Liver transplantation for post-COVID-19 cholangiopathy: A case series.

BACKGROUND: Post-COVID-19 cholangiopathy is an emerging cholestatic liver disease observed in patients recovering from severe COVID-19 infection. Its prognosis is poor, necessitating liver transplantation in some cases. This study aimed to investigate the outcomes of liver transplantation for post-COVID-19 cholangiopathy. METHODS: Seven patients who underwent liver transplantation for post-COVID-19 cholangiopathy at three institutions between 2020 and 2022 were included in this retrospective multi-center case series. RESULTS: At the time of initial COVID-19 infection, all patients developed acute respiratory distress syndrome, and six patients (86%) required ICU admission. Median time intervals from the initial COVID-19 diagnosis to the diagnosis of post-COVID-19 cholangiopathy and liver transplantation were 4 and 12 months, respectively. Four patients underwent living donor liver transplantation, and three patients underwent deceased donor liver transplantation. The median MELD score was 22 (range, 10-38). No significant intraoperative complications were observed. The median ICU and hospital stays were 2.5 and 12.5 days, respectively. One patient died due to respiratory failure 5 months after liver transplantation. Currently, the patient and graft survival rate is 86% at a median follow-up of 11 months. CONCLUSIONS: Liver transplantation is a viable option for patients with post-COVID-19 cholangiopathy with acceptable outcome. Timely identification of this disease and appropriate management, including evaluation for liver transplantation, are essential.

Cell-free plasma next-generation sequencing assists in the evaluation of secondary pneumonia in patients with COVID-19: a case series.

Secondary pneumonia occurs in 8-24% of patients with Coronavirus 2019 (COVID-19) infection and is associated with increased morbidity and mortality. Diagnosis of secondary pneumonia can be challenging. The purpose of this study was to evaluate the use of plasma microbial cell free DNA sequencing (mcfNGS) in the evaluation of secondary pneumonia after COVID-19. We performed a single-center case series of patients with COVID-19 who underwent mcfNGS to evaluate secondary pneumonia and reported the organisms identified, concordance with available tests, clinical utility, and outcomes. In 8/13 (61%) cases, mcfNGS detected 1-6 organisms, with clinically significant organisms identified in 4 cases, including Pneumocystis jirovecii, and Legionella spp. Management was changed in 85% (11/13) of patients based on results, including initiation of targeted therapy, de-escalation of empiric antimicrobials, and avoiding contingent escalation of antifungals. mcfNGS may be helpful to identify pathogens causing secondary pneumonia, including opportunistic pathogens in immunocompromised patients with COVID-19. However, providers need to carefully interpret this test within the clinical context.

Cell-free next-generation sequencing impacts diagnosis and antimicrobial therapy in immunocompromised hosts: A retrospective study.

BACKGROUND: Cell-free next-generation sequencing (cfNGS) may have a unique role in the diagnosis of infectious complications in immunocompromised hosts. The rapid turnaround time and non-invasive nature make it a promising supplement to standard of care. METHODS: This retrospective, observational single-center study at a tertiary care medical center in Virginia investigated the use of cfNGS in clinical practice. Patients over age 18 years with cfNGS performed for any indication were included. The primary outcome was detection of bacteria and/or fungi on cfNGS. The secondary outcomes were concordance, and abundance of fungal and bacterial organism concentration detected over time from symptom onset, and clinical impact. RESULTS: Thirty-six patients (92% immunosuppressed) were identified and included. Twenty-one (58%) tests detected one to five organisms (14/21 bacteria, 8/21 fungi, and 6/21 viruses). The clinical impact of cfNGS was positive in 52.8% of cases, negative in 2.8%, and negligible in 44.4%. Positive tests prompted therapy changes in 12 of 21 patients; six of 20 bacteria and seven of eight fungi identified were considered clinically pathogenic. Three bacteria identifications and six fungi identifications prompted targeted treatment. When fungal species were not identified by cNFGS, antifungal de-escalation occurred in seven patients. CONCLUSION: cfNGS assisted in critical management changes, including initiation of treatment for identified organisms and antimicrobial de-escalation. Its non-invasive nature and rapid turnaround time make this an important adjunct to standard of care testing that may assist in providing earlier, targeted therapy, especially when opportunistic pathogens remain high on the differential diagnosis.

A review of transplant infectious diseases and pediatric transplant infectious diseases curriculum.

PURPOSE OF REVIEW: As the volume and complexity of solid organ and hematopoietic stem cell transplantation continue to see rapid growth, the training of a specialized transplant infectious diseases physician workforce is of increasing interest and importance. This review provides an overview of the evolution of transplant infectious diseases training programs, essential elements of training, as well as future needs. RECENT FINDINGS: Despite the first publication of a transplant infectious diseases curriculum in 2010, more recent surveys of infectious diseases trainees have identified gaps in didactic curriculum, donor and recipient assessment, and safe living practices. SUMMARY: This review of transplant infectious diseases training summarizes growth through the decades, the current landscape of recommend training elements, suggested areas for continued development and expansion in training as well as novel methodologies to reach a modern trainee audience.

Bordetella hinzii Meningitis in Patient with History of Kidney Transplant, Virginia, USA.

A patient in Virginia, USA, who had previously undergone multiple kidney transplantations showed signs of Bordetella hinzii bacteremia and meningitis. This emerging pathogen has been increasingly identified as a clinically significant pathogen in immunosuppressed and, less frequently, immunocompetent patients. This patient was treated and recovered without further issue.

Toxoplasma-induced hemophagocytic lymphohistiocytosis after haploidentical allogeneic stem cell transplantation.

Hemophagocytic lymphohistiocytosis (HLH) is a disorder of immune regulation, manifested by fever, pancytopenia, hyperferritiniemia, hypertriglyceridemia, and extensive hemophagocytosis involving the bone marrow and spleen. HLH can occur in adults with an underlying hematopoietic malignancy, or with systemic infections. HLH following hematopoietic stem cell transplantation (HSCT) is unusual, and the diagnosis may be challenging particularly because the diagnostic criteria in the HLH-2004 guidelines overlap with common post-transplant complications such as engraftment syndrome, graft-vs-host disease, and infections. HLH is commonly triggered by viral, bacterial and, less commonly, parasitic infections. Following HSCT, patients with latent Toxoplasma infection may develop systemic disease secondary to reactivation, and rarely this may lead to a HLH physiology, with a very high mortality rate. Herein we describe the successful management of disseminated toxoplasmosis associated with life-threatening HLH using tocilizumab and antimicrobial therapy.

An unusual case of Nocardia cyriacigeorgica presenting with spinal abscesses in a renal transplant recipient and a review of the literature.

Nocardia species represent a well-recognized yet uncommon cause of opportunistic infections in humans. It most frequently presents as a pulmonary infection with or without central nervous system involvement. It is a very rare cause of spinal abscesses, with only 26 cases reported in the literature. Here we report a 49-year-old man with a history of renal transplantation who presented with low back pain and was diagnosed with epidural and paraspinal abscesses due to Nocardia cyriacigeorgica that was successfully treated with antimicrobial therapy alone. In addition to the case reported here, we also conducted a systematic review of the existing literature regarding spinal abscesses due to Nocardia species and examined the success of the various treatments utilized.

Graded isavuconazole introduction in a patient with voriconazole allergy.

Triazole antifungal drugs may rarely cause serious allergic reactions including angioedema. No standardized tests are available to predict cross-reactivity within the azole class and little guiding information exists on whether to change therapy within the class or to another class after a serious allergic reaction. Herein we report the first successful use, to our knowledge, of graded isavuconazole introduction for treatment of aspergillosis in a liver transplant recipient with severe voriconazole allergy.

Bartonella Endocarditis and Pauci-Immune Glomerulonephritis: A Case Report and Review of the Literature.

Among culture-negative endocarditis in the United States, Bartonella species are the most common cause, with Bartonella henselae and Bartonella quintana comprising the majority of cases. Kidney manifestations, particularly glomerulonephritis, are common sequelae of infectious endocarditis, with nearly half of all Bartonella patients demonstrating renal involvement. Although a pauci-immune pattern is a frequent finding in infectious endocarditis-associated glomerulonephritis, it is rarely reported in Bartonella endocarditis. Anti-neutrophil cytoplasmic antibody (ANCA) positivity can be seen with many pathogens causing endocarditis and has been previously reported with Bartonella species. In addition, ANCA-associated vasculitis can also present with renal and cardiac involvement, including noninfectious valvular vegetations and pauci-immune glomerulonephritis. Given the overlap in their clinical presentation, it is difficult to differentiate between Bartonella endocarditis and ANCA-associated vasculitis but imperative to do so to guide management decisions. We present a case of ANCA-positive Bartonella endocarditis with associated pauci-immune glomerulonephritis that was successfully treated with medical management alone.

Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate use case series.

