Late Infection Research Articles

A Novel Recognition by the E3 Ubiquitin Ligase of HSV-1 ICP0 Enhances the Degradation of PML Isoform I to Prevent ND10 Reformation in Late Infection.

Upon viral entry, components of ND10 nuclear bodies converge with incoming DNA to repress viral expression. The infected cell protein 0 (ICP0) of herpes simplex virus 1 (HSV-1) contains a RING-type E3 ubiquitin ligase that targets the ND10 organizer, PML, for proteasomal degradation. Consequently, ND10 components are dispersed and viral genes are activated. Previously, we reported that ICP0 E3 differentiates two similar substrates, PML isoforms I and II, and demonstrated that SUMO-interaction has profound regulatory effects on PML II degradation. In the present study, we investigated elements that regulate the PML I degradation and found that: (i) two regions of ICP0 flanking the RING redundantly facilitate the degradation of PML I; (ii) downstream of the RING, the SUMO-interaction motif located at residues 362-364 (SIM362-364) targets the SUMOylated PML I in the same manner as that of PML II; (iii) upstream of the RING, the N-terminal residues 1-83 mediate PML I degradation regardless of its SUMOylation status or subcellular localization; (iv) the reposition of residues 1-83 to downstream of the RING does not affect its function in PML I degradation; and (v) the deletion of 1-83 allows the resurgence of PML I and reformation of ND10-like structures late in HSV-1 infection. Taken together, we identified a novel substrate recognition specific for PML I, by which ICP0 E3 enforces a continuous PML I degradation throughout the infection to prevent the ND10 reformation.

Mortality Risk Factors in Neonates Requiring Interhospital Transport

Objective. To identify predictors of newborn infants mortality before medical evacuation.Materials and methods. The observational, cohort, retrospective study included 564 newborns: 526 patients survived and 38 died after 604 visits of the resuscitation-consultation Center transport team (critical care transport — CCT team). Patient's anamnesis, objective data of a patient at the time of examination by CCT team, the volume of intensive care provided and treatment adjustments during preparation for the transfer, records of patient's monitored parameters and indicators of prognosis were analyzed.Results. Compared to survivors, non-survivors neonates exhibited significant increases in premature new-borns (gestation period <29 weeks in 55.26% vs 10.27% in survivors, P<0.001) and significantly increased need in a high-frequency ventilation (7.89% [1.66-21.38] vs 0.57% [0.12-1.66] in survivors, P=0.005), and in cate-cholamines support (use of adrenaline was 13.51% [4.54-28.77] in non-survivors vs 0.76% [0.21-1.94] in survivors, P<0.001). Both early and late neonatal infections predominated in non-survivors: ([26.32% [13.40-43.10] vs 8,75% [6,47-11,49, early infection, non-survivors vs. survivors, respectively, P=0.002) and (23.6% 8 [11.44-40.24] vs 10.46% [7.97-13.39], late infection, non-survivors vs. survivors, respectively, P=0.028). Significant differences in the fraction of inspired oxygen (30% [30-30] vs 45% [30-60], P<0.001), oxygenation saturation index (2.71 [2.54-3.03] vs 4.48 [2.55-7.67], P<0.001), and SpO2/FiO2 ratio (316.67 [313.33-320] vs 207.25 [151.67-313.33] P<0.001) were found between the groups of survived vs. non-survived neonates, respectively. Logistic regression model revealed following markers of neonatal mortality: birth weight, development of early and late neonatal infection, and the oxygenation saturation index.Conclusion. Low birth weight, development of early or late neonatal infection and an increase in the oxygenation saturation index are the risk factors of death in newborns requiring medical evacuation.

Lyme Disease Neuroretinitis: A Case Report and Review of Immunologic Workup

Background: Lyme disease is an infection caused by a bacterial spirochete of the borrelia genus. The human vector is from a tick bite by an infected tick of the ixodes genus, commonly referred to as the deer tick or black legged tick. The incidence of Lyme disease is increasing in the United States. Once infected, Lyme disease manifestations usually depend on the stage of infection with late stage infection often causing debilitating illness.1 Case Report: Neuroborreliosis refers to borrelia, causing neurological infection and can occur as acute or late manifestation of Lyme disease. Neuroretinitis is a rare but reported manifestation of neuroborreliosis. Lyme diagnosis requires a two-step serologic test to meet CDC guidelines for Lyme confirmation.1 Testing may be negative early in disease but may turn positive as the disease progresses. Conclusion: Presented is a case where treatment decisions were made based on equivocal Lyme testing results.

