Late Infection Research Articles

Periprosthetic joint infections: a 20 years retrospective epidemiological study in a single european accademic hospital

Introduction: Periprosthetic Joint infections (PJIs) still represent one of the most challenging complications in orthopaedic reconstructive surgery. The aim of our work is to present a retrospective observational analysis with 20 years of follow up of PJIs referred to a single center equipped with a regional referral infectious diseases department. Materials and methods: 368 case of deep PJIs following a primary or revision hip and knee arthroplasty procedure referred to our center between January 1996 and December 2016 were included in the study. Criteria of inclusion in the study was a primary PJI entirely managed in our hospital. We collected demographic data, risk factors, microbiology (identification pathogenic agent), previous surgical treatments, type of implant, diagnostic criteria of infection, type of infection and medical or surgical treatments performed in our institution Results: A total of 200 (54,3%) infection occurs in hip arthroplasty and 168 (45,7%) in knee arthroplasty. Mean age was 64,7 years. The majority were late infections (58,8%). Respectively polymicrobial infections was identified in 83 (22,6%) cases and in 54 (14,7%) patients no isolation was possible. S. Aureus was the most frequently identified pathogen. The major risk factors were hypertension in 254 (69,1%), cardiovascular diseases in 167 (45,7%), obesity in 97 (26,5%) and diabetes mellitus in 92 (25%). Discussion: Epidemiological analysis of PJI in our hospital which collects data relating to the last 20 years, has permitted to obtain a summary of our scenario. Ideal PJI management should include an accurate patient history considering carefully risk factors, patients conditions, and previous surgical procedures ideally in a multispecialist enviroment.

Laser Microdissection of Pisum sativum L. Nodules Followed by RNA-Seq Analysis Revealed Crucial Transcriptomic Changes during Infected Cell Differentiation

Garden pea (Pisum sativum L.) is a globally important legume crop. Like other legumes, it forms beneficial symbiotic interactions with the soil bacteria rhizobia, gaining the ability to fix atmospheric nitrogen. In pea nodules, the meristem is long-lasting and results in the formation of several histological zones that implicate a notable differentiation of infected host cells. However, the fine transcriptional changes that accompany differentiation are still unknown. In this study, using laser microdissection followed by RNA-seq analysis, we performed transcriptomic profiling in the early infection zone, late infection zone, and nitrogen fixation zone of 11-day-old nodules of pea wild-type line SGE. As a result, a list of functional groups of differentially expressed genes (DEGs) in different nodule histological zones and a list of genes with the most prominent expression changes during nodule development were obtained. Their analyses demonstrated that the highest amount of DEGs was associated with the nitrogen fixation zone. Among well-known genes controlling nodule development, we revealed genes that can be novel players throughout nodule formation. The characterized genes in pea were compared with those previously described in other legumes and their possible functions in nodule development are discussed.

Decreasing Trend in Incidence of Late Onset Culture Positive Bloodstream Infections but Not Late Onset Meningitis in Preterm Infants

Introduction: Recent studies reported decreased incidence of late onset sepsis in the neonatal intensive care unit (NICU), but it is unclear whether this is also true for late onset meningitis. Recent reports that both meningitis and intraventricular hemorrhage (IVH) are associated with systemic inflammation also raise questions about an association between the 2. Methods: All preterm infants <33 weeks gestational age admitted to CNN NICUs from 2010 to 2018 were included. We compared incidence trends of late onset culture positive bloodstream infection (CPBSI) and late onset meningitis, and examined the association of meningitis and IVH (exposure), after adjustment for potential confounders. Results: Of 36,573 infants included, 32,198 had no infection, 3,977 had only late onset CPBSI and 398 had late onset meningitis. There was significant decrease in incidence of late onset CPBSI (14%–10%; adjusted odds ratio (AOR) = 0.93; 95% confidence interval [CI] 0.92, 0.95) but not late onset meningitis (1.6%–1.2%; AOR = 0.98; 95% CI 0.94, 1.01). Compared to infants with no IVH grade 3 or above, infants with IVH grade 3, or above had higher odds of late onset meningitis versus no infection (AOR 4.16; 95% CI 3.17, 5.44), and higher odds of late onset meningitis versus late onset CPBSI (AOR 4.11; 95% CI 3.08, 5.50). Conclusions: There was a decreasing trend of late onset CPBSI but not late onset meningitis. An association between late onset meningitis and IVH grade 3 or above was observed. Late onset CPBSI and meningitis may have different risk factors and require different prevention strategies.

