A Systematic Review of Safety and Immunogenicity of Influenza Vaccination Strategies in Solid Organ Transplant Recipients

Immunogenicity from seasonal inactivated influenza vaccine (IIV) remains suboptimal in solid organ transplant recipients (SOTRs). We conducted a systematic review that compared the safety and immunogenicity of nonstandard influenza vaccination strategies with single-dose IIV in SOTRs. Booster doses and possibly high-dose (HD) influenza vaccination strategies seem to hold promise for improving vaccination immunogenicity in SOTRs. Administration of intradermal and MF59-adjuvanted trivalent IIV (IIV3) did not improve vaccine immunogenicity compared with single-dose intramuscular IIV. Alternative vaccine strategies were generally well tolerated; SOTRs who received HD, intradermal or adjuvanted IIV3 had a higher frequency of infection site reactions, while systemic adverse events were more frequent in SOTRs who received HD IIV3. Allograft rejection rates were similar in both groups. SOTRs should continue to receive standard-dose IIV annually in accordance with current recommendations, pending future studies to determine the optimal timing, frequency, and dosage of IIV using the booster-dose strategy

Successful Diagnosis of Intestinal Mycobacterium avium Complex Infection in a Kidney Transplant Recipient Using Nasogastric Aspirate Culture: A Case Report

Intestinal Mycobacterium avium complex (MAC) infections are rare and can be challenging to diagnose. We describe a case of intestinal MAC infection in a kidney transplant recipient with 5 months of unexplained weight loss and abdominal pain who developed intestinal obstruction. Esophagoduodenoscopy with biopsies was performed but was nondiagnostic. Intestinal MAC was diagnosed via nasogastric aspirate culture results. The patient's symptoms rapidly improved after initiation of appropriate treatment, but he later died of aspiration pneumonia and candidemia

Predictors of persistent diarrhea in norovirus enteritis after solid organ transplantation

Solid organ transplant (SOT) recipients may develop protracted diarrheal illness from norovirus. We performed a retrospective chart review between January 2010 and April 2014 to identify predictors of persistent diarrhea in transplant recipients with norovirus enteritis. A total of 152 SOT recipients with mean age of 31.5 years (SD 23.1) were included: 43.4% male, 34.2% pediatric patients. Allograft types were abdominal 136 (89.5%) (kidney [39.5%], liver-small bowel [23%], other [27%]) and thoracic 16 (10.5%). The median time to diagnosis of first norovirus enteritis episode from date of transplantation was 1.7 (0.3-5.3) years. At time of presentation, diarrhea was present in 141 (93%). Thirty percent had persistent diarrhea at 2 weeks. Hospitalization was required for treatment in 121 (80%) of episodes with the mean length of stay of 10±15.2 days. Most (91%) infections were due to norovirus genogroup II, and gastrointestinal coinfections were seen in 23 (19%) norovirus enteritis episodes. Nausea at time of diagnosis (P=.002) and cytomegalovirus (CMV) infection in the preceding 90 days (P=.036) were identified as independent risk factors for persistent diarrhea using univariate and multivariable logistic regression. Our study shows that nausea on presentation and prior CMV infection were associated with persistent diarrhea in patients with norovirus enteritis

Clinical presentation and outcomes of norovirus infection in intestinal allograft compared to native intestine

Background: No data are available on clinical manifestations and course of norovirus gastroenteritis (NVE) in intestinal allograft (from intestinal and multivisceral transplant recipients, ITR) compared to native intestine (from other allograft recipients, nITR). Methods: This was a retrospective study of solid organ transplant recipients with NVE at two centers from January 1, 2010 to April 1, 2014. Chi-square, t-test, linear and logistic regression analyses were done to compare NVE in ITR vs nITR patients. Results: The ITR (45 patients) were compared to nITR (107 patients). ITR were younger (odds ratio [OR]=0.90; P<.0001), less likely to receive anti-lymphocyte induction therapy (OR=0.15; P<.0001), and had shorter time from transplant to NVE (OR=0.99; P=.008). On presentation ITR had less frequent nausea (OR=0.11; P<.0001) or vomiting (OR=0.36; P=.01), higher white blood cell count (OR=1.09; P=.001), and higher glomerular filtration rate (OR=1.02; P<.0001). ITR were less likely to receive anti-motility agents (OR=9.6; P<.0001). ITR were more likely to stay longer on intravenous (IV) fluids (OR=1.18; P<.0001); have recurrent NVE (OR=4.25; P<.0001); have longer hospital stay (OR=1.07; P<.0001); develop acute rejection (OR=5.1; P=.006); and have lower overall survival (OR=0.28; P=.006). Conclusions: Compared to nITR, the ITR with NVE were significantly younger, had less nausea and vomiting at presentation, received less anti-motility agents, required more IV fluids, and had longer hospital stay. A trend was seen for lower survival with NVE in ITR

Vancomycin-resistant Enterococcal Bloodstream Infections in Hematopoietic Stem Cell Transplant Recipients and Patients with Hematologic Malignancies: Impact of Daptomycin MICs of 3 to 4 mg/L

