi:10.1016/j.phrs.2021.105780
Berro A, Assi A, Farhat M, et al. Unlocking hope: Anti-VEGFR inhibitors and their potential in glioblastoma treatment. Crit Rev Oncol Hematol. 2024;198:104365. doi:10.1016/j.critrevonc.2024.104365
Agnihotri TG, Salave S, Shinde T, Srikanth I, Gyanani V, Haley JC, Jain A. Understanding the role of endothelial cells in brain tumor formation and metastasis: a proposition to be explored for better therapy. J Natl Cancer Cent. 2023;3(3):222-235. doi:10.1016/j.jncc.2023.08.001.
Eckerdt FD, Bell JB, Gonzalez C, et al. Combined PI3Kα-mTOR Targeting of Glioma Stem Cells. Sci Rep. 2020;10(1):21873. Published 2020 Dec 14. doi:10.1038/s41598-020-78788-z
Xue Z, Wang J, Wang Z, et al. SLC25A32 promotes malignant progression of glioblastoma by activating PI3K-AKT signaling pathway. BMC Cancer. 2023;23(1):589. Published 2023 Jun 26. doi:10.1186/s12885-023-11097-6
Li D, Zhang Q, Li L, et al. β2-Microglobulin Maintains Glioblastoma Stem Cells and Induces M2-like Polarization of Tumor-Associated Macrophages. Cancer Res. 2022;82(18):3321-3334. doi:10.1158/0008-5472.CAN-22-0507
Wang M, Zhang W, Liu Y, et al. PDIA4 promotes glioblastoma progression via the PI3K/AKT/m-TOR pathway. Biochem Biophys Res Commun. 2022;597:83-90. doi:10.1016/j.bbrc.2022.01.115
Kaley TJ, Panageas KS, Pentsova EI, et al. Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma. Ann Clin Transl Neurol. 2020;7(4):429-436. doi:10.1002/acn3.51009


AMA Research Challenge 2025 

Targeting the PI3K/mTOR/AKT Pathway to Induce Apoptosis in Glioblastoma Multiforme: A Mechanistic Review

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poster

Over 65 million people live with epilepsy. The most devastating consequence of epilepsy is sudden death. The cause of sudden unexpected death in epilepsy (SUDEP) is unknown. Convulsive seizures can impair awareness and induce respiratory failure. SUDEP usually occurs at night with victims found prone in bed. Brain 5-HT neurons regulate seizure severity, respiratory physiology, are required for awakening to rising CO2 (CO2 arousal). In humans and nocturnal rodents, 5-HT levels are lowest at night. Mouse models of induced and spontaneous seizures (including the Scn1aR1407X/+ model of Dravet Syndrome (DS mice)) are more fatal at night. We hypothesized that the timing of seizure-associated death is regulated by a circadian rhythm and time-of-day variability in 5-HT. To address this, we employed three seizure models (DS mice, MES, and amygdala kindling) and two methods to eliminate brain 5-HT (genetic and chemical elimination). DS mice were used for spontaneous seizure experiments, and Lmx1bf/f/p (KO) or wild-type (WT) littermates were used for induced seizure experiments. KO mice lack >99% of brain 5-HT neurons. DS mice were continuously monitored in constant darkness. Spontaneous sudden deaths exhibited circadian timing, which was greatest during the subjective dark-phase. Deaths occurred more often while mice were awake, and the timing of death was independent of seizure duration, severity, and the timing of potentially fatal seizures. KO mice and WT littermates were subjected to one MES seizure at different times of day. WT mice were more likely to die during the night. However, KO mice had high mortality regardless of time of day. A cohort of DS mice received daily injections of the tryptophan hydroxylase inhibitor para-chlorophenylalanine (800 mg/kg, PCPA) or volume-matched saline. Saline-treated DS mice were more likely to die during the dark-phase, compared to PCPA-treated mice, which died more during the light-phase. Potentially fatal seizures were associated with full hindlimb extension and prolonged recovery. Recovery took longest when seizures occurred during the subjective nighttime. WT mice instrumented for amygdala kindling were used to examine the role of time-of-day seizures on CO2 arousal. Daytime seizures in kindled mice impaired CO2 arousal; however, nighttime seizures profoundly impaired CO2 arousal (over 10-fold increase). SUDEP occurs more frequently during the night and victims are often found in the prone position. Nighttime seizures may exacerbate 5-HT-associated arousal physiology and increase risk of death. Identification of mechanism of death and biomarkers that predict may help develop chronotherapeutic strategies to eliminate nighttime risk of SUDEP.

