Search

Pretransplant respiratory virus infections (RVIs) have been shown to negatively affect hematopoietic cell transplantation (HCT) outcomes. The impact of and need for delay of HCT for pretransplant infection with human rhinovirus (HRV) or endemic human coronavirus (HCoV; 229E, OC43, NL63, and HKU1) remain controversial. We analyzed the impact of symptomatic RVI within ≤90 days before HCT on overall mortality, posttransplant lower respiratory tract disease (LRD), and days alive and out of hospital (DAOH) by day 100 post-HCT in multivariable models. Among 1,643 adult HCT recipients (58% allogeneic recipients), 704 (43%) were tested for RVI before HCT, and 307 (44%) tested positive. HRV was most commonly detected (56%). Forty-five (15%) of 307 HCT recipients had LRD with the same virus early after HCT. Pretransplant upper respiratory tract infection (URI) with influenza, respiratory syncytial virus, adenovirus, human metapneumovirus, parainfluenza virus, HRV, or endemic HCoV was not associated with increased overall mortality or fewer DAOH. However, in allogeneic recipients who received myeloablative conditioning, LRD due to any respiratory virus, including HRV alone, was associated with increased overall mortality (adjusted hazard ratio, 10.8 [95% confidence interval, 3.29-35.1] for HRV and 3.21 [95% confidence interval, 1.15-9.01] for all other viruses). HRV LRD was also associated with fewer DAOH. Thus, the presence of LRD due to common respiratory viruses, including HRV, before myeloablative allogeneic HCT was associated with increased mortality and hospitalization. Pretransplant URI due to HRV and endemic HCoV was not associated with these outcomes. Improved management strategies for pretransplant LRD are warranted.

The outbreak of COVID-19 has engendered extensive challenges for conventional hospital operations. To adapt to this problematic issue, a mixed-use hospital functioning system for normal and epidemic situations is proposed. However, the inherent complexity of a hospital embedded with a function of epidemic prevention and control renders a restrained construction process that may compromise quality. In this stance, we developed a BIM (building information modelling)-based simulation approach addressing life-cycle quality control in post-pandemic hospitals. An illustrative case study approach, which draws on the grey literature, was used to address the research question. BIM forward design was employed to integrate with such elements as functional streamline, emergency site, and ward conversion in the process of transformation from normal to epidemic-related operations. Computational fluid dynamics-based fluid simulation was conducted to obtain the most suitable air supply and exhaust solutions for negative pressure wards. BIM forward design method contributed to improving design efficiency and quality. The results of ventilation simulation and environmental analysis showed that the design scheme met all the functional requirements and technical specifications. Meanwhile, the best pipeline synthesis scheme was obtained, which reduced the rework and saved on construction time. The proposed method is beneficial to improve the efficiency of design information sharing and business collaboration. Implications generated from this study can be used as a significant reference for the future construction of various healthcare facilities.

With the rapid development of Internet technology, the problem of client-side source storage resources is gradually exposed. In view of the problems of small capacity, uneven distribution, and diversification of attributable entities of user-side source storage resources, the current blockchain energy storage is difficult to schedule, and user-side sources and storage resources cannot be added to power scheduling optimization, resulting in unusable resources. In order to effectively utilize user-side resources, this paper proposes a blockchain energy storage scheduling visualization system (BESSVS) that takes into account the optimal scheduling of user-side source storage resources. The BESSVS can coordinate and optimize the management and control of decentralized power resources and load resources, and effectively combine the Internet of Things and the power plant storage energy corresponding to the BESSVS for optimal scheduling. The design of blockchain energy storage scheduling visualization system is mainly carried out from the system main body and data information structure. The advantages of blockchain in data storage, information security, data interoperability, etc., are introduced into the economic scheduling of blockchain energy storage. It is conducive to the stable scheduling of information transparency and also improves the data security and storage security of the system. Finally, the feasibility and practicability of the method are verified by an example.