Purpose Case reports of treatment failure with standard-dose daptomycin (6 mg/kg) have recently surfaced in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) episodes with daptomycin MICs of 3 to 4 mg/L. The clinical implications of daptomycin MICs of 3 to 4 mg/L in VRE BSIs have not been elucidated. Methods We performed a single institutional retrospective analysis of adult stem cell transplant recipients and patients with hematologic malignancies diagnosed with VRE BSI from 2006 to 2014 and compared outcomes between those with daptomycin MICs of 3 to 4 mg/L those with 2 mg/L, as determined by Etest. Findings Forty-two daptomycin-treated VRE BSI episodes, all due to Enterococcus faecium were identified; 19 episodes with daptomycin MICs of 3 to 4 mg/L and 23 episodes with a daptomycin MIC of 2 mg/L. Patients in the higher daptomycin MIC group were more likely to be male, to be stem cell transplant recipients, and to have received high-dose daptomycin treatment (>6 mg/kg). In unadjusted analyses, microbiological failure in the daptomycin MICs 3 to 4 mg/L versus 2 mg/L groups (odds ratio = 1.79, 95% CI, 0.52–6.11; P = 0.35), the median duration of bacteremia (4 days in daptomycin MICs 3–4 mg/L vs 3 days in daptomycin MIC 2 mg/L; P = 0.18) and all-cause 30-day mortality (21% in daptomycin MICs 3–4 mg/L vs 35% in daptomycin MIC 2 mg/L group; P = 0.49) were not different. In adjusted analyses, the association between higher Pitt bacteremia scores and all-cause 30-day mortality was statistically significant (P = 0.0006), whereas the association between daptomycin MICs of 3 to 4 mg/L and all-cause 30-day mortality approached statistical significance (P = 0.06). Implications Duration of bacteremia and microbiological failure rates did not differ by daptomycin MICs in VRE BSI episodes in our patients, composed of adult stem cell transplant recipients and patients with hematologic malignancies. There was a nonsignificant trend in multivariable analysis suggesting that all-cause 30-day mortality was lower in patients whose VRE bloodstream isolates were with daptomycin MICs of 3 to 4 mg/L

Increasing rates of fluoroquinolone resistance in escherichia coli isolated from the blood and urine of patients with hematologic malignancies and stem cell transplant recipients

Fluoroquinolone (FQ) antibiotics have been shown to reduce mortality and the number of febrile episodes when used as prophylaxis during neutropenia. Prior studies suggest that prophylaxis may result in increasing rates of FQ resistance. Fluoroquinolone non-susceptibility trends in Escherichia coli isolated from blood and urine cultures were evaluated over a 16-year period during which prophylaxis was initiated in patients with hematologic malignancies and stem cell transplants. Non-susceptibility rates increased after the introduction of prophylaxis, with yearly non-susceptibility rates rising from 30%–33% to 40%–88% in blood isolates. The high rates of non-susceptibility now observed raise concerns about the continued efficacy of FQ prophylaxis. This concern exists particularly in those patients undergoing stem cell transplants where the total FQ non-susceptibility rates over the study period were 82.3%. Further evaluation of the effect of FQ prophylaxis on antibiotic resistance and its efficacy in the setting of increased rates of resistance is warranted

New Phenolic Constituents from the Fruit Juice of Phyllanthus emblica

Six new phenolic constituents, L-malic acid 2-O- (1), mucic acid 2-O- (5), mucic acid 1, 4-lactone 2-O- (6), 5-O- (8), 3-O- (10), and 3, 5-di-O- (11) gallates, were isolated from the fruit juice of Phyllanthus emblica together with their methyl esters (2-4, 7, 9), and their structures were determined by spectral and chemical methods. Compounds 5, 6, and 8, the major phenolic constituents of the juice, were present as an equilibrium mixture in aqueous solution

Fibulin-3 is necessary to prevent cardiac rupture following myocardial infarction

Published online: 11 September 2023Despite the high prevalence of heart failure in the western world, there are few effective treatments. Fibulin-3 is a protein involved in extracellular matrix (ECM) structural integrity, however its role in the heart is unknown. We have demonstrated, using single cell RNA-seq, that fibulin-3 was highly expressed in quiescent murine cardiac fibroblasts, with expression highest prior to injury and late post-infarct (from ~ day-28 to week-8). In humans, fibulin-3 was upregulated in left ventricular tissue and plasma of heart failure patients. Fibulin-3 knockout (Efemp1-/-) and wildtype mice were subjected to experimental myocardial infarction. Fibulin-3 deletion resulted in significantly higher rate of cardiac rupture days 3-6 post-infarct, indicating a weak and poorly formed scar, with severe ventricular remodelling in surviving mice at day-28 post-infarct. Fibulin-3 knockout mice demonstrated less collagen deposition at day-3 post-infarct, with abnormal collagen fibre-alignment. RNA-seq on day-3 infarct tissue revealed upregulation of ECM degradation and inflammatory genes, but downregulation of ECM assembly/structure/organisation genes in fibulin-3 knockout mice. GSEA pathway analysis showed enrichment of inflammatory pathways and a depletion of ECM organisation pathways. Fibulin-3 originates from cardiac fibroblasts, is upregulated in human heart failure, and is necessary for correct ECM organisation/structural integrity of fibrotic tissue to prevent cardiac rupture post-infarct.Lucy A. Murtha, Sean A. Hardy, Nishani S. Mabotuwana, Mark J. Bigland, Taleah Bailey, Kalyan Raguram, Saifei Liu, Doan T. Ngo, Aaron L. Sverdlov, Tamara Tomin, Ruth Birner, Gruenberger, Robert D. Hume, Siiri E. Iismaa, David T. Humphreys, Ralph Patrick, James J. H. Chong, Randall J. Lee, Richard P. Harvey, Robert M. Graham, Peter P. Rainer and Andrew J. Boyl

Highly-parallelized simulation of a pixelated LArTPC on a GPU

The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype