Primary amebic meningoencephalitis: a review of Naegleria fowleri and analysis of successfully treated cases.

Primary amebic meningoencephalitis (PAM) is a necrotizing and hemorrhagic inflammation of the brain and meninges caused by Naegleria fowleri, a free-living thermophilic ameba of freshwater systems. PAM remains a neglected disease that disproportionately affects children in tropical and subtropical climates, with an estimated mortality rate of 95-98%. Due to anthropogenic climate change, the average temperature in the USA has increased by 0.72 to 1.06 °C in the last century, promoting the poleward spread of N. fowleri. PAM is often misdiagnosed as bacterial meningitis or viral encephalitis, which shortens the window for potentially life-saving treatment. Diagnosis relies on the patient's history of freshwater exposure and the physician's high index of suspicion, supported by cerebrospinal fluid studies. While no experimental trials have been conducted to assess the relative efficacy of treatment regimens, anti-amebic therapy with adjunctive neuroprotection is standard treatment in the USA. We performed a literature review and identified five patients from North America between 1962 and 2022 who survived PAM with various degrees of sequelae.

Expanding the Donor Pool: First Use of Hepatitis B Virus Nat Positive Solid Organ Allografts Into Seronegative Recipients.

OBJECTIVES: The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients. SUMMARY BACKGROUND DATA: Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated. METHODS: From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival. RESULTS: With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT- with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT- recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P < 0.01). CONCLUSIONS: This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage.

Keeping the lights on: Telehealth, testing, and 6-month outcomes for orthotopic liver transplantation during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has seen transplant volume decrease nationwide, resulting in a 2.2-fold increase in waitlist mortality. In particular, solid organ transplant patients are subjected to increased morbidity and mortality from infection. In the face of these challenges, transplant centers need to develop innovative protocols to ensure high-quality care. METHODS: A multidisciplinary protocol was developed that included the following: virtual selection meetings, coronavirus disease 2019 negative donors, pretransplant symptom screening, rapid testing on presentation, telehealth follow-up, and weekly community outreach town halls. All orthotopic liver transplants completed between January 2018 and August 2020 were included in the study (n = 344). The cohort was stratified from January 2018 to February 2020 as "pre-COVID-19," and from March 2020 to August 2020 as "COVID-19." Patient demographics and postoperative outcomes were compared. RESULTS: From March 2020 to August 2020, there was a significant decrease in average monthly referrals for orthotopic liver transplantation (29.8 vs 37.1, P = .01). However, listings (11.0 vs 14.3, P = .09) and transplant volume remained unchanged (12.2 vs 10.6, P = .26). Rapid testing was utilized on arrival for transplant, zero patients tested positively preoperatively, and median time from test result until abdominal incision was 4.5 h [interquartile range, 1.2, 9.2]. Simultaneously, telehealth visits increased rapidly, peaking at 85% of all visits. It is important to note that there was no difference in outcomes between cohorts. CONCLUSION: Orthotopic liver transplant can be accomplished safely and effectively in the COVID-19 era without compromising outcomes through increasing utilization of telehealth, rapid COVID-19 testing, and multidisciplinary protocols for managing immunosuppressed patients.

Treatment Options for Coronavirus Disease 2019 in Patients With Reduced or Absent Kidney Function.

Coronavirus disease 2019, the disease caused by the severe acute respiratory syndrome coronavirus 2 virus, was first identified in the Hubei Province of China in late 2019. Currently, the only role for therapy is treatment of the disease, as opposed to postexposure prophylaxis, however multiple clinical trials are currently ongoing for both treatment and prophylaxis. Treating coronavirus disease 2019 relies on two components; the first is inhibition of the viral entrance and replication within the body and the second is inhibition of an exacerbated immune response which can be seen in patients with severe disease. Many drugs have shown in vitro antiviral activity; however, clinical trials have not been as promising. This review summarizes the current data for the most commonly used drugs for coronavirus disease 2019 and will cover the unique factors that may affect the dosing of these medications in patients with CKD. While clinical trials are ongoing, most are in patients with normal kidney function. During a pandemic, when patients with CKD are at higher risk of both infection and death, it is imperative to include patients these patients in the clinical trials.