Exploring the Potential of UAV-Based Hyperspectral Imagery on Pine Wilt Disease Detection: Influence of Spatio-Temporal Scales

Pine wilt disease (PWD), caused by pine wood nematode (PWN, Bursaphelenchus xylophilus), poses a serious threat to the coniferous forests in China. This study used unmanned aerial vehicle (UAV)-based hyperspectral imaging conducted at different altitudes to investigate the impact of spatio-temporal scales on PWD detection in an monoculture Masson pine plantation. The influence of spatio-temporal scales on hyperspectral responses of pine trees infected with PWD and detection accuracies were evaluated by Jeffries–Matusita (J-M) distances and the random forest (RF) algorithm. The optimal vegetation indices (VIs) and spatial resolutions were identified by comparing feature importance and model accuracy. The main results showed that the VIs and J-M distances were greatly affected by spatio-temporal scales. In the early, mid-, and late infection stages, the RF-based PWD detection model had accuracies ranging between 72.05 and 79.48%, 83.71 and 89.59%, and 96.81 and 99.28%, peaking at the 10 cm, 8 cm, and 4 cm spatial resolutions, respectively. The green normalized difference vegetation index (GNDVI) and red edge position (REP) were the optimal VIs in early and mid-infection stages, respectively. This study can be important to improve the efficiency of PWD detection and reducing the loss of forests resources.

Diseases associated with prematurity in correlation with N-terminal pro-brain natriuretic peptide levels during the early postnatal life

The aim of this observational study was to investigate the influence of different typical preterm diseases on NT-proBNP serum levels in the early postnatal period of life of a preterm infant. NT-proBNP levels of 118 preterm infants born ≤ 31 weeks GA were determined at the first week of life, after 4 ± 1 weeks of life, and at a corrected gestational age of 36 + 2 weeks. Relevant complications with a possible influence on NT-proBNP values in the first week of life such as early neonatal infection, hemodynamically significant PDA (hsPDA), early pulmonary hypertension (early PH), and intraventricular hemorrhage (IVH) were evaluated; at 4 ± 1 weeks of life, bronchopulmonary dysplasia (BPD), BPD-related pulmonary hypertension (BPD-associated PH), late infection, IVH, and intestinal complications were evaluated. At a corrected gestational age of 36 ± 2 weeks, we examined the effect of retinopathy of prematurity (ROP), BPD, BPD-associated PH, and late infection on NT-proBNP levels. In the first days of life, only the isolated occurrence of hsPDA resulted in significantly increased NT-proBNP levels. In multiple linear regression analysis, early infection remained independently associated with NT-proBNP levels. At 4 ± 1 weeks of age, the isolated presence of BPD and BPD-related PH resulted in increased levels, and the effect remained significant in the multiple regression analysis. At a corrected gestational age of 36 ± 2 weeks, infants with relevant complications at this final evaluation time tended to have lower NT-proBNP values than our exploratory reference values. Conlusion: NT-proBNP in the first week of life seems to be mainly influenced by an hsPDA and infection or inflammation. BPD and BPD-related PH are the most important factors influencing NT-proBNP serum levels in the first month of life. When preterm infants reach a corrected GA of 36 ± 2 weeks, chronological age rather than complications of prematurity must be considered when interpreting NT-proBNP levels.What is Known:• Several complications associated with prematurity, such as hemodynamically significant PDA, pulmonary hypertension, bronchopulmonary dysplasia, and retinopathy of prematurity, have been shown to influence NT-proBNP levels in preterm infants in their early postnatal life.What is New:• Hemodynamically relevant PDA is a major factor in the increase of NT-proBNP levels in the first week of life.• Bronchopulmonary dysplasia and pulmonary hypertension associated with bronchopulmonary dysplasia are important factors in the increase in NT-proBNP levels in preterm infants at approximately 1 month of age.

COVID-19 association with multidrug-resistant bacteria superinfections: Lessons for future challenges.

