Site Infection Research Articles

Artery Grafting for Arterial Anastomoses in Head and Neck Free Tissue Transfer Reconstruction.

Vessel grafting is an important technique in head and neck free tissue transfer (FTT) reconstruction when a tension-free anastomosis is not otherwise feasible. To our knowledge, there are limited data regarding interposition artery grafts for arterial anastomoses in head and neck reconstruction. Here, we present a multi-institutional cohort of arterial interposition grafts for FTT reconstruction for head and neck defects. A retrospective review was conducted at four tertiary care institutions for patients who underwent FTT reconstruction for head and neck defects which utilized an interposition artery graft for the arterial anastomosis. Charts were reviewed for type and length of artery grafts harvested, surgical indication, indication for artery graft, types of flaps harvested, and various preoperative characteristics (including history of radiation or previous FTT reconstruction surgery). Postoperative complications within postoperative day 30 were measured and reported. Nine patients met inclusion criteria. The lateral circumflex femoral artery (either transverse or descending branches) (n = 3) and facial artery (n = 3) were the most commonly harvested arteries. The scalp (n = 5) was the most common primary defect site. Seven grafts were harvested initially and in a planned fashion, while two were harvested as salvage techniques (either for flap salvage or vein graft failure). In planned grafts, arteries were the preferred interposition grafting method due to either size match preferences (n = 4) or similarities in wall thickness (n = 3) between graft and recipient artery. There were no reported cases of unplanned readmission, postoperative hematoma, fistula formation, wound infection, or donor site morbidities. Two patients required unplanned return to the operating room for flap compromise, both of which ultimately resulted in flap failure secondary to clot formation at both arterial and venous anastomoses. When arterial pedicle length is insufficient, interposition artery grafting is both a feasible and viable technique to achieve tension-free arterial anastomoses for select cases of highly complex head and neck free tissue reconstruction.

Risk Factors for E2SKAPE Infections and Mortality Among Liver Transplant Recipients

Infections caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp (ESKAPE) plus Escherichia coli (E2SKAPE), in particular multidrug-resistant (MDR) E2SKAPE infections, occur frequently and pose a life-threatening to liver transplant (LT) recipients. To prevent E2SKAPE infections and improve the prognosis of LT recipients, the identification of risk factors for E2SKAPE infections and mortality is necessary. E2SKAPE pathogens were isolated and identified from clinical samples following standard microbiological procedures. All episodes of E2SKAPE infections and mortality documented among LT recipients were analyzed. A total of 83 episodes of E2SKAPE infections, including 75 (90.4%) episodes of MDR-E2SKAPE infections, occurred in 23.1% (53/229) of LT recipients. E. faecium was the dominant causative bacterium (37/83; 44.6%). The most common site of infections was the urinary tract (14/53; 26.4%). Sixteen (7%) patients died within 2 months after LT, and 7 deaths were E2SKAPE infections-related. Multivariate logistic regression analysis revealed that female sex [odds ratio (OR) = 3.665, 95% confidence interval (CI): 1.614-8.321, P = 0.002], duration of surgery ≥ 400 min [OR = 2.328, 95%CI: 1.151-4.707, P = 0.019], intraoperative red blood cell (RBC) transfusion ≥ 12U [OR = 2.542, 95%CI: 1.218-5.306, P = 0.013] and indwelling urethral catheter use ≥ 3 days [OR = 3.96, 95%CI: 1.309-11.981, P = 0.015] were independent risk factors for E2SKAPE infections after LT, and that only exposure to more than 2 intravenous antibiotics post-LT [OR = 0.318, 95%CI: 0.15-0.674, P = 0.003] was negatively associated with acquisition of E2SKAPE infections. The predictors of crude mortality included female sex [OR = 4.822, 95%CI: 1.299-17.904, P = 0.019], creatinine on day 3 post-LT > 1.5 mg/dL [OR = 11.014, 95%CI: 2.985-40.637, P < 0.001], mechanical ventilation post-LT [OR = 10.724, 95%CI: 2.695-42.676, P = 0.001] and recipients with E2SKAPE infections [OR = 4.112, 95%CI: 1.169-14.47, P = 0.028]. A high incidence of E2SKAPE infections was noted in the early post-LT period. The most common infection site was the urinary tract, and the dominant pathogenic bacterium was E. faecium. Female sex, prolonged surgery time, massive RBC transfusion, or delayed urethral catheter removal were associated with E2SKAPE infections. Only exposure to more than 2 intravenous antibiotics post-LT was negatively related to the acquisition of E2SKAPE infections. The predictors of mortality included female sex, creatinine on day 3 post-LT>1.5 mg/dL, mechanical ventilation post-LT, and recipients with E2SKAPE infections.

The phytopathogen Xanthomonas campestris senses and effluxes salicylic acid via a sensor HepR and an RND family efflux pump to promote virulence in host plants.

Salicylic acid (SA) plays an essential role in plant defense against biotrophic and semi-biotrophic pathogens. Following pathogen recognition, SA biosynthesis dramatically increases at the infection site of the host plant. The manner in which pathogens sense and tolerate the onslaught of SA stress to survive in the plant following infection remains to be understood. The objective of this work was to determine how the model phytopathogen Xanthomonas campestris pv. campestris (Xcc) senses and effluxes SA during infection inside host plants. First, RNA-Seq analysis identified an SA-responsive operon Xcc4167-Xcc4171, encoding a MarR family transcription factor HepR and an RND (resistance-nodulation-cell division) family efflux pump HepABCD in Xcc. Electrophoretic mobility shift assays and DNase I footprint analysis revealed that HepR negatively regulated hepABCD expression by specifically binding to an AT-rich region of the promoter of the hepRABCD operon, Phep. Second, isothermal titration calorimetry and further genetic analysis suggest that HepR is a novel SA sensor. SA binding released HepR from its cognate promoter Phep and then induced the expression of hepABCD. Third, the RND family efflux pump HepABCD was responsible for SA efflux. The hepRABCD cluster was also involved in the regulation of culture pH and quorum sensing signal diffusible signaling factor turnover. Finally, the hepRABCD cluster was transcribed during the XC1 infection of Chinese radish and was required for the full virulence of Xcc in Chinese radish and cabbage. These findings suggest that the ability of Xcc to co-opt the plant defense signal SA to activate the multidrug efflux pump may have evolved to ensure Xcc survival and virulence in susceptible host plants.

Biomimetic Metal-Organic Framework Gated Nanoplatform for Sonodynamic Therapy against Extensively Drug Resistant Bacterial Lung Infection.

Novel antimicrobial strategies are urgently needed to treat extensively drug-resistant (XDR) bacterial infections due to the high mortality rate and lack of effective therapeutic agents. Herein, nanoengineered human umbilical cord mesenchymal stem cells (hUC-MSCs), named PMZMU, are designed as a sonosensitizer for synergistic sonodynamic-nano-antimicrobial therapy against gram-negative XDR bacteria. PMZMU is composed of a bacterial targeting peptide (UBI29-41) modified hUC-MSCs membrane (MSCm), a sonosensitizer meso-tetra(4-car-boxyphenyl) porphine doped mesoporous organo-silica nanoparticle and an acidity-responsive metal-organic framework ZIF-8. This innovative formulation enables efficient loading of polymyxin B, reduces off-target drug release, increases circulation and targeting efficacy, and generates reactive oxygen species upon ultrasound irradiation. PMZMU exhibits remarkable in vitro inhibitory activity against four XDR bacteria: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa (PA), and Escherichia coli. Taking advantage of the bacterial targeting ability of UBI29-41 and the inflammatory chemotaxis of hUC-MSC, PMZMU can be precisely delivered to lung infection sites thereby augmenting polymyxin B concentration. PMZMU-mediated sonodynamic therapy significantly reduces bacterial burden, relieves inflammatory damage by promoting the polarization of macrophages toward M2 phenotype, and improves survival rates without introducing adverse events. Overall, this study offers promising strategies for treating deep-tissue XDR bacterial infections, and guides the design and optimization of biomimetic nanomedicine.

Hyaluronic Acid-Modified Micelles of Azithromycin and Quercetin Against Infections Caused by Methicillin-Resistant Staphylococcus Aureus.

