Mycotic Aneurysms in Fungal Meningitis: The management in a case of Fusarium Solani meningitis

Introduction: We present a 31 y.o previously healthy woman who developed Fusarium solani fungal meningitis after undergoing cosmetic surgeries in Mexico. Fungal meningitis and particularly F. solani meningitis is very rare, and little is known about the extent and frequency of neurovascular complications in patients with this condition. To our knowledge, previous reports of fungal meningitis don’t recognize or emphasize enough the importance and extension of neurovascular complications noticed in our patient. Case Presentation: A 31-year-old female presented with severe headaches and intermittent fever, two weeks after receiving epidural anesthesia during cosmetic surgery near the Texas-Mexico border. Lab results showed normal WBC at 3.3 x10(3)/mc, and a high-titer ANA of 1:32 but negative for rheumatoid factor, anti-Ro/SSA, Anti-La/SSB, anti-smith and anti-dsDNA, anti-cardiolipin Ab (IgA, IgG, IgM), and lupus anticoagulant. CSF analysis revealed cloudy fluid with an opening pressure of 25cm, a WBC count of 712 per mm3, protein levels of 50 mg/dl, and glucose levels of 38 mg/dl. Other studies, including routine bacterial CSF cultures were unrevealing. Empirical therapy with Amphotericin and Voriconazole was initiated. A CSF 1,3 B-D glucan testing was over 500. Magnetic resonance venography (MRV) reported increased intracranial pressure. A repeated LP opening pressure was 35cm H2O, glucose was 30 mg/dl, protein levels were over 200 mg/dl, and a WBC count of 743 per mm3. Subsequently, a fungal broad-range PCR and next generation sequencing of the CSF confirmed the presence of Fusarium solani. Despite receiving Intravenous (IV) dual antifungal therapy, the patient\u27s severe headaches and nausea persisted, A cerebral angiogram identified a mycotic aneurysm on the left RCA, treated with an external ventricular drain and coil embolization. She remained in the medical intensive care unit (MICU) to receive ongoing antifungal therapy and close monitoring. Conclusion: Fungal meningitis is predominantly observed in immunocompromised patients, with rare occurrences in immunocompetent individuals. However, our patient developed fungal meningitis following epidural anesthesia, presumptively with contaminated medications and/or equipment. Broad-range PCR of the CSF provided the opportunity to achieve a rapid diagnosis.s. Screening for infection in exposed patients and prompt initiation of empirical dual antifungal therapy is essential to optimize outcomes. CSF testing, such as B-D glucan, can also help to provide a presumptive non-specific diagnosis of fungal meningitis. To our knowledge, this was the first confirmed case of F.solani meningitis during this outbreak, helping guide therapy for this and other exposed patients here and elsewhere. The course of our patient\u27s illness also suggests that ongoing severe headaches and changes in the headache patterns should be further investigated for neurovascular complications, including intracranial hypertension, vasculitis, and mycotic aneurysms. A multidisciplinary collaboration, including Internal Medicine, Infectious Disease, pharmacists, neurosurgeons, and neurologists, has been crucial for the comprehensive care of our patients

Case Report: Kidney Transplant Pyelonephritis

Background: Individuals with end-stage kidney disease (ESKD), and especially those who have received kidney transplants, are at an increased risk of developing urinary tract infection (UTI). UTI, especially recurrent UTI, is a common problem occurring in \u3e75% of kidney transplant (KTX) recipients. Progression of infection can have significant consequences on the functioning of the transplanted kidney. It may be challenging to distinguish complicated UTI from acute or chronic rejection when patients present with fever and abdominal pain at the transplanted location. In this case study, we present the clinical scenario of a patient with a history of hypertension and ESKD who has one functioning transplanted kidney and went on to develop a UTI that progressed to pyelonephritis. Case presentation: A female patient, 55 years old, with a medical history including appendectomy, hypertension (HTN), recurrent urinary tract infections (UTI), and end-stage kidney disease (ESKD) following a kidney transplant in 2017, is currently taking post-transplant anti-rejection medications, namely Tacrolimus and Mycophenolate. She visited the emergency department seeking evaluation for pain in the lower right abdomen that radiates to the back. She also reported intermittent fevers, chills, and increased urinary frequency. During the physical examination, tenderness was noted in the lower right quadrant. Laboratory tests revealed leukocytosis, a slightly elevated Creatinine level of 1.8 mg/dl, and the presence of numerous bacteria in the urine. A CT scan of the abdomen showed atrophic native kidneys and a transplanted kidney in the lower right quadrant without hydronephrosis. In the previous month, the patient had been diagnosed with a complicated UTI caused by pan-sensitive Escherichia coli (E. Coli). She received three days of intravenous Cefepime and was discharged with Cephalexin. Since her kidney transplant six years ago, she has been consistently taking Tacrolimus and Mycophenolate to prevent rejection of the transplanted organ. Her blood pressure has been well controlled, and chronic allograft rejection is considered less likely as the cause of her symptoms. Considering her history of recurrent UTIs and previous use of a fourth-generation cephalosporin, Zosyn (Piperacillin-Tazobactam) is a suitable choice of antibiotic for the current infection. This is particularly relevant as the urine culture results showed that the E. Coli strain is resistant to multiple drugs but susceptible to Zosyn. The patient responded positively to the antibiotic therapy and was discharged with plans for ambulatory infusion follow-up using intravenous Zosyn at home. Conclusion: Escherichia coli (E. coli) continues to be a prevalent pathogen responsible for urinary tract infections (UTIs), both in individuals without underlying health conditions and in patients who have undergone kidney transplantation. When dealing with suspected complicated UTIs, it is crucial to rule out the possibility of acute or chronic renal allograft rejection. In addition, it is important to gather information about the patient\u27s healthcare settings, such as nursing homes, as this can aid in guiding antibiotic therapy. Utilizing broad-spectrum antimicrobials may be necessary while awaiting the results of urine culture and sensitivity testing to ensure appropriate treatment

