Abstract: This scoping review of original literature published before 1 March 2025 examined the de-mographic, clinical and simple laboratory findings associated with the development of severe leptospirosis. The definition of severe leptospirosis varied in different studies, but for the purposes of this review it included death or patients with a more complicated clinical course. There were 35 articles that satisfied the review’s inclusion criteria. Increasing age was asso-ciated with severe disease in 7 studies. Abnormal respiratory examination findings (18 stud-ies), hypotension (11 studies), oliguria (8 studies), jaundice (7 studies) and altered mental status (4 studies) also helped identify high-risk patients. Abnormal laboratory tests – specifi-cally the complete blood count (17 studies), measures of renal function (16 studies) and liver function (14 studies) – were also associated with severe disease. There was geographical heterogeneity in the clinical phenotype of severe disease, but the presence of hypotension, respiratory or renal involvement had prognostic utility in all regions. Simple bedside findings and basic laboratory tests can provide valuable clinical information in patients with lepto-spirosis. Integration of these indices into early risk stratification tools may facilitate recogni-tion of the high-risk patient and expedite escalation of care in resource-limited settings where most cases of life-threatening leptospirosis are seen.

Abstract:

Introduction: Chronic obstructive pulmonary disease (COPD) is a progressive condition and a leading cause of morbidity and mortality worldwide. The rate of forced expiratory volume in one second (FEV1) decline is a key prognostic marker. This study aimed to evaluate the impact of demographic, clinical, and therapeutic factors, including respiratory muscle strength and inhaled corticosteroid (ICS) use, on FEV1 decline.Methods: A prospective study was conducted in 2019 at the Clinic for Pulmonology, Clinical Center of Serbia. Fifty patients with stable COPD underwent spirometry, body plethysmography, respiratory muscle strength testing, and laboratory analyses. Demo-graphic and clinical data were collected via questionnaire. All assessments were repeated after six months of regular inhalation therapy.Results: Significant reductions were observed in FEV1, FVC, TLC, PImax, and PEmax. Lower baseline respiratory muscle strength predicted a faster FEV1 decline. Patients in GOLD stage 2 and those with greater hyperinflation exhibited accelerated functional deterioration. Therapy type affected selected parameters: LABA/ICS and LAMA/LABA/ICS regimens significantly reduced residual volume, but not the rate of FEV1 decline. Higher eosinophil counts were associated with a slower reduction in FEV1, suggesting a potential protective effect of ICS.Conclusion: Respiratory muscle strength, hyperinflation, and eosinophil count represent important predictors of COPD progression. Incorporating these parameters into diagnostic and therapeutic algorithms may improve early risk stratification and support indi-vidualized treatment strategies.

Abstract: Diffuse large B-cell lymphoma (DLBCL) is the most common and clinically aggressive subtype of non-Hodgkin lymphoma (NHL). Although novel therapeutic agents, in-cluding rituximab and polatuzumab vedotin, have improved outcomes, almost one-third of patients ultimately develop relapsed or refractory disease. MicroRNAs (miRNAs), a class of endogenous single-stranded RNAs approximately 22 nucleotides in length, play a pivotal role in the regulation of gene expression at the post-transcriptional level through interactions with complementary target RNAs and contribute significantly to the de-velopment, progression, and treatment response of DLBCL. Oncogenic miRNAs, such as miR-155, miR-21, and the miR-17–92 cluster, promote proliferation, survival, immune evasion, and therapy resistance by modulating pathways including PI3K/AKT, NF-κB, and MYC. Conversely, tumor-suppressive miRNAs such as miR-34a, miR-144, miR-181a, and miR-124-3p inhibit oncogene activity and enhance apoptosis, with their loss often associated with adverse outcomes. Among these, miR-155 and miR-21 are particularly well studied, playing central roles in both tumor progression and remodeling of the tumor microenvironment. This review summarizes current evidence on the biological and clinical relevance of miRNAs in DLBCL, emphasizing their diagnostic and prognostic potential.

Abstract: Background/Objectives: Next to malaria, respiratory viruses, particularly respiratory syncytial virus (RSV), are responsible for the hospitalization and death of thousands of young children each year in sub-Saharan Africa. During peak seasons, conducting separate tests is time-consuming and distressing. This underscores the need for efficient, rapid multiplexed diagnostic tools. This study evaluated the clinical performance of a lateral flow assay (LFA) based antigen combo rapid diagnostic test (ML Ag Combo RDT, manufactured by MobiLab) that detects RSV, influenza A and B, and SARS-COV-2. Methods: The Allplex rRT-qPCR assay was used as a reference assay to evaluate the clinical performance of the LFA Ag Combo RDT in pediatric hospital settings and performed using 470 nasopharyngeal swab (NPS) specimens from hospitalized children under two with respiratory symptoms. Results: Based on the comparative analysis of the testing results for 470 NPS, the ML Ag Combo RDT demonstrated high sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 90.06%, 98.33%, 93.45%, and 97.38% for RSV, and 71.43%, 100%, 100%, and 92.94% for influenza A/B, respectively. Agreement with the Allplex rRT-qPCR was strong (κ = 0.90 for RSV and 0.82 for Flu A/B), with overall accuracies of 96.60% for RSV and 94.47% for Flu A/B. This was further supported by ROC analysis for aggregated data (RSV and Flu) with an AUC value of 0.925. As expected, in samples with high viral loads (Ct < 20), the Ag Combo RDT achieved 100% sensitivity for RSV and Flu A/B. Sensitivity declined slightly at lower viral loads (Ct > 35). Conclusions: The ML Ag Combo RDT demonstrates high specificity and strong diagnostic accuracy for the detection of RSV and Flu A/B in pediatric hospital settings, where timely diagnosis is critical.

Abstract: Background: Rheumatoid arthritis (RA) is a chronic inflammatory condition affecting joints. It is managed with pharmacological therapies, but it is speculated that dietary intervention may be of significant benefit to patients in helping to manage the condition alongside their medication. This may be mediated through effects on levels of chronic inflammation and thus can influence disease activity. Previous research has indicated the potential of diet to aid in the condition’s management, but a comprehensive review is required to pull together the evidence. Objective: Conduct a systematic review of existing literature on the impact of differing dietary interventions on disease activity and inflammatory status in rheumatoid arthritis patients. Then draw conclusions about the strength of evidence and identify patterns amongst identified papers in a narrative synthesis. Methods: The existing literature was searched according to a pre-determined search strategy, using the databases PubMed, Embase and MEDLINE. Data was then extracted according to a template and results related in a narrative synthesis. Meta-analysis was not conducted. Results: Eight studies, all randomised controlled trials, were included in the review. Outcomes included disease activity score 28 and inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein. Dietary patterns such as an anti-inflammatory diet showed inconclusive evidence with regards to impact on disease outcomes. Strong evidence for the reduction of inflammation and disease activity was demonstrated in studies investigating probiotic supplementation. Conclusion: Results demonstrated the ability of probiotics to have a beneficial impact for RA patients, which may allow healthcare professionals to develop treatment plans and advice including this intervention. However more research should be conducted in different regions and in combination with other interventions to further the understanding of its effects and safety. Other dietary interventions included showed significant associations for some outcomes and not others. Therefore, further research should be conducted to determine whether they are feasible for use in the management of RA patients.

Abstract: T-2 mycotoxins are known to induce toxic effects in animals. Kidneys are highly susceptible to oxidative stress caused by toxins, leading to cellular injury, apoptosis, and altered cell cycle regulation. Critical regulators of these processes include tumor suppressor protein p53 and cyclin-dependent kinase inhibitor p21. As up to now knowledeges on immunolocalization of p53 and p21 during T-2 mycotoxicosis in avian kidney are limited, the study aims to investigate immunolocalization of two critical apoptosis regulatory proteins - p53 and p21 - in kidneys of broiler chickens exposed to T-2 mycotoxin. In the study ten 7-day-old female layer-type Ross chickens (Gallus gallus domesticus) were divided into control and T-2 toxin groups. For T-2 toxin group T-2 toxin was administered orally for three days. 24 hours after last dose, chickens were sacrificed, kidney tissues were collected and fixed for immunohistochemical staining. Immunohis-tochemical study using polyclonal primary antibodies p21 and p53 (Abcam, UK) revealed stronger expression of p53 and p21 in kidneys of T-2-treated chickens than in healthy chicken of control group. Both proteins localized mainly in renal proximal tubules’ epithelial cells. Increased expression of p53 and p21 highlights their role in T-2-induced renal toxicity and suggests potential biomarkers for early nephrotoxicity detection.