The future waves of COVID 19 infections will continue to raise serious problems in patients with severe forms of the disease. Bacterial infections associated with SARS-CoV-2 disease may complicate the progress of hospitalized patients with COVID-19. The present study aimed to evaluate the etiological spectrum of superinfection in adult patients with COVID-19 and to investigate the correlation between superinfection with multidrug-resistant (MDR) bacteria and serum procalcitonin (PCT). A total of 82 COVID-19 hospitalized patients with COVID-19 and bacterial superinfection were included. The superinfections were classified into early infections (3-7 days from admission) and late infections (>7 days from admission). Bacterial superinfection etiological spectrum, MDR bacteria profile and levels of serum PCT were studied. The most frequently isolated bacteria were Klebsiella pneumoniae, Acinetobacter baumannii and Enterococcus spp. MDR bacteria were involved in 73.17% of COVID-19 patients with bacterial superinfections. Most MDR bacteria superinfections (73.52%) occurred in the late infection period. Klebsiella pneumoniae, Enterococcus spp. and Methicillin-resistant Staphylococcus aureus were the most common MDR bacteria identified in late infections after hospitalization in 20.43, 4.30 and 4.30% of all infections, respectively. Serum PCT values were significantly higher in patients with MDR bacteria superinfection compared with patients with sensitive bacteria superinfection (P=0.009). The principal findings of the present study were the high prevalence of superinfection with MDR bacteria among the COVID-19 patients with bacterial superinfections and the presence of a statistically significant association between serum PCT levels and the presence of superinfection with MDR bacteria. The most effective way to fight against microbial resistance to antibiotics, whether it occurs independently or overlaps with viral infections, is to pursue a national policy for the rational use of antibiotics.

Low-density lipoprotein receptor-related protein 1 (LRP1) as an auxiliary host factor for RNA viruses.

Viruses with an RNA genome are often the cause of zoonotic infections. In order to identify novel pro-viral host cell factors, we screened a haploid insertion-mutagenized mouse embryonic cell library for clones that are resistant to Rift Valley fever virus (RVFV). This screen returned the low-density lipoprotein receptor-related protein 1 (LRP1) as a top hit, a plasma membrane protein involved in a wide variety of cell activities. Inactivation of LRP1 in human cells reduced RVFV RNA levels already at the attachment and entry stages of infection. Moreover, the role of LRP1 in promoting RVFV infection was dependent on physiological levels of cholesterol and on endocytosis. In the human cell line HuH-7, LRP1 also promoted early infection stages of sandfly fever Sicilian virus and La Crosse virus, but had a minor effect on late infection by vesicular stomatitis virus, whereas encephalomyocarditis virus was entirely LRP1-independent. Moreover, siRNA experiments in human Calu-3 cells demonstrated that also SARS-CoV-2 infection benefitted from LRP1. Thus, we identified LRP1 as a host factor that supports infection by a spectrum of RNA viruses.

COMPARISON OF INTRODUCED IRON-RICH GENOTYPES TO NATIVELY DEVELOPED GENOTYPES OF POTATO FOR YIELD AND YIELD ATTRIBUTES IN MIDHILL OF NEPAL

A co-ordinated varietal trial was carried out in mid-hill environment (1000-1200 masl) of Lahachok in Kaski district to compare yield and yield attributes of six introduced iron-rich (T 303381.3, T 30439456, T 393371.58, T 304368.46, T 304351.109, T 391058175) genotypes and three natively developed (PRP 6267.1, PRP 056267.1, PRP 1468 71.3) genotypes of potato during the winter seasons of the years 2021 and 2022. The experiment was set to an RCBD with 3 replications and nine treatments. The iron-rich genotypes were introduced from International Potato Center, Peru and remaining genotypes were developed by National Potato Research Programme, Nepal. Well-sprouted seed tubers (25-50 g size) were planted in ridges at 60 cm inter-row and 25 cm intra-row spacing in 7.2 m2 plot area. Fertilizers were applied at the rate of 20 tons farm yard manure and 100:100:60 kg N: P2O5: K2O per hectare. Observations were recorded on vegetative parameters, damage by late blight disease and major insect pests, tuber yield and tuber size distribution. Average of two-year results revealed that the genotypes were significantly different (p =<0.05) for emergence, ground cover, vigor, plant height, number and weight of under size, seed size and over size tubers, number of tubers per hectare, tuber yield and late blight infection. The genotypes were statistically similar for uniformity, stems per plant and insect damage. Based on yield and other attributes, PRP 146871.3 (37.13 t/ha) from natively developed and T 393371.58 (29.78 t/ha) and T 304351.109 (28.23 t/ha) from introduced iron-rich genotypes were promising for further evaluation in similar agro-ecological domains.