Use of HCV Ab+/NAT- donors in HCV naïve renal transplant recipients to expand the kidney donor pool.

Hepatitis C (HCV) disease transmission from the use of HCV antibody-positive and HCV nucleic acid test-negative (HCV Ab+/NAT-) kidneys have been anecdotally reported to be absent. We prospectively analyzed kidney transplant (KT) outcomes from HCV Ab+/NAT- donors to HCV naïve recipients under T-cell depleting early steroid withdrawal immunosuppression. Allografts from 40 HCV Ab+/NAT- donors were transplanted to 52 HCV Ab- recipients between July 2016 and February 2018. Thirty-three (82.5%) of donors met Public Health Service (PHS) increased risk criteria. De novo HCV infection was detected at 3 months post-KT in one recipient (1.9%). This was a case of transmission from a HCV Ab+ NAT+ donor with an initial false-negative NAT completed using sample collected on donor hospital admission (day 2). At the time of HCV diagnosis, a stored donor sample collected during procurement (day 4) was tested and resulted NAT-positive. Subsequently, sustained virologic response (SVR) was achieved with 12 weeks of glecaprevir/pibrentasvir. One death with functioning graft at 261 days post-KT was determined not related to HCV or donor factors. This experience provides evidence of a low transmission rate of HCV from HCV Ab+/ NAT- kidney donors, thereby arguing for increasing utilization.

Use of Hepatitis C Virus Antibody-Positive Donor Livers in Hepatitis C Nonviremic Liver Transplant Recipients.

BACKGROUND: Given the shortage of available liver grafts, transplantation (LTx) of hepatitis C virus antibody-positive, nucleic acid test-negative (HCV Ab+/NAT-) livers into nonviremic HCV recipients can expand the donor pool. Having previously described the sentinel experience of HCV Ab+/NAT- allografts in nonviremic recipients, we report the growth and extended follow-up of this program for 55 patients compared with recipients of Public Health Services (PHS) increased-risk donor HCV Ab-/NAT- allografts. STUDY DESIGN: A prospective review of all HCV nonviremic LTx patients receiving HCV Ab+/NAT- organs between March 2016 and August 2018 was performed. All HCV Ab+/NAT- organ recipients underwent HCV testing at 3 months and 1-year post-LTx to determine HCV transmission. RESULTS: Fifty-five HCV nonviremic candidates received HCV Ab+/NAT- organs; 64% male, median age 59 years (range 36 to 69 years) and median Model for End-Stage Liver Disease score of 22.5. Two recipients were excluded due to death before HCV testing. The HCV disease transmission occurred in 5 recipients (9%). Of these, 4 (80%) underwent anti-HCV treatment with eradication of virus. No patient found to be negative at 3 months seroconverted at 1-year follow-up. No patients who received PHS increased-risk donor HCV Ab-/NAT- organs had viremia develop (0 of 57) and there was no difference in graft and renal function, complications, or survival between HCV Ab+/NAT- recipients and PHS increased-risk donor HCV Ab-/NAT- recipients. CONCLUSIONS: We report the largest experience with LTx from HCV Ab+/NAT- donors into 55 seronegative recipients with a HCV transmission rate of 9% with no late conversions at 1 year and no difference in function or graft loss compared with PHS increased-risk donor HCV Ab-/NAT- recipients. Due to availability of safe and effective HCV therapies, the use of such organs should be strongly considered to increase the donor organ pool.

Hepatitis C transmission from seropositive, nonviremic donors to non-hepatitis C liver transplant recipients.