Abstract: Cardiac hypertrophy and fibrosis are hallmark responses to pressure overload, driving the progression of heart failure. Fucoidan, a sulfated polysaccharide derived from brown algae, has demonstrated anti-inflammatory and antioxidant effects in cardiovascular models. Building on prior evidence of its ability to suppress galectin-3 secretion and re-duce myocardial fibrosis, this study investigates the proteomic mechanisms underlying fucoidan’s cardioprotective actions in a murine model of transverse aortic constriction (TAC). Male mice subjected to TAC received either fucoidan or vehicle control. Cardiac function was evaluated via transthoracic echocardiography, and histological analyses quantified hypertrophy and fibrosis. Left ventricular tissues, enriched for fibroblasts and cardiomyocytes, underwent proteomic profiling using liquid chromatography–tandem mass spectrometry. Differentially expressed proteins were identified using stringent cri-teria (log₂ fold change < 0.58; P < 0.001). Fucoidan treatment significantly attenuated cardiac remodeling, with proteomic signatures revealing consistent upregulation of mi-tochondrial enzymes, ribosomal subunits, and cytoskeletal proteins in fucoidan-treated TAC mice compared to untreated controls. Enrichment analysis indicated activation of pathways related to energy metabolism, mitochondrial biogenesis, protein synthesis, and structural integrity. Notably, proteins involved in oxidative stress regulation, iron-sulfur cluster assembly, and extracellular matrix remodeling were restored toward baseline levels. These findings suggest that fucoidan mitigates pressure overload-induced cardiac remodeling through coordinated modulation of mitochondrial function, translational machinery, and cytoskeletal architecture. The study provides proteomic evidence sup-porting fucoidan as a promising marine-derived therapeutic candidate for heart failure.

Abstract: Human papillomavirus (HPV) plays a crucial role in the pathogenesis of oropharyngeal squamous cell carcinomas (OPSCC). Accurate HPV status classification is essential for therapeutic stratification. While p16 immunohistochemistry (IHC) is the clinical surrogate marker, it has limited specificity. In this study, we implemented a weakly supervised deep learning approach using the Clustering-constrained Attention Multiple Instance Learning (CLAM) framework to directly predict HPV status from hematoxylin and eosin (H&amp;E)-stained whole-slide images (WSIs) of OPSCC. A total of 123 WSIs from two cohorts (TCGA and OPSCC-UNINA) were used. Attention heatmaps revealed that the model predominantly focused on tumor-rich regions. Errors were primarily observed in slides with conflicting p16/ISH status or suboptimal quality. Morphological analysis of high-attention patches confirmed that cellular features extracted from correctly classified slides align with HPV status, with a Random Forest classifier achieving 83% accuracy at the cell level. This work supports the feasibility of deep learning-based HPV prediction from routine H&amp;E slides, with potential clinical implications for streamlined, cost-effective diagnostics.

Abstract: The chromatin remodelling proteins DAXX and ATRX are key regulators of ge-nome stability and epigenetic processes. Alterations in their expression have been as-sociated with tumour stage and prognostic outcomes in various humane cancer types, whereas their role in veterinary oncology has received little investigation to date. We analysed canine prostate and urinary bladder samples, including 18 prostate carcino-mas (12 adenocarcinomas, 6 prostatic urothelial carcinomas), 10 non-malignant pros-tate tissues, 22 carcinomas of the urinary bladder and 6 non-malignant bladder tissues. Nuclear expression of DAXