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Decoding the Lion - Roaring Flank Pain in a Male Patient: Challenges in Diagnosis and Management
No full textBackground: Loin Pain-Hematuria Syndrome (LPHS) is a rare condition, affecting approximately 0.012% of the population. Here, we present an unusual case of bilateral loin pain with gross hematuria Case Presentation: A 52-year-old male presented with two months of intermittent bilateral flank pain and blood clots in his urine, now daily for the past three days. He had diabetes and hypertension but no history of kidney stones. His vital signs were normal, with tenderness in both costovertebral angles. Laboratory tests showed a white blood cell count of 8.5, hemoglobin 15.2 g/dL, platelets 202, and creatinine 0.7 mg/dL. Urinalysis revealed 10 leukocytes and >150 red blood cells per high-power field. A CT scan showed normal kidneys with no cortical thinning, hydronephrosis, cysts, mass, or stones. A full urological workup, including cystoscopy, identified no cause, leading to an LPHS diagnosis. He required opioid-based pain management and supportive care. Discussion: LPHS is termed primary when it occurs without any acquired glomerular disease and secondary when linked to conditions like immunoglobulin A nephropathy. In primary LPHS, biopsies show normal glomeruli, but red cells or casts in the tubules suggest glomerular bleeding. Loin pain stems from tubular obstruction, backflow, tissue swelling, and stretching of the kidney capsule. Patients usually report recurring or persistent pain near one or both costovertebral angles. Hematuria is typically microscopic with dysmorphic red cells, indicating a glomerular source. Non-glomerular causes, like kidney stones, infections, polycystic kidney disease, and tumors, must be ruled out, as well as urinary tract obstruction through imaging. LPHS does not impair kidney function or lead to infections or secondary injury. Due to its rarity and unclear pathophysiology, specific treatments are limited, typically involving Angiotensin-Enzyme Converting inhibitors, Angiotensin receptor blockers, and pain management with opioid and non-opioid medications. Renal denervation and auto-transplantation have shown limited success, though spontaneous resolution can occur. Diagnosis of LPHS is essential for primary care providers to avoid misdiagnosis, as it often mimics somatic or psychiatric disorders. Early recognition and exclusion of other causes allow providers to manage symptoms, guide referrals, and support patients effectively, preventing unnecessary interventions and disability from this painful condition
Gastrostomy Tube and Growth Parameters in Patients with Hypoplastic Left Heart Syndrome
No full textPurpose: Hypoplastic Left Heart Syndrome (HLHS) has an incidence of 8-25 per 100,000 live births. Adequate nutrition is an essential component throughout childhood to ensure proper growth, development, and milestone achievements. Feeding dysfunction and subsequent growth failure can occur necessitating the use of supplemental feeds through a gastrostomy tube/button (GB). We hypothesize that HLHS patients with GB will have higher growth rates at stage II surgery, stage II discharge and at Fontan surgery. This study aims to evaluate the impact of gastrostomy tube placement on the growth trajectory of HLHS patients and to identify potential factors influencing their growth outcomes. Methods: This study involved a retrospective review of patients who underwent the Norwood procedure for HLHS from 2007 to 2024 at Cook Children’s Medical Center (CCMC). Patients were excluded for remaining inpatient from Norwood to Glenn procedures, or having a G-button implanted prior to Norwood surgery. Growth was assessed by using World Health Organization (WHO) and the Center for Disease Control and Prevention (CDC) growth charts to compute gender- and age-adjusted z-scores for body mass index (BMI), height, and weight, followed by calculation of the difference in z-scores. Patients with and without G-buttons were compared using two-tailed independent samples t-tests. Results: One hundred and ninety-two patients met criteria for this study. 192 patients underwent Norwood procedure with 146 patients undergoing stage II palliation. 84 patients underwent GB placement in the interstage period. 95 patients underwent Fontan completion. Statistical significance was demonstrated in BMI z-scores from stage II discharge to Fontan, height z-scores from Norwood surgery and discharge to Fontan, and weight z-scores from Norwood discharge, stage II surgery, and discharge to Fontan, with patients without a GB showing more favorable growth outcomes compared to those with a GB. However, patients with a GB showed positive trends in BMI and weight z-scores, particularly from Norwood surgery to stage II discharge and from Norwood discharge to stage II discharge respectively. Conclusions: In patients with HLHS, the use of a gastrostomy tube following the Norwood procedure does not result in a statistically significant improvement in growth compared to those who do not receive a GB. However, our findings suggest that GB placement may offer benefits during specific interstage periods, with positive changes observed in BMI and weight z-scores. While statistical significance was not reached overall, these trends highlight the potential role of GBs in mitigating growth failure during critical developmental stages. Further investigation is warranted to explore underlying factors that influence growth, such as genetic syndromes, comorbidities, or other clinical variables that may necessitate the use of gastrostomy tubes. As such, these findings offer valuable insights into the role of GB placement in the growth management of HLHS patients in our center and underscore the need for further research to refine clinical strategies for improving outcomes in this challenging patient population
Allergic interstitial nephritis following cefazolin and nafcillin exposure in the inpatient setting
No full textBackground: Allergic interstitial nephritis, also called drug-induced acute interstitial nephritis (DI-AIN), is a common cause of hospital-acquired acute kidney injury (AKI). AKI in hospitalized patients correlates positively to mortality. Cefazolin is regarded as a safe alternative in patients with suspected non-IgE-mediated hypersensitivity reaction to nafcillin. However, data is scarce regarding the renal tolerability of nafcillin following cefazolin-induced DI-AIN. Here we present a case of DI-AIN leading to AKI following suspected non-IgE-mediated hypersensitivity reactions to both cefazolin and nafcillin. Case Presentation: A 54-year-old male with uncontrolled type 2 diabetes, hypertension, and no history of drug allergy presented to the emergency department for knee pain and erythema. Arthrocentesis showed purulent fluid. Cultures confirmed methicillin-sensitive staphylococcal aureus (MSSA) arthritis and bacteremia. Empiric vancomycin, cefepime, and metronidazole was narrowed to cefazolin based on sensitivities. Patient was discharged on peripherally inserted central catheter line administered cefazolin but re-admitted within 24h due to home circumstances no longer permitting parenteral antibiotics. Inpatient labs revealed creatinine and blood urea nitrogen (BUN) twice above the patient’s baseline with 50% reduction in glomerular filtration rate (GFR) and hemoglobin 5.8 g/dL that warranted transfusion. Cefazolin was replaced with nafcillin, followed by a negative hemolytic anemia workup. Repeat labs showed further GFR reduction and BUN and creatinine elevation. Urinalysis revealed red blood cells, white blood cells, eosinophils, and proteinuria. Patient was switched to renally dosed daptomycin. While creatinine and GFR improved, inpatient labs indicated ongoing renal impairment that ultimately required dialysis in the intensive care unit. Conclusions: Successive exposure to cefazolin and nafcillin may have facilitated AKI leading to renal derangements in the setting of probable pre-existing diabetic nephropathy. Drugs that precipitate DI-AIN may lead to chronic kidney disease since such patients may not gain full recovery of kidney function. Although kidney biopsy was not performed in this patient, urinalysis and temporal association of AKI onset with the initiation and cessation of beta-lactam antibiotics supports the likelihood of DI-AIN precipitating rapid renal dysfunction. While cefazolin and nafcillin are first-line agents for MSSA bacteremia with extremely low cross-reactivity, caution should be used in patients with probable pre-existing renal dysfunction when switching from cefazolin to nafcillin with concerns over renal tolerability
Structural Analysis of Prime Editors
No full textPurpose: Prime editing is a gene-editing technology that allows a more precise alternative to the traditional CRISPR-Cas9 methods. Prime editing allows for targeted modifications of the genome with minimal off-target effects. The technique relies on a fusion of a catalytically impaired Cas9 protein, called a prime editing guide RNA (pegRNA), and a reverse transcriptase enzyme (RT), and creates single-strand nicks in the DNA instead of double-strand breaks. Two notable versions of prime editors are PE2 and Pemax. PE2 is an early version of the prime editor system, while PEmax is an optimized variant designed to improve efficiency and expand the scope of targetable sequences. Both versions utilize the same fundamental mechanism but differ in their structural and functional properties. From PE2 and PEmax there are 10 different models respectively each derived from removing different functional domains in the RT that affect editing efficiency. By analyzing these 20 truncated models, we can determine which models are most similar to the wild-type PE2 and PEmax and which functional