CLAG-M (cladribine, high-dose cytarabine [HiDAC], G-CSF, mitoxantrone)/CLAG are contemporary intensive chemotherapy regimens associated with higher and deeper complete remission rates than 7+3 (cytarabine, anthracycline)/HiDAC, but with greater myelosuppression and potential infection risks. Here, we compared the cumulative incidence (CI) and patterns of invasive fungal disease (IFD) between these regimens by identifying proven/probable and possible cases of IFD following CLAG-M (n=332) and 7+3 (n=115) chemotherapy and subsequent treatment cycles in adults ≥18 years old with newly diagnosed (ND) or relapsed/refractory (R/R) AML or other high-grade myeloid neoplasms between 2006 and 2018. By 90 days (D90) after initiating treatment, the CI of proven/probable IFD was 20% with CLAG-M and 12% with 7+3 (p=0.17). There was no significant difference in the CI of IFD between ND CLAG-M and R/R CLAG-M. Without mold-active prophylaxis, the D90 CI of proven/probable IFD was significantly higher in the CLAG-M than the 7+3 cohort (28% versus 11%; p=0.007), but this difference was mitigated with mold-active prophylaxis (CLAG-M, 7.5%; 7+3, 0%; p=0.65). After each chemotherapy treatment cycle, the CI of newly diagnosed IFD was similar, ranging from 15-20%. Use of mold-active prophylaxis was the only factor associated with reduced IFD risk in adjusted models (HR, 0.32; 95% confidence interval, 0.18-0.56). Together, these data indicate that the IFD risk with CLAG-M is higher than with 7+3 in the absence of mold-active prophylaxis; use of mold-active prophylaxis mitigates this risk.

We assessed novel factors and the immunodeficiency scoring index (ISI) to predict progression to lower respiratory tract infection (LRTI) among hematopoietic cell transplant (HCT) recipients presenting with upper respiratory tract infection (URTI) with 12 viruses in the PCR era. We retrospectively analyzed the first respiratory virus detected by multiplex PCR in allogeneic HCT recipients (4/2008-9/2018). We used Cox proportional hazards models to examine factors for progression to LRTI within 90 days among patients presenting with URTI. A total of 1027 patients (216 children and 811 adults) presented with URTI only. Among these, 189 (18%) progressed to LRTI (median: 12 days). Multivariable models demonstrated a history of 1 transplant, age ≥40 years, time post-HCT (≤30 days), systemic steroids, hypoalbuminemia, hyperglycemia, cytopenia, and high ISI (scores 7-12) were associated with an increased risk of progression to LRTI. Respiratory syncytial virus and human metapneumovirus showed the highest progression risk. Patients with ≥3 independent risk factors or high ISI scores were highly likely to progress to LRTI. We identified novel risk factors for progression to LRTI, including history of multiple transplants and hyperglycemia, suggesting an intervention opportunity with glycemic control. ISI and number of risk factors appear to predict disease progression across several viruses.

The purpose is to realize the decentralized microgrid economic dispatch, improve the information transparency and security of microgrid systems, and make the power grid move towards a clean, safe, efficient, and reliable development path. Deep learning optimization of microgrid economic dispatch and wireless power transmission based on blockchain technology are studied. First, the related theories and methods of microgrid systems, wireless power transmission, and deep learning optimization based on blockchain technology are introduced. Next, the microgrid economic dispatch is simulated and analyzed on a large scale. Finally, the comparison results between microgrid economic dispatch and common radio energy transmission technologies are analyzed. The results show that daily planning can better coordinate the state of distributed generation, energy storage system, and public connection. The operation results of the previous day correspond to the long-term operation economy of the microgrid. The total operation cost of the microgrid is 4668 yuan/day, and the remaining power is maintained between 500 and 600 kW, which helps to prevent excessive battery discharge, prolong battery life, and reduce operation cost. The simulation results show that the total power imbalance of the microgrid can reduce the output fluctuation of controllable load shedding of distributed generation. When the load characteristics are not important, the output fluctuation of controllable distributed generation can be reduced. The proposed economic dispatch model can optimize the data security, information storage, and information release of the microgrid and has a certain guiding role for the development of the national power grid and power industry.

