Infections In Clinical Practice Research Articles

Genetic variations underlying aminoglycoside resistance in antibiotic-induced Mycobacterium intracellulare mutants.

Mycobacterium avium complex (MAC) is an emerging pathogen leading to public health concerns in developing and developed countries, particularly among immunocompromised individuals and patients with structural lung diseases. Current clinical guidelines recommend combination antibiotic therapy for treating MAC pulmonary disease (MAC-PD). However, the rising prevalence of antibiotic resistance poses significant challenges, including treatment failure and clinical recurrence. A deeper understanding of the mechanisms underlying MAC antibiotic resistance is essential to improve treatment outcomes. This study investigates the genetic variations associated with aminoglycoside resistance in an antibiotic-induced Mycobacterium intracellulare mutant derived from a clinical strain. Whole-genome analysis identified seven mutations in the aminoglycoside-resistant mutant, including single nucleotide polymorphisms (SNPs) and insertions/deletions (InDels). Key genetic alterations included a frameshift variant in a gene encoding a secreted protein antigen, missense mutations in rpsL and rsmG, and synonymous and in-frame deletion variants in srfAB and mtrB, respectively. These findings highlight the complex genetic landscape of aminoglycoside resistance in M. intracellulare. Understanding these resistance determinants provides valuable insights for developing diagnostic tools to detect drug-resistant MAC strains and optimizing therapeutic strategies for managing MAC infections in clinical practice.

Intra-articular procedures and associated septic arthritis: A mini-review.

Native joint septic arthritis (SA) is a severe, potentially life-threatening condition characterized by the invasion of synovial fluid and membrane by pathogens, most commonly bacteria. The rising frequency of intra-articular procedures such as joint aspirations and injections has led to increased concern regarding iatrogenic septic arthritis. This mini-review aims to summarize current understanding of the incidence, risk factors, bacterial etiology, and strategies for preventing SA associated with intra-articular procedures. Recent studies report that while iatrogenic SA incidence remains low, ranging between 0.002% and 0.008% following injections, it is higher following arthroscopy (0.14%). Risk factors for iatrogenic SA mirror those of hematogenous SA, comprising older age, male gender, comorbidities such as diabetes mellitus, and systemic corticosteroid therapy. Staphylococcus aureus remains the most frequently implicated pathogen, followed by coagulase-negative staphylococci and streptococci. Preventive measures, including hand antisepsis, patient skin disinfection, and the wearing of surgical masks, are essential to reducing the risk of SA during intra-articular procedures. Despite low incidence, SA poses significant morbidity and mortality risks, underscoring the need for adherence to infection control protocols. This review highlights the importance of standardized preventive measures and further research into optimized aseptic techniques, the objective being to mitigate the risk of iatrogenic infections in clinical practice.

Rapid and accurate testing for urinary tract infection: new clothes for the emperor.

SUMMARYUrinary tract infection (UTI) is among the most common infections in clinical practice. In some cases, if left untreated, it can lead to pyelonephritis and urosepsis. In other cases, UTI resolves without treatment. Clinical diagnosis is typically based on patient symptoms and/or urinalysis, including urine dipsticks. The standard urine culture method is sometimes employed to identify the suspected urinary pathogen (uropathogen) and/or guide antimicrobial choice, but results are rarely available before 24 h. The standard urine culture method also misses fastidious, anaerobic, and slow-growing uropathogens and rarely reports polymicrobial infections. The unexplained combination of negative urine cultures with persistent urinary tract symptoms is distressing to both patients and clinicians. Given the broad appreciation of the advantages provided by rapid testing (e.g., for COVID-19 or influenza A), a rapid, accurate diagnostic test is needed to deliver timely treatment to patients seeking care for UTI that optimizes antibiotic stewardship. Herein, we discuss progress being made toward an accessible, timely (i.e., within hours), accurate assay with results that are clinically useful for the treating clinician within the timeframe of the infection (i.e., the growth rate of the pathogen(s)). New and emerging uropathogens often overlooked by current diagnostic techniques are also reviewed.

Retrospective Analysis of the Characteristics of the Post-COVID Period in Patients with Type 2 Diabetes, Infected During Different Variant-Associated Periods of COVID-19

BACKGROUND: Since the emergence of coronavirus infection in clinical practice, particular attention has been paid to its acute phase. However, to date, the direct and indirect impact on patients with type 2 diabetes mellitus after recovery from coronavirus infection remains an open question.OBJECTIVE: To determine the clinical and laboratory features of the post-COVID period in patients with type 2 diabetes mellitus during different phases of the infection.MATERIALS AND METHODS: A descriptive retrospective study was conducted using the electronic medical records of 134 patients who had recovered from coronavirus infection.RESULTS: The majority of the patients were women, with no significant differences in age and gender distribution across the groups (p=0.384 and p=0.207, respectively). During the «Omicron» period, there were fewer comorbidities and fewer hospitalized patients compared to the other groups (p<0.0167). Regarding diabetes-related conditions, frequent urination was observed only in patients during the «Alpha» period, while the frequency of hypoglycemia, hyperglycemia, the severity of chronic kidney disease, and manifestations of polyneuropathy did not differ significantly between the groups (p>0.0167). When examining newly diagnosed diseases, a statistically significant difference was found only in musculoskeletal disorders (16.7% in «Alpha» vs. 30.2% in «Delta» vs. 3.7% in «Omicron», p=0.015). In the analysis of laboratory indicators, a difference was detected in platelet counts and activated partial thromboplastin time (APTT): median platelet counts were significantly lower in the «Alpha» and «Delta» groups compared to the «Omicron» group (210 [179.2–249.7] x10⁹/L and 218 [196.5–281] x10⁹/L vs. 255 [208–327] x10⁹/L, respectively, p=0.016). The APTT was significantly longer for «Alpha» and «Delta» compared to «Omicron» (28 [23.6–31.3] seconds vs. 30.3 [26.1–34.9] seconds vs. 27.1 [22.4–30.3] seconds, respectively, p=0.013).CONCLUSION: Real-world data allow tracking the development of new symptoms and diseases in patients during the post-COVID period. Patients with type 2 diabetes mellitus during the «Omicron» variant-associated period had a lower risk of developing new symptoms and diseases. It is necessary to implement solutions for monitoring target HbA1c levels through medical information systems and to enhance reporting standards for patient symptoms to enable more accurate analysis Real world data (RWD).

A Comparative Study of the Rate of Helicobacter pylori infection Using Three Diagnostic Techniques among Patients in Rivers State

Background: Approximately 89% of gastric cancers are attributable to H. pylori infection, however, only 1 in 5 patients survive longer than 5 years after diagnosis. Evidence has shown that screening and eradication of H. pylori in young adults would be cost-effective and could prevent 1 gastric cancer in every 4 to 6 cases. Diagnostic tests used to detect Helicobacter pylori are either invasive or noninvasive methods. These tests have varying sensitivity and specificity, having about 90% accuracy in the diagnosis of H. pylori infection in clinical practice. Aim: This study aims at detecting Helicobacter pylori using antibody-antigen, stool antigen and polymerase chain reaction (PCR) and to compare the infection rate among the different diagnostic techniques. Methodology: This was a cross-sectional study. The participants included attendants to tertiary and private hospitals in Port Harcourt metropolis for medical treatment. Blood and stool samples were collected from one hundred and eighty (180) subjects aged 1 to 60 years and above. Ethical approval for the study was obtained from the Rivers State University Teaching Hospital Ethics Committee. Convenience sampling technique was deployed. Samples were collected from subjects who consented to the study. All samples collected were analyzed in Medical Microbiology Laboratory, Rivers State Teaching Hospital and subsequently, molecular analysis was carried out. Results: The blood antibodies test (serology) method shows a greater number of positive cases (43.9%) than stool antigen method (8.3%). Also, out of the 75% stool antigen positive samples, subjected to more specific PCR, only 25% were positive. There was a significant difference (p-value of <0.001) in sensitivity between antigen and serology, there was also a significant difference (p-value of <0.025) between antigen and PCR result outcomes. Conclusion: The study has shown that there is a notable variation in the diagnosis of H pylori among the laboratory techniques used.

Sobrerol in Managing Acute Respiratory Infections in Clinical Practice During the "Cold" Season: An Italian Primary Care Experience.

Acute upper respiratory infections (AURI) represent a daily challenge in primary care practice. Mucus production may impair during AURI. Sobrerol is a muco-active agent that improves rheological characteristics and exerts other ancillary activities. The aim of this retrospective case-series study was to compare the efficacy and safety of different uses of sobrerol (only oral, only nebulized, and combined or standard treatment for infections alone) in patients with AURIs. The present clinical experience retrospectively collected clinical data of patients with AURIs visited by ten primary care doctors (pediatricians and general practitioners) over a long period. Patients could take standard therapy for infections, or as add-on: oral sobrerol, nebulized sobrerol, or combined oral and nebulized aerosol during the infection for 3 days. Patients treated with combined oral and nebulized sobrerol experienced less intense symptoms, mainly concerning cough (p < 0.001) and nasal complaints (p = 0.043). In addition, the patients taking the combined therapy reported a more rapid disappearance of cough and nasal symptoms at day 7 than patients treated with the other options (OR 4.47 and 3.16, respectively). The current retrospective and observational study showed that a three-day combined (oral and nebulized) sobrerol course may represent a valuable add-on option in patients with AURIs.

Disseminated Yersinia enterocolitica infection associated to Sweet’s syndrome

We report the case of a young woman sough care for disseminated form of Yersinia enterocolitica infection (pseudoappendicitis with mesenteric lymph node, arthralgia, glomerulonephritis and hepatitis) diagnosed on Western Blot method for the detection of Yersinia antibodies. The patient also presented a rare concomitant cutaneous manifestation, as Sweet’s syndrome, confirmed histologically. Neutrophilic dermatosis is an exceptional skin features among post-infectious autoimmune disorders when encountering Yersinia enterocolitica infection in clinical practice.

Enhancing lower respiratory tract infection diagnosis: implementation and clinical assessment of multiplex PCR-based and hybrid capture-based targeted next-generation sequencing

Shotgun metagenomic next-generation sequencing (mNGS) is widely used to detect pathogens in bronchoalveolar lavage fluid (BALF). However, mNGS is complex and expensive. This study explored the feasibility of targeted next-generation sequencing (tNGS) in distinguishing lower respiratory tract infections in clinical practice. We used 229 retrospective BALF samples to establish thresholds and diagnostic values in a prospective cohort of 251 patients. After target pathogen selection, primer and probe design, optimization experiments, and bioinformatics analysis, multiplex PCR-based tNGS (mp-tNGS) and hybrid capture-based tNGS (hc-tNGS), targeting 198 and 3060 pathogens (DNA and RNA co-detection workflow) were established and performed. mp-tNGS and hc-tNGS took 10.3 and 16h, respectively, with low sequencing data sizes of 0.1M and 1M reads, and test costs reduced to a quarter and half of mNGS. The LoDs of mp-tNGS and hc-tNGS were 50-450CFU/mL. mp-tNGS and hc-tNGS were highly accurate, with 86.5% and 87.3% (vs. 85.5% for mNGS) sensitivities and 90.0% and 88.0% (vs. 92.1% for mNGS) specificities. tNGS detection rates for casual pathogens were 84.3% and 89.5% (vs. 88.5% for mNGS), significantly higher than conventional microbiological tests (P<0.001). In seven samples, tNGS detected Pneumocystis jirovecii, a fungus not detected by mNGS. Whereas mNGS detected six samples with filamentous fungi (Rhizopus oryzae, Aureobasidium pullulans, Aspergillus niger complex, etc.) which missed by tNGS. The anaerobic bacteria as pathogen in eight samples was failed to detect by mp-tNGS. tNGS may offer a new, broad-spectrum, rapid, accurate and cost-effective approach to diagnosing respiratory infections. National Natural Science Foundation of China (81625014 and 82202535).

Cardiovascular and Neurological Diseases and Association with Helicobacter Pylori Infection-An Overview.

This article investigates the link between Helicobacter pylori (H. pylori) infection and cardiovascular and neurological disorders. Recent research suggests that H. pylori may play a role in cardiovascular diseases like atherosclerosis, myocardial infarction, and stroke, as well as neurological diseases including Alzheimer's disease, multiple sclerosis, and Parkinson's disease. Cardiovascular Diseases: H. pylori induces endothelial dysfunction and chronic inflammation, promoting atherosclerotic plaque formation and other cardiac complications. High infection prevalence in cardiovascular patients implies that systemic inflammation from H. pylori accelerates disease progression. Eradication therapies combined with anti-inflammatory and lipid-lowering treatments may reduce cardiovascular risk. Neurological Diseases: H. pylori may contribute to Alzheimer's, multiple sclerosis, and Parkinson's through systemic inflammation, neuroinflammation, and autoimmune responses. Increased infection prevalence in these patients suggests bacterial involvement in disease pathogenesis. The eradication of H. pylori could reduce neuroinflammation and improve outcomes. Discussions and Future Research: Managing H. pylori infection in clinical practice could impact public health and treatment approaches. Further research is needed to clarify these relationships. Longitudinal and mechanistic studies are essential to fully understand H. pylori's role in these conditions. Conclusions: H. pylori infection is a potential risk factor for various cardiovascular and neurological conditions. Additional research is critical for developing effective prevention and treatment strategies. Targeted therapies, including H. pylori eradication combined with anti-inflammatory treatments, could improve clinical outcomes. These findings highlight the need for an integrated clinical approach to include H. pylori evaluation and treatment.

Appropriateness of antimicrobial prescribing for oral and dental conditions in Australian hospitals: 2013 to 2022

ObjectivesDentists manage a variety of oral infections in clinical practice. Inappropriate antimicrobial prescribing by dentists occurs frequently and antimicrobial stewardship strategies should include dentistry. The aim of this retrospective analysis of the Australian Hospital National Antimicrobial Prescribing Survey (Hospital NAPS) dataset, was to describe the types of oral and dental indications where antimicrobials were prescribed, and assess the guideline compliance and appropriateness of the antimicrobials in Australian hospitals. MethodsData from the Hospital NAPS was extracted for oral and dental indications from 2013 to 2022. The types of oral and dental indications presented, and the corresponding antimicrobials prescribed were assessed for compliance according to national prescribing guidelines, and appropriateness according to the NAPS structured algorithm. ResultsA total of 8,001 prescriptions for 7,477 patients were identified, from 433 hospitals. Antifungal, antibiotic and antiviral agents accounted for 84.5 %, 15.4 % and 0.03 % of prescriptions respectively. A greater proportion of antibiotics were prescribed in regional and rural areas compared to antifungals. The prescriptions assessed as compliant were 80.0 % and 44.7 % of antifungals and antibiotics respectively. Prescriptions assessed as appropriate were 84.4 % of antifungals, and 65.3 % of antibiotic prescriptions. ConclusionsA wide variety of antimicrobials were used with moderate levels of compliance and appropriateness. Future interventions should include targeted education, utilisation of prescribing guidelines, and tools to diagnose and manage oral and dental conditions. Consideration can be given to adjustment of the Hospital NAPS tool to cater for oral conditions and include the provision of dental treatment in the management of these infections. Clinical significanceA wide variety of oral and dental conditions are presented in Australian hospital settings, managed by a range of antibiotics and antifungals, with moderate levels of compliance to guidelines and appropriateness. Antimicrobial stewardship strategies should target and support dentistry in hospital settings.

Research Progress on the Risk and Prevention Measures of Peripheral Arterial Catheter Infection in ICU Patients

Peripheral arterial catheter (PAC) is an important assistant method in the treatment of critical patients. However, the related infection risk is significantly underestimated, especially the occurrence of catheter-related bloodstream infections (CRBSI), which also affects the prognosis of patients severely. After literature review, this paper summarized the risk of PAC related infections, PAC retention and maintenance infection prevention measures, and existing problems in PAC related infection research. The progress of intervention measures was collected such as strict adherence to aseptic principles, use of maximum aseptic barrier, selection of arterial puncture site, ultrasound assisted visual puncture, combination of patch and assistant fixation device, shortening of catheter retention period, use of chlorhexidine patch, and regular education and training, to provide scientific and actionable practical guidance for the prevention and control of PAC related infections in clinical practice.

CircCDC42-encoded CDC42-165aa regulates macrophage pyroptosis in Klebsiella pneumoniae infection through Pyrin inflammasome activation

The circular RNA (circRNA) family is a group of endogenous non-coding RNAs (ncRNAs) that have critical functions in multiple physiological and pathological processes, including inflammation, cancer, and cardiovascular diseases. However, their roles in regulating innate immune responses remain unclear. Here, we define Cell division cycle 42 (CDC42)−165aa, a protein encoded by circRNA circCDC42, which is overexpressed in Klebsiella pneumoniae (KP)-infected alveolar macrophages. High levels of CDC42-165aa induces the hyperactivation of Pyrin inflammasomes and aggravates alveolar macrophage pyroptosis, while the inhibition of CDC42-165aa reduces lung injury in mice after KP infection by inhibiting Pyrin inflammasome-mediated pyroptosis. Overall, these results demonstrate that CDC42-165aa stimulates Pyrin inflammasome by inhibiting CDC42 GTPase activation and provides a potential clinical target for pathogenic bacterial infection in clinical practice.

Care bundles to reduce surgical site infections and promote positive outcomes

All surgical patients are at risk of surgical site infections which can cause serious wound healing complications. To improve patient care and promote good patient outcomes, veterinary nurses must be aware of the pathophysiology and clinical signs of surgical site infections, in addition to how to reduce the risks of surgical site infections in clinical practice. There are many evidence-based techniques that can be implemented to reduce the risk of surgical site infections; multiple techniques may be combined into a care bundle, a relatively novel concept in veterinary medicine. Individual practices should be aware of emerging techniques and implement care bundles that are most relevant to their surgical case load. This article discusses surgical site infections and considers the appropriateness and application of care bundles into veterinary practice through governance techniques.

Prevention and Risk Assessment of Cardiac Device Infections in Clinical Practice.

The implantation of cardiac electronic devices (CIEDs), including pacemakers and defibrillators, has become increasingly prevalent in recent years and has been accompanied by a significant rise in cardiac device infections (CDIs), which pose a substantial clinical and economic burden. CDIs are associated with hospitalizations and prolonged antibiotic therapy and often necessitate device removal, leading to increased morbidity, mortality, and healthcare costs worldwide. Approximately 1-2% of CIED implants are associated with infections, making this a critical issue to address. In this contemporary review, we discuss the burden of CDIs with their risk factors, healthcare costs, prevention strategies, and clinical management.

CLINICAL AND PHARMACOLOGICAL ASPECTS OF APPLYING GLUCOCORTICOSTEROIDS FOR SARS-COVID-2 INFECTION: REVIEW ARTICLE

In recent years, the SARS-CoV-2 pandemic has become one of the unexpected and very serious challenges for public health around the world. Moreover, SARS-CoV-2 infection led to the development of acute respiratory distress syndrome as a result of excessive systemic inflammation, and the development of multiple organ failure, and later death. Moreover, the problem of eliminating excessive systemic inflammation, that is, reducing the production of pro-inflammatory cytokines in SARS-CoV-2, remains open. In this regard, the use of glucocorticosteroids for infection caused by SARS-CoV-2 remains quite controversial. The basis for the routine use of steroids in intensive care protocols for SARS-CoV-2 is clearly insufficient and remains the subject of further research. This review provides an analysis of literary sources, guidelines, and modern international recommendations on pathogenetic therapy of SARS-CoV-2 to prevent and eliminate hyperproduction of pro-inflammatory cytokines using glucocorticosteroid agents. The purpose of the work is to conduct an analysis of modern literary sources regarding the modern features of the clinical and pharmacological justification of the use of glucocorticosteroids in SARS-CoV-2 infection in clinical practice. The analysis of the scientific literature demonstrates that today glucocorticosteroid therapy cannot be recommended for routine use in therapeutic practice in patients with SARS-CoV-2 infection. Thus, with a mild course of SARS-CoV-2 infection, when the patient does not need oxygen support, GCS therapy is contraindicated. With a severe course of SARS-CoV-2, when the patient develops acute respiratory distress syndrome with severe respiratory failure, when there is a need for oxygen therapy, mechanical ventilation or ECMO, the use of corticosteroids is extremely necessary, and may be recommended for mandatory use. There is a pressing need for a comprehensive definition of the optimal glucocorticosteroid agent, indications, dosage, and duration of use in SARS-CoV-2 infection therapy programs. This should be done while considering biomarkers of the severity of the inflammatory process and biomarkers of the body's response to glucocorticosteroid agents.

The small RNA PrrH aggravates Pseudomonas aeruginosa-induced acute lung injury by regulating the type III secretion system activator ExsA.

Pseudomonas aeruginosa is a Gram-negative bacterium and the leading cause of nosocomial pneumonia. The pathogenicity of P. aeruginosa is due to the secretion of many virulence factors. Small regulatory RNAs (sRNAs) regulate various bacterial adaptations, especially virulence. Therefore, understanding the mechanism by which sRNAs regulate virulence is necessary for understanding the pathogenicity of P. aeruginosa and the treatment of the related disease. In this study, we demonstrated that PrrH enhances the pathogenicity of P. aeruginosa by binding to the coding sequence regions of the ExsA, the master regulatory protein of type III secretion system, causing severe lung injury and exacerbating the inflammatory response and apoptosis. These findings revealed that PrrH is a crucial molecule that positively regulates ExsA. Type III-positive strains are often associated with a high mortality rate in P. aeruginosa infections in clinical practice. Therefore, this discovery may provide a new target for treating P. aeruginosa infections, especially type III-positive strains.

Sub-minimum inhibitory concentrations (sub-MICs) of colistin on Acinetobacter baumannii biofilm formation potency, adherence, and invasion to epithelial host cells: an experimental study in an Iranian children's referral hospital.

Here, we described the efficacy of colistin sub-minimum inhibitory concentrations (sub-MICs) on biofilm-forming activity, host epithelial cell adherence, and invasion capacity of Acinetobacter baumannii strains collected from children admitted to the Children's Medical Center Hospital. Biofilm formation potency of A. baumannii clinical isolates was measured using a 96-well microtiter plate assay. Distribution of biofilm-related genes, including bap, abaI, ompA, csuE, and blaPER-1, was detected by PCR. The mRNA expression level of ompA and csuE was measured by qPCR in the presence of ¼ and ½ MICs of colistin. A. baumannii adhesion and invasion to eukaryotic host cells were phenotypically assayed at sub-MICs of colistin. Eighty percent (56/70) and 35.7% (25/70) of A. baumannii isolates were multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes, respectively. The strong, moderate, and weak biofilm producers of A. baumannii were 37.1% (26/70), 32.8%, (23/70), and 22.8% (16/70), respectively. The frequencies of biofilm-associated genes were 100% for abaI, ompA, and csuE, followed by 22.8% (16/70) and 24.3% (17/70) for bap and blaPER-1, respectively. The downregulation of csuE and ompA expression levels was observed in the sub-MIC of colistin. In vitro cell culture study showed a decreased capability of A. baumannii to adhere to the human epithelial cells at sub-inhibitory doses of colistin; however, none of the isolates could invade HEp-2 cells. Our study showed that the genes encoding biofilm-associated proteins undergo downregulation in expression levels after exposure to sub-MICs of colistin in A. baumannii. Longitudinal in vivo studies are needed to fully understand the clinical aspects of pathogenicity mechanisms and evolutionary dynamics of drug resistance.IMPORTANCESince the toxicity of colistin is dose dependent, there is a focus on strategies that reduce the dose while maintaining the therapeutic effect of the drug. Our findings about sub-inhibitory doses of colistin provide a novel insight into the logical use of colistin to treat and control Acinetobacter baumannii-related infections in clinical practice.

Functional antimicrobial peptide-loaded 3D scaffolds for infected bone defect treatment with AI and multidimensional printing.

Infection is the most prevalent complication of fractures, particularly in open fractures, and often leads to severe consequences. The emergence of bacterial resistance has significantly exacerbated the burden of infection in clinical practice, making infection control a significant treatment challenge for infectious bone defects. The implantation of a structural stent is necessary to treat large bone defects despite the increased risk of infection. Therefore, there is a need for the development of novel antibacterial therapies. The advancement in antibacterial biomaterials and new antimicrobial drugs offers fresh perspectives on antibacterial treatment. Although antimicrobial 3D scaffolds are currently under intense research focus, relying solely on material properties or antibiotic action remains insufficient. Antimicrobial peptides (AMPs) are one of the most promising new antibacterial therapy approaches. This review discusses the underlying mechanisms behind infectious bone defects and presents research findings on antimicrobial peptides, specifically emphasizing their mechanisms and optimization strategies. We also explore the potential prospects of utilizing antimicrobial peptides in treating infectious bone defects. Furthermore, we propose that artificial intelligence (AI) algorithms can be utilized for predicting the pharmacokinetic properties of AMPs, including absorption, distribution, metabolism, and excretion, and by combining information from genomics, proteomics, metabolomics, and clinical studies with computational models driven by machine learning algorithms, scientists can gain a comprehensive understanding of AMPs' mechanisms of action, therapeutic potential, and optimizing treatment strategies tailored to individual patients, and through interdisciplinary collaborations between computer scientists, biologists, and clinicians, the full potential of AI in accelerating the discovery and development of novel AMPs will be realized. Besides, with the continuous advancements in 3D/4D/5D/6D technology and its integration into bone scaffold materials, we anticipate remarkable progress in the field of regenerative medicine. This review summarizes relevant research on the optimal future for the treatment of infectious bone defects, provides guidance for future novel treatment strategies combining multi-dimensional printing with new antimicrobial agents, and provides a novel and effective solution to the current challenges in the field of bone regeneration.

Odontogenic infections in the antibiotic era: approach to diagnosis, management, and prevention.

The prevalence of odontogenic infections remains one of the highest in the world. If untreated, odontogenic infections can break through the limitation, disseminate to other organs or spaces, and cause high mortality rates. However, it is still difficult to rapidly target limited or disseminated infections in clinical practice. The type of disseminated odontogenic infections and the responsible bacteria have not been described in detail. Search databases (e.g., PubMed, MEDLINE, Web of Science, Embase) for reports published from 2018.1 to 2022.9. Use search strategies: ("odontogenic infections" OR "pulpitis" OR "periapical lesions" OR "periodontal diseases") AND ("disseminated infections" OR "complication"). Fourteen different types of disseminated odontogenic infections, most of which are polymicrobial infections, can spread through the body either direct or through hematogenous diffusion. Multiple microbial infections can be more invasive in the transmission of infection. Secondary infections are commonly associated with bacteria like Fusobacterium spp., Streptococcus spp., Peptostreptococcus spp., Prevotella spp., and Staphylococcus spp. Antibiotics with broad-spectrum activity are fundamental as first-line antimicrobial agents based on the microorganisms isolated from disseminated infections. This review elaborates on the epidemiology, microorganisms, risk factors, and dissemination routes, and provides evidence-based opinions on the diagnosis, multidisciplinary management, and prevention of odontogenic infections for dentists and clinicians.

Determination of the Diagnostic Performance of Laboratory Tests in the Absence of a Perfect Reference Standard: The Case of SARS-CoV-2 Tests.

Currently, assessing the diagnostic performance of new laboratory tests assumes a perfect reference standard, which is rarely the case. Wrong classifications of the true disease status will inevitably lead to biased estimates of sensitivity and specificity. Using Bayesian' latent class models (BLCMs), an approach that does not assume a perfect reference standard, we re-analyzed data of a large prospective observational study assessing the diagnostic accuracy of an antigen test for the diagnosis of SARS-CoV-2 infection in clinical practice. A cohort of consecutive patients presenting to a COVID-19 testing facility affiliated with a Swiss University Hospital were recruited (n = 1465). Two real-time PCR tests were conducted in parallel with the Roche/SD Biosensor rapid antigen test on nasopharyngeal swabs. A two-test (PCR and antigen test), three-population BLCM was fitted to the frequencies of paired test results. Based on the BLCM, the sensitivities of the RT-PCR and the Roche/SD Biosensor rapid antigen test were 98.5% [95% CRI 94.8;100] and 82.7% [95% CRI 66.8;100]. The specificities were 97.7% [96.1;99.7] and 99.9% [95% CRI 99.6;100]. Applying the BLCM, the diagnostic accuracy of RT-PCR was high but not perfect. In contrast to previous results, the sensitivity of the antigen test was higher. Our results suggest that BLCMs are valuable tools for investigating the diagnostic performance of laboratory tests in the absence of perfect reference standard.