domains play a more significant role in the editing process. Methods: Using AlphaFold, a predicted 3D protein structure from the prime editor truncated sequences is generated. The predicted structure is loaded to the simulation program YASARA which allows for 3D visualization of protein and can run a MUSTANG Alignment which utilizes an algorithm for a structural alignment of multiple protein structures and gives an RMSD value indicating the mean deviation between corresponding structures. Results: For PE2, RMSD values fall below 1.0, with one exception (PE2.5), indicating that most truncations introduce moderate changes to the structure. This suggests that PE2 is relatively robust to truncations in the RT domain, with certain truncations leading to more substantial structural alterations. In contrast, PEmax shows more significant structural deviations in some truncated forms. The higher RMSD values indicate that PEmax is more sensitive to RT truncations, leading to greater structural changes. Conclusions: The differences in RMSD values between PE2 and PEmax suggest that PEmax might be more structurally sensitive to truncations than PE2. This could have implications for the design of truncated PEmax variants, where maintaining functionality might require more careful consideration of truncation sites compared to PE2
Control of in situ-forming implant formation in vitro using a dissolvable gel
No full textPurpose: Parenteral controlled release drug delivery systems are becoming increasingly popular, seen in the forms of preformed implants, microparticles and nanoparticles, and in situ-forming implants. In situ-forming implants are unique due to being injected as liquid and then form a solid implant in situ via phase separation and solvent/non-solvent exchange. The shape and size of the implant contributes to the initial burst release and continued drug release kinetics. One obstacle in in situ-forming implant development is the lack of standardized dissolution testing. Implants are often formed in vitro and then transferred to a suitable media for incubation and drug release. This two-step process limits our ability to standardize in situ implant dissolution testing. Our research focuses on developing an in vitro dissolution method for in situ-forming implants that employs a dissolvable gel to form implants of consistent shape and size. After implant formation, the gel is dissolved and cleared from the implant surface, allowing drug diffusion during the dissolution testing, resulting in a one-step implant formation and incubation process. Methods: Sterile, water soluble, unscented lubricating jelly (McKesson, Inc) was used as dissolvable gel mixed with phosphate-buffered saline (PBS). In situ- forming implant injections consisted of 20% percent Poly(lactic-co-glycolic acid) (PLGA) in dimethyl sulfoxide (DMSO). 50µL of in situ-forming implant formulation was injected into each dilution of dissolvable gel and PBS in 5mL Eppendorf tubes and incubated at 37°C for one hour at 50 rpm after which implant size and shape was assessed using digital calipers. In addition, implant formation in select dissolvable gels was studied in dialysis tubing in preparation for in vitro dissolution testing. Results: Injecting the implant formulation into dissolvable gel or gel/PBS produced more consistent shape and size of implants than in pure PBS. The implants shapes ranged from spherical to ribbon-like, impacted both by the constitution of the media and injection technique. By visual inspection, injection into 100% or 80% gel resulted in the most consistent shape, with the surface of the implant more even and smooth when compared to implants formed in PBS. Implants in the aforementioned concentrations had less trailing of implant formulation as the needle was removed. This trailing was seen at lower concentrations of gel, resulting in string-like structures protruding from the implant. Implants in pure PBS showed most inconsistent shape. Conclusion: Our results showed that in-situ forming implant formulation injected into dissolvable gel concentrations of at least 80% had more consistent and predictable implant shape and size formation. This confirms that a gel that dissolves away after incubation in water, allowing drug to be released freely long term, can be used to form in situ-forming implants in vitro, eliminating the need for standard two step in vitro dissolution testing. The identified 80% dissolvable gel in PBS will be used to obtain complete drug release profiles in dialysis sacs towards the development of a one-step dissolution testing method for in situ-forming implants
Assessing the Need for a Culturally-Tailored, Technology-Enabled Intervention for Hypertension Management among Keetoowah Band of Cherokee Native American Adults
