Abstract
Until recently, available drugs for cytomegalovirus (CMV) prevention and treatment in transplant patients included (val)ganciclovir, foscarnet, and cidofovir. Use of these drugs is limited ...by toxicity and the development of resistance. The 2017 approval of letermovir for prevention of CMV after stem cell transplant marked the first approval of an anti-CMV agent since 2003. The role of letermovir in treatment of established CMV infection or disease remains largely unstudied, although early reports suggest that a low barrier to resistance will likely limit efficacy as primary therapy for patients with refractory or resistant disease. The investigational agent maribavir has shown promise as preemptive treatment; in patients with refractory or resistant disease the emergence of resistance while on treatment has been observed and ongoing studies will define efficacy in this population. Both agents have unique mechanisms of action limiting cross resistance, and neither exhibit myelotoxicity or nephrotoxicity.
We describe a case of proven transmission of SARS‐CoV‐2 from lung donor to recipient. The donor had no clinical history or findings suggestive of infection with SARS‐CoV‐2 and tested negative by ...reverse transcriptase polymerase chain reaction (RT‐PCR) on a nasopharyngeal (NP) swab obtained within 48 h of procurement. Lower respiratory tract testing was not performed. The recipient developed fever, hypotension, and pulmonary infiltrates on posttransplant day (PTD) 3, and RT‐PCR testing for SARS‐CoV‐2 on an NP swab specimen was non‐reactive, but positive on bronchoalveolar lavage (BAL) fluid. One thoracic surgeon present during the transplantation procedure developed COVID‐19. Sequence analysis of isolates from donor BAL fluid (obtained at procurement), the recipient, and the infected thoracic surgeon proved donor origin of recipient and health‐care worker (HCW) infection. No other organs were procured from this donor. Transplant centers and organ procurement organizations should perform SARS‐CoV‐2 testing of lower respiratory tract specimens from potential lung donors, and consider enhanced personal protective equipment for HCWs involved in lung procurement and transplantation.
This report describes a proven case of SARS‐CoV‐2 transmission during lung transplantation from a deceased donor to both the recipient and to a healthcare worker. La Hoz et al. comment on page 2635.
Superhydrophobic titanium surfaces with different line spacing (pitch) of 20, 50, 80 and 100 μm are fabricated using nanosecond laser patterning and their antibiofouling, superhydrophobicity, ...abrasion resistance and self-cleaning properties are studied. The surface morphology, surface profiles and surface roughness are obtained from scanning electron microscopy (SEM), optical microscopy and surface profilometry. Initially, the dual scale roughness structured laser patterned surfaces were hydrophilic but on prolonged storage time in ambient conditions, average water contact angle (WCA) > 160° was obtained due to the accumulation of atmospheric hydrocarbon compounds on the surface which was confirmed by laser Raman spectroscopy (LRS) and X-ray photoelectron spectroscopy (XPS). The laser patterned titanium samples exposed to the Pseudomonas sp., bacterial culture showed a 4-order reduction in bacterial adhesion as compared to control samples. Furthermore, the superhydrophobic laser patterned samples exhibited excellent water repellency at different ionic strength chloride solutions, photo-catalytic activity under visible light and abrasion resistance. The laser patterned titanium samples are found to regain the superhydrophobicity by replenishing the carbonaceous layer (denuded in organic solvents) on exposure to an open atmosphere for 14 days. This study provides new avenues to engineer the wetting properties of surfaces by varying laser patterning conditions.
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•Superhydrophobic surface modification of titanium is done by laser patterning•Surface topography and surface chemistry contributes to SHP•SHP titanium samples exhibited excellent repellence to chloride solutions•SHP titanium showed excellent photo-catalytic activity and self-cleaning ability•SHP titanium showed less bacterial adhesion
We report the first case of cytomegalovirus (CMV) disease treated with AIC246, a novel anti‐CMV compound which targets the viral terminase complex and remains active against virus resistant to DNA ...polymerase inhibitors. A lung transplant recipient developed refractory multidrug‐resistant CMV disease involving the lungs, gastrointestinal tract and retina. His disease progressed despite treatment with all DNA polymerase inhibitors; multiple agents reported to have activity against CMV in case series, and reduction in his immunosuppressive medications. AIC246 which is in clinical development was obtained for emergency use, and combined with additional reduction in immunosuppression resulted in rapid clinical, virological and radiological resolution of disease. The patient has remained free of CMV disease or viremia off treatment for greater than 3 months. In summary AIC246, while still in development, may be a promising alternative to current therapies.
The authors describe a lung transplant recipient with disseminated multidrug‐resistant Cytomegalovirus disease who was successfully treated with the investigational compound AIC246, which targets the viral terminase complex.
We synthesize and study single crystals of a new double-perovskite Sr2YIrO6. Despite two strongly unfavorable conditions for magnetic order, namely, pentavalent Ir5+(5d4) ions which are anticipated ...to have Jeff=0 singlet ground states in the strong spin-orbit coupling (SOC) limit and geometric frustration in a face-centered cubic structure formed by the Ir5+ ions, we observe this iridate to undergo a novel magnetic transition at temperatures below 1.3 K. We provide compelling experimental and theoretical evidence that the origin of magnetism is in an unusual interplay between strong noncubic crystal fields, local exchange interactions, and "intermediate-strength" SOC. Sr2YIrO6 provides a rare example of the failed dominance of SOC in the iridates.
Background. Cytomegalovirus (CMV) disease remains an important problem in solid-organ transplant recipients, with the greatest risk among donor CMV-seropositive, recipient-seronegative (D + /R − ) ...patients. CMV-specific cell-mediated immunity may be able to predict which patients will develop CMV disease. Methods. We prospectively included D + /R − patients who received antiviral prophylaxis. We used the Quantiferon-CMV assay to measure interferon-γ levels following in vitro stimulation with CMV antigens. The test was performed at the end of prophylaxis and 1 and 2 months later. The primary outcome was the incidence of CMV disease at 12 months after transplant. We calculated positive and negative predictive values of the assay for protection from CMV disease. Results. Overall, 28 of 127 (22%) patients developed CMV disease. Of 124 evaluable patients, 31 (25%) had a positive result, 81 (65.3%) had a negative result, and 12 (9.7%) had an indeterminate result (negative mitogen and CMV antigen) with the Quantiferon-CMV assay. At 12 months, patients with a positive result had a subsequent lower incidence of CMV disease than patients with a negative and an indeterminate result (6.4% vs 22.2% vs 58.3%, respectively; P < .001). Positive and negative predictive values of the assay for protection from CMV disease were 0.90 (95% confidence interval CI, .74–.98) and 0.27 (95% CI, .18–.37), respectively. Conclusions. This assay may be useful to predict if patients are at low, intermediate, or high risk for the development of subsequent CMV disease after prophylaxis. Clinical Trials Registration. NCT00817908.
Aims
Immobilization of microbial cells is a useful strategy for developing high cell density bioreactors with improved stability and productivity for production of different chemicals. ...Functionalization of the immobilization matrix or biofilm forming property of some strains has been utilized for achieving cell attachment. The aim of the present study was to investigate the production of exopolysaccharide (EPS) by Propionibacterium freudenreichii C.I.P 59.32 and utilize this feature for immobilization of the cells on porous glass beads for production of propionic acid.
Methods and Results
Propionibacterium freudenreichii was shown to produce both capsular and excreted EPS during batch cultivations using glucose as carbon source. Different electron microscopy techniques confirmed the secretion of EPS and formation of cellular aggregates. The excreted EPS was mainly composed of mannose and glucose in a 5·3 : 1 g g−1 ratio. Immobilization of the cells on untreated and polyethyleneimine (PEI)‐treated Poraver beads in a bioreactor was evaluated. Higher productivity and yield of propionic acid (0·566 g l−1 h−1 and 0·314 g g−1, respectively) was achieved using cells immobilized to untreated beads and EPS production reached 617·5 mg l−1 after 48 h.
Conclusion
These results suggest an important role of EPS‐producing strains for improving cell immobilization and propionic acid production.
Significance and Impact of the Study
This study demonstrates the EPS‐producing microbe to be easily immobilized on a solid matrix and to be used in a bioprocess. Such a system could be optimized for achieving high cell density in fermentations without the need for functionalization of the matrix.