Superior vena cava graft infection in thoracic surgery: a retrospective study of the French EPITHOR database.

OBJECTIVESTo report our experience on the management of superior vena cava graft infection.METHODSBetween 2001 and 2018, patients with superior vena cava synthetic graft or patch reconstruction after resection of intrathoracic tumours or benign disease were selected retrospectively from the French EPITHOR database and participating thoracic centres. Our study population includes patients with superior vena cava graft infection, defined according to the MAGIC consensus. Superior vena cava synthetic grafts in an empyema or mediastinitis were considered as infected.RESULTSOf 111 eligible patients, superior vena cava graft infection occurred in 12 (11.9%) patients with a polytetrafluoroethylene graft secondary to contiguous contamination. Management consisted of either conservative treatment with chest tube drainage and antibiotics (n = 3) or a surgical graft-sparing strategy (n = 9). Recurrence of infection appears in 6 patients. Graft removal was performed in 2 patients among the 5 reoperated patients. The operative mortality rate was 25%.CONCLUSIONSSuperior vena cava graft infection may develop as a surgical site infection secondary to early mediastinitis or empyema. Graft removal is not always mandatory but should be considered in late or recurrent graft infection or in infections caused by aggressive microorganisms (virulent or multidrug resistant bacteria or fungi).

926. COVID-19 Infections After SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients

BackgroundSolid organ transplant recipients (SOTR) have lower humoral responses following SARS-CoV-2 vaccination. Whether this equates to reduced vaccine effectiveness in SOTR or impacts disease severity is not yet known. We used the IDSA Emerging Infections Network (EIN) to identify SARS-CoV-2 cases in vaccinated SOTR. We describe their clinical characteristics and outcomes.MethodsOn 4/7/21, we requested case reports via the EIN listserv of COVID-19 infection following SARS-CoV-2 vaccination in immunocompromised individuals. Case reports were collected until June 7th. Online data collection included patient demographics, dates of SARS-CoV-2 vaccine administration and clinical data related to COVID-19 infection. We performed a descriptive analysis of these patient factors and compared differences between early onset (< / = 21 days after completing vaccine series) and late onset infection ( > 21 days after completing vaccine series).ResultsAs of 6/7/21, 34 cases of COVID-19 infection after vaccination in SOTR were submitted. Most cases (79%) occurred in individuals who were fully vaccinated. Only 3 cases (8.5%) occurred in SOTR within their first year after transplantation. Clinical characteristics are listed in Table 1. The vaccine administration date was known for 26 SOTR among whom symptoms occurred a median of 26.5 days (IQR 21.75 days, range 5-79 days) after completing the COVID-19 vaccine series. Twenty-three SOTR (68%) required hospitalization of which 12 had critical illness. Outcome data was available for 29 individuals of whom 20 (69%) demonstrated improvement. When comparing SOTR with early versus late onset COVID-19 infection in relation to vaccination timing, there were no differences in disease severity (80% vs 75% with severe or critical disease, p=NS) or outcome (30% vs 31% died or deteriorating, p=NS).Table 1: Characteristics of Solid Organ Transplant Recipients with COVID-19 Infection Following SARS-CoV-2 Vaccination ConclusionSARS-CoV-2 infections after vaccination are occurring in SOTR, including cases of critical illness, suggesting reduced vaccine effectiveness within this vulnerable population. We did not appreciate any correlation between time from vaccination and COVID-19 disease severity or outcome. Further studies evaluating the true incidence of and risk factors for breakthrough infections among vaccinated SOTR are needed.Disclosures Matthew Kuehnert, M.D., American Association of Tissue Banks (Board Member)ICCBBA (Board Member)Musculoskeletal Transplant Foundation (Employee) John W. Baddley, M.D., Eli Lilly (Consultant)Pfizer (Consultant)R-Pharm (Consultant)Viela Bio (Consultant)

Transcriptomic Response to Perkinsus marinus in Two Crassostrea Oysters Reveals Evolutionary Dynamics of Host-Parasite Interactions.