The nighttime risk of seizure-associated death is influenced by serotonin and coincident with ...

Background
Despite current treatment strategies for atherosclerosis focusing on lifestyle modification and cholesterol reduction, extracoronary vascular diseases affects >200 million patients worldwide and often remain indolent before progressing to severe disease with morbid complications. The aims of this cohort study were to (1) characterize biomarkers associated with development of severe outcomes and (2) compare pathways driving disease progression in different vascular beds in individuals with existing extracoronary vascular disease. 
Methods
We used proteomic data from individuals in the UK Biobank with extracoronary vascular disease at baseline, defined as peripheral artery disease (PAD), carotid artery stenosis (CAS), and renal artery stenosis (RAS). Severe outcomes were defined by major adverse limb events (MALE; developed after PAD), stroke (after CAS), and hemodialysis (after RAS). The first aim utilized Cox proportional hazards regression models to estimate the associations of 1,463 proteins and 249 metabolites with adjustment for age at enrollment, age at prevalent disease diagnosis, sex, cigarette smoking, systolic blood pressure, and statin prescriptions. The second aim utilized Gene Ontology and hypergeometric enrichment tools to identify enriched pathways. 
Results
There were 1370 individuals with a primary diagnosis of extracoronary vascular disease and 1463 individuals with a secondary complication. Patient with secondary complications were more likely to be older (primary diagnosis mean age = 75.63, secondary complication mean age = 76.36) with similar distributions in sex (P = 0.18), body mass index (P = 0.15), and systolic blood pressure (P = 0.40). There were 17 proteins significantly associated (P<0.001) with MALE and 15 proteins significantly associated with stroke (P<0.001). Progression of PAD and MALE was associated with proteins underlying biomineral tissue development, endothelial cell processes, and pathways involved extracellular signal-regulated kinases 1 and 2 (ERK1/2), mitogen-activated protein kinase (MAPK), interleukin-17 (IL-17), phosphoinositide 3-kinase/protein kinase B (PI3K/PKB), and signal transducer and activator of transcription (STAT). Progression of any severe complications, encompassing MALE, stroke, and hemodialysis were associated with proteins involved in vasculogenesis, endothelial cell migration, connective tissue wound healing, collagen catabolism, and pathways involving tumor necrosis factor (TNF) and nuclear factor kappa-light-chain-enhancer of activated B cells (NK-kB). 
Conclusions
Overall, severe complications of extracoronary vascular disease were associated with proteins involved in angiogenesis (PI3K/PKB, STAT), inflammation (IL-17, TNF, NK-kB), and remodeling (biomineral tissue development, connective tissue wound healing, collagen catabolism). This study provides evidence of the complex role of biomarkers in extracoronary vascular disease pathogenesis and highlights specific proteins as potential targets to improve therapeutic strategies.

Proteomics associated with development of severe complications in patients with extracoronary vascular diseases

Background 
Pancreatic neuroendocrine tumors (P-NETs) are hormone-secreting tumors originating from neuroendocrine cells in the pancreas. Due to the rarity of P-NETs, they remain under studied. Treatment involves surgical resection. Evaluation of margin definition involves both surgery and pathology as cancerous tissue is difficult to visually distinguish from normal tissue without stain. Developing methods for intraoperative margin definition could greatly improve treatment and management. A promising emerging technique is optical redox ratio imaging, a noninvasive metric of cellular metabolism quantified by the ratio of the intrinsic autofluorescence signals of nicotinamide adenine dinucleotide (NADH) to flavin adenine dinucleotide (FAD). This study aims to evaluate the use of multiphoton imaging for margin definition for fresh ex vivo P-NET samples without the use of stains. 

Methods 
Mouse xenografts were utilized, where eight mice were injected with BON-1 cells at the pancreatic tail. The resected tumor was placed immediately in fixative, and the other half was coated with DMEM (basal medium) and imaged using a Zeiss LSM 880 microscope with a tunable MaiTai HP titanium:sapphire light source. Two-photon tissue autofluorescence was excited at 780 nm. Several regions of the tumor-normal boundary were imaged. In total, 32 images were captured, 16 for NADH channel (emission at 425 nm) and 16 for FAD channel (emission at 500 nm). Three 50x50 pixel regions of interest representing tumor, tumor margin, and normal tissue were selected for each image based on the reference H&E slides. The average optical redox ratio was calculated and, statistical significance was evaluated using the pairwise Wilcoxon test with Bonferroni correction. 

