Early Infection Research Articles

Molecular rapid diagnostic testing for bloodstream infections: Nanopore targeted sequencing with pathogen-specific primers

Nanopore sequencing, known for real-time analysis, shows promise for rapid clinical infection diagnosis but lacks effective assays for bloodstream infections (BSIs). We prospectively assessed the performance of a novel nanopore targeted sequencing (NTS) assay in identifying pathogens and predicting antibiotic resistance in BSIs, analyzing 387 blood samples from December 2021 to April 2023. The positivity rate for NTS (69.5%, 269/387) nearly matches that of metagenomic next-generation sequencing (mNGS) (74.7%, 289/387; p=0.128) and surpasses the positivity rate of conventional blood culture (BC) (33.9%, 131/387; p<0.01). Frequent pathogens detected by NTS included Klebsiella pneumoniae (n=54), Pseudomonas aeruginosa (n=36), Escherichia coli (n=36), Enterococcus faecium(n=30), Acinetobacter baumannii(n=26), Staphylococcus aureus(n=23), and Human cytomegalovirus (n=37). Against a composite BSI diagnostic standard, NTS demonstrated a sensitivity and specificity of 84.0% (95% CI 79.5%-87.7%) and 90.1% (95% CI 81.7%-88.5%), respectively. The concordance between NTS and mNGS results (the percentage of total cases where both either detected BSI-related pathogens or were both negative) was 90.2% (359/387), whereas the consistency between NTS and BC was only 60.2% (233/387). In 80.6% (50/62) of the samples with identical pathogens identified by both NTS tests and BCs, the genotypic resistance identified by NTS correlated with culture-confirmed phenotypic resistance. Using NTS, 95% of samples can be tested and analyzed in approximately 7h, allowing for early patient diagnosis. NTS is rapid, sensitive, and efficient for detecting BSIs and drug-resistant genes, making it a potential preferred diagnostic tool for early infection identification in critically ill patients.

Systemic Inflammation Response Index (SIRI) and Monocyte-to-Lymphocyte Ratio (MLR) Are Predictors of Good Outcomes in Surgical Treatment of Periprosthetic Joint Infections of Lower Limbs: A Single-Center Retrospective Analysis.

Periprosthetic joint infection (PJI) is a devastating complication that develops after total joint arthroplasty (TJA), whose incidence is expected to increase over the years. Traditionally, surgical treatment of PJI has been based on algorithms, where early infections are preferably treated with debridement, antibiotics, and implant retention (DAIR) and late infections with two-stage revision surgery. Two-stage revision is considered the "gold standard" for treatment of chronic prosthetic joint infection (PJI) as it enables local delivery of antibiotics, maintenance of limb-length and mobility, and easier reimplantation. Many studies have attempted to identify potential predicting factors for early diagnosis of PJI, but its management remains challenging. In this observational retrospective study, we investigated the potential role of inflammatory blood markers (neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI)) as prognostic factors in two-stage exchange arthroplasty for PJI. A single-center retrospective analysis was conducted, collecting clinical data and laboratory parameters from patients submitted to prosthetic explantation (EP) for chronic PJI. Laboratory parameters (PCR, NLR, MLR, PLR, SIRI, SII, and AISI) were evaluated at the explantation time; at 4, 6, and 8 weeks after surgery; and at reimplantation time. The correlation between laboratory parameters and surgery success was evaluated and defined as infection absence/resolution at the last follow-up. A total of 57 patients with PJI were evaluated (62% males; average age 70 years, SD 12.14). Fifty-three patients with chronic PJI were included. Nine patients underwent DAIR revision surgery and chronic suppressive therapy; two patients died. Nineteen patients completed the two-stage revision process (prosthetic removal, spacer placement, and subsequent replanting). Among them, none showed signs of reinfection or persistence of infection at the last available follow-up. The other twenty-three patients did not replant due to persistent infection: among them, some (the most) underwent spacer retention; others (fewer in number) were submitted to resection arthroplasty and arthrodesis (Girdlestone technique) or chronic suppressive antibiotic therapy; the remaining were, over time, lost to follow-up. Of the patients who concluded the two-stage revision, the ones with high SIRI values (mean 3.08 SD 1.7 and p-value 0.04) and MLR values (mean 0.4 SD 0.2 and p-value 0.02) at the explantation time were associated with a higher probability of infection resolution. Moreover, higher variation in the SIRI and PCR, also defined, respectively, as delta-SIRI (mean -2.3 SD 1.8 and p-value 0.03) and delta-PCR (mean -46 SD 35.7 and p-value 0.03), were associated with favorable outcomes. The results of our study suggest that, in patients with PJI undergoing EP, the SIRI and MLR values and delta-SIRI and delta-PCR values could be predictive of a favorable outcome. The evaluation of these laboratory indices, especially their determination at 4 weeks after removal, could therefore help to determine which patients could be successfully replanted and to identify the best time to replant. More studies analyzing a wider cohort of patients with chronic PJI are needed to validate the promising results of this study.

Retrospective analysis of pathogens for guided creation of an EMPIRIc antibiotic prEscribing pathway (EMPIRE).

The objective of this study was to evaluate the susceptibilities of pathogens isolated from cultures within the first 7 days of admission to the burn center and in the absence of healthcare-associated infection risk factors (HAIRF) to determine if current empiric antibiotics can be narrowed for refinement of an empiric antibiotic prescribing pathway according to the suspected source. A 3-year sample of patients and cultures was utilized in hopes of obtaining at least 30 isolates of the most common pathogens and their respective susceptibilities. A total of 268 clinically relevant (e.g., deemed infectious, versus colonization) pathogens were included in the final sample with sources including wounds, respiratory, blood, urine, and bone. Of the 268 pathogens included, 45% were Gram-negative and 69% of all pathogens were isolated from wound cultures. The existing empiric pathway, vancomycin plus cefepime, covered 98% and 84% of all Gram-positive and Gram-negative pathogens, respectively. In patients without HAIRF, coverage rose to 98% and 90%, respectively. Initial use of vancomycin and cefepime remains adequate for pathogens isolated within 1 week of admission in patients without HAIRF. For pneumonias, a narrower spectrum beta-lactam would not sufficiently cover respiratory pathogens isolated within the first week of admission. Regarding early wound infections, difficult-to-treat pathogens remain as a rare isolate of wound cultures within 1 week of admission.

Indole-3 acetic acid negatively regulates rose black spot disease resistance through antagonizing the salicylic acid signaling pathway via jasmonic acid.

IAA cooperates with JA to inhibit SA and negatively regulates rose black spot disease resistance. Black spot disease caused by the fungus Marssonina rosae is the most prevalent and severe ailment in rose cultivation, leading to the appearance of black spots on leaves and eventual leaf fall, significantly impacting the utilization of roses in gardens. Salicylic acid (SA) and jasmonic acid (JA) are pivotal hormones that collaborate with indole-3 acetic acid (IAA) in regulating plant defense responses; however, the detailed mechanisms underlying the induction of black spot disease resistance by IAA, JA, and SA remain unclear. In this study, transcript analysis was conducted on resistant (R13-54) and susceptible (R12-26) lines following M. rosae infection. In addition, the impact of exogenous interference with IAA on SA- and JA-mediated disease resistance was examined. The continuous accumulation of JA, in synergy with IAA, inhibited activation of the SA signaling pathway in the early infection stage, thereby negatively regulating the induction of effective resistance to black spot disease. IAA administration alleviated the inhibition of SA on JA to negatively regulate the resistance of susceptible strains by further enhancing the synthesis and accumulation of JA. However, IAA did not contribute to the negative regulation of black spot resistance when high levels of JA were inhibited. Virus-induced gene silencing of RcTIFY10A, an inhibitor of the JA signaling pathway, further suggested that IAA upregulation led to a decrease in disease resistance, a phenomenon not observed when the JA signal was inhibited. Collectively, these findings indicate that the IAA-mediated negative regulation of black spot disease resistance relies on activation of the JA signaling pathway.

Seroconversion in syphilis screening without positive confirmatory tests points at early infection

IntroductionThe chemiluminescence immunoassay (CLIA) is a widely used screening test for syphilis. A CLIA seroconversion in the absence of a positive line immunoassay (LIA) or rapid plasma reagin (RPR) could...

Recent Advances in Lateral Flow Assays for Viral Protein Detection with Nanomaterial-Based Optical Sensors.

Controlling the progression of contagious diseases is crucial for public health management, emphasizing the importance of early viral infection diagnosis. In response, lateral flow assays (LFAs) have been successfully utilized in point-of-care (POC) testing, emerging as a viable alternative to more traditional diagnostic methods. Recent advancements in virus detection have primarily leveraged methods such as reverse transcription-polymerase chain reaction (RT-PCR), reverse transcription-loop-mediated isothermal amplification (RT-LAMP), and the enzyme-linked immunosorbent assay (ELISA). Despite their proven effectiveness, these conventional techniques are often expensive, require specialized expertise, and consume a significant amount of time. In contrast, LFAs utilize nanomaterial-based optical sensing technologies, including colorimetric, fluorescence, and surface-enhanced Raman scattering (SERS), offering quick, straightforward analyses with minimal training and infrastructure requirements for detecting viral proteins in biological samples. This review describes the composition and mechanism of and recent advancements in LFAs for viral protein detection, categorizing them into colorimetric, fluorescent, and SERS-based techniques. Despite significant progress, developing a simple, stable, highly sensitive, and selective LFA system remains a formidable challenge. Nevertheless, an advanced LFA system promises not only to enhance clinical diagnostics but also to extend its utility to environmental monitoring and beyond, demonstrating its potential to revolutionize both healthcare and environmental safety.

Debridement, Antibiotic Pearls, and Retention of the Implant (DAPRI) in the Treatment of Early Periprosthetic Knee Joint Infections: A Literature Review.

(1) Background: Periprosthetic joint infections (PJIs) are severe and frightening complications in orthopaedic surgery, and they are generally divided into three categories: early infections (those occurring within the first 4-6 weeks), delayed infections (those occurring between 3 and 24 months), and late infections (those occurring more than 2 years after surgery). PJI treatment comprises "debridement, antibiotics, and implant retention" (DAIR), single-stage revision, and double-stage revision. Nowadays, to improve the chances of retaining an infected implant and to improve the traditional DAIR method, a modified surgical technique has been developed, named DAPRI (debridement, antibiotic pearls, and retention of the implant). Our study aims to present an up-to-date concept evaluation of the DAPRI technique and its success rate. (2) Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards were followed, applying a protocol defined by the authors: a total of 765 articles were identified, and at the end of the screening process only 7 studies were included. (3) Results: Currently, the DAPRI procedure can be performed only on patients who have had PJI symptoms for less than 4 weeks, and in order to achieve the highest success rate, indications are quite strict: it is appropriate in patients with acute, superficial infections without sinus tract presence, and well-fixed implants with known sensitive bacteria. The DAPRI surgical method follows a step-by-step process consisting of a first phase of biofilm identification with intra-articular injection of methylene blue, followed by biofilm removal (thermic, mechanical, and chemical aggression), and a last step consisting of prevention of PJI recurrence by using calcium sulphate antibiotic-added beads. (4) Conclusions: The DAPRI approach improves the traditional DAIR technique. It is a correct treatment for acute and early haematogenous PJI, and improves the DAIR success rate.

The Use of Next Generation Sequencing to Detect Early Implant Infections: The Future of Microbiology and Targeted Antibiotic Treatment

Abstract Goals/Purpose The presence of fluid around foreign bodies, particularly breast implants, is a well-established phenomenon; However scant data exists regarding the composition of this fluid. The difficulty in studying this fluid arises from the lack of safe access to aspirate fluid post-breast augmentation, and by the loss of sterility once fluid exits the body via a drain bulb as traditionally placed during breast reconstruction. Our innovative breast reconstruction approach utilizes a drainless technique with a dual chamber tissue expander (TE) in the pre-pectoral plane, offering a unique avenue to sterilely aspirate peri-implant fluid through a percutaneous drainage port. In this study, we employ Next Generation Sequencing (NGS), utilizing polymerase chain reaction technology, to discern the composition of microbial DNA within peri-prosthetic breast implant fluid. NGS, known for its precision and cost-effectiveness, circumvents the biases inherent in traditional culture methods. By integrating this cutting-edge technology with our breast reconstruction methodology, we sought to study peri-prosthetic breast implant fluid to better understand when implant infections arise and if peri-prosthetic fluid could detect infections before clinical symptoms arise. Methods/Technique This is a single surgeon, prospective study of patients undergoing mastectomy, followed by pre-pectoral, drainless, TE reconstruction. Peri-prosthetic fluid was collected through the TE drainage port in the OR immediately after closure, at 1 week post op, and 3 weeks post op. This fluid was sent for traditional culture and NGS. Patients were observed for signs of infection, antibiotics, return to OR, or implant loss. Results/Complications 33 breasts from 20 patients were included. Patients had a mean age of 50 years. The average length of drainage was 21 days post-operative, with a mean of 131 cc of fluid drained per breast per week. Eight breasts had concern for skin necrosis. In 25 breasts (76%), complete sterility was achieved at the end of the case with no NGS detection of microorganisms in the initial peri-implant fluid sample. However, NGS detected microorganisms in the initial sample in 8 breasts (24%). In 5 of these 8 breasts, microorganisms were cleared by the 1-week sample and another 2 cleared by 3 weeks. The remaining 1 breast continued to have positive NGS and developed clinical signs of infections by week 2, which were not picked up by traditional culture until week 3. One breast with skin necrosis developed a positive NGS at week 3 and clinical signs of infection at week 4. No other clinical infections were seen throughout the study. Conclusion We are one of the first groups to demonstrate the ability to achieve peri-implant sterility at the time of implant insertion in the operating room. This could have significant implications for understanding the necessity of peri-operative antibiotics following breast implant placement. Our investigation into the microbial composition of ostensibly "sterile" peri-prosthetic breast implant fluid provides insight into when microorganisms arise and when they become clinical infections. These promising preliminary results suggests that peri-prosthetic fluid monitoring through Next-Generation Sequencing (NGS) holds significant potential in preemptively detecting implant infections before the onset of clinical symptoms, thereby reducing infection rates. Furthermore, our findings open avenues for targeted antibiotic therapy, contributing to the imperative goal of antibiotic stewardship. Ongoing work is beginning to explore the impact of microorganisms within the fluid on breast capsule formation, as we strive to enhance our understanding of breast implants and infections.

Lingering Effects of Early Institutional Rearing and Cytomegalovirus Infection on the Natural Killer Cell Repertoire of Adopted Adolescents.

Adversity during infancy can affect neurobehavioral development and perturb the maturation of physiological systems. Dysregulated immune and inflammatory responses contribute to many of the later effects on health. Whether normalization can occur following a transition to more nurturing, benevolent conditions is unclear. To assess the potential for recovery, blood samples were obtained from 45 adolescents adopted by supportive families after impoverished infancies in institutional settings (post-institutionalized, PI). Their immune profiles were compared to 39 age-matched controls raised by their biological parents (non-adopted, NA). Leukocytes were immunophenotyped, and this analysis focuses on natural killer (NK) cell populations in circulation. Cytomegalovirus (CMV) seropositivity was evaluated to determine if early infection contributed to the impact of an atypical rearing. Associations with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), two cytokines released by activated NK cells, were examined. Compared to the NA controls, PI adolescents had a lower percent of CD56bright NK cells in circulation, higher TNF-α levels, and were more likely to be infected with CMV. PI adolescents who were latent carriers of CMV expressed NKG2C and CD57 surface markers on more NK cells, including CD56dim lineages. The NK cell repertoire revealed lingering immune effects of early rearing while still maintaining an overall integrity and resilience.

The efficacy and safety of different does of intravenous tranexamic acid on blood loss in fresh foot and ankle fractures: a prospective, randomized controlled study

BackgroundThere are a few studies on the effectiveness and safety of intravenous administration of tranexamic acid(TXA) in patients who underwent foot and ankle surgery, especially for preoperative hidden blood loss in patients with freshfoot and ankle fractures. Thus, the aim of this study was to investigate whether intravenous administration of different doses of TXA can effectively reduce perioperative blood loss and blood loss before surgery and to determine its safety.MethodsA total of 150 patients with fresh closed foot and ankle fractures from July 2021 to July 2023 were randomly divided into a control group (placebo controlled [PC]), standard-dose group (low-dose group [LD], 1 g/24 h; medium-dose group [MD], 2 g/24 h), and high-dose group (HD, 3 g/24 h; ultrahigh-dose group [UD], 4 g/24 h). After admission, all patients completed hematological examinations as soon as possible and at multiple other time points postsurgery.ResultsThere was a significant difference in the incidence of hidden blood loss before the operation between the TXA group and the control group, and the effect was greater in the overdose groups than in the standard-dose groups. There were significant differences in surgical blood loss (intraoperative and postoperative), postoperative HGB changes, and hidden blood loss among the groups. The TXA groups showed a significant decrease in blood loss compared to that of the control group, and the overdose groups had a more significant effect than the standard-dose groups. A total of 9 patients in the control group had early wound infection or poor healing, while only 1 patient in the other groups had this complication, and the difference among the groups was significant. No patients in any group suffered from late deep wound infection, cardiovascular or cerebrovascular events or symptomatic VTE.ConclusionThis is the first study on whether TXA can reduce preoperative hidden blood loss in patients with freshfoot and ankle fractures. In our study, on the one hand, intravenous application of TXA after foot and ankle fractures as soon as possible can reduce preoperative blood loss and postoperative blood loss. On the other hand, TXA can also lower wound complications, and over-doses of TXA are more effective than standard doses. Moreover, overdoses of TXA do not increase the incidence of DVT.

Oncolytic Adenovirus for the Targeting of Paclitaxel-Resistant Breast Cancer Stem Cells.

Adjuvant systemic therapies effectively reduce the risk of breast cancer recurrence and metastasis, but therapy resistance can develop in some patients due to breast cancer stem cells (BCSCs). Oncolytic adenovirus (OAd) represents a promising therapeutic approach as it can specifically target cancer cells. However, its potential to target BCSCs remains unclear. Here, we evaluated a Cox-2 promoter-controlled, Ad5/3 fiber-modified OAd designed to encode the human sodium iodide symporter (hNIS) in breast cancer models. To confirm the potential of OAds to target BCSCs, we employed BCSC-enriched estrogen receptor-positive (ER+) paclitaxel-resistant (TaxR) cells and tumorsphere assays. OAd-hNIS demonstrated significantly enhanced binding and superior oncolysis in breast cancer cells, including ER+ cells, while exhibiting no activity in normal mammary epithelial cells. We observed improved NIS expression as the result of adenovirus death protein deletion. OAd-hNIS demonstrated efficacy in targeting TaxR BCSCs, exhibiting superior killing and hNIS expression compared to the parental cells. Our vector was capable of inhibiting tumorsphere formation upon early infection and reversing paclitaxel resistance in TaxR cells. Importantly, OAd-hNIS also destroyed already formed tumorspheres seven days after their initiation. Overall, our findings highlight the promise of OAd-hNIS as a potential tool for studying and targeting ER+ breast cancer recurrence and metastasis.

PEI-Mediated Assembly of Fe3O4 onto SiO2-Encapsulated CsPbBr3 for Highly Sensitive Fluorescent Lateral Flow Immunoassay.

The conventional lateral flow immunoassay (LFIA) method using colloidal gold nanoparticles (Au NPs) as labeling agents faces two inherent limitations, including restricted sensitivity and poor quantitative capability, which impede early viral infection detection. Herein, we designed and synthesized CsPbBr3 perovskite quantum dot-based composite nanoparticles, CsPbBr3@SiO2@Fe3O4 (CSF), which integrated fluorescence detection and magnetic enrichment properties into LFIA technology and achieved rapid, sensitive, and convenient quantitative detection of the SARS-CoV-2 virus N protein. In this study, CsPbBr3 served as a high-quantum-yield fluorescent signaling probe, while SiO2 significantly enhanced the stability and biomodifiability of CsPbBr3. Importantly, the SiO2 shell shows relatively low absorption or scattering toward fluorescence, maintaining a quantum yield of up to 74.4% in CsPbBr3@SiO2. Assembly of Fe3O4 nanoparticles mediated by PEI further enhanced the method's sensitivity and reduced matrix interference through magnetic enrichment. Consequently, the method achieved a fluorescent detection range of 1 × 102 to 5 × 106 pg·mL-1 after magnetic enrichment, with a limit of detection (LOD) of 58.8 pg·mL-1, representing a 13.3-fold improvement compared to nonenriched samples (7.58 × 102 pg·mL-1) and a 2-orders-of-magnitude improvement over commercial colloidal gold kits. Furthermore, the method exhibited 80% positive and 100% negative detection rates in clinical samples. This approach holds promise for on-site diagnosis, home-based quantitative tests, and disease procession evaluation.

Risk factors for infection and outcomes in infants with neonatal encephalopathy: a cohort study

BackgroundTo determine the association between early infection risk factors and short-term outcomes in infants with neonatal encephalopathy following perinatal asphyxia (NE).MethodsA retrospective population-based cohort study utilizing the National Neonatal Research Database that included infants with NE admitted to neonatal units in England and Wales, Jan 2008–Feb 2018. Exposure: one or more of rupture of membranes >18 h, maternal group B streptococcus colonization, chorioamnionitis, maternal pyrexia or antepartum antibiotics. Primary outcome: death or nasogastric feeds/nil by mouth (NG/NBM) at discharge. Secondary outcomes: organ dysfunction; length of stay; intraventricular hemorrhage; antiseizure medications use.Results998 (13.7%) out of 7265 NE infants had exposure to early infection risk factors. Primary outcome (20.3% vs. 23.1%, OR 0.87 (95% CI 0.71–1.08), p = 0.22), death (12.8% vs. 14.0%, p = 0.32) and NG/NBM (17.4% vs. 19.9%. p = 0.07) did not differ between the exposed and unexposed group. Time to full sucking feeds (OR 0.81 (0.69–0.95)), duration (OR 0.82 (0.71–0.95)) and the number of antiseizure medications (OR 0.84 (0.72–0.98)) were lower in exposed than unexposed infants after adjusting for confounders. Therapeutic hypothermia did not alter the results.ConclusionsInfants with NE exposed to risk factors for early-onset infection did not have worse short-term adverse outcomes.ImpactRisk factors for early-onset neonatal infection, including rupture of membranes >18 h, maternal group B streptococcus colonization, chorioamnionitis, maternal pyrexia or antepartum antibiotics, were not associated with death or short-term morbidity after cooling for NE.Despite exposure to risk factors for early-onset neonatal infection, infants with NE reached oral feeds earlier and needed fewer anti-seizure medications for a shorter duration than infants with NE but without such risk factors.This study supports current provision of therapeutic hypothermia for infants with NE and any risk factors for early-onset neonatal infection.

Do early-life allergic sensitization and respiratory infection interact to increase asthma risk?

Objective The ‘two-hit’ hypothesis theorizes that early life allergic sensitization and respiratory infection interact to increase asthma risk. Methods We sought to determine in a high allergy risk birth cohort whether interactions between early life allergic sensitization and respiratory infection were associated with increased risk for asthma at ages 6–7 years and 18 years. Allergic sensitization was assessed at 6, 12, and 24 months by skin prick testing to 3 food and 3 aeroallergens. Respiratory infection was defined as reported “cough, rattle, or wheeze” and assessed 4-weekly for 15 months, at 18 months, and age 2 years. Regression analysis was undertaken with parent-reported asthma at age 6–7 years and doctor diagnosed asthma at 18 years as distinct outcomes. Interactions between allergic sensitization and respiratory infection were explored with adjustment made for potential confounders. Results Odds of asthma were higher in sensitized compared to nonsensitized children at age 6–7 years (OR = 14.46; 95% CI 3.99–52.4), There was no evidence for interactions between allergic sensitization and early life respiratory infection, with a greater frequency of respiratory infection up to 2 years of age associated with increased odds for asthma at age 6–7 years in both sensitized (OR = 1.13; 95% CI 1.02–1.25, n = 199) and nonsensitized children (OR = 1.31; 1.11–1.53, n = 211) (p interaction = 0.089). At age 18 years, these associations were weaker. Conclusions Our findings do not support ‘two-hit’ interactions between early life allergic sensitization and respiratory infection on asthma risk. Both early life respiratory infections and allergic sensitization were risk factors and children with either should be monitored closely for development of asthma.

A Prospective Evaluation of a 3D-Printed 4th-Generation Total Ankle Prosthesis with 1-Year Follow- Up

Introduction/Purpose: Fixation of fourth-generation ankle replacements is evolving. Given the concern for tibial tray loosening or radiolucencies, three-dimensional (3-D) printing has been suggested as a solution. Additive manufacturing allows for the creation of an optimal implant surface for improved initial stability and bony on growth. To date, there are no reported data concerning survivorship and clinical improvement following a 3-D printed ankle replacement. Documentation of implant survivability and comparison studies of the latest generation implants are limited. The purpose of this study is report on prospectively-collected patient reported outcome measures (PROMs) in a multi-institutional study of a 3-D printed fourth-generation total ankle. Methods: Patients presenting for a total ankle replacement at 12 institutions were prospectively enrolled and implanted in both academic and private settings. Patients had demographics and PROMs recorded pre-operatively and at 6 month and 12-month intervals. The following PROMs were collected: Ankle Osteoarthritis Score (AOS), PROMIS Global Physical Health, Foot and Ankle Outcome Score (FAOS), and satisfaction scores. The preoperative and latest follow-up scores for patients with two years of follow-up were analyzed. Results: 91 of 177 subjects enrolled have reached one-year in follow-up currently. From the 177 enrolled (52.5% male) with an average age of 64.0±10.3 years old with an average BMI of 30.8±6.2. The pre-operative diagnosis for arthritis type was degenerative arthritis (27.7%), rheumatoid arthritis (1.7), post-traumatic arthritis (70.1%), and other (0.50%). There were 3 (1.69%) clinical failures:1 early infection: at 2 months, 1 tibial subsidence at 7 months, and 1 deep infection associated with trauma at 8 months post-operatively. The patients improved in all PROMs domains at one year including: Mean Total AOS (19.0. ± 17.5) p&lt;.0001); PROMIS Global Physical Health (49.6 ± 17.1 p&lt;.0001); Total FAOS Symptom Scores at 1 year (75.0 ± 19.5, p&lt;.0001). The Total FAOS QOL at 1 year is 65.3 ± 25.2. Conclusion: At one-year post-implantation follow-up, the fourth generation 3D printed total ankle replacement had a low revision rate and proved to be safe and effective compared to historical ankle replacement outcomes. Patients were overwhelmingly satisfied and had statistically significant clinical improvements in each domain of their PROMs.

Current Therapeutic Strategies for Chagas Disease

Abstract: Trypanosoma cruzi, the parasite that causes Chagas disease, can only be cured with one of two drugs, benznidazole or nifurtimox. The main disadvantages of these drugs include their ineffectiveness outside of the acute or early infection phase, their unpleasant effects, and the parasite's tolerance to their activities. On the other hand, several institutions and research groups have been working on a number of ways that can help find a solution to the problem. These strategies have evolved over the last few years. Several examples of such advancements include the utilization of combination therapy, the repurposing of current treatments, and the change of dosages for traditional drugs. Research has also been conducted on antiparasitic plants and the substances that may be obtained from them, and it makes use of existing knowledge gathered through medical procedures. Some works have studied the parasite in order to identify important genes that have the potential to be used as therapeutic targets in the development of novel targeted medications. Even though a lot of these studies have shown promising results, only a small fraction of them make it to the clinical testing phase of the study. Institutions and research organizations should be rewarded for coordinating their efforts and addressing all areas of drug development, given their resources and information. Last but not least, distributing this information will result in novel Chagas disease therapies, which would assist impacted populations.

Surface-enhanced raman spectroscopy with machine learning in non-invasive detection of dengue-NS1 fingerprint

The surface-enhanced Raman spectroscopy (SERS) method exploits the plasmonic effect of nano-sized metallic materials to intensify the Raman scattering of the monochromatic light of analyte molecules. This promotes the sensitivity and specificity of the Raman spectroscopy analysis method. This study integrated SERS with machine learning (ML) to detect dengue fever, a disease infecting more than 40% of the world’s population. Non-structural protein 1 (NS1), detected in the sera of infected dengue patients during the early infection stage, is currently recognised as a biomarker for the early diagnosis of DF. However, no attempts have been made to detect NS1 in the salivary Raman spectra. Given this situation, this study delves into the potential of SERS as an early, non-invasive DF detection technique using salivary NS1. The SERS spectra of saliva samples (n=289) were collected and subsequently classified as positive and negative for DF, using principal component analysis (PCA) integrated with support vector machine (SVM) models. The PCA-SVM model's performance was benchmarked against two clinical diagnostic NS1-enzyme-linked immunosorbent assay (ELISA) tests recommended by the World Health Organization (WHO). The PCA-SVM model outperformed both tests regarding radial basis function kernel (RBF) and cumulative percent variance (CPV; 83.22% accuracy, 88.27% sensitivity, 78.13% specificity). It is encouraging that the sensitivity level of the PCA-SVM model is above the benchmark set by the saliva-based NS1-ELISA tests proposed by the WHO, demonstrating the potential of SERS for the non-invasive detection of DF.

Usability and outcomes of self-monitored surgical wound healing using a smartphone-based application by patients following neurosurgery

The Radboudumc developed a smartphone application (WondGezond) to collect surgical wound-healing information provided by the patient. To evaluate usability and outcomes to assess its potential for early surgical site infection (SSI) detection. Patients surgically treated for degenerative spinal disorders or carpal tunnel syndrome between August 2020 and February 2023 were enrolled one day post surgery and asked to download the app via a quick-response (QR) code. Participants uploaded a photoand answered four questions about their wound daily, for 14 days. Afterwards, participants indicated whether they received treatment for a suspected SSI (participant-reported outcome). Two neurosurgeons independently assessed photos and questionnaire answers for suspected SSIs (physician-assessed outcome). The association between both outcomes was determined by calculating sensitivity, specificity, and positive and negative predictive value (PPV/NPV). After 2009 surgeries, 1695 QR-codes were distributed and 412 (21%) were activated. In all, 232 (56%) participants completed the 14-day period of whom 22 (10%) reported SSI treatment. Physician assessment identified 15 (7%) SSIs. Concordance was reached in 88% of cases. Among 27 discordant cases were 17 false-positives and 10 false-negatives, resulting in low sensitivity (33%) and PPV (23%), but high NPV (95%). WondGezond provides clinicians with information regarding wound healing and SSIs to follow-up on patients at risk, while possibly also reducing antibiotic (over)treatment and unnecessary visits for patients without issues in wound healing. However, the low participation and false-positive results render the app in its current form unsuitable for surveillance purposes. Further validation of WondGezond is required.

Anatomic shoulder arthroplasty in patients 40 years or younger

BackgroundGlenohumeral arthritis in adults less than 40 years old represents a challenging clinical scenario to manage. While patients older than 55 have had reproducible success with current shoulder arthroplasty techniques, young patients have historically had less successful outcomes, possibly due to higher physical demands and more complex pathologies. Despite these concerns, anatomic total shoulder arthroplasty (TSA) remains the treatment of choice for young, active patients with severe glenohumeral arthritis and intact rotator cuff. We hypothesize that TSA provides significant relief in pain and functional outcomes in patients less than 40 years old. MethodsWe performed a single-institution retrospective analysis of consecutive patients aged 40 years and younger who underwent TSA between 2007 and 2022. Demographic data included age, sex, body mass index, Charlson comorbidity index, and preoperative diagnosis. Outcome measures included the Single-Assessment Numerical Evaluation (SANE) score, final range of motion, complications, and revision rate. Statistically significant differences between variables were evaluated using a 2-sample t-test at an α level of P < .05. ResultsTwenty-six TSAs were performed in 23 patients with an average final follow-up of 2 years after the procedure. The average age was 33.4 ± 5.3 years with a range of 19-39 years. The most common preoperative diagnosis was osteoarthritis (46%), followed by rheumatoid arthritis (27%) and osteonecrosis/avascular necrosis (19%). The most common glenoid morphology was type B (15) of which 14 were B2 glenoid, followed by type A (11). The SANE score, mean active forward elevation, abduction, external rotation, and internal rotation all improved significantly (P < .05) by the final follow-up. On average, patients in all groups were able to achieve minimal clinically important difference in SANE score after 1 year. There was 1 complication reported of an early postoperative infection treated with irrigation and débridement, and no revision surgeries were performed during the follow-up period. Discussion/ConclusionTSA significantly improved functional outcome measures in patients less than 40 years old with a low rate of complications and revisions in short-term outcomes. As the frequency of TSA continues to increase in adults less than 40 years old, additional studies recording long-term functional outcomes and implant survivorship in this population can be explored.

THE USE OF A POLYVALENT KLEBSIELLA BACTERIOPHAGE IN INFECTION AFTER RECONSTRUCTIVE PLASTIC SURGERY ON THE SPINE IN A CHILD (A CLINICAL CASE)

The incidence of infection after reconstructive plastic surgery on the spine (in particular, spondylodesis) in children remains at a fairly high level and ranges from 0.4% to 8.7%. These complications are often caused by polyresistant bacterial pathogens; this accentuates the need for new effective therapeutic approaches. Bacteriophage preparations in combination with antibiotics can optimize existing strategies for the treatment of infectious diseases, since they are able to selectively destroy bacteria, including biofilm-forming ones. The aim of the study was to draw the attention of practitioners to modern problems of treating polyresistant infections on the example of a case of purulent complication after spinal surgery in a child. Materials and methods. On the basis of the FSBI "Federal Center for Traumatology, Orthopedics and Endoprosthetics" under the Health Ministry of the Russian Federation (the town of Cheboksary) a retrospective analysis of a clinical case of treating early infection after reconstructive plastic surgery on the spine caused by a polyresistant strain of Klebsiella pneumoniae was conducted. Research results. Patient P., 2.2 years old, with congenital pathology of the musculoskeletal system, who repeatedly received medical care in various medical organizations, underwent surgical spine stabilization. In the early postoperative period, an infectious complication developed caused by a polyresistant strain of Klebsiella pneumoniae (a producer of extended-spectrum beta-lactamases and carbapenemases). Along with surgical debridement of the postoperative wound, a combined etiotropic antibacterial therapy was performed (12 weeks). However, complete healing of the postoperative wound was achieved in combination with the administration of a polyvalent klebsiella bacteriophage (10 weeks). Conclusions. This clinical case demonstrates that the use of a polyvalent klebsiella bacteriophage can increase the effectiveness of antibacterial pharmacotherapy in surgical treatment with preservation of metal structures.