Patient Navigation Services in the Rio Grande Valley: Impacts on Clinicians, Students, and Patients

Abstract Introduction: Social determinants of health, such as financial instability, lack of a safe and sanitary housing environment, low educational attainment, language barriers, and a high level of disease/trauma burden, have a profound impact on the RGV colonia patient population. These factors continue to adversely impact patient access to needed health care services and contribute to the health disparities seen in the region. To address and mitigate these barriers to quality care, UTRGV SOM, The AHEC Scholars Program, and HRSA have sponsored a student-run patient navigation service initiative for patients of three AHEC Clinics (San Carlos, Bob Clark, and La Victoria). By facilitating communication between AHEC clinicians, patients, and community resources and services, health professions students can improve coordination of care and reduce barriers to care recommendations for patients while also gaining a valuable educational supplement experience. Methods: A mixed-methods exploratory pilot study was conducted to determine the feasibility and acceptability of this ongoing initiative. Three stakeholder groups of the intervention were surveyed: clinicians, health professions student navigators, and patients. Clinicians and health professions students were administered an online survey via email. Patients who have completed their use of patient navigation services were administered satisfaction surveys via telephone in their preferred language. Each stakeholder group was surveyed monthly for the first three months of program implementation to account for the possible addition of members and/or a shift in opinion over time. Results: Survey results revealed uniformly positive feedback from clinicians, HCSNs, and patients This ongoing program intervention is determined to be efficacious and feasible in the lower RGV AHEC clinics. Suggestions for further improvement were qualitatively analyzed and recorded in a sunburst graph to visualize the diversity of opinions. Effective communication and HCSN training were the most substantial categories for change. The importance of the other domains impacting successful healthcare navigation varied across stakeholder groups, but nonetheless, provided quality feedback for improvement. Discussion: A centralized effort amongst health professions student, clinicians, and administrative staff of the AHEC Scholars program led to the successful design and implementation of a multidisciplinary healthcare systems navigation intervention to address health disparities experienced by residents of the colonias in the lower RGV. Our data suggest that the HCSN intervention is a promising and acceptable to link patients, providers, and community resources to address barriers to care and to instill the importance of addressing social determinants of health for health professional trainees

Avoiding a Perfect Storm: Delving into the Consequences of a Complex case of Superimposed Cellulitis after a Herpes Zoster infection