Objectives Present study aimed to illustrate the role of miR-144-3p in rheumatoid arthritis (RA). Methods N1511 chondrocytes were stimulated by interleukin (IL)-1β to mimic RA injury model in vitro. Rats were subjected to injection of type II collagen to establish an in vivo RA model, and the arthritis index score was calculated. Cell viability was determined by Cell Counting Kit-8. The expression of cartilage extracellular matrix proteins (collagen II and aggrecan) and matrix metalloproteinase protein were determined by quantitative real-time polymerase chain reaction and western blots. Cell apoptosis was measured by flow cytometry. Enzyme-linked immunosorbent assay was applied to test the secretion of pro-inflammatory cytokines (IL-1β and tumour necrosis factor-α). Tissue injury and apoptosis were detected by haematoxylin–eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling assay staining. Interaction of miR-144-3p and bone morphogenetic protein 2 (BMP2) was verified by dual-luciferase assay. Results miR-144-3p was dramatically increased in IL-1β-induced N1511 cells. miR-144-3p depletion elevated cell viability, suppressed apoptosis, pro-inflammatory cytokine releasing, and extracellular matrix loss in IL-1β-induced N1511 cells. Moreover, miR-144-3p targeted BMP2 to modulate its expression negatively. Activation of phosphatidylinositol 3-kinase (PI3K)/Akt signalling compromised inhibition of BMP2 induced aggravated N1511 cell injury with IL-1β stimulation. Inhibition of miR-144-3p alleviated cartilage injury and inflammatory in RA rats. Conclusion Collectively, miR-144-3p could aggravate chondrocyte injury inflammatory response in RA via BMP2/PI3K/Akt axis.

The kinetics of early and late CMV reactivation after hematopoietic cell transplantation using various methods of graft-versus-host-disease (GVHD) prophylaxis are poorly defined. We retrospectively compared CMV reactivation and disease among 780 seropositive patients given HLA-matched peripheral blood stem cell (PBSC) grafts and calcineurin-inhibitor plus post-transplantation cyclophosphamide (PTCy; n=44), mycophenolate mofetil (MMF; n=414) or methotrexate (MTX; n=322). Transplantation occurred between 2007-2018; CMV-monitoring/management followed uniform standard practice. Hazards of CMV reactivation at various thresholds were compared. Spline curves were fit over average daily viral load, and areas under the curve (AUC) within one-year were calculated. PTCy and MMF were associated with an increased risk of early (day 100) CMV reactivation ≥250 IU/mL after multivariable adjustment (PTCy vs. MTX: HR=1.64; 95% CI: 1.03-2.61; p=0.039; MMF vs. MTX: HR=1.50; 95% CI: 0.97-2.32; p=0.067). The viral load AUC at one-year was highest with MMF (mean difference 0.125 units vs. MTX; 95% CI 0.061-0.189; p.001) and similar between PTCy vs. MTX (mean difference 0.016 units vs. MTX group; 95% CI, -0.126-0.158, p=0.827). CMV disease risk was similar across groups. There was no interaction between GVHD prophylaxis and CMV reactivation on chronic GVHD risk. Despite PTCy-associated increased risk of early CMV reactivation, the CMV disease risk by 1 year was low in HLA-matched PBSC transplant recipients. In contrast, MMF was associated with higher overall CMV viral burden in the 1-year posttransplant. While different mechanisms of immunosuppressive agents may impact CMV reactivation risk, effective prevention of GVHD may reduce corticosteroid exposure and mitigate infection risk over time.