BACKGROUND: A growing number of compassionate phage therapy cases were reported in the last decade, with a limited number of clinical trials conducted and few unsuccessful clinical trials reported. There is only a little evidence on the role of phages in refractory infections. Our objective here was to present the largest compassionate-use single-organism/phage case series in 16 patients with non-resolving Pseudomonas aeruginosa infections. METHODS: We summarized clinical phage microbiology susceptibility data, administration protocol, clinical data, and outcomes of all cases treated with PASA16 phage. In all intravenous phage administrations, PASA16 phage was manufactured and provided pro bono by Adaptive Phage Therapeutics. PASA16 was administered intravenously, locally to infection site, or by topical use to 16 patients, with data available for 15 patients, mainly with osteoarticular and foreign-device-associated infections. FINDINGS: A few minor side effects were noted, including elevated liver function enzymes and a transient reduction in white blood cell count. Good clinical outcome was documented in 13 out of 15 patients (86.6%). Two clinical failures were reported. The minimum therapy duration was 8 days with a once- to twice-daily regimen. CONCLUSIONS: PASA16 with antibiotics was found to be relatively successful in patients for whom traditional treatment approaches have failed previously. Such pre-phase-1 cohorts can outline potential clinical protocols and facilitate the design of future trials. FUNDING: The study was funded in part by The Israeli Science Foundation IPMP (ISF_1349/20), Rosetrees Trust (A2232), United States-Israel Binational Science Foundation (2017123), and the Milgrom Family Support Program.

Aspergillus lentulus: An Under-recognized Cause of Antifungal Drug-Resistant Aspergillosis.

Aspergillus lentulus is a drug-resistant species that is phenotypically similar to A. fumigatus. It was discovered as a cause of azole-breakthrough disease, consistent with in vitro resistance. Clinical labs can misidentify the species as fumigatus based on phenotypic typing. We describe 4 recent cases and provide a brief review.

Effects of antiepileptic drugs on lipids, homocysteine, and C-reactive protein.

OBJECTIVE: The widely prescribed anticonvulsants phenytoin and carbamazepine are potent inducers of cytochrome P450 enzymes, which are involved in cholesterol synthesis. We sought to determine whether these drugs have an effect on cholesterol and other serological markers of vascular risk. METHODS: We recruited 34 epilepsy patients taking carbamazepine or phenytoin in monotherapy whose physicians had elected to change treatment to one of the noninducing anticonvulsants lamotrigine or levetiracetam. Fasting blood samples were obtained both before and 6 weeks after the switch to measure serum lipid fractions, lipoprotein(a), C-reactive protein, and homocysteine. A comparator group of 16 healthy subjects underwent the same serial studies. RESULTS: In the epilepsy patients, switch from either phenytoin or carbamazepine produced significant declines in total cholesterol (-24.8 mg/dl), atherogenic (non-high-density lipoprotein) cholesterol (-19.9 mg/dl), triglycerides (-47.1mg/dl) (all p < 0.0001), and C-reactive protein (-31.4%; p = 0.027). Patients who stopped taking carbamazepine also had a 31.2% decline in lipoprotein(a) level (p = 0.0004), whereas those taken off phenytoin had a decrease in homocysteine level (-1.7 micromol/L; p = 0.005). All of these changes were significant when compared with those seen in healthy subjects (p < 0.05). Results were similar whether patients were switched to lamotrigine or levetiracetam. INTERPRETATION: Switching epilepsy patients from the enzyme-inducers carbamazepine or phenytoin to the noninducing drugs levetiracetam or lamotrigine produces rapid and clinically significant amelioration in several serological markers of vascular risk. These findings suggest that phenytoin and carbamazepine may substantially increase the risk for cardiovascular and cerebrovascular disease.

Genetic and biochemical determinants of serum concentrations of monocyte chemoattractant protein-1, a potential neural tube defect risk factor.

BACKGROUND: Women with the AA genotype at the (-2518)A>G promoter polymorphism of CCL-2, which encodes the potent pro-inflammatory chemokine monocyte chemoattractant protein 1 (MCP-1), may be at increased risk for having offspring affected by spina bifida. As the A allele at this locus has been associated with decreased transcription of MCP-1 mRNA relative to the G allele, the observed genetic association suggests that the risk of spina bifida may be increased in the offspring of women with low MCP-1 levels. The present study was undertaken to identify potential determinants of MCP-1 levels in women of reproductive age. METHODS: A small cohort of Caucasian and African-American women of reproductive age was recruited to participate in an exploratory investigation of the determinants of several disease-related, biochemical phenotypes, including MCP-1. Subjects completed a brief questionnaire and provided a fasting blood sample for biochemical and genetic studies. Potential biochemical, genetic, and lifestyle factors were assessed for their association with MCP-1 levels using linear regression analyses. RESULTS: In this cohort, MCP-1 levels were significantly higher in Caucasians as compared to African-Americans. Further, among women of both races, there was evidence that MCP-1 levels were associated with smoking status, MTHFR 677C>T genotype, and red blood cell tetrahydrofolate levels. CONCLUSIONS: The results of these analyses indicate that, if maternal CCL-2 genotype is related to the risk of spina bifida, this relationship is likely to be more complex than initially hypothesized, perhaps depending upon folate intake, MTHFR 677C>T genotype, the distribution of folate derivatives, and immune/inflammatory activity.