Long-Term Results of Femorodistal Sequential Composite-Bypass Combining Heparin-Bonded PTFE-Prosthesis and Autologous Vein Using the Deutsch Bridge Technique in Critical Limb-Threatening Ischemia.

Autologous vein bypass provides excellent long-term results in critical limb-threatening ischemia (CLTI), but a substantial portion of patients have insufficient vein length. In limbs with two distal outflow vessels and limited vein length, a vascular prosthesis may be combined with autologous vein for a sequential composite bridge bypass (SCBB). Results regarding graft function, limb salvage and reinterventions are presented. Between January 2010 and December 2019, 47 consecutive SCBB operations with a heparin-bonded PTFE-prosthesis and autologous vein were performed. Grafts were followed with a duplex scan with prospective documentation in a computerized vascular database. Retrospective analysis of graft patency, limb salvage and patient survival was performed. Mean follow-up was 34 months (range 1-127 months). 30-day mortality was 10.6% and 5-year patient survival 32%. Postoperative bypass occlusion occurred in 6.4% and late occlusions or graft stenoses in 30%. Two prostheses developed late infection and seven legs were amputated. Primary, primary assisted, secondary patency and limb salvage rate were 54%, 63%, 66% and 85% after 5 years, respectively. SCBB patency and limb salvage were good despite a high early postoperative mortality. Combination of a heparin-bonded PTFE-prosthesis and autologous vein appears to be a valuable tool in CLTI in case of insufficient vein.

Long COVID and risk of erectile dysfunction in recovered patients from mild to moderate COVID-19

Patients with coronavirus disease 2019 (COVID-19) were shown to have reduced serum testosterone levels compared to healthy individuals. Low testosterone levels are linked with the development of erectile dysfunction (ED). In this case-controlled study, 20 healthy controls and 39 patients with ED 3 months after recovering from mild-to-moderate COVID-19 pneumonia were studied. The patients ranged in age from 31 to 47 years. To identify early and late COVID-19 infections, real-time polymerase-chain reaction (RT-PCR) and COVID-19 antibody testing were done. The levels of luteinizing hormone (LH), follicular stimulating hormone (FSH), total testosterone (TT), free testosterone (FT), free androgenic index (FAI), and sex hormone-binding globulin (SHBG) were measured. The sexual health inventory for patients (SHIM) score was used to measure the erectile function of the patients and controls. When compared to the controls, the TT serum level in long COVID-19 (LC) patients with ED was low (p = 0.01). In contrast to controls, FT and FAI were both lower in LC patients with ED. (p = 0.001). FSH serum levels did not significantly differ (p = 0.07), but in ED patients, LH serum levels were elevated. SHIM scores were associated with low TT (p = 0.30), FT (p = 0.09), and high LH (p = 0.76) in LC patients with ED. Male patients with decreased serum levels of LH and testosterone may have hypothalamic-pituitary–gonadal axis dysfunction, which could lead to the development of LC-induced ED. Therefore, an in-depth research is necessary to confirm the causal link between COVID-19 and ED in LC patients.

Обоснование выбора спейсера на первом этапе лечения поздней глубокой перипротезной инфекции коленного сустава