Infectious disease outbreaks are causing widespread declines of marine invertebrates including corals, sea stars, shrimps, and molluscs. Dermo is a lethal infectious disease of the eastern oyster Crassostrea virginica caused by the protist Perkinsus marinus. The Pacific oyster Crassostrea gigas is resistant to Dermo due to differences in the host-parasite interaction that is not well understood. We compared transcriptomic responses to P. marinus challenge in the two oysters at early and late infection stages. Dynamic and orchestrated regulation of large sets of innate immune response genes were observed in both species with remarkably similar patterns for most orthologs, although responses in C. virginica were stronger, suggesting strong or over-reacting immune response could be a cause of host mortality. Between the two species, several key immune response gene families differed in their expansion, sequence variation and/or transcriptional response to P. marinus, reflecting evolutionary divergence in host-parasite interaction. Of note, significant upregulation of inhibitors of apoptosis (IAPs) was observed in resistant C. gigas but not in susceptible C. virginica, suggesting upregulation of IAPs is an active defense mechanism, not a passive response orchestrated by P. marinus. Compared with C. gigas, C. virginica exhibited greater expansion of toll-like receptors (TLRs) and positive selection in P. marinus responsive TLRs. The C1q domain containing proteins (C1qDCs) with the galactose-binding lectin domain that is involved in P. marinus recognition, were only present and significantly upregulated in C. virginica. These results point to previously undescribed differences in host defense genes between the two oyster species that may account for the difference in susceptibility, providing an expanded portrait of the evolutionary dynamics of host-parasite interaction in lophotrochozoans that lack adaptive immunity. Our findings suggest that C. virginica and P. marinus have a history of coevolution and the recent outbreaks may be due to increased virulence of the parasite.

Risk of Hernia Mesh Explantation following Early Versus Late Onset Skin and Soft Tissue Infection.

Infectious complications occurring after hernia repair with synthetic mesh require prolonged treatment, and eventual mesh explantation. Little is known whether early versus late onset infection is associated with differential risk of mesh removal, and whether treatment with long-term antibiotics or debridement are associated with mesh salvage. This was a retrospective observational cohort study. We obtained data on all inguinal, umbilical, and ventral hernia repairs with implanted synthetic mesh performed in Veterans Affairs hospitals during 2008-2015. Participants without a 5-year infection after hernia surgery were excluded. Logistic regression estimated the association of mesh explantation with exposure to mesh-related infection during postoperative days 0-90, versus days 91-365 versus after 1 year. Additional covariates included any subsequent abdominal operation, antibiotic administration, and incision and drainage (I&D) or debridement procedures. One thousand eight hundred eighty-five patients underwent index hernia repair and developed a skin and soft tissue infection within 5 years. Infection onset during days 91-365 was associated with increased explantation risk (OR, 1.62; 95% CI, 1.04-2.48), as was increased antibiotic use (OR, 1.04; 95% CI, 1.03-1.05) and surgical treatments (OR, 3.74; 95% CI, 3.02-4.67). Subsequent abdominal operation was associated with lower explantation risk (OR, 0.46; 95% CI, 0.33-0.61). Early infections may be more suitable for conservative management. Later-onset infections have lower probability of mesh salvage and should be considered for earlier explantation to save the patients prolonged courses of antibiotics and surgical interventions.

Comparison of Viral Replication, Antiviral Gene Expression and Antioxidant Enzyme Activity in Gibel Carp (Carassius auratus gibelio) Infected with Cyprinid Herpesvirus 2 at Susceptible and Less-susceptible Temperatures

Cyprinid herpesvirus 2 is a DNA virus that is a concern for the aquaculture worldwide. Here, the challenge of CyHV-2 infection was conducted in gibel carp at a host susceptible temperature (25 ℃) and a less-susceptible temperature (15 ℃). The viral replication and expression of antiviral genes were analyzed by real time PCR, and the activities of antioxidative enzymes in serum were also examined. Results showed that CyHV-2 was in normal proliferative in 25 ℃ group, while the growth was inhibited in 15 ℃ group. Moreover, IFNφ1 and Mx were highly expressed from 12 hpi to 48 hpi in both groups, but the 15 ℃ group showed quicker and stronger response. TNF-α and IL-1β showed early upregulation at 12 hpi followed by a sharp decline in both groups. Fatty acid synthase (FAS) and Caspase-8 showed a higher expression level in 15 ℃ group than that in 25 ℃ group during 48-96 hpi. Furthermore, the activities of antioxidant enzymes (SOD and CAT) in 15 ℃ group were higher than those in 25 ℃ group at late infection. Thus, water temperature affected the immune response against CyHV-2 infection, which may ultimately lead to host survival in the less-susceptible temperatures.

Role of CXCL5 in Regulating Chemotaxis of Innate and Adaptive Leukocytes in Infected Lungs Upon Pulmonary Influenza Infection.

Respirovirus such as influenza virus infection induces pulmonary anti-viral immune response, orchestration of innate and adaptive immunity restrain viral infection, otherwise causes severe diseases such as pneumonia. Chemokines regulate leukocyte recruitment to the inflammation site. One chemokine CXCL5, plays a scavenging role to regulate pulmonary host defense against bacterial infection, but its role in pulmonary influenza virus infection is underdetermined. Here, using an influenza (H1N1) infected CXCL5-/- mouse model, we found that CXCL5 not only responds to neutrophil infiltration into infected lungs at the innate immunity stage, but also affects B lymphocyte accumulation in the lungs by regulating the expression of the B cell chemokine CXCL13. Inhibition of CXCL5-CXCR2 axis markedly induces CXCL13 expression in CD64+CD44hiCD274hi macrophages/monocytes in infected lungs, and in vitro administration of CXCL5 to CD64+ alveolar macrophages suppresses CXCL13 expression via the CXCL5-CXCR2 axis upon influenza challenge. CXCL5 deficiency leads to increased B lymphocyte accumulation in infected lungs, contributing to an enhanced B cell immune response and facilitating induced bronchus-associated lymphoid tissue formation in the infected lungs during the late infection and recovery stages. These data highlight multiple regulatory roles of CXCL5 in leukocyte chemotaxis during pulmonary influenza infection.

Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads.

A flavonoid is a versatile core structure with various cellular, immunological, and pharmacological effects. Recently, flavones have shown anti-dengue activities by interfering with viral translation and replication. However, the molecular target is still elusive. Here we chemically modified apigenin by adding an alkyne moiety into the B-ring hydroxyl group. The alkyne serves as a chemical tag for the alkyne-azide cycloaddition reaction for subcellular visualization. The compound located at the perinuclear region at 1 and 6 h after infection. Interestingly, the compound signal started shifting to vesicle-like structures at 6 h and accumulated at 24 and 48 h after infection. Moreover, the compound treatment in dengue-infected cells showed that the compound restricted the viral protein inside the vesicles, especially at 48 h. As a result, the dengue envelope proteins spread throughout the cells. The alkyne-tagged apigenin showed a more potent efficacy at the EC50 of 2.36 ± 0.22, and 10.55 ± 3.37 µM, respectively, while the cytotoxicities were similar to the original apigenin at the CC50 of 70.34 ± 11.79, and 82.82 ± 11.68 µM, respectively. Molecular docking confirmed the apigenin binding to the previously reported target, ribosomal protein S9, at two binding sites. The network analysis, homopharma, and molecular docking revealed that the estrogen receptor 1 and viral NS1 were potential targets at the late infection stage. The interactions could attenuate dengue productivity by interfering with viral translation and suppressing the viral proteins from trafficking to the cell surface.

Abstract 14249: Response to Cardiac Resynchronization Therapy in Cancer Patients With Heart Failure

Introduction: Heart failure is associated with poor clinical outcomes in cancer patients. Cardiac resynchronization therapy (CRT) provides a therapeutic avenue to improve left ventricular function and decrease symptoms. Historically, CRT has been underutilized in cancer patients. We assessed the hypothesis that cancer patients have a similar response to cardiac resynchronization therapy as the general heart failure population. Methods: This study included 37 patients with cancer who underwent CRT implantation between 2012 and 2020. The primary endpoints were response to CRT as measured by an improvement in left ventricular ejection fraction (LVEF) by &gt;=10% or decrease in left ventricular end systolic volume index (LVESVi) by &gt;=15% over 3 to 24 months. Secondary endpoints were change in LVEF, LVESVi, and New York Heart Association (NYHA) class. Results: Of 37 patients, primary and secondary endpoints were available for 34 patients (mean [SD] age, 68 [9] years; 24 men (71%); 26 nonischemic cardiomyopathy (76%), 8 ischemic (24%); mean QRSd 152 ms; 10 patients with NYHA II symptoms (29%), 24 NYHA III (71%)). 20 patients met the primary endpoint (65% [46%-80%]). This response rate is not significantly different than published response rates to CRT of 70% in the general heart failure population. The average improvement in LVEF was 12.9% ([9.4%-16.4%], p&lt;0.001). The average decrease in LVESVi was 25.4% ([17.2%-33.5%], p&lt;0.001). 23 of 34 patients had an improvement in NYHA classification (20 by one class, 3 by two), whereas 9 patients had no improvement and 2 patients had worsening symptoms (mean improvement 0.7 [0.46-0.96], p&lt;0.001). 2 of 37 patients had a complication (one late device infection, one right atrial lead dislodgment requiring reimplantation). 4 of 37 patients (10.8%) died within 12 months of primary oncologic cause. 4 of 34 (11.7%) CRT-D patients had received appropriate therapies on device interrogation at time of submission. Conclusions: CRT improves left ventricular function, reverses left ventricular remodeling, and improves exertional dyspnea in patients with cancer. Response rate is similar to that of a general heart failure population. Oncologic prognoses of over 12 months life expectancy at time of implant were reasonably accurate.

MK2a inhibitor CMPD1 abrogates chikungunya virus infection by modulating actin remodeling pathway.

Chikungunya virus (CHIKV) epidemics around the world have created public health concern with the unavailability of effective drugs and vaccines. This emphasizes the need for molecular understanding of host-virus interactions for developing effective targeted antivirals. Microarray analysis was carried out using CHIKV strain (Prototype and Indian) infected Vero cells and two host isozymes, MAPK activated protein kinase 2 (MK2) and MAPK activated protein kinase 3 (MK3) were selected for further analysis. The substrate spectrum of both enzymes is indistinguishable and covers proteins involved in cytokines production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling and transcriptional regulation. Gene silencing and drug treatment were performed in vitro and in vivo to unravel the role of MK2/MK3 in CHIKV infection. Gene silencing of MK2 and MK3 abrogated around 58% CHIKV progeny release from the host cell and a MK2 activation inhibitor (CMPD1) treatment demonstrated 68% inhibition of viral infection suggesting a major role of MAPKAPKs during late CHIKV infection in vitro. Further, it was observed that the inhibition in viral infection is primarily due to the abrogation of lamellipodium formation through modulation of factors involved in the actin cytoskeleton remodeling pathway. Moreover, CHIKV-infected C57BL/6 mice demonstrated reduction in the viral copy number, lessened disease score and better survivability after CMPD1 treatment. In addition, reduction in expression of key pro-inflammatory mediators such as CXCL13, RAGE, FGF, MMP9 and increase in HGF (a CHIKV infection recovery marker) was observed indicating the effectiveness of the drug against CHIKV. Taken together it can be proposed that MK2 and MK3 are crucial host factors for CHIKV infection and can be considered as important target for developing effective anti-CHIKV strategies.

Phlebotomus papatasi Antimicrobial Peptides in Larvae and Females and a Gut-Specific Defensin Upregulated by Leishmania major Infection.

Phlebotomus papatasi is the vector of Leishmania major, causing cutaneous leishmaniasis in the Old World. We investigated whether P. papatasi immunity genes were expressed toward L. major, commensal gut microbes, or a combination of both. We focused on sand fly transcription factors dorsal and relish and antimicrobial peptides (AMPs) attacin and defensin and assessed their relative gene expression by qPCR. Sand fly larvae were fed food with different bacterial loads. Relish and AMPs gene expressions were higher in L3 and early L4 larval instars, while bacteria 16S rRNA increased in late L4 larval instar, all fed rich-microbe food compared to the control group fed autoclaved food. Sand fly females were treated with an antibiotic cocktail to deplete gut bacteria and were experimentally infected by Leishmania. Compared to non-infected females, dorsal and defensin were upregulated at early and late infection stages, respectively. An earlier increase of defensin was observed in infected females when bacteria recolonized the gut after the removal of antibiotics. Interestingly, this defensin gene expression occurred specifically in midguts but not in other tissues of females and larvae. A gut-specific defensin gene upregulated by L. major infection, in combination with gut-bacteria, is a promising molecular target for parasite control strategies.

Long-Term Outcomes of Patients with Large B-Cell Lymphoma Treated with Standard-of-Care Axicabtagene Ciloleucel: Results from the US Lymphoma CAR-T Cell Consortium

Long-Term Outcomes of Patients with Large B-Cell Lymphoma Treated with Standard-of-Care Axicabtagene Ciloleucel: Results from the US Lymphoma CAR-T Cell Consortium

Bcl-xL Reduces Chinese Giant Salamander Iridovirus-Induced Mitochondrial Apoptosis by Interacting with Bak and Inhibiting the p53 Pathway.

Chinese giant salamander iridovirus (GSIV) infection could lead to mitochondrial apoptosis in this animal, a process that involves B-cell lymphoma-2 (BCL-2) superfamily molecules. The mRNA expression level of Bcl-xL, a crucial antiapoptotic molecule in the BCL-2 family, was reduced in early infection and increased in late infection. However, the molecular mechanism remains unknown. In this study, the function and regulatory mechanisms of Chinese giant salamander (Andrias davidianus) Bcl-xL (AdBcl-xL) during GSIV infection were investigated. Western blotting assays revealed that the level of Bcl-xL protein was downregulated markedly as the infection progressed. Plasmids expressing AdBcl-xL or AdBcl-xL short interfering RNAs were separately constructed and transfected into Chinese giant salamander muscle cells. Confocal microscopy showed that overexpressed AdBcl-xL was translocated to the mitochondria after infection with GSIV. Additionally, flow cytometry analysis demonstrated that apoptotic progress was reduced in both AdBcl-xL-overexpressing cells compared with those in the control, while apoptotic progress was enhanced in cells silenced for AdBcl-xL. A lower number of copies of virus major capsid protein genes and a reduced protein synthesis were confirmed in AdBcl-xL-overexpressing cells. Moreover, AdBcl-xL could bind directly to the proapoptotic molecule AdBak with or without GSIV infection. In addition, the p53 level was inhibited and the mRNA expression levels of crucial regulatory molecules in the p53 pathway were regulated in AdBcl-xL-overexpressing cells during GSIV infection. These results suggest that AdBcl-xL plays negative roles in GSIV-induced mitochondrial apoptosis and virus replication by binding to AdBak and inhibiting p53 activation.

Dengue and Zika virus infection patterns vary among Aedes aegypti field populations from Belo Horizonte, a Brazilian endemic city.

Dengue virus (DENV) and Zika virus (ZIKV) belong to the same viral family, the Flaviviridae. They cause recurring threats to the public health systems of tropical countries such as Brazil. The primary Brazilian vector of both viruses is the mosquito Aedes aegypti. After the mosquito ingests a blood meal from an infected person, the viruses infect and replicate in the midgut, disseminate to secondary tissues and reach the salivary gland (SG), where they are ready to be transmitted to a vertebrate host. It is thought that the intrinsic discrepancies among mosquitoes could affect their ability to deal with viral infections. This study confirms that the DENV and ZIKV infection patterns of nine Ae. aegypti field populations found in geographically separate health districts of an endemic Brazilian city vary. We analyzed the infection rate, disseminated infection, vector competence, and viral load through quantitative PCR. Mosquitoes were challenged using the membrane-feeding assay technique and were tested seven and fourteen days post-infection (early and late infection phases, respectively). The infection responses varied among the Ae. aegypti populations for both flaviviruses in the two infection phases. There was no similarity between DENV and ZIKV vector competencies or viral loads. According to the results of our study, the risk of viral transmission overtime after infection either increases or remains unaltered in ZIKV infected vectors. However, the risk may increase, decrease, or remain unaltered in DENV-infected vectors depending on the mosquito population. For both flaviviruses, the viral load persisted in the body even until the late infection phase. In contrast to DENV, the ZIKV accumulated in the SG over time in all the mosquito populations. These findings are novel and may help direct the development of control strategies to fight dengue and Zika outbreaks in endemic regions, and provide a warning about the importance of understanding mosquito responses to arboviral infections.

Dual Transcriptional Profiling of Carrot and 'Candidatus Liberibacter solanacearum' at Different Stages of Infection Suggests Complex Host-Pathogen Interaction.

The interactions between the phloem-limited pathogen 'Candidatus Liberibacter solanacearum' haplotype C and carrot (Daucus carota subsp. sativus) were studied at 4, 5, and 9 weeks postinoculation (wpi), by combining dual RNA-Seq results with data on bacterial colonization and observations of the plant phenotype. In the infected plants, genes involved in jasmonate biosynthesis, salicylate signaling, pathogen-associated molecular pattern- and effector-triggered immunity, and production of pathogenesis-related proteins were up-regulated. At 4 wpi, terpenoid synthesis-related genes were up-regulated, presumably as a response to the psyllid feeding, whereas at 5 and 9 wpi, genes involved in both the terpenoid and flavonoid production were down-regulated and phenylpropanoid genes were up-regulated. Chloroplast-related gene expression was down-regulated, in concordance with the observed yellowing of the infected plant leaves. Both the RNA-Seq data and electron microscopy suggested callose accumulation in the infected phloem vessels, likely to impair the transport of photosynthates, while phloem regeneration was suggested by the formation of new sieve cells and the upregulation of cell wall-related gene expression. The 'Ca. L. solanacearum' genes involved in replication, transcription, and translation were expressed at high levels at 4 and 5 wpi, whereas, at 9 wpi, the Flp pilus genes were highly expressed, suggesting adherence and reduced mobility of the bacteria. The 'Ca. L. solanacearum' genes encoding ATP and C4-dicarboxylate uptake were differentially expressed between the early and late infection stages, suggesting a change in the dependence on different host-derived energy sources. HPE1 effector and salicylate hydroxylase were expressed, presumably to suppress host cell death and salicylic acid-dependent defenses during the infection.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Individual megaspacers in two-stage revision of infected total hip arthroplasty-clinical and functional results after 2 years : Individual metal-endoskeleton cement spacer (iMECS)

HintergrundGroße Femurdefekte bei periprothetischem Spätinfekt (PPI) nach Hüfttotalendoprothese (HTEP) erfordern oft den Einsatz großer, individueller Metallendoskelett-armierter Zementspacer (iMECS).Ziel der ArbeitZiele waren die Erfassung der klinischen, radiologischen und funktionellen Ergebnisse (Harris Hip Score [HHS]) 2 Jahre nach Behandlung eines PPI unter Verwendung eines iMECS. Zentrale patientenspezifische Parameter sollten im Hinblick auf das Behandlungsergebnis ausgewertet werden.Material und MethodenDas Kollektiv dieser monozentrischen retrospektiven Kohortenstudie umfasste 29 Patienten. Das Follow-up zum Zeitpunkt der Nachuntersuchung (NU) betrug durchschnittlich 24,4 Monate (23,0–27,6 Monate). Als Behandlungserfolg wurde eine Infektfreiheit nach endoprothetischer Gelenkrekonstruktion gewertet. Die beiden Patientengruppen (mit Erfolg [E]/kein Erfolg [kE]) wurden hinsichtlich Geschlechterverteilung, Komorbiditätenindex nach Charlson (CCI), Anzahl früherer septischer Wechsel, Rate an polymikrobiellen und „difficult-to-treat“-Infekten verglichen.ErgebnisseDer durchschnittliche CCI im Gesamtkollektiv betrug 6,4 Punkte. Bei 23 von 29 Patienten (79 %) war eine Gelenkrekonstruktion möglich. Bei 4 Patienten war 2 Jahre nach operativer PPI-Behandlung keine NU möglich (2 verstorben, 2 nicht teilnahmefähig). Zur NU waren 17 von initial 29 Patienten infektfrei rekonstruiert mit einem durchschnittlichen HHS von 75 Punkten. Es traten keine iMECS-assoziierten revisionsbedürftigen Komplikationen auf. Zwischen den Patientengruppen war nur der initiale CCI (E: 4,1 Punkte; kE: 9,7 Punkte) signifikant unterschiedlich (p < 0,05).DiskussionBei großen Femurdefekten leisten iMECS eine sichere temporäre Stabilisierung. Die Chance auf eine erfolgreiche Gelenkrekonstruktion ist eng mit dem individuellen Komorbiditätenprofil verbunden.Zusatzmaterial onlineDie Online-Version dieses Beitrags 10.1007/s00132-021-04185-7 enthält eine tabellarische Übersicht der individuellen Pathogenlagen