Results 
The results of the pairwise Wilcoxon tests with Bonferroni correction showed significant differences for tumor vs margin (p = 0.0059) and margin vs normal (p = 0.0059), but not for tumor vs normal (p = 0.2520). 

Conclusion 
Utilizing the optical redox ratio shows promise to distinguish between tumor, tumor margin, and normal tissue in fresh P-NETs in an ex vivo xenograft model with high translational potential. This work should be further advanced by utilizing a larger dataset and training a machine learning. Future steps include intravital animal imaging, human tissue imaging, and developing custom probes for in-vivo measurements. Overall, this work shows great promise as a preliminary study to distinguish P-NET margins which could be applied within the fields of oncology, surgery and pathology.

Optical Redox Ratio Distinguishes Pancreatic Tumor Margins in an Ex Vivo Xenograft Model

Background:
Obstructive sleep apnea (OSA) is increasingly recognized as a risk factor for cognitive decline and dementia, but treatment adherence and efficacy in real-world settings may influence long-term outcomes. While continuous positive airway pressure (CPAP) is the standard of care, surgical options provide an alternative path for managing OSA. In this retrospective cohort study, we utilized the TriNetX database to examine whether surgical interventions for OSA were associated with a reduced incidence of dementia diagnoses and dementia-related pharmacotherapy compared to CPAP therapy.

Methods:
We identified adult patients (ages 45–80) with OSA using ICD-10-CM codes and divided them into two cohorts based on CPT codes indicating either CPAP initiation or surgical intervention (palatopharyngoplasty or inferior turbinate resection). Patients with cancer or cranial nerve stimulators were excluded. Propensity score matching was performed (1:1) on key demographic and clinical variables, including age, sex, race, BMI, and comorbidities. Patients were followed up from 6 months up to 10 years post-intervention for new diagnoses of Alzheimer’s disease, vascular dementia, unspecified dementia, and prescriptions for memantine or acetylcholinesterase inhibitors (AChEIs).

Results:
After propensity score matching, 9,739 patients remained in each group. Compared to surgical patients, CPAP patients had significantly higher risks of vascular dementia (RR 3.01, P=0.002), unspecified dementia (RR 5.12, P<0.001), memantine use (RR 2.92, P=0.001), and AChEIs use (RR 1.91, P=0.017). Alzheimer’s disease incidence was higher in the CPAP group (RR 2.00, P=0.054), though not statistically significant. 

Conclusion:
Surgical interventions for OSA were associated with significantly reduced long-term incidence of dementia and the need for dementia-related medications compared to CPAP in this real-world cohort. These findings suggest that in practice, where CPAP adherence is variable, surgical treatment may offer superior cognitive protection. Further prospective studies are needed to confirm causality and explore underlying mechanisms.


Dementia Outcomes in Obstructive Sleep Apnea: Surgical vs. CPAP Intervention

Background: Oropouche virus (OROV), an arbovirus transmitted by Culex and
Culicoides mosquitoes, was first identified in Trinidad in 1955. While commonly reported in South America, it had not been seen in the continental United States until 2024. We report the first two confirmed pediatric cases of OROV in South Florida, both with travel history to Cuba amid a regional outbreak in May 2024. These cases underscore the need for increased awareness, diagnostic
capability, and vector control. The first case is of a 16-year-old male on immunosuppressive therapy that presented with recurrent fever, headaches, fatigue, and decreased appetite following travel to Cienfuegos, Cuba. Initial tests for Dengue were negative and OROV antibodies returned positive (1:20). He recovered fully with outpatient supportive care. The second case we present was of a 15-year-old male who developed fever, vomiting, diarrhea, headaches, and fatigue after returning from Cuba. Multiple ED visits led to the findings of elevated monocytes and negative Dengue titers, and was ultimately admitted for supportive care. OROV antibody testing returned positive (1:160). These cases highlight OROV as an emerging arboviral illness with potential for geographic spread. Both patients exhibited biphasic illness, with symptoms including fever, headaches, and gastrointestinal upset. Laboratory findings consistently revealed monocytosis and atypical lymphocytes. Neither patient developed complications such as aseptic meningitis, although both exhibited headaches—an important consideration given the virus’s reported neuroinvasive potential. Current testing protocols rely on Dengue exclusion before pursuing OROV diagnostics, risking delayed or missed diagnoses. Broader multiplex PCR testing may improve timely detection. These cases emphasize the need for enhanced surveillance and preparedness, especially in Dengue-endemic regions. Public health measures, including vector control, travel advisories, and expanded testing access, will be essential in mitigating the impact of this emerging virus.