Background Periprosthetic infection develops in 0.5 to 5.0 % of cases after knee replacement, which is a social and economic problem. The most common causes of periprosthetic infection are methicillin-resistant staphylococcus aureus (MRSA) (36 %), gram-negative bacteria, and microbial associations. The study was aimed at improving the results of the sanitizing stage of revision arthroplasty in patients with periprosthetic infection of the knee joint by a developed long-acting antimicrobial composition and improving the designs of articulating spacers of the knee joint. Materials and Methods The treatment results of 121 patients with knee joint periprosthetic infection were analyzed. Nine patients had an early periprosthetic infection and 112 had a late one. Patients in satisfactory condition with stable implant components who had early periprosthetic infection underwent surgical treatment of the purulent focuses, replacement of a polyethylene tibial insert, thorough surgical wound washing using pulse lavage, drainage, and VAC-therapy. Patients with late periprosthetic infection were divided into 3 groups on the basis of the spacer used. An articulating spacer based on the developed antimicrobial composition of prolonged action (RU 191236 patent) was used in 59 patients of the first group. Preformed spacers were implanted in 29 patients of the second group, and 18 patients of the third group got a block-shaped spacer. Results An antibacterial anti-adhesive non-toxic composition with a prolonged action based on bone cement with gentamicin and such antiseptics as poviargol, dioxydine, and high-molecular polyvinylpyrrolidone has been developed. All the patients underwent the sanitizing stage of revision arthroplasty, implant removal, and spacer installation. Periprosthetic infection recurrence developed in 3 patients of the first group, 9 patients of the second group and 7 patients of the third one. The average time from the sanitizing stage to the second final stage of revision was 3-6 (4.8 ± 1.9) months. Discussion According to scientific data, the impregnation of new antibiotics into bone cement with gentamicin does not improve the antimicrobial effect of a spacer, especially in case of antibiotic-resistant strains. Block-shaped and preformed spacers lead to infection recurrence and complications. Antiseptic impregnation with different mechanisms of action is able to affect antibiotic-resistant bacteria, and the polymer is able to prolong the effect. Conclusion The use of articulating spacers for the knee joint, which include an antimicrobial composition, allows preserving the function of the joint and reducing the number of infectious complications, which facilitates the final stage of revision arthroplasty.

Hyperspectral Non-Imaging Measurements and Perceptron Neural Network for Pre-Harvesting Assessment of Damage Degree Caused by Septoria/Stagonospora Blotch Diseases of Wheat

The detection and identification of plant diseases is a fundamental task for sustainable crop production. Septoria tritici and Stagonospora nodorum blotch (STB and SNB) are two of the most common diseases of cereal crops that cause significant economic damage. Both pathogens are difficult to identify at early stages of infection. Determining the degree of the disease at a late infection stage is useful for assessing cereal crops before harvesting, as it allows the assessment of potential yield losses. Hyperspectral sensing could allow for automatic recognition of Septoria harmfulness on wheat in field conditions. In this research, we aimed to collect information on the hyperspectral data on wheat plants with different lesion degrees of STB&SNB and to create and train a neural network for the detection of lesions on leaves and ears caused by STB&SNB infection at the late stage of disease development. Spring wheat was artificially infected twice with Septoria pathogens in the stem elongation stage and in the heading stage. Hyperspectral reflections and brightness measurements were collected in the field on wheat leaves and ears on the 37th day after STB and the 30th day after SNB pathogen inoculation using an Ocean Insight “Flame” VIS-NIR hyperspectrometer. Obtained non-imaging data were pre-treated, and the perceptron model neural network (PNN) was created and trained based on a pairwise comparison of datasets for healthy and diseased plants. Both statistical and neural network approaches showed the high quality of the differentiation between healthy and damaged wheat plants by the hyperspectral signature. A comparison of the results of visual recognition and automatic STB&SNB estimation showed that the neural network was equally effective in the quality of the disease definition. The PNN, based on a neuron model of hyperspectral signature with a spectral step of 6 nm and 2000–4000 value datasets, showed a high quality of detection of the STB&SNB severity. There were 0.99 accuracy, 0.94 precision, 0.89 recall and 0.91 F-score metrics of the PNN model after 10,000 learning epochs. The estimation accuracy of diseased/healthy leaves ranged from 88.1 to 97.7% for different datasets. The accuracy of detection of a light and medium degree of disease was lower (38–66%). This method of non-imaging hyperspectral signature classification could be useful for the identification of the STB and SNB lesion degree identification in field conditions for pre-harvesting crop estimation.

Tonsil biopsy to detect chronic wasting disease in white-tailed deer (Odocoileus virginianus) by immunohistochemistry.