Resistance of intracellular pathogens is a challenge in microbial therapy. Methicillin-resistant Staphylococcus aureus (MRSA), which is able to persist inside the cells of infected tissues, is protected from attack by the immune system and many antimicrobial agents. To overcome these limitations, nano-delivery systems can be used for targeted therapy of intracellular MRSA. Hyaluronic acid-modified azithromycin/quercetin micelles (HA-AZI/Qe-M) were synthesized by thin film hydration. The micelles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR), and the drug loading (DL) and encapsulation efficiency (EE) were detected by high performance liquid chromatography (HPLC). The uptake ability of RAW264.7 cells was investigated, and its distribution in mice was evaluated by in vivo imaging. The inhibitory effect of the micelles against MRSA in vitro and its ability to eliminate intracellular bacteria were evaluated. Bacterial muscle-infected mice were constructed to evaluate the therapeutic effect of the micelles on bacterial infections in vivo and the biocompatibility of the micelles was investigated. HA-AZI/Qe-M had suitable physical and chemical properties and characterization. In vitro antibacterial experiments showed that HA-AZI/Qe-M could effectively inhibit the growth of MRSA, inhibit and eliminate the biofilm formed by MRSA, and have an excellent therapeutic effect on intracellular bacterial infection. The results of RAW264.7 cells uptake and in vivo imaging showed that HA-AZI/Qe-M could increase the cellular uptake, target the infection site, and prolong the treatment time. The results of in vivo antibacterial infection experiments showed that HA-AZI/Qe-M was able to ameliorate the extent of thigh muscle infections in mice and reduce the expression of inflammatory factors. HA-AZI/Qe-M is a novel and effective nano-drug delivery system that can target intracellular bacterial infection, and it is expected to be safely used for the treatment of MRSA infection.

Prediction of intensive care unit admission using machine learning in patients with odontogenic infection.

This study aimed to develop and validate a model to predict the need for intensive care unit (ICU) admission in patients with dental infections using an automated machine learning (ML) program called H2O-AutoML. Two models were created using only the information available at the initial examination. Model 1 was parameterized with only clinical symptoms and blood tests, excluding contrast-enhanced multi-detector computed tomography (MDCT) images available at the initial visit, whereas model 2 was created with the addition of the MDCT information to the model 1 parameters. Although model 2 was expected to be superior to model 1, we wanted to independently determine this conclusion. A total of 210 patients who visited the Department of Oral and Maxillofacial Surgery at the Dankook University Dental Hospital from March 2013 to August 2023 was included in this study. The patients' demographic characteristics (sex, age, and place of residence), systemic factors (hypertension, diabetes mellitus [DM], kidney disease, liver disease, heart disease, anticoagulation therapy, and osteoporosis), local factors (smoking status, site of infection, postoperative wound infection, dysphagia, odynophagia, and trismus), and factors known from initial blood tests were obtained from their medical charts and retrospectively reviewed. The generalized linear model algorithm provided the best diagnostic accuracy, with an area under the receiver operating characteristic values of 0.8289 in model 1 and 0.8415 in model 2. In both models, the C-reactive protein level was the most important variable, followed by DM. This study provides unprecedented data on the use of ML for successful prediction of ICU admission based on initial examination results. These findings will considerably contribute to the development of the field of dentistry, especially oral and maxillofacial surgery.

Implantable and wireless-controlled antibacterial patch for deep abscess eradication and therapeutic efficacy monitoring

Pyogenic abscesses in deep organs represent severe bacterial infections that can be life-threatening. Traditional photodynamic and sonodynamic hybrid therapy (PDT/SDT) faces various limitations when treating deep organ abscess, including difficulties in drug release control, limited penetration of external laser, a hypoxic microenvironment, and challenges in therapeutic efficacy monitoring. To address these issues, we developed an implantable and wireless-controlled antibacterial patch integrated with modules for on-demand drug release, light control and therapeutic efficacy monitoring, providing a comprehensive solution to the clinical challenges of PDT/SDT in treating deep organ abscess. This self-adhesive and miniaturized patch can easily attach to internal tissues, and be wirelessly powered and controlled by external ultrasound. Initially, ultrasound powered the patch’s drug release module through the lead zirconate titanate piezoelectric transducer (PZT), providing distinct electrical-thermal release signals for indocyanine green (ICG) and hemoglobin (Hb). This ensured that Hb was released first to generate oxygen, alleviating the hypoxic microenvironment at the infection site, followed by the release of ICG as both a photosensitizer and sonosensitizer. Subsequently, ultrasound directly activated the sonosensitizer and powered the µLEDs in the light control module, ultimately initiating SDT/PDT hybrid antibacterial treatment. The therapeutic efficacy monitoring module in the patch used hydrogels with infection detection capabilities to provide timely feedback on the treatment status of the infected lesions, enabling doctors to rapidly adjust treatment plans and significantly improve the flexibility and effectiveness of treatments. Both in vitro and in vivo experiments have demonstrated that the patch can completely cure pyogenic liver abscesses. This research also exhibits promise for extending the application of the patch to treat other types of deep infections.