Breakthroughs in hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors who are HCV antibody-positive but serum nucleic acid test (NAT)-negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody-negative (n = 25) or NAT-negative (n = 1) transplant recipients who received a liver graft from donors who were HCV antibody-positive but serum NAT-negative between March 2016 and March 2017. HCV transmission was considered to have occurred if recipients exhibited a positive HCV PCR test by 3 months following transplantation. Drug overdose was listed as the cause of death in 15 (60%) of the donors. One recipient died 18 days after transplantation from primary graft nonfunction and was excluded. Of the remaining 25 recipients, HCV transmission occurred in 4 (16%), at a median follow-up of 11 months, all from donors who died of drug overdose. Three of these patients were treated with direct-acting antiviral therapy, with two achieving a sustained virologic response and one an end-of-treatment response. One patient with HCV transmission died after a complicated postoperative course and did not receive antiviral therapy. CONCLUSION: In this prospective cohort of non-HCV liver recipients receiving grafts from HCV antibody-positive/NAT-negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose; given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. (Hepatology 2018;67:1673-1682).

Histoplasmosis in Patients With Cell-Mediated Immunodeficiency: Human Immunodeficiency Virus Infection, Organ Transplantation, and Tumor Necrosis Factor-α Inhibition.

Background. Histoplasmosis causes severe disease in patients with defects of cell-mediated immunity. It is not known whether outcomes vary related to the type of immunodeficiency or class of antifungal treatment. Methods. We reviewed cases of active histoplasmosis that occurred at Vanderbilt University Medical Center from July 1999 to June 2012 in patients with human immunodeficiency virus (HIV) infection, a history of transplantation, or tumor necrosis factor (TNF)-α inhibitor use. These groups were compared for differences in clinical presentation and outcomes. In addition, outcomes were related to the initial choice of treatment. Results. Ninety cases were identified (56 HIV, 23 transplant, 11 TNF-α inhibitor). Tumor necrosis factor-α patients had milder disease, shorter courses of therapy, and fewer relapses than HIV patients. Histoplasma antigenuria was highly prevalent in all groups (HIV 88%, transplant 95%, TNF-α 91%). Organ transplant recipients received amphotericin B formulation as initial therapy less often than other groups (22% vs 57% HIV vs 55% TNF-α; P = .006). Treatment failures only occurred in patients with severe disease. The failure rate was similar whether patients received initial amphotericin or triazole therapy. Ninety-day histoplasmosis-related mortality was 9% for all groups and did not vary significantly with choice of initial treatment. Conclusions. Histoplasmosis caused milder disease in patients receiving TNF-α inhibitors than patients with HIV or solid organ transplantation. Treatment failures and mortality only occurred in patients with severe disease and did not vary based on type of immunosuppression or choice of initial therapy.

Multinuclear NMR studies of single lipid bilayers supported in cylindrical aluminum oxide nanopores.

Lipid bilayers were deposited inside the 0.2 microm pores of anodic aluminum oxide (AAO) filters by extrusion of multilamellar liposomes and their properties studied by 2H, 31P, and 1H solid-state NMR. Only the first bilayer adhered strongly to the inner surface of the pores. Additional layers were washed out easily by a flow of water as demonstrated by 1H magic angle spinning NMR experiments with addition of Pr3+ ions to shift accessible lipid headgroup resonances. A 13 mm diameter Anopore filter of 60 microm thickness oriented approximately 2.5 x 10(-7) mol of lipid as a single bilayer, corresponding to a total membrane area of about 500 cm2. The 2H NMR spectra of chain deuterated POPC are consistent with adsorption of wavy, tubular bilayers to the inner pore surface. By NMR diffusion experiments, we determined the average length of those lipid tubules to be approximately 0.4 microm. There is evidence for a thick water layer between lipid tubules and the pore surface. The ends of tubules are well sealed against the pore such that Pr3+ ions cannot penetrate into the water underneath the bilayers. We successfully trapped poly(ethylene glycol) (PEG) with a molecular weight of 8000 in this water layer. From the quantity of trapped PEG, we calculated an average water layer thickness of 3 nm. Lipid order parameters and motional properties are unperturbed by the solid support, in agreement with existence of a water layer. Such unperturbed, solid supported membranes are ideal for incorporation of membrane-spanning proteins with large intra- and extracellular domains. The experiments suggest the promise of such porous filters as membrane support in biosensors.