Chronic wasting disease (CWD) continues to spread in wild and farmed cervid populations. Early antemortem CWD testing of farmed cervids is of considerable interest to producers and regulatory agencies as a tool to combat this spread. The tissues accessible for antemortem sampling are limited and include biopsy of the tonsil and recto-anal mucosa-associated lymphoid tissue (RAMALT). The sensitivity to detect CWD by immunohistochemistry (IHC)-the regulatory gold standard-using biopsy samples of RAMALT from naturally infected white-tailed deer (WTD) has been determined by several studies. However, similar information is lacking for tonsil biopsy. In this study, two-bite tonsil biopsies from 79 naturally infected farmed WTD were used to determine the diagnostic sensitivity of tonsil IHC compared to the official CWD status based on results from the medial retropharyngeal lymph nodes and obex. IHC detection of CWD by tonsil biopsy was compared to the result and follicle metrics from the contralateral whole tonsil. The sensitivity of two-bite tonsil biopsy for detecting CWD by IHC was 72% overall. When the stage of infection was considered, the sensitivity was 92% for deer in late preclinical infection but only 55% for early preclinical infection. For deer with early preclinical infection, the sensitivity for deer homozygous for the prion protein gene (PRNP) coding for glycine at codon 96 (GG) was 66% but only 30% when heterozygous for the serine substitution (GS). The results indicate that the sensitivity of two-bite tonsil biopsy in WTD, and consequently its potential utility as an antemortem diagnostic, is limited during early infection, especially in WTD heterozygous for the serine substitution at PRNP codon 96.

Multiresistant Bacteria in Neonatal Intensive Care and the Contribution of Molecular Biology

Epigenetics is a very active field of research today. This is a mechanism by which environmental factors can influence gene expression. Indeed, epigenetics has been defined as a new science aimed at studying the mechanisms by which the genotype generates the phenotype, without there being any modifications in the DNA sequence. In this context, we conducted a prospective study on the records of 523 patients hospitalized in the neonatal intensive care unit of the CHU Mohamed VI in Marrakech, over a period of 6 months, from July 01, 2019 to December 31, 2019. Main results obtained were as follows: A high MRB carriage rate affecting 45.5% of hospitalized patients during the study period. Late MRB infections are an important part of this. The analysis of the risk factors of these infections had demonstrated the major role of invasive procedures, in particular mechanical ventilation and KTVO, as well as the high duration of hospitalization which was on average 17.47 days in our study. The bacteriological profile was dominated by enterobacteriaceae, particularly K. pneumoniae and E. cloacae. Of all the MRBs sent to the Kremlin Bicêtre hospital, 55 strains were analyzed by MLST; including 36 strains of K. pneumonia and 19 strains of E. cloacae. The Enterobacteriaceae strains analyzed in our study were mainly carbapenemase producers, of the NDM and OXA-48 type, and ESBL type CTX-15M. Of all the bacterial clones identified, a high rate of resistance to antibiotics, in particular carbapenems, was noted in the following clones: ST 1805, ST 1158 and ST 307. The ST 1805 clone was exclusively found in our series.

Sonication in Patients With Spinal Cord Stimulation: A New Approach for Infection Diagnostics

IntroductionSpinal cord stimulation (SCS) offers improvement in pain and function for several chronic pain conditions. There are concerns regarding bacterial colonization of the temporary lead extensions and subsequent infection risk in a two-session implantation procedure. Although there is no standardized evaluation of SCS lead contamination, this study evaluates the infection rate and microbial colonization of SCS lead extensions with sonication, a method that is established in implant-related infection diagnostics. Materials and MethodsThis prospective observational study comprised 32 patients with a two-stage SCS implantation procedure. Microbial colonization of the lead extensions was assessed with sonication. The presence of organisms in the subcutaneous tissue was evaluated separately. Surgical-site infections were recorded. Patient demographics and risk factors including diabetes, tobacco use, obesity, trial length, and infection parameters in serum were recorded and analyzed. ResultsThe mean age of the patients was 55 years. On average, the trial length was 13 days. In seven cases (21.9%), a microbial lead colonization was found with sonication. In contrast, there was one positive culture (3.1%) from the subcutaneous tissue samples. The C-reactive protein and leukocyte count remained at the preoperative level. One early surgical-site infection (3.1%) occurred. No other late infections occurred six months after surgery. ConclusionsThere is a discrepancy between the presence of microbial colonization and the occurrence of clinically relevant infections. Although the rate of microbial colonization of the lead extensions is high (21.9%), the surgical-site infection rate remained low (3.1%). Therefore, we can conclude that the two-session procedure is a safe approach that is not associated with a higher incidence of infection. Although the sonication method cannot be used as the sole tool for detecting infections in patients with SCS, it can provide additional value in microbial diagnostics in combination with clinical and laboratory parameters and conventional microbiological methods.

The Frequency and the character of bacterial infection in patients with COVID-19

The first human cases of new coronavirus (COVID-19), for the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were in Wuhan, in December 2019. By June 2022 there had been more than 500 million with confirmed cases of new coronavirus and over 5 million lives lost to the disease. During the earlier SARS-CoV-1 and MERSCoV epidemics, patients often developed bacterial coinfections and had a higher mortality rate. The aim of this work is to summarize the results of a study of the frequency and nature of bacterial infection in patients with COVID-19. Various studies was been in USA and countries of Asia and Europe show conflicting results regarding the prevalence of secondary bacterial infections in patients with COVID-19, from 1% to 50%. Bacterial co-infection is relatively infrequent in hospitalized patients with COVID-19. Risk factors of bacterial infections in patients with COVID-19 are more 60 years old, prolonged hospital length of stay, reanimation unit admission (severe disease COVID-19), chronic bacterial infection in anamnesis, immunosuppression therapy. The most common bacterial microorganisms identified in patients with infection of the lower respiratory tract, who hospital length of stay less than 48 hours are Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae. In patients, who hospital length of stay more than 48 hours the main pathogens are P. aeruginosa, Klebsiella spp., S. aureus. The data obtained indicate a low frequency of bacterial infections in patients hospitalized for COVID-19. Early infections are quite rare, more often bacterial infections are secondary and develop after 48 hours of the patient's stay in the hospital. The causative agents of early and late infections are different. Most often, an infection of the respiratory tract is noted, less often — the urinary system and bacterial infections of other localization.

Complications of total knee arthroplasty and the development of late deep infection in patients with rheumatoid arthritis

Aim: This study aimed to assess complications and the presence of late deep infection in patients with rheumatoid arthritis (RA) who underwent primary and revision total knee arthroplasty (TKA). 
 Materıial and Method: Between June 1997 and October 2022, cemented TKA that cut the posterior cruciate ligament (PCL) was applied to 50 knees of 34 patients with RA, and posterior-stabilized (PS) revision TKA was applied to 7 knees of 5 patients. All the patients enclosed in this study were adults diagnosed with RA by a rheumatology or physical therapy physician according to the RA diagnostic criteria recommended by the American College of Rheumatology in 1987. The diagnosis of infection was based on the Periprosthetic Infection Diagnostic Criteria of the 2018 International Periprosthetic Joint Infections Consensus Meeting.
 Results: Complications were found in 9 (18%) of the 50 knees who underwent primary TKA. Postoperative serous discharge was observed in 3 (6%) knees, serous discharge and late partial rupture of the quadriceps tendon in 1 (2%), early deep infection in 1 (2%), late deep infection in 3 (6%), and hematoma in 1 (2%). Revision surgery was performed on 3 (6%) knees due to infection and on 4 (8%) knees due to aseptic loosening. Complications developed in 2 of these knees who underwent revision TKA, 1 (14.3%) knee with periprosthetic fracture in the femur in the first postoperative year, and 1 (14.3%) knee with early deep infection. Deep vein thrombosis (DVT), pulmonary emboli (PE) and heterotopic ossification (HO) were not observed in any patient.
 Conclusion: In patients with rheumatoid arthritis, total knee arthroplasty increased chronic late deep infection and the associated need for revision surgery, and decreased the rates of DVT, PE, HO.

A Study of the Clinical Profile and Management of Children With Anorectal Malformations.

Introduction The diagnosis of anorectal malformations (ARMs) antenatally is rare, and most of these cases are diagnosed in theneonatal period. The defects range from easily treated minor anomalies with good prognosisto those that are difficult and complex. The associated anomalies in these malformations are important determinants for the prognosis and outcome of these cases. Material and methods The present study was carried out in the department of pediatric surgery in a tertiary care institute. Patients presenting with ARMs in the neonatal period, those reported for definitive surgery, and patients for colostomy closure surgery were included. Patients who died before surgical treatment were excluded from the study. Convenience sampling of 100 patients who met the inclusion criteria was performed until the sample size was reached. Results Out of 63 cases of high variety, 84.12% were males and 15.87% were females. Out of 37 patients of low variety, 43.24% were males and 56.75% were females.The anomaliesof the urogenital system were present in 22 (34.92%) out of 63 cases of high ARMs and 10 (27.02%) out of 37 cases of low ARMs. In the male patients,anocutaneous fistula was in 16 (23.18%) of cases. Out of 31 females in the present study, anorectal agenesis with anovestibular fistula was seen in 19 (61.29%) cases. In the early complications, significant bleeding and urethral injury were seen in one (2.63%) patient each. However, among thelatecomplications, anal stenosis, mucosal prolapse, and wound infection were seen in seven (18.42%), five (13.15%), and four (10.52%) patients, respectively. Conclusion A holistic approach to the management of ARMs is needed with a long-term goal of achieving urinaryand fecal continence with good quality of life.The outcome of surgery is dependent on the specific type of malformation, but the results are better when intervention is done early.

Utility of Diagnostic Markers in Late Periprosthetic Joint Infection Workup for Total Knee Arthroplasty Patients Who Received Antibiotics 48 Hours Before Aspiration

BackgroundDiagnosing periprosthetic joint infection (PJI) following total knee arthroplasty (TKA) remains challenging despite recent advancements in testing and evolving criteria over the last decade. Moreover, the effects of antibiotic use on diagnostic markers are not fully understood. Thus, this study sought to determine the influence of antibiotic use within 48 hours before knee aspiration on synovial and serum laboratory values for suspected late PJI. MethodsPatients who underwent a TKA and subsequent knee arthrocentesis for PJI workup at least 6 weeks after their index arthroplasty were reviewed across a single healthcare system from 2013 to 2020. Median synovial white blood cell (WBC) count, synovial polymorphonuclear (PMN) percentage, serum erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), and serum WBC count were compared between immediate antibiotic and nonantibiotic PJI groups. Receiver operating characteristic (ROC) curves and Youden’s index were used to determine test performance and diagnostic cutoffs for the immediate antibiotics group. ResultsThe immediate antibiotics group had significantly more culture-negative PJIs than the no antibiotics group (38.1 versus 16.2%, P = .0124). Synovial WBC count demonstrated excellent discriminatory ability for late PJI in the immediate antibiotics group (area under curve, AUC = 0.97), followed by synovial PMN percentage (AUC = 0.88), serum CRP (AUC = 0.86), and serum ESR (AUC = 0.82). ConclusionAntibiotic use immediately preceding knee aspiration should not preclude the utility of synovial and serum lab values for the diagnosis of late PJI. Instead, these markers should be considered thoroughly during infection workup considering the high rate of culture-negative PJI in these patients. Level of EvidenceLevel III, retrospective comparative study.

Antibody-dependent enhancement of porcine reproductive and respiratory syndrome virus infection downregulates the levels of interferon-gamma/lambdas in porcine alveolar macrophages in vitro.

Fc gamma receptor-mediated antibody-dependent enhancement (ADE) can promote virus invasion of target cells, sometimes exacerbating the severity of the disease. ADE may be an enormous hurdle to developing efficacious vaccines for certain human and animal viruses. ADE of porcine reproductive and respiratory syndrome virus (PRRSV) infection has been demonstrated in vivo and in vitro. However, the effect of PRRSV-ADE infection on the natural antiviral immunity of the host cells is yet to be well investigated. Specifically, whether the ADE of PRRSV infection affects the levels of type II (interferon-gamma, IFN-γ) and III (interferon-lambdas, IFN-λs) interferons (IFNs) remains unclear. In this study, our results showed that PRRSV significantly induced the secretion of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 in porcine alveolar macrophages (PAMs) in early infection, and weakly inhibited the production of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 in PAMs in late infection. Simultaneously, PRRSV infection significantly increased the transcription of interferon-stimulated gene 15 (ISG15), ISG56, and 2', 5'-oligoadenylate synthetase 2 (OAS2) in PAMs. In addition, our results showed that PRRSV infection in PAMs via the ADE pathway not only significantly decreased the synthesis of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 but also significantly enhanced the generation of transforming growth factor-beta1 (TGF-β1). Our results also showed that the ADE of PRRSV infection significantly reduced the mRNAs of ISG15, ISG56, and OAS2 in PAMs. In conclusion, our studies indicated that PRRSV-ADE infection suppressed innate antiviral response by downregulating the levels of type II and III IFNs, hence facilitating viral replication in PAMs in vitro. The ADE mechanism demonstrated in the present study furthered our understanding of persistent pathogenesis following PRRSV infection mediated by antibodies.