Risk factors assessment for radiographically guided port implantations with forearm access.

IntroductionPort implantations at the forearm are associated with an increased risk of relevant vein thrombosis. Therefore, with this study we sought to identify the responsible risk factors to improve technical quality of the method.MethodsThis is a retrospective analysis of 313 patients with port implantation at the forearm in 2019. Then, exploratory statistics were conducted comprising Cox-Regression and Kaplan-Meier-Analyses.ResultsMean age was 60 ± 14 years. 232 (74%) of the patients were female. No early infection was observed. 29 late infections and 57 cases of thrombosis occurred. In only 9% of the patients with thrombosis hospital admission was necessary for treatment. Median interval to the diagnosis of thrombosis was 23 days; inter-quartile-range: 16–75. Mean interval to elective port explantation was 227 ± 128 days. There was no effect of occurrence of thrombosis of the interventionalist, the assistance nor of several technical aspects. However, there was a significantly lower risk of thrombosis for primary implanted port system compared to replacement ports, Hazard-ratio: 0.34 [Confidence interval: 0.172, 0.674], p = 0.002. Age was a significant risk factor for late infections, Hazard-ratio: 3.35 [Confidence interval:1.84, 6.07], p < 0.0001.ConclusionThe main risk factor for adverse outcome after radiographically guided port implantation at the forearm is the type of the implanted port system. The reason for that might not be the material itself but the experience of a team with a certain port system. Age is a risk factor for late complications.

Are deep infections that present before and after 90 days from orthopaedic trauma different? An analysis of the validity of the recent change in CDC criteria for infections

BackgroundIn 2016, the Centers for Disease Control and Prevention (CDC) changed the time frame for their definition of deep surgical site infection (SSI) from within 1 year to within 90 days of surgery. We hypothesized that a substantial number of infections in patients who have undergone fracture fixation present beyond 90 days and that there are patient or injury factors that can predict who is more likely to present with SSI after 90 days. MethodsA retrospective review yielded 452 deep SSI after fracture fixation. These patients were divided into two groups—those infected within 90 days of surgery and those infected beyond 90 days . Data were collected on risk factors for infection. Univariate and multiple logistic regression analyses were performed to compare the two groups. A randomly selected control group was used to build infection prediction models for both outcomes. The two outcomes were then modelled against each other to determine whether differences in predictors for early versus late infection exist. ResultsOf the 452 infections, 144 occurred beyond 90 days (32% [95% CI, 28%–36%]). No statistically significant patient factors were found in multivariable analysis between the early and late infection groups. The need for flap coverage was the only injury characteristic that differed significantly between groups, with patients in the late infection group more likely to have needed a flap. When modelled against the control group and directly comparing the two models, predictors for early infection include male sex and fractures of the pelvis, acetabulum, or hip, whereas predictors of late infection include hepatitis C and/or human immunodeficiency virus (HIV) and admission to the intensive care unit (ICU). ConclusionUse of the recent CDC definition will underestimate the rate of actual postoperative infections when applied to orthopaedic trauma patients. Hepatitis C and/or HIV and ICU admission are predictors of late infection, whereas male sex and pelvis, acetabulum, or hip fractures are predictors of early infection. Patients who receive flap coverage may be more likely to present with late infection.