Background CMV reactivation is occasionally detected during the work-up for hematopoietic cell transplantation (HCT) but its natural history and significance on posttransplant CMV risk is unknown. Methods CMV seropositive 1st HCT allograft recipients in the preemptive therapy era (2010-17) were analyzed. CMV PCR testing was routinely performed before and after HCT. Cumulative incidences of CMV reactivation after HCT were calculated at multiple PCR thresholds by pre-HCT viral loads (peak: < or >150 IU/mL; last prior to HCT positive vs positive to negative). Treatment of pre-HCT reactivation was recommended for viral loads >50 IU/mL. Multivariable Cox proportional hazard models were used to determine the association of pre-transplant CMV reactivation on post-HCT CMV reactivation at different PCR thresholds. Results Among 1536 patients (median age 50 y, range 0.1-81), 155 (10%), 53 (3.5%) and 24 (1.6%) had pre-HCT reactivation in the month before HCT at any level, >150 IU/mL, and >500 IU/mL, respectively. Pre-transplant CMV reactivation was associated with a higher risk of post-HCT CMV reactivation at all examined PCR thresholds and with CMV disease after transplantation in cumulative incidence (Figure 1) and multivariable analyses (Figure 2A). Patients who had CMV DNA detected that subsequently became negative before HCT (with or without treatment) had a lower risk than those who proceeded to HCT with viremia (Figure 2B). Cumulative Incidence of CMV Infection and Disease Multivariable Cox Regression Conclusion CMV reactivation occurs pre-HCT in ∼10% of CMV seropositive HCT candidates and is a risk factor for post-HCT CMV events at all severity levels, placing a HCT recipient in a high-risk category. Thus, pre-HCT PCR testing and antiviral treatment as well as the use of optimized posttransplant antiviral or immunotherapy prevention strategies are recommended. Disclosures Joshua A. Hill, MD, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Covance/CSL: Advisor/Consultant|CRISPR: Advisor/Consultant|Deverra: Grant/Research Support|Gilead: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck: Grant/Research Support|Octapharma: Advisor/Consultant|OptumHealth: Advisor/Consultant|Oxford Immunotec: Grant/Research Support|Pfizer: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Advisor/Consultant Leona Holmberg, MD, PhD, Bristol Myers Squibb: Grant/Research Support|Janssen: Grant/Research Support|Merck: Grant/Research Support|Millennium-Takada: Grant/Research Support|Sanofi: Grant/Research Support|Seattle Genetics: Grant/Research Support|Up to Date: Royalty Alpana Waghmare, MD, Allovir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|Devarra Therapeutics: DSMB|Kyorin Pharmaceutical: Advisor/Consultant|Pfizer: Grant/Research Support|Vir/GSK: Grant/Research Support Alexander L. Greninger, MD, PhD, Abbott: Contract Testing|Cepheid: Contract Testing|Gilead: Grant/Research Support|Gilead: Contract Testing|Hologic: Contract Testing|Merck: Grant/Research Support|Novavax: Contract Testing|Pfizer: Contract Testing Mary Flowers, MD, Incyte Corp.: Grant/Research Support|Janssen: Honoraria|Johnson & Johnson: Honoraria|Novartis: Honoraria|Pharmacyclics, Inc.: Grant/Research Support Geoffrey Hill, M.D., FRACP, FRCPA, Applied Molecular Transport: Grant/Research Support|Compass Therapeutics: Grant/Research Support|Generon Corporation: Advisor/Consultant|Heat Biologics: Grant/Research Support|iTeos Therapeutics: Advisor/Consultant|iTeos Therapeutics: Grant/Research Support|Laevoroc Oncology: Grant/Research Support|NapaJen Pharma: Advisor/Consultant|Neoleukin Therapeutics: Advisor/Consultant|Serplus Technology: Grant/Research Support|Syndax Pharmaceuticals: Grant/Research Support Michael J. Boeckh, MD PhD, Allovir: Advisor/Consultant|Amazon: Grant/Research Support|Ansun Biopharma: Grant/Research Support|EvrysBio: Advisor/Consultant|Gates Ventures: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Helocyte: Advisor/Consultant|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kyorin Pharmaceuticals: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Regeneron: Grant/Research Support|ReViral: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Grant/Research Support|Vir Biotechnology: Advisor/Consultant|Vir Biotechnology: Grant/Research Support.

Background Respiratory virus infections (RVIs) in adult hematopoietic cell transplant (HCT) candidates have been shown to impact posttransplant outcomes; however, there are few studies in pediatric patients. We sought to evaluate the role of specific viruses and the location of viral infection on post HCT outcomes. Methods We evaluated allogeneic pediatric HCT recipients receiving myeloablative conditioning from 3/2010–3/2018. All patients had a multiplex PCR for RVIs prior to HCT, regardless of symptoms. Delaying HCT was recommended when feasible for RSV, parainfluenza, metapneumovirus, adenovirus, and influenza, but not routinely for human rhinovirus (HRV) and endemic coronaviruses. We utilized Cox proportional hazards models to evaluate progression to lower respiratory disease (LRD) post HCT and linear regression models to evaluated days alive and out of hospital (DAOH) by 100 days post HCT. Results Of 310 allogeneic HCT recipients receiving myeloablative conditioning, 133 (43%) were positive for a RVI before HCT. Baseline characteristics were notable for differences for age, recipient CMV serostatus, and delayed HCT (Table 1). The most common RVI was HRV (97, 73%) and 81 (61%) patients were symptomatic at the time of detection. Most patients had a URI (92%) and 11 patients had LRD (3 proven, 8 possible). In univariate analysis, HRV as virus type was associated with fewer DAOH and preHCT URI as location of viral infection (with and without symptoms) trended towards fewer DAOH (Figure 1a). When adjusted for age, preHCT lymphocyte count, cell source, and conditioning regimen, both HRV and preHCT URI showed a trend towards fewer DAOH, but no significant association was found (Figure 1b,c). Twenty patients progressed to LRD after HCT with the same preHCT RVI; no factors, including delay of transplant, were associated with reduced progression to LRD. (A) Univariable linear regression for DAOH, (B) Multivariable linear regression for DAOH by viral type, (C) Multivariable linear regression for DAOH by viral location and symptom composite. Conclusion In this single center study, HRV as virus type and URI as location of viral infection before myeloablative allogeneic HCT were associated with increased hospitalization after HCT, but not in multivariate models. Larger multicenter studies are needed to provide timely evaluation and adequate statistical power to definitively determine role of URI versus LRD and the impact of transplant delay and treatment strategies. Disclosures Yae-Jean Kim, MD, PhD, Janssen: Grant/Research Support|Korean Society of Pediatric Infectious Diseases: Grant/Research Support|Ministry of Trade, Industry and Energy: Grant/Research Support|MSD: Grant/Research Support chikara Ogimi, MD, Horiba: payment for a lecture Michael J. Boeckh, MD PhD, Allovir: Advisor/Consultant|Amazon: Grant/Research Support|Ansun Biopharma: Grant/Research Support|EvrysBio: Advisor/Consultant|Gates Ventures: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Helocyte: Advisor/Consultant|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kyorin Pharmaceuticals: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Regeneron: Grant/Research Support|ReViral: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Grant/Research Support|Vir Biotechnology: Advisor/Consultant|Vir Biotechnology: Grant/Research Support Janet A. Englund, MD, Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccine: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|SanofiPasteur: Advisor/Consultant Alpana Waghmare, MD, Allovir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|Devarra Therapeutics: DSMB|Kyorin Pharmaceutical: Advisor/Consultant|Pfizer: Grant/Research Support|Vir/GSK: Grant/Research Support.