Introduction: Cellulitis is an acute bacterial infection causing inflammation affecting the deep dermis layer as well as the surrounding subcutaneous tissue that does not contain an abscess. In this case study we aim to describe the clinical presentation of a middle aged Hispanic woman who developed a superimposed cellulitis infection following a flare-up of a zoster infection. Herpes Zoster is typically considered a typically benign infection but in immunocompromised individuals severe complications of the infection include bacterial superinfections, coagulopathies including disseminated intravascular coagulation, and central nervous system manifestations including encephalopathy with long term detrimental outcomes [1]. Management of Herpes Zoster Virus complications in immunocompromised patients has been a historically challenging task as there is limited reference data because of the unique presentation of each patient and their varying levels of immunocompetence adds an extra layer of variability to each patient’s presentation. Our patient’s past medical history of Polycystic Ovarian Syndrome, uncontrolled diabetes mellitus type 2, and hypertension created an immunocompromised state predisposing her to an acute cellulitis infection following her most recent flare-up of shingles rash. Social determinants that contributed to her disease progression were her lack of healthcare access including regular check-ups for glucose monitoring and suboptimal treatment for her chronic medical conditions [2]. This is a recurrent theme in patients in a similar situation located in the US-Mexico border where social determinants exponentially affect the healthcare outcomes of patients and often lead to severe outcomes that increase morbidity and mortality in this highly vulnerable population [3]. Case Description: Our patient is a 37-year-old Hispanic woman who presented to the clinic complaining of a rash in her left lower abdominal region, as well as systemic symptoms including a fever and an episode of chills. Her past medical history includes Polycystic Ovarian Syndrome (PCOS), Diabetes Mellitus type 2, hypertension, and hyperlipidemia. She has a history of a Zoster virus rash that flared-up 2 weeks ago that had not resolved and stated that it had progressively worsened and became more erythematous leading to increased pruritus. At the time of her flare-up she was treated with Acyclovir 800 mg Q5h which she said provided minimal resolution of her symptoms. Physical examination revealed a wound covered with a bullous pustular lesion with a warm erythematous portion in the right flank. Her vital signs revealed a low grade fever of 100.8 F and a tachycardic state with a pulse 112 bpm. Further evaluation included a point of care ultrasound (POCUS) to rule out a potential abscess, results were unremarkable . Her most recent laboratory values included a CBC significant for a WBC of 19 and a hemoglobin A1c of 13.6. Patient was treated with an antibiotic regimen including topical clindamycin and 1 dose of intramuscular injection of Ceftriaxone 750 mg. After the administration of the antibiotics available to us at the outpatient center, the patient was told to check in at the emergency room for closer monitoring and possible continuation of IV antibiotic treatment. The patient declined and decided she was going to monitor the symptoms herself because she stated she couldn’t cover the costs of a prolonged hospital stay. She was then advised to report to the emergency room if she noticed worsening symptoms including crackling or crepitation as well as worsening systemic symptoms such as high fevers, chills, or severe abdominal pain. She was seen at the clinic 1 week later to follow up on the progression of the rash and symptom resolution following the completion of her antibiotic regimen. Fig. 1 depicts the localization of the rash when the patient arrived at clinic Day 1. Following antibiotic treatment and appropriate symptomatic monitoring after 1 week, Fig. 2 reveals resolution and subsequent abdominal scarring. During the patient’s follow up, we discussed the importance of continuation of care for her chronic medical conditions to prevent further complications in the future including her predisposition to CAD and susceptibility to infections, her hyperglycemic monitoring, and compliance to treatment regimen. Discussion: This case highlights the unique clinical presentation of cellulitis post-shingles infection in a middle-aged Hispanic woman with multiple unmanaged chronic conditions. The summation of which led to a weakened immune response and superimposed cellulitis infection. This case highlights the potential for superimposed bacterial infections to occur on compromised skin. This case emphasizes the importance of prompt intervention and appropriate health care maintenance to prevent further complications. Limited access to healthcare services can hinder disease management and increase the risk of complications in underserved populations [2] . This case underscores the significance of addressing healthcare disparities and improving access to comprehensive healthcare resources, particularly for individuals with multiple unmanaged chronic conditions, in order to mitigate risk of disease progression and enhance overall patient outcomes. Conclusion: This case illustrates the impact of social determinants on disease progression in a middle-aged Hispanic woman with limited healthcare access and under-managed chronic conditions who developed superimposed cellulitis following HZV infection. The conclusion emphasizes the need for timely intervention, improved healthcare resources, and addressing healthcare disparities to mitigate complications which ultimately leads to improved patient outcomes, especially in underserved populations with limited resources

Results from an Association-Scan of the Extended MHC-class-II Region Using Novel Association-Based Statistical Methods Establish that DQ Allotypes Influence the Risk of FVIII Inhibitor Development in Hemophilia-A Patients

Background: Hemophilia-A (HA) is caused by factor VIII (FVIII)-gene (F8) mutations, variably deficient plasma FVIII activity (FVIII:C), and reduced to absent intrinsic-pathway amplification of coagulation. Infused therapeutic-FVIII-proteins (tFVIIIs) prevent bleeding in all HA patients (HAPs) but about 25-30% with severe-HA and 5-10% with non-severe-HA become refractory with the development of neutralizing-tFVIII-antibodies (“FVIII-inhibitors (FEIs)”). We use Immunochip genotyping in the PATH Study to screen the MHC-class-II (MHCII)-region for classical- and non-classical-HLA-class-II (HLAII)-genes and -pseudogenes for association with FEI-risk while accounting for the non-independence of data due to genetic relatedness and F8 mutational heterogeneity using novel statistical methods. Our results establish that HLAII DQ-allotypes influence the risk of FEI development in HAPs. Methods: The FEI-status of 438 North American HAPs—200 with black-African-ancestry and 238 with white-European-ancestry—was the dependent-variable of interest. The F8-mutation data and a genetic-relatedness matrix were incorporated into a binary-linear-mixed model of genetic-association with FEI-status (Yes vs. No), with ‘Yes’ designating those HAPs having FEIs of either any titer (i.e., \u3e0.4 Bethesda Units (BUs) mL-1) or only high-titer (i.e., ³5.0 BUs mL-1). We used the ImmunoChip to conduct an MHCII-region-wide association screen of FEI-risk against the set of 926 distinct single-nucleotide-variations (SNVs) with high-quality genotypes that passed QC. Results: Following the analytical procedure used in prior studies designed to identify determinants of FEI-risk, we performed the extended-MHCII-region-wide association screen on two groups of FEI-positive HAPs, those with any titer or those with only high-titer. HAPs in the high-titer FEI group are suspected to be more homogeneous with respect to the underlying immunobiology as they appear clinically to have induced full adaptive immunity. In contrast, HAPs in the any titer group are heterogenous as some will have transient FEIs that spontaneously disappear, and others will have FEIs that may remain low-titer despite continued FVIII-replacement-therapy. We found several SNPs that were not only significantly associated in both FEI groups—or significant and suggestive respectively in the high-titer and any titer groups—but also increased in significance (i.e., their p-values decreased) under the high-titer analysis (see Figure). The latter observation indicates that these significant results correspond to true associations that became more apparent as sources of “noise” were removed upon going from the any titer to high-titer analysis. These included a SNP in the 3’-untranslated-region (UTR) of DQB1 (rs1049225, p-value=5.7E-7) and two intergenic HLAII region SNPs (rs2647012, p-value=1.1E-5; and rs2858324, p-value=1.1E-5). The DQB1 SNP reached an ImmunoChip-wide significance threshold in the high-titer analysis (i.e., a p-value \u3c 5.9E-7) and extended-MHCII-region-wide significance in the any titer analysis (i.e., p-value \u3c 5.4E-5). Although the two HLAII-intergenic SNPs were not ImmunoChip-wide significant, they were significant across the extended-MHCII-region (i.e., p-value \u3c 5.4E-5). We found two SNPs that were significant and suggestive respectively in the high-titer and any titer FEI analyses (rs9276189, p-value=1.3E-5; and rs2856717, p-value=3.3E-5) as well as one SNP that was significant in the high-titer FEI analyses but not significant or suggestive in the any titer analysis (rs9271366, p-value=1.9E-6). Conclusion: Our results establish that a novel DQB1 genetic variant is associated with FEIs

TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis.

BackgroundT cell immunoglobulin mucin domain-1 (TIM-1) is a phosphatidylserine (PS) receptor, mediating filovirus entry into cells through interactions with PS on virions. TIM-1 expression has been implicated in Ebola virus (EBOV) pathogenesis; however, it remains unclear whether this is due to TIM-1 serving as a filovirus receptor in vivo or, as others have suggested, TIM-1 induces a cytokine storm elicited by T cell/virion interactions. Here, we use a BSL2 model virus that expresses EBOV glycoprotein to demonstrate the importance of TIM-1 as a virus receptor late during in vivo infection.Methodology/principal findingsInfectious, GFP-expressing recombinant vesicular stomatitis virus encoding either full length EBOV glycoprotein (EBOV GP/rVSV) or mucin domain deleted EBOV glycoprotein (EBOV GPΔO/rVSV) was used to assess the role of TIM-1 during in vivo infection. GFP-expressing rVSV encoding its native glycoprotein G (G/rVSV) served as a control. TIM-1-sufficient or TIM-1-deficient BALB/c interferon α/β receptor-/- mice were challenged with these viruses. While G/rVSV caused profound morbidity and mortality in both mouse strains, TIM-1-deficient mice had significantly better survival than TIM-1-expressing mice following EBOV GP/rVSV or EBOV GPΔO/rVSV challenge. EBOV GP/rVSV or EBOV GPΔO/rVSV in spleen of infected animals was high and unaffected by expression of TIM-1. However, infectious virus in serum, liver, kidney and adrenal gland was reduced late in infection in the TIM-1-deficient mice, suggesting that virus entry via this receptor contributes to virus load. Consistent with higher virus loads, proinflammatory chemokines trended higher in organs from infected TIM-1-sufficient mice compared to the TIM-1-deficient mice, but proinflammatory cytokines were more modestly affected. To assess the role of T cells in EBOV GP/rVSV pathogenesis, T cells were depleted in TIM-1-sufficient and -deficient mice and the mice were challenged with virus. Depletion of T cells did not alter the pathogenic consequences of virus infection.ConclusionsOur studies provide evidence that at late times during EBOV GP/rVSV infection, TIM-1 increased virus load and associated mortality, consistent with an important role of this receptor in virus entry. This work suggests that inhibitors which block TIM-1/virus interaction may serve as effective antivirals, reducing virus load at late times during EBOV infection