First Two Cases of Oropouche Virus detected at a Pediatric Hospital in South Florida

Background
Infective endocarditis (IE) typically presents with fever, malaise, and embolic phenomena. Risk factors include structural heart disease, prosthetic valves, IV drug use, and invasive procedures (1,2). Persistent hiccups (singultus), lasting over 48 hours, are rarely associated with IE and more often linked to gastrointestinal, neurologic, or metabolic disturbances (3,4). Limited reports suggest that IE may cause hiccups via phrenic or vagus nerve irritation or septic emboli to the brainstem (5–8). Group B Streptococcus (GBS) is a rare cause of adult IE but is associated with aggressive infection, especially in patients with uncontrolled diabetes (10). We describe a rare case of bivalvular GBS IE presenting with persistent hiccups.
Case Presentation
A 58-year-old man with no significant medical history presented with four days of persistent hiccups, fever, chills, diaphoresis, polydipsia, polyuria, and right upper extremity pain. Exam revealed a 3/6 holosystolic murmur and right hand swelling with limited range of motion. Labs showed WBC 17,000/µL, glucose 400 mg/dL, HbA1c 11.0%, CRP 296 mg/L, and hyponatremia. Urinalysis showed glucosuria and ketonuria. Chest X-ray revealed multifocal infiltrates. Initial management targeted presumed pneumonia. Blood cultures grew Streptococcus agalactiae (GBS). Echocardiography revealed a large mitral valve vegetation with severe regurgitation and posterior leaflet perforation, as well as a smaller tricuspid vegetation with moderate regurgitation. Diagnosis of bivalvular IE was made per Duke criteria. Antibiotics were escalated to IV ampicillin and gentamicin. The patient was transferred for surgical evaluation.
Discussion
IE remains diagnostically challenging due to its diverse presentations (1,2). Persistent hiccups are an unusual symptom, but may indicate serious underlying pathology when accompanied by systemic signs (3,4,9). In this case, persistent hiccups were linked to bivalvular GBS IE, possibly due to autonomic nerve irritation or central embolization (5–8,11). The patient’s uncontrolled diabetes likely predisposed him to severe infection, as hyperglycemia impairs neutrophil function and increases the risk of invasive disease (10,12). This case reinforces the importance of considering IE in patients with persistent hiccups and fever, even in the absence of classic risk factors, and highlights the value of early echocardiography in guiding diagnosis and management.


Persistent Hiccups as an Unusual Presentation of Group B Streptococcal Infective Endocarditis with Bivalvular Involvement

Background

Blastomycosis is a fungal infection endemic to regions of North America, including Ohio and the Mississippi River Valleys. While pulmonary disease is the most common manifestation of blastomycosis, extrapulmonary dissemination can occur, with the skin being a frequent site of involvement. Cutaneous blastomycosis often presents as verrucous or ulcerated lesions. It can also present as pustular nodules, mimicking bacterial folliculitis, and lead to a delay in diagnosis and treatment.


Case Presentation

A male in his mid-60s with no history of immunosuppression presented with 6 weeks of tender, violaceous dermal nodules on his thigh, heel, back, abdomen, and chin. The patient initially believed the nodules were spider bites. These nodules burned, developed rapidly, and eventually formed tense blisters that drained a serosanguinous exudate. He had been treated unsuccessfully with multiple courses of antibiotics for presumed bacterial folliculitis. He then developed systemic symptoms, including fevers, malaise, and prostatitis.


Examination revealed multiple crusted, annular, violaceous nodules on his calf, arm, thigh, back, and jaw. Some lesions contained a collarette of scale with heme crust. The right heel was found to have a tense bulla with mild red inflammation. A punch biopsy and fungal cultures identified broad-based budding yeast, confirming blastomycosis. Blood tests were positive for Blastomyces antigen and antibody. A chest CT showed cavitary pulmonary nodules. A urine culture confirmed genitourinary involvement.


Treatment was initiated with an itraconazole loading dose of 200mg three times a day for three days followed by 200mg twice daily with a plan for 6-12 months of therapy. Despite adherence and attempts to optimize absorption, his serum itraconazole level was subtherapeutic. To achieve appropriate levels, the dose was increased to 300mg twice daily.


Discussion

This case highlights the diagnostic challenge of atypical cutaneous blastomycosis in immunocompetent patients. While classic lesions are verrucous or ulcerated, non-specific lesions of cutaneous blastomycosis can closely resemble bacterial folliculitis, especially if it manifests as pustular or nodular lesions. Ultimately, this misdiagnosis led to an incorrect use of antibiotics and the worsening of his clinical condition.


Clinicians must maintain a high index of suspicion for deep fungal infections in lesions that are persistent, atypical, or unresponsive to antibiotics. In endemic areas, immunocompetent patients without clear risk factors/behaviors can develop blastomycosis. Early biopsy and fungal-specific testing are crucial for timely diagnosis and treatment. Optimal management of blastomycosis requires awareness of itraconazole pharmacokinetics, including the need for acid-mediated absorption and therapeutic drug monitoring.

Cutaneous Blastomycosis Masquerading as Bacterial Folliculitis: A Diagnostic Challenge

Background
Invasive ductal carcinoma (IDC) is the most common type of breast cancer in women, and metastasizes most commonly to bone, lung, liver, and central nervous system. Breast cancer metastasis to the gallbladder is exceptionally rare and seen mostly in cases of invasive lobular carcinoma or mixed lobular and ductal origin; gallbladder metastasis is even more rarely reported from breast cancer with ductal origin.

Case Presentation
A 43 year old female with depression was diagnosed with IDC of the right breast, receptors ER+/PR+/HER-2+. She underwent six cycles of neoadjuvant chemotherapy, which was delayed significantly due to lapses in insurance. She underwent right lumpectomy, completed adjuvant breast radiation, and initiated a partial course of adjuvant biologic therapy and hormone therapy which was halted early due to suicidal ideation. Subsequently, the patient did not present for her follow-up appointments or surveillance mammograms.
Three years and nine months after her lumpectomy, she presented with two days of right upper quadrant abdominal pain. Physical exam, labs, and imaging workup were consistent with early acute cholecystitis, and she underwent laparoscopic cholecystectomy. Gallbladder pathology was compatible with metastatic carcinoma of breast origin, likely invasive mammary ductal carcinoma. Before the patient was able to follow-up with outpatient oncology, she presented to the emergency department 18 days after cholecystectomy with epigastric pain, vomiting, and shortness of breath. CT scan showed pelvic ascites, liver metastasis, bony metastasis, and bilateral lung metastasis. She was admitted inpatient and started on goserelin injections every 28 days as well as Herceptin and Perjeta. However, patient began to have worsening mentation and respiratory distress, was placed on comfort care, and died three years and ten months after her lumpectomy.

Discussion
Our literature review of eight cases reporting breast cancer metastasis to the gallbladder found no obvious trends in receptor status, time to gallbladder symptoms after breast cancer diagnosis, or survival after gallbladder removal. The only universal aspect within our literature review was that each symptomatic presentation was diagnosed as cholecystitis, and gallbladder metastasis was diagnosed on review of the pathology after cholecystectomy. Therefore, adequate suspicion should be maintained when evaluating patients with a history of breast cancer who present with symptoms of cholecystitis in order to promptly identify breast cancer metastasis to the gallbladder. 


Invasive ductal carcinoma of the breast with gallbladder metastasis: a rare case involving the natural course of invasive ductal carcinoma with incomplete adjuvant treatment

Background: This report details a rare case of fulminant babesiosis in a splenectomized patient, emphasizing key diagnostic and therapeutic dilemmas. Babesiosis is a globally emerging tick-borne disease caused by the protozoan Babesia, posing a significant public health burden with mortality reportedly greater than 20% in immunocompromised individuals and those with transfusion-acquired infections. Splenectomized individuals are especially vulnerable to life-threatening Babesia infections, often manifesting as a more hazardous course requiring aggressive treatment.

Case Presentation: A 62-year-old pre-diabetic male with a history of traumatic total splenectomy presented with three days of high-grade fever, chills, bodyache, weakness, and near-syncopal episodes. Laboratory evaluations indicated anemia, haptoglobinemia, thrombocytopenia, leukocytosis, elevated creatinine and blood urea nitrogen, hepatic transaminitis, hyperbilirubinemia, and hypoalbuminemia. A peripheral blood smear confirmed the diagnosis, revealing extra- and intra-corpuscular Babesia microti with prominent vacuoles and ring forms, with a high parasitemia level of 17.6%. The patient was diagnosed with severe babesiosis complicated by multi-organ failure - including acute kidney injury and liver failure. Antiparasitic therapy with atovaquone and azithromycin was instituted. Additionally, the patient required multiple red blood cell exchange (RCE) transfusions with 12 units of packed red blood cells (PRBCs), to reduce the parasitemia down to a safer level (4%) leading to gradual clinical stabilization over the next few days.

Discussion: This case emphasizes the importance of high clinical suspicion and prompt diagnosis of babesiosis in susceptible patient groups, such as asplenic patients, presenting with unexplained fever, especially with hemolytic anemia or multi-organ dysfunction. Diagnosis relies on blood smear microscopy or polymerase chain reaction (PCR) test. Standard treatment combines atovaquone and azithromycin, or clindamycin and quinine. Exchange transfusion is typically recommended for severe babesiosis, especially for parasitemia exceeding 10% or organ dysfunction, to reduce parasite burden and clear out harmful toxins. While high parasitemia strongly correlates with disease severity, the definitive clinical benefit of RCE, particularly when compared to antibiotic therapy alone, is a topic of ongoing debate in the literature. The optimal administration and precise indications for RCE are not well studied, with current guidelines based on weak evidence and vaguely-defined criteria. RCE predisposes to potentially serious complications including transient hypotension, dyselectrolytemia, transfusion reactions, transfusion-related infections, fluid overload, and acute respiratory distress syndrome (ARDS). As babesiosis cases continue to rise in endemic regions of the US, targeted research is urgently needed to determine definitive effectiveness of RCE and to develop clear, evidence-based guidelines for its use in severe cases, ensuring safe patient outcomes.

Severe Babesiosis in an Asplenic Patient Treated with Red Cell Exchange: Highlighting the Critical Need for Evidence-Based Guidelines – A Case Report and Literature Review

Background:
The posterior femoral cutaneous nerve (PFCN) is a purely sensory nerve arising from the sacral plexus that supplies sensation to the posterior thigh, gluteal fold, and upper medial thigh. Isolated PFCN mononeuropathies are rare, underrecognized, and present with neuropathic pain without motor deficits; very few cases are documented as of 2025. Posterior thigh pain is often misattributed to sciatic or pudendal nerve involvement or musculoskeletal strain, leading to misdiagnosis and ineffective treatment and the deep anatomical location further complicates identification. While peripheral nerve blocks are increasingly used in pain management, selective ultrasound-guided blockade of the PFCN is seldomly reported.

Case Presentation:
A 20-year-old collegiate track athlete presented with persistent right posterior thigh, hip, and gluteal pain following a hamstring strain during sprint training. Despite physical therapy and MRI ruling out musculoskeletal or sciatic nerve pathology, she reported sharp, stabbing pain with numbness radiating to the posterior thigh and gluteal fold. The pain impaired daily activities and prevented her from competing in her track meets. Examination revealed sensory changes along the PFCN distribution without motor weakness. Given the pure sensory distribution, an ultrasound-guided PFCN block was performed using 0.25% Bupivacaine with epinephrine and betamethasone. The patient experienced immediate, near-complete pain relief with no motor deficit, allowing ambulation and return to activity the same day. Within two weeks, she returned to full competition, reaching the state finals. At four-week follow-up, she remained over 90% symptom-free.

Discussion:
This case highlights the therapeutic potential of selectively targeting the PFCN in isolated posterior thigh neuropathic pain. While nerve blocks are well-established for mixed motor-sensory nerves such as the sciatic nerve, there is minimal literature on ultrasound-guided sensory-only blocks for the PFCN. Anatomically, the PFCN lies within the gluteal deep investing fascia (GDIF), medial to the inferior gluteal artery and superficial to the sciatic nerve, which lies deeper and lateral. Accurate identification of this fascial plane is critical. Hydrodissection separates the gluteus maximus from the fascia to safely visualize the PFCN. Advancing too deep risks spread into the sciatic compartment, potentially causing motor blockade. This precise approach enabled the patient to receive a purely sensory blockade without motor compromise to allow her to return to competition. This rare but effective intervention for isolated posterior thigh neuropathic pain emphasizes the need to include PFCN mononeuropathy in the differential for athletes with refractory thigh pain and highlights the role of targeted nerve blocks in restoring function while preserving motor integrity.

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