Background We previously demonstrated frequent detection of HHV-6B DNA in bronchoalveolar lavage fluid (BALF) and its positive association with mortality in HCT recipients from 1992-2015 with lower respiratory tract disease (LRTD). Whether these findings remain pertinent in contemporary patients, the additive value of testing for viral gene transcription, and the correlation of HHV-6 detection in blood and BALF, are unknown. Methods We conducted a prospective study of allogeneic HCT recipients undergoing BAL for LRTD within 120 days of HCT at three cancer centers from 2015-2019. We collected and tested paired blood and BALF for HHV-6B DNA by qPCR and HHV-6B mRNA (U38 and U90 gene transcripts) among DNA positive samples using RT-qPCR. We described the detection of HHV-6B DNA and mRNA in blood and BALF, generated receiver operating characteristic (ROC) curves to determine the ability of BALF HHV-6B DNA detection to predict HHV-6B mRNA detection, and analyzed the association of HHV-6B DNA detection with mortality. Results We enrolled 116 allogeneic HCT recipients who underwent 125 BALs. HHV-6B DNA was detected in 45 of 122 BALF (37%) compared to 19 of 124 (15%) plasma samples. Among the 45 BALF samples with HHV-6B DNA detected, either HHV-6B mRNA transcript was detected in 22 (49%) (Figure 1). BALF HHV-6B DNA ≥ 218 copies/ml had an area under the curve of 0.93 for predicting detection of BALF viral mRNA (Figure 2). In turn, patients with BALF HHV-6B DNA ≥ 218 copies/mL had increased risk for mortality and death due to LRTD within 60 days after the BAL (Figure 3). This association remained after adjustment for age, oxygen use, and steroid use at the time of BAL in a multivariable Cox model (Figure 3). Conclusion HHV-6B was detected more frequently in BALF than plasma, suggesting compartment-specific reactivation. BALF HHV-6B DNA ≥ 218 copies/mL had high sensitivity and specificity for detection of viral gene transcription in BALF and was associated with increased mortality; this viral load is strikingly similar to the BALF viral load threshold of 251 copies/mL associated with mortality in our prior retrospective study. Together, these data suggest transcriptionally active HHV-6B is a clinically impactful pulmonary pathogen in contemporary HCT recipients. Disclosures Joshua A. Hill, MD, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Covance/CSL: Advisor/Consultant|CRISPR: Advisor/Consultant|Deverra: Grant/Research Support|Gilead: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck: Grant/Research Support|Octapharma: Advisor/Consultant|OptumHealth: Advisor/Consultant|Oxford Immunotec: Grant/Research Support|Pfizer: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Advisor/Consultant Alpana waghmare, MD, Allovir: Grant/Research Support|Ansun BioPharma: Grant/Research Support|Kyorin Pharmaceutical: Advisor/Consultant|Pfizer: Grant/Research Support|Vir/GSK: Grant/Research Support Geoffrey Hill, M.D., FRACP, FRCPA, Applied Molecular Transport: Grant/Research Support|Compass Therapeutics: Grant/Research Support|Generon Corporation: Advisor/Consultant|Heat Biologics: Grant/Research Support|iTeos Therapeutics: Advisor/Consultant|iTeos Therapeutics: Grant/Research Support|Laevoroc Oncology: Grant/Research Support|NapaJen Pharma: Advisor/Consultant|Neoleukin Therapeutics: Advisor/Consultant|Serplus Technology: Grant/Research Support|Syndax Pharmaceuticals: Grant/Research Support Danielle M. Zerr, MD MPH, AlloVir: Advisor/Consultant Sanjeet S. Dadwal, MD, FACP, FIDSA, AlloVir: Advisor/Consultant|AlloVir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|Aseptiscope: Advisor/Consultant|Aseptiscope: Stocks/Bonds|Astellas: Speaker's Bureau|Cidara: Advisor/Consultant|Gilead: Grant/Research Support|Karius: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Speaker's Bureau|Takeda: Speaker's Bureau Michael J. Boeckh, MD PhD, Allovir: Advisor/Consultant|Amazon: Grant/Research Support|Ansun Biopharma: Grant/Research Support|EvrysBio: Advisor/Consultant|Gates Ventures: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Helocyte: Advisor/Consultant|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kyorin Pharmaceuticals: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Regeneron: Grant/Research Support|ReViral: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Grant/Research Support|Vir Biotechnology: Advisor/Consultant|Vir Biotechnology: Grant/Research Support.

Data are limited regarding risk factors for lower respiratory tract infection (LRTI) caused by seasonal human coronaviruses (HCoVs) and the significance of virologic documentation by bronchoalveolar lavage (BAL) on outcomes in hematopoietic cell transplant (HCT) recipients. We retrospectively analyzed patients undergoing allogeneic HCT (4/2008-9/2018) with HCoV (OC43/NL63/HKU1/229E) detected by polymerase chain reaction during conditioning or post-HCT. Risk factors for all manifestations of LRTI and progression to LRTI among those presenting with HCoV upper respiratory tract infection (URTI) were analyzed by logistic regression and Cox proportional hazard models, respectively. Mortality rates following HCoV LRTI were compared according to virologic documentation by BAL. A total of 297 patients (61 children and 236 adults) developed HCoV infection as follows: 254 had URTI alone, 18 presented with LRTI, and 25 progressed from URTI to LRTI (median, 16 days; range, 2-62 days). Multivariable logistic regression analyses showed that male sex, higher immunodeficiency scoring index, albumin 150 mg/dL, and presence of respiratory copathogens were associated with occurrence of LRTI. Hyperglycemia with steroid use was associated with progression to LRTI (P < .01) in Cox models. LRTI with HCoV detected in BAL was associated with higher mortality than LRTI without documented detection in BAL (P < .01). In conclusion, we identified factors associated with HCoV LRTI, some of which are less commonly appreciated to be risk factors for LRTI with other respiratory viruses in HCT recipients. The association of hyperglycemia with LRTI might provide an intervention opportunity to reduce the risk of LRTI., Key Points • We demonstrate risk factors for HCoV LRTI in allogeneic HCT recipients and significance of virologic documentation by BAL on mortality. • Hyperglycemia associated with steroid use appears to be a strong predictor of HCoV disease progression.

BACKGROUND: Some respiratory viruses have been evaluated for the association between viral burden and respiratory disease progression in hematopoietic cell transplant (HCT) recipients, and no significant association has been reported. OBJECTIVES: To assess whether initial viral burden of respiratory viruses predicts risk of progression to lower respiratory tract infection (LRTI) in among adult allogeneic HCT recipients who presented with upper respiratory tract infection (URTI) with 12 viruses in the PCR era. STUDY DESIGN: We reviewed adult allogeneic HCT recipients (4/2008–9/2018) who presented with their first symptomatic respiratory viral infection following transplantation at the Fred Hutchinson Cancer Research Center and the Seattle Cancer Care Alliance. Cox proportional hazards models were used to investigate whether viral burden as measured by initial Ct values at the diagnosis of URTI is associated with progression to LRTI within 90 days for each virus, treating death as a competing risk. RESULTS: Among 2,148 adult HCT recipients during the study periods, 1,102 episodes of URTI met the study inclusion criteria. Higher viral burden (lower Ct value) were associated with an increased risk of progression to LRTI for influenza after adjusting for immunodeficiency scoring index and initiation of antiviral therapy, respectively. The association between viral burden and progression to LRTI was not found for other viruses. CONCLUSIONS: Our findings suggest that routine reporting of viral burden in current molecular diagnostic platforms may be beneficial. Further studies are needed to investigate the impact of viral burden on LRTI in other populations including pediatric HCT recipients.

Decreased cytomegalovirus (CMV)-specific immunity after hematopoietic cell transplantation (HCT) is associated with late CMV reactivation and increased mortality. Whether letermovir prophylaxis-associated reduction in viral exposure influences CMV-specific immune reconstitution is unknown. In a prospective cohort of allogeneic HCT recipients who received letermovir, we compared polyfunctional CMV-specific T-cell responses to those of controls who received PCR-guided preemptive therapy before the introduction of letermovir. Thirteen-color flow cytometry was used to assess T-cell responses at 3 months after HCT following stimulation with CMV immediate early-1 (IE-1) antigen and phosphoprotein 65 (pp65) antigens. Polyfunctionality was characterized by combinatorial polyfunctionality analysis of antigen-specific T-cell subsets. Use of letermovir and reduction of viral exposure were assessed for their association with CMV-specific T-cell immunity. Polyfunctional T-cell responses to IE-1 and pp65 were decreased in letermovir recipients and remained diminished after adjustment for donor CMV serostatus, absolute lymphocyte count, and steroid use. Among letermovir recipients, greater peak CMV DNAemia and increased viral shedding were associated with stronger CD8+ responses to pp65, whereas the CMV shedding rate was associated with greater CD4+ responses to IE-1. In summary, our study provided initial evidence that letermovir may delay CMV-specific cellular reconstitution, possibly related to decreased CMV antigen exposure. Evaluating T-cell polyfunctionality may identify patients at risk for late CMV infection after HCT.

We sought to determine whether donor-derived human herpesvirus (HHV) 6B–specific CD4+ T-cell abundance is correlated with HHV-6B detection after allogeneic hematopoietic cell transplantation. We identified 33 patients who received HLA-matched, non–T-cell–depleted, myeloablative allogeneic hematopoietic cell transplantation and underwent weekly plasma polymerase chain reaction testing for HHV-6B for 100 days thereafter. We tested donor peripheral blood mononuclear cells for HHV-6B–specific CD4+ T cells. Patients with HHV-6B detection above the median peak viral load (200 copies/mL) received approximately 10-fold fewer donor-derived total or HHV-6B–specific CD4+ T cells than those with peak HHV-6B detection at ≤200 copies/mL or with no HHV-6B detection. These data suggest the importance of donor-derived immunity for controlling HHV-6B reactivation.

BK polyomavirus (BKPyV) has been associated with hemorrhagic cystitis (HC) after allogeneic hematopoietic cell transplantation (HCT), but the natural history of HC and factors associated with the clinical course are incompletely understood. We retrospectively analyzed allogeneic HCT patients transplanted from 2007-2017 who presented after platelet engraftment or after day 28 post-HCT with BKPyV-associated HC (BKPyV-HC), which was defined as a positive urine BKPyV PCR, ≥1 plasma BKPyV viral load result, and macroscopic hematuria (Bedi grade ≥2). Factors associated with resolution of macroscopic hematuria and resolution of all cystitis symptoms within 90 days after HC diagnosis were investigated in multivariable models. In 128 patients with BKPyV-HC, the median times from diagnosis to resolution of all symptoms, macroscopic hematuria, and urinary clots (present in 55% [71/128]) were 24 days (15-44), 17 days (10-30), and 14 days (5-26), respectively. Ninety percent of patients had BKPyV viremia at the onset of HC with a median viral load of 1850 copies/mL (interquartile range, 240-8550). In multivariable models, high plasma viral load (≥10 000 copies/mL) and cytopenias at the beginning of BKPyV-HC were significantly associated with longer macroscopic hematuria and cystitis symptoms. Use of cidofovir was not associated with shorter duration of illness. In conclusion, BKPyV-HC after allogeneic HCT is characterized by prolonged and severe symptoms and requires improved management strategies. High-grade viremia and cytopenias were associated with a longer duration of BKPyV-associated HC. Accurate descriptions of disease and factors associated with prolonged recovery will inform end points of future clinical trials.

PURPOSE Human herpesvirus 6B (HHV-6B) DNA is frequently detected in bronchoalveolar lavage fluid (BALF) from immunocompromised subjects with lower respiratory tract disease (LRTD). Whether HHV-6B is a pulmonary pathogen is unclear. METHODS We tested BALF for HHV-6B DNA using polymerase chain reaction in allogeneic hematopoietic cell transplantation (HCT) recipients who underwent a BAL for evaluation of LRTD from 1992 to 2015. We used multivariable proportional hazards models to evaluate the association of HHV-6B+ BALF with overall mortality, death from respiratory failure, and the effect of anti–HHV-6B antivirals on these outcomes. We used branched-chain RNA in situ hybridization to detect HHV-6 messenger RNA ( U41 and U57 transcripts) in lung tissue. RESULTS We detected HHV-6B+ BALF from 147 of 553 (27%) individuals. Subjects with HHV-6B+ BALF, with or without copathogens, had significantly increased risk of overall mortality (adjusted hazard ratio [aHR], 2.18; 95% CI, 1.41-3.39) and death from respiratory failure (aHR, 2.50; 95% CI, 1.56-4.01) compared with subjects with HHV-6B- BALF. Subjects with HHV-6B+ BALF who received antivirals within 3 days pre-BAL had an approximately 1 log10 lower median HHV-6B BALF viral load, as well as a lower risk of overall mortality (aHR, 0.42; 95% CI, 0.16-1.10), compared with subjects with HHV-6B+ BALF not receiving antivirals. We detected intraparenchymal HHV-6 gene expression by RNA in situ hybridization in lung tissue in all three tested subjects with HHV-6B+ BALF and sufficient tissue RNA preservation. CONCLUSION These data provide evidence that HHV-6B detection in BALF is associated with higher mortality in allogeneic hematopoietic cell transplantation recipients with LRTD. Definitive evidence of causation will require a randomized prevention or treatment trial.

Transmission line operation environment is complex, prone to tilt collapse accident, so a transmission tower tilt real-time early warning model based on multi-sensor data is established to judge whether the tower is stable operation by detecting the tilt state of the early warning tower. The pressure and inclination sensors are deployed at different positions of the transmission tower to collect the inclination and stress of the tower in real time, and transmit them to the remote monitoring terminal through the wireless network to send out an alarm. The operators can timely adjust according to the alarm situation to maintain the safe operation of the transmission line. The experimental results show that the model can realize the real-time warning of transmission tower tilt, the measurement accuracy can meet the needs of comprehensive detection of tower state, and the application can effectively ensure the safety of staff and reduce the work intensity.