Evaluation of [68Ga]Ga-DOTA-AeK as a Potential Imaging Tool for PET Imaging of Cell Wall Synthesis in Bacterial Infections.

The ability of bacteria to recycle exogenous amino acid-based peptides and amino sugars for peptidoglycan biosynthesis was extensively investigated using optical imaging. In particular, fluorescent AeK-NBD was effectively utilized to study the peptidoglycan recycling pathway in Gram-negative bacteria. Based on these promising results, we were inspired to develop the radioactive AeK conjugate [68Ga]Ga-DOTA-AeK for the in vivo localization of bacterial infection using PET/CT. An easy-to-implement radiolabeling procedure for DOTA-AeK with [68Ga]GaCI3 followed by solid-phase purification was successfully established to obtain [68Ga]Ga-DOTA-AeK with a radiochemical purity of ≥95%. [68Ga]Ga-DOTA-AeK showed good stability over time with less protein binding under physiological conditions. The bacterial incorporation of [68Ga]Ga-DOTA-AeK and its fluorescent Aek-NBD analog were investigated in live and heat-killed Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Unfortunately, no conclusive in vitro intracellular uptake of [68Ga]Ga-DOTA-AeK was observed for E. coli or S. aureus live and heat-killed bacterial strains (p > 0.05). In contrast, AeK-NBD showed significantly higher intracellular incorporation in live bacteria compared to the heat-killed control (p < 0.05). Preliminary biodistribution studies of [68Ga]Ga-DOTA-AeK in a dual-model of chronic infection and inflammation revealed limited localization at the infection site with non-specific accumulation in response to inflammatory markers. Finally, our study demonstrates proof that the intracellular incorporation of AeK is necessary for successful bacteria-specific imaging using PET/CT. Therefore, Ga-68 was not a suitable radioisotope for tracing the bacterial uptake of AeK tripeptide, as it required chelation with a bulky metal chelator such as DOTA, which may have limited its active membrane transportation. An alternative for optimization is to explore diverse chemical structures of AeK that would allow for radiolabeling with 18F or 11C.

Synergistic effects of quorum-sensing molecules and antimicrobials against Candida albicans and Pseudomonas aeruginosa biofilms: in vitro and in vivo studies.

Candida albicans can form polymicrobial biofilms with other microorganisms, such as Pseudomonas aeruginosa, at infection sites. As biofilms are highly resistant to antibiotics there is a need for new antibiofilm agents that have unique targets and modes of action. In this study the antibiofilm effects of two quorum-sensing molecules (QSMs), farnesol and tyrosol, were investigated alone and in combination with antibiotics (aztreonam, colistin, tobramycin) and antifungals (fluconazole, amphotericin B, caspofungin), against single- and dual-species biofilms of C. albicans and P. aeruginosa in in vitro and in vivo systems. It was observed that QSMs alone, especially farnesol, showed at least a 1-log reduction against preformed single- and dual-species biofilms of C. albicans and P. aeruginosa. Combination of QSMs with colistin or fluconazole was found to be effective against both single- and dual-species biofilms in vitro. Increased survival was observed in C. elegans when treated with colistin or fluconazole in combination with QSMs, compared with no treatment. Additionally, the QSMs and colistin and farnesol combinations effectively inhibited biofilm formation by C. albicans and P. aeruginosa on bronchial epithelial cells, and reduced IL-1β expression in lung bronchial epithelial cells. There is a need for effective treatments for bacterial-fungal biofilm infections and, to our knowledge, there have been no studies of QSMs and antimicrobial combinations against dual-species biofilms involving C. albicans and P. aeruginosa. Hence these findings will make a significant contribution to the literature.

Fungal Enzyme-Responsive Hydrogel Drug Delivery Platform for Triggered Antifungal Release.

Fungal infections can lead to debilitating consequences if they are not treated effectively. Antifungal drugs used to treat these infections can be toxic and overuse contributes to growing antifungal resistance. Candida spp., particularly C. albicans, are implicated in a majority of these infections. Virulent C. albicans produce secreted aspartic proteases (Saps) that aid in pathogen tissue invasion and proliferation at an infected site. Here, fungi-responsive hydrogels are developed that degrade in the presence of Saps to provide a triggered release of encapsulated liposomal antifungals. The hydrogel backbone incorporates a Sap-cleavable peptide sequence enabling Sap-responsive degradation. Hydrogels are found to effectively degrade in the presence of Saps extracted from C. albicans. Encapsulated liposomal antifungals show similar release kinetics as hydrogel degradation products in the presence of Saps, supporting a degradation-dependent release mechanism. Antifungal liposome-loaded responsive hydrogels exhibit successful eradication of C. albicans cultures and remain stable in sterile murine wound fluid. Finally, no significant cytotoxicity is observed for murine fibroblast cells and red blood cells exposed to hydrogel degradation products. These fungi-responsive hydrogels have the potential to be used for local, on-demand delivery of antifungal drugs, for effective treatment of fungal infections while helping to limit unnecessary exposure to thesetherapeutics.

Analysis of HSV1/2 Infection Reveals an Association between HSV-2 Reactivation and Pregnancy.

The herpes simplex viruses consist of the strains, HSV-1 and HSV-2, which are prevalent worldwide and lack a definitive cure. We aimed to explore the specific characteristics of HSV 1 and 2 infections, such as differences between gender assigned at birth, age at infection, site of infection, comorbidities, and effect of pregnancy, through a data analysis. Between 2011 and 2018, the Israeli Central Virology Laboratory diagnosed 9189 samples using multiplexed real-time PCR. In addition, we extracted all of the medical data for 287 females hospitalized at the Sheba Medical Center with HSV-1 (161) or HSV-2 (126) genital infections. HSV-2 was almost absent in the orofacial samples from both genders, while in other lesion sites, HSV-2 was significantly more abundant in females than in males (p < 0.05,). HSV-2 was initially detected at puberty. In the hospitalized females' malignancies, both HSV-1 and HSV-2 were found with a non-significant difference. Simultaneously, pregnancies were more common in females who were HSV-2-positive compared with those who were HSV-1-positive (27.8% vs. 12.4%, respectively, p < 0.01). Primary infections occur more with HSV-1 than with HSV-2 (15.6% vs. 3.2%, respectively). Our findings demonstrate that genital HSV-2 infection episodes are more frequent during pregnancy, suggesting that pregnancy may serve as a risk factor for HSV-2 reactivation or infection.

An active & passive dual-targeting platform for the precise treatment, process monitoring and effective protection of central nervous system infection

Precise antibacterial activity and effective inflammatory response reduction are critical for successful treatment of Intracranial infection after craniocerebral surgery, which remains an unmet clinical challenge. Herein, an intracranial drug delivery liposome (AFAA-lipo) that possesses dual active&passive targeting capability, direct antibacterial ability, favorable inflammation regulation, and excellent biocompatibility is developed as an antibiotics-free and hardly bacterial-resistance-induced platform for the management of intracranial infection. The surface-anchored specific peptide sequence HRERMS (the oligopeptide designed sourced from β-amyloid precursor protein) makes AFAA-lipo actively penetrate the blood–brain barrier and then perforated and lysed under the stimulation of α-toxin secreted by methicillin-resistant Staphylococcus aureus (MRSA, a severe and widespread intracranial infection type) in the infected site. Our results demonstrate that the AFAA-lipo can eliminate bacteria and biofilms, and reduce inflammatory response through mitochondrial function protection, DNA preservation from damage, TNFR1/NF-κB signaling pathway inhibition, and promotion of microglial polarization towards the anti-inflammatory subtype, ultimately improving post-infection prognosis and survival rate. More interestingly, the pre-intake of AFAA-lipo is capable to reduce MRSA infection risk and alleviate inflammatory response. Furthermore, the near-infrared (NIR) II region imaging fluorescence signal intensity variations of AFAA-lipo is proved the validation to monitor the course of the disease.

Prosthetic Joint Infections due to Candida Species: A Multicenter International Study.

Prosthetic joint infection (PJI) caused by Candida spp is a severe complication of arthroplasty. We investigated the outcomes of Candida PJI. This was a retrospective observational multinational study including patients diagnosed with Candida-related PJI between 2010 and 2021. Treatment outcome was assessed at 2-year follow-up. A total of 269 patients were analyzed. Median age was 73.0 (interquartile range [IQR], 64.0-79.0) years; 46.5% of patients were male and 10.8% were immunosuppressed. Main infection sites were hip (53.0%) and knee (43.1%), and 33.8% patients had fistulas. Surgical procedures included debridement, antibiotics, and implant retention (DAIR) (35.7%), 1-stage exchange (28.3%), and 2-stage exchange (29.0%). Candida spp identified were Candida albicans (55.8%), Candida parapsilosis (29.4%), Candida glabrata (7.8%), and Candida tropicalis (5.6%). Coinfection with bacteria was found in 51.3% of cases. The primary antifungal agents prescribed were azoles (75.8%) and echinocandins (30.9%), administered for a median of 92.0 (IQR, 54.5-181.3) days. Cure was observed in 156 of 269 (58.0%) cases. Treatment failure was associated with age >70 years (OR, 1.811 [95% confidence interval {CI}: 1.079-3.072]), and the use of DAIR (OR, 1.946 [95% CI: 1.157-3.285]). Candida parapsilosis infection was associated with better outcome (OR, 0.546 [95% CI: .305-.958]). Cure rates were significantly different between DAIR versus 1-stage exchange (46.9% vs 67.1%, P = .008) and DAIR versus 2-stage exchange (46.9% vs 69.2%, P = .003), but there was no difference comparing 1- to 2-stage exchanges (P = .777). Candida PJI prognosis seems poor, with high rate of failure, which does not appear to be linked to immunosuppression, use of azoles, or treatment duration.

Molecular epidemiology of Leptospira spp. serogroup Sejroe associated with chronic bovine leptospirosis

Pathogenic bacteria Leptospira spp. are commonly associated with bovine leptospirosis, characterized chiefly by chronic and subclinical reproductive disorders. Strains from the Sejroe serogroup play a significant role in these chronic genital infections known as Bovine Genital Leptospirosis (BGL), which notably impact cattle health. This study aims to deepen our understanding of BGL by investigating the genetic diversity, geographical distribution, and specific anatomical sites of infection of the causative agents. Initially, uterine fragments and cervicovaginal mucus were collected from 47 cows and subjected to PCR targeting the lipL32 gene. Positive samples in lipL32-PCR (9 samples) underwent genotyping based on the secY gene. Subsequently, sequences were aligned with GenBank entries (108 sequences) and analyzed in silico. All nine sequences from this study were identified as L. interrogans with an identity >99 % to serogroup Sejroe reference strains (Norma and L53). In the broader analysis, the most prevalent species observed was L. borgpetersenii, followed by L. interrogans and L. santarosai. The haplotype network of L. interrogans revealed that haplogroups B and C exclusively included L. interrogans strains of genital origin, while haplogroup A encompassed strains from renal sources as well. These findings underscore the significance of the L. borgpetersenii genotype Hardjobovis and L. interrogans genotype Hardjoprajitno as the predominant circulating strains and highlight the existence of distinct haplogroups of pathogenic leptospires originating from genital sources. We advocate for the use of secY as an effective genetic marker for Leptospira spp. and stress the necessity for additional research prioritizing the genital tract. The outcomes of this study contribute to the development of improved control measures for chronic cattle diseases and provide valuable guidance for future investigations.

Infections in Children with Acute Lymphoblastic Leukemia.

Background and Objectives: Infections are the most common and potentially life-threatening complications of the treatment of children with acute lymphoblastic leukemia (ALL). The aim of this study was to determine epidemiological, clinical, and microbiological characteristics of infections in pediatric patients with ALL. Materials and Methods: Twenty-three children (16 males and 7 females, with a mean age of 5.9 years (range of 1.3 to 12.2 years)) with ALL, treated at the Division of Hematology, Oncology, and Clinical Genetics, Department of Pediatrics, Clinical Hospital Center Rijeka, Croatia, from 1 January 2015 to 31 December 2020, were included in the study. Results: One hundred and four infectious episodes (IEs) were reported (an average of 4.5 IE per patient). IEs were more frequent in the intensive phases of antileukemic treatment. Neutropenia was present in 48 IEs (46.2%) with a duration greater than 7 days in 28 IEs (58.3%). The respiratory tract was the most common infection site (48.1%). We documented 49 bacterial (47.1%), 4 viral (3.9%), 4 fungal (3.9%), and 10 mixed isolates (9.6%), while in 37 IEs (35.6%), a pathogen was not isolated. The most common causes of bacteremia were coagulase-positive staphylococci. The most frequent empirical therapy was third- and fourth-generation cephalosporins, followed by piperacillin/tazobactam. The modification of first-line antimicrobial therapy was performed in 56.9% of IEs. Granulocyte-colony stimulating factor was administered in 53.8% of IEs, and intravenous immunoglobulins were administered in 62.5% of IEs. One patient required admission to the intensive care unit. No infection-related mortality was reported. Conclusions: ALL patients have frequent IEs. Close monitoring, the identification of risk factors, the rapid empirical use of antibiotics in febrile neutropenia, and the timely modification of antimicrobial therapy play key roles in reducing infection-related morbidity and mortality in children with ALL.

Tuberculosis is the predominant infection in systemic sclerosis: thirty-year retrospective study of serious infections from a single centre.

To look for the spectrum of infections and the factors predisposing to infection in patients with systemic sclerosis (SSc). In this retrospective study, demographic, clinical features, details of infections, immunosuppressive therapy, and outcomes of patients with SSc attending clinics at department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India from 1990 to 2022 were captured. Multivariable-adjusted logistic regression was applied to identify independent predictors of infection. Data of 880 patients, mean age 35.5 ± 12 years, and female: male ratio 7.7:1, were analyzed. One hundred and fifty-three patients had at least 1 infection with a total of 233 infectious episodes. Infections were most common in lung followed by skin and soft tissue. Tuberculosis was diagnosed in 45 patients (29.4%). Klebsiella was the commonest non-tubercular organism in lung and Escherichia coli in urinary tract infections. In comparison to matched control group, patients with infection had a greater number of admissions due to active disease, odds ratio (OR) 6.27 (CI 3.23-12.18), were receiving immunosuppressive medication OR, 5.05 (CI 2.55-10.00), and had more digital ulcers OR, 2.53 (CI 1.17-5.45). Patients who had infection had more likelihood for death OR, 13.63 (CI 4.75 -39.18). Tuberculosis is the commonest infection and lung remains the major site of infection in patients with SSc. Number of hospital admissions, digital ulcers and immunosuppressive therapy are predictors of serious infection in patients with SSc. Patients with infections had more likelihood of death.

Translationally controlled tumor protein interacts with TaCIPK23 to positively regulate wheat resistance to Puccinia triticina.

Hypersensitive response-programmed cell death (HR-PCD) regulated by Ca2+ signal is considered the major regulator of resistance against Puccinia triticina (Pt.) infection in wheat. In this study, the bread wheat variety Thatcher and its near-isogenic line with the leaf rust resistance locus Lr26 were infected with the Pt. race 260 to obtain the compatible and incompatible combinations, respectively. The expression of translationally controlled tumor protein (TaTCTP) was upregulated upon infection with Pt., through a Ca2+-dependent mechanism in the incompatible combination. The knockdown of TaTCTP markedly increased the area of dying cell and the number of Pt. haustorial mother cells (HMCs) at the infection sites, whereas plants overexpressing the gene exhibited enhanced resistance. The interaction between TaTCTP and calcineurin B-like protein-interacting protein kinase 23 (TaCIPK23) was also investigated, and the interaction was found occurred in the endoplasmic reticulum. TaCIPK23 phosphorylated TaTCTP in vitro. The expression of a phospho-mimic TaTCTP mutant in Nicotiana benthamiana promoted HR-like cell death. Silencing TaCIPK23 or TaCIPK23/TaTCTP co-silencing resulted in the same results as silencing TaTCTP. This suggested that TaTCTP is a novel phosphorylation target of TaCIPK23, and both participate in the resistance of wheat to Pt. in the same pathway.

Factors associated with hospitalization and mortality in adult and pediatric extrapulmonary tuberculosis at a tertiary care hospital in Central India

Background Comorbidities complicate the management of tuberculosis (TB) and have become an essential part of the end TB strategy to eradicate TB. However, pulmonary TB has received the most attention, and little is known about the impact of comorbidities and other factors on outcomes in patients with extrapulmonary tuberculosis (EPTB). Objectives Our aim was to analyze the factors associated with hospitalization and mortality in EPTB at a hospital in Central India, using non-TB patients with similar clinical presentations as a comparison. Methods Patients with presumptive EPTB were prospectively enrolled and followed up until the end of treatment or for at least 6 months. Detailed demographic and clinical information was collected for all participants, and patients were categorized as TB or non-TB using a composite reference standard. Multivariate logistic regression was used to analyze the impact of various clinical findings and risk factors on hospitalization and mortality. Results A total of 276 patients were categorized as TB cases and 175 as non-TB cases. Factors associated with hospitalization in children were younger age and non-adenitis site of disease. In adults, factors associated with mortality were older age, non-adenitis site of disease and HIV infection regardless of TB diagnosis, while diabetes mellitus increased the odds of mortality in EPTB patients. Conclusion Our results show that comorbidities increase the odds of death in both TB and non-TB patients in low-resource settings. This argues for a shift away from the traditional vertical management of diseases in these areas and supports a continued focus on building robust healthcare systems.

Emerging Roles of Circular RNA in Macrophage Activation and Inflammatory Lung Responses.

Circular RNA (circRNA) is a type of single-stranded RNA that forms a covalently closed continuous loop, unlike linear RNA. The expression of circRNAs in mammals is often conserved across species and shows tissue and cell specificity. Some circRNA serve as gene regulators. However, the biological function of most circRNAs is unclear. CircRNA does not have 5' or 3' ends. The unique structure of circRNAs provides them with a much longer half-life and more resistance to RNase R than linear RNAs. Inflammatory lung responses occur in the pathogenesis and recovery of many lung diseases. Macrophages form the first line of host defense/innate immune responses and initiate/mediate lung inflammation. For example, in bacterial pneumonia, upon pro-inflammatory activation, they release early response cytokines/chemokines that recruit neutrophils, macrophages, and lymphocytes to sites of infection and clear pathogens. The functional effects and mechanisms by which circRNAs exert physiological or pathological roles in macrophage activation and lung inflammation remain poorly understood. In this article, we will review the current understanding and progress of circRNA biogenesis, regulation, secretion, and degradation. Furthermore, we will review the current reports on the role of circRNAs in macrophage activation and polarization, as well as in the process of inflammatory lung responses.

Role of volume and inoculum in MIC assessment: a study with meropenem and Klebsiella pneumoniae.

Pharmacodynamic parameters evaluated under conditions that simulate an infection site volume and microbial load might reveal hidden risks of resistance selection and subsequent treatment failure. The study aimed to investigate the predictive potential of MICs determined at various conditions on the antimicrobial effect and emergence of resistance. We assessed meropenem MICs (microdilution: 0.2 mL, 5 × 105 cfu/mL; macrodilution: 2 mL, 5 × 105 cfu/mL), MICHVs (220 mL, 5 × 105 cfu/mL), MICHIs (0.2 mL, 5 × 107 cfu/mL) and MICHVIs (220 mL, 5 × 107 cfu/mL) for five Klebsiella pneumoniae strains and analysed these values alongside the results of experiments in a dynamic in vitro model. A clinically relevant meropenem dosing regimen was simulated and the starting bacterial inocula were 106 and 108 cfu/mL. The effectiveness of meropenem agreed with MICHVs for the 106 cfu/mL inoculum and with MICHIs or MICHVIs for the 108 cfu/mL inoculum. Strains characterized as resistant according to these values grew during meropenem exposure, and resistant mutants were selected. Our results suggest that MICHV-based parameters may be suitable for predicting antibacterial effects and the risk of resistance development when the inoculum is 106 cfu/mL, while MICHI- or MICHVI-based parameters are suitable for these purposes when the inoculum is 108 cfu/mL. Also, the correlation between resistance selection and the MICHI-based parameter was as high as one that corresponds with a mutant prevention concentration (MPC)-based parameter; this suggests that the MPC can be replaced by the more easily determined alternative parameter MICHI.