No full textBackground: Native American communities face a disproportionate burden of chronic diseases, with hypertension (HTN) being one of the most prevalent conditions. HTN significantly increases the risk of severe complications, including heart failure, stroke, kidney failure, and premature death. Additionally, healthcare services for managing HTN often fall short due to limited access to culturally competent care, particularly in rural or underserved areas where many Native American populations reside. Technology-enabled interventions for heart health have shown promise in increasing access to health management resources and enabling real-time data collection for personalized interventions. To date, Native American representation in studies involving such interventions remains insufficient. This study aims to assess the needs for a tailored, technology-enabled HTN self-management (SM) intervention targeting members of the Keetoowah Band of Cherokee Native American adults. We hypothesize that culturally tailored approaches will result in a digital tool for HTN-SM with increased utility, acceptability, and improved SM outcomes for the target population. Methods: This prospective study will employ a mixed-methods approach to collect data on the needs for a technology-enabled HTN-SM intervention. Qualitative data will be collected through focus group sessions to explore attitudes, perceptions, and preferences regarding digital health tools for health management, including features and elements that enhance acceptability and engagement. Quantitative data will include assessments of HTN knowledge, digital literacy, and other metrics related to feasibility and usability, adapted from validated digital technology self-efficacy, chronic disease self-efficacy, and eHealth literacy surveys. There are approximately 14,000 Keetoowah Band of Cherokee Native American adults in Oklahoma. The proportion of digital literacy within this population is unknown. Assuming that half of the population lacks digital literacy, this study aims to recruit 96 individuals to achieve a 95% confidence level with a 10% margin of error. Results: We anticipate identifying specific cultural, functional, and technological preferences that will inform the development of a tailored digital intervention. Based on our similar work targeting African American adults, we expect this study to reveal high levels of acceptability and feasibility for a culturally tailored HTN-SM tool and highlight significant gaps in existing health management resources within this community. Conclusion: This study will provide critical insights into the needs and perceptions of Keetoowah Band of Cherokee Native American adults regarding a tailored, technology-enabled HTN intervention designed to improve HTN-SM outcomes and address health disparities in Native American populations. The findings will also inform the development of a personalized, technology-enabled HTN-SM tool that would not only be accepted and feasible but sustainable, as it would be designed through the cultural lens of this vulnerable population
Early weaning impacts craniofacial morphology and integration in Osteogenesis imperfecta
No full textPoster Highlight: College of Biomedical and Translational Science, RAD 2025 Award Winning Posters & Oral PresentationsDuring early life, mammalian infants progress through crucial oral motor stages, from suckling to mastication. Difficulties in any phase can profoundly impact adult craniofacial structure and function. Infants diagnosed with osteogenesis imperfecta, a genetic disorder characterized by impaired type I collagen production and disrupted biomineralization, frequently exhibit difficulties with latching and suckling. These difficulties often necessitate interventions such as feeding tubes or premature cessation of breastfeeding that leads to early weaning. Here we investigate whether early weaning differentially affects craniofacial development in mice with OI (OIM-/-) compared to their unaffected wild type littermates (WT mice). We hypothesize that early weaned (EW) mice will exhibit more dysmorphologies than typically weaned (TW) mice, ie. EW-OIM mice will have decreased facial growth and increased macrocephaly compared to all WT and TW-OIM mice. EW mice were separated from the dam at postnatal day (P15), and TW mice at P21 (n=20 EW-OIM/ 20 TW-OIM/ 27 EW-WT/ 26 TW-WT). All crania were imaged with microCT, and SlicerMorph (3DSlicer software) was used to generate point clouds and fixed landmarks. Geometric morphometric analyses were used to compare craniofacial size and shape differences at P21. Morphological integration between cranial regions (face, cranial vault, cranial base, palate, and zygomatic arches) was assessed using pairwise comparisons of landmark data with the integration.test function in geomorph (R). This study found significant differences in morphological shape between genotypes (p=0.001) and weaning conditions for OIM mice (p=0.015). Overall, OIM mice had lower integration among modules than WT mice. All mice had significant integration between the palate-rostrum, palate-cranial base, and cranial base-cranial vault (p<0.05). EW-OIM mice also had significant integration between the cranial base-rostrum (p=0.05) while TW-OIM mice had significant integration between palate-cranial vault (p<0.01). Integration between the zygomatic arches and rostrum were only significant for the TW-WT mice (p=0.03). Overall, OIM mice were significantly different in craniofacial morphology and integration than WT mice. Early weaning impacts the shape differences between genotypes and weaning conditions in OIM. These findings highlight the potential impact of the timing of weaning in shaping adult OI craniofacial morphology. These results also suggest that supporting nursing and/or non-nutritive suckling in care plans for infants with OI could improve developmental outcomes
Differentiating Alzheimer’s Disease and Vascular Dementia Through Verbal Fluency and Confrontational Word Naming Profiles
No full textPurpose: Alzheimer’s disease (AD) and vascular dementia (VaD) are the two most common forms of dementia, each presenting with distinct cognitive profiles. AD is characterized by semantic memory degradation, leading to deficits in semantic fluency and confrontation naming, while phonemic fluency remains relatively intact. In contrast, VaD is associated with executive dysfunction, resulting in impaired phonemic fluency but preserved naming ability. This study investigates the hypothesis that individuals with AD will exhibit significantly lower semantic fluency and Boston Naming Test (BNT) scores compared to those with VaD, while individuals with VaD will demonstrate greater deficits in phonemic fluency. Objective: To determine whether impairments in phonemic and semantic fluency, coupled with naming deficits, can distinguish AD from VaD in a clinical outpatient setting. Methods: Neuropsychological test data from 40 participants (AD = 20, VaD = 20) would be retrospectively analyzed. The dataset would include performance on the BNT, phonemic fluency (e.g., generating words starting with “F”), and semantic fluency (e.g., naming animals). Group differences would be examined using independent samples t-tests, and multinomial logistic regression would evaluate the predictive power of these measures in classifying dementia types. Results: It is hypothesized that individuals with AD will show significantly lower semantic fluency and BNT scores compared to those with VaD. It is hypothesized that phonemic fluency scores will be significantly lower in the VaD group, with relatively intact confrontation naming. It is hypothesized that a multinomial logistic regression will correctly classify a high percentage of cases, with semantic fluency and naming deficits strongly predicting AD, while phonemic fluency deficits will predict VaD. Conclusions: The anticipated results would support the hypothesis that distinct fluency and naming profiles differentiate AD from VaD, providing a useful neuropsychological tool for improving diagnostic accuracy and informing targeted interventions. Future research should validate these findings in larger, more diverse samples to enhance clinical applicability. Keywords: Alzheimer’s disease, vascular dementia, Boston Naming Test, semantic fluency, phonemic fluency, neuropsychological assessment References: Henry, J. D., Crawford, J. R., & Phillips, L. H. (2004). Verbal fluency performance in dementia of the Alzheimer’s type: A meta-analysis. Neuropsychologia, 42(9), 1212–1222. https://doi.org/10.1016/j.neuropsychologia.2004.02.001 Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Ikeda, M., & Yamashita, H. (1998). Neurobehavioral correlates of memory preservation in Alzheimer’s disease. Journal of Geriatric Psychiatry and Neurology, 11(2), 59–63. https://doi.org/10.1002/gps.2229 Price, S. E., Jefferson, A. L., & Walker, R. Q. (2011). Recognition memory and verbal fluency differentiate probable Alzheimer’s disease from subcortical ischemic vascular dementia. Journal of the International Neuropsychological Society, 17(5), 687–696. https://doi.org/10.1017/S1355617711000574 Troyer, A. K., Moscovitch, M., & Winocur, G. (1997). Clustering and switching as two components of verbal fluency: Evidence from younger and older healthy adults. Neuropsychology, 11(1), 138–146. https://doi.org/10.1037/0894-4105.11.1.13
Neuronal cell-derived extracellular vesicle microRNA signatures implicated in Alzheimer’s Disease
No full textBackground. Alzheimer’s disease (AD) is a neurodegenerative illness that disproportionately affects Mexican Americans due to a combination of population-specific environmental exposures and genetic risk factors. Exosomes are a class of small, membrane-bound extracellular vesicles that mediate cell-to-cell communication through their bioactive cargo. Small extracellular vesicles (sEVs) generated within the brain cells are known to carry bioreactive molecules such as microRNAs (miRNAs) that are indicative of the early alterations in the AD brain. sEVs are capable of crossing the blood-brain barrier, hence the miRNAs within them are selectively packaged and transported to a distal location to influence gene expression in target cells, thus offering a more accessible window into brain health in living humans. Oxidative stress (OS), a critical driver of both aging and AD pathology, has been shown to affect sEV release and composition, making sEV-derived miRNAs promising candidates for early biomarkers of AD progression. Purpose. This study aimed to identify miRNA signatures related to AD within sEVs released from neurons into (1) the blood of individuals with cognitive impairment or AD that correlate with disease progression and key comorbidities (e.g., T2D, hyperlipidemia, hypertension), and (2) the supernatant of neuronal cultures exposed to OS. Methods. (1) Longitudinal plasma samples (two time points, 2 years apart) from the Texas Alzheimer’s Research and Care Consortium were processed using a two-step method: total exosomes were precipitated, and neuronal-enriched extracellular vesicles (NEEVs) were captured with a biotinylated antibody targeting the neuronal marker CD171. NEEV-derived miRNAs were profiled through next-generation sequencing (NGS) and compared for differential expression between cognitively impaired individuals and healthy controls. (2) SK-N-MC neuronal cells were treated with hydrogen peroxide (H₂O₂) to induce OS. sEVs were isolated from the cell culture supernatant, and miRNAs were extracted from both sEVs and cells. miRNAs were sequenced with NGS, and differentially expressed miRNAs were validated using quantitative PCR. Results. (1) Distinct miRNA profiles in NEEVs from cognitively impaired individuals were identified compared to healthy controls, with notable differences between Mexican Americans (MAs) and non-Hispanic Whites (NHWs), suggesting their involvement in AD pathophysiology. (2) Six overrepresented and two underrepresented miRNAs in sEVs from SK-N-MC cells were identified linked to H₂O₂ exposure which are connected to the NF-κB signaling pathway associated genes. Conclusion: sEV-derived miRNAs from both human plasma and neuronal cell models hold promise as early biomarkers for AD detection, particularly in diverse populations such as MAs and NHWs
Determining the Impact of TOMM40 Single Nucleotide Polymorphisms on Metabolic Syndrome and White Matter Hyperintensity Volume in African Americans.
No full textPoster Highlight: Texas College of Osteopathic Medicine - Research, RAD 2025 Award Winning Posters & Oral PresentationsBackground: Single nucleotide polymorphisms (SNPs) in the TOMM40 gene have been implicated in Alzheimer’s Disease (AD) susceptibility, independent of the well-studied APOE genotype. Furthermore, the SNP rs157582 has been associated with metabolic syndrome in African American populations, prompting an investigation into its potential effects on cognitive decline Method: This study aims to elucidate the impact of 3 different rs157582 genotypes on metabolic syndrome variables and white matter hyperintensity (WMH) volumes in African Americans with mild cognitive impairment (MCI) and AD. Participants included African American adults diagnosed with MCI or AD and cognitively unimpaired (CU) recruited via the Health and Aging Brain Study - Health Disparities (HABS-HD). We analyzed seven key variables: diabetes diagnosis, HbA1c levels, glucose levels, hypertension diagnosis, dyslipidemia diagnosis, triglyceride levels, total cholesterol, and white matter hyperintensity volume. Genotypes for rs157582 were derived from the HABS-HD consortium Infinium Global Screening Array SNP (Illumina) data, and genotypes were tested for association with the metabolic and AD-related outcome variables. Result: Preliminary analyses indicate that individuals carrying the rs157582-T allele exhibited significantly higher rates of metabolic syndrome (i.e., diabetes, hypertension and/or dyslipidemia) diagnoses and indicators of elevated WMH volumes, suggesting a correlation between this genetic variant and both metabolic dysregulation and risk for cognitive dysfunction. Interestingly, the risk of this allele appears to stand independent of APOE allele e4 status, which has previously been linked to TOMM40 genetic associations. Additional studies of mediation/moderation effects of SNP and metabolic comorbidity on cognitive and AD-related imaging outcomes are pending. Conclusion: The findings suggest that the TOMM40 SNP rs157582 may play a crucial role in the intersection of metabolic syndrome and Alzheimer’s disease risk among African Americans. This underscores the importance of genetic screening and metabolic assessment in high-risk populations, potentially informing targeted prevention strategies and interventions to mitigate cognitive decline in individuals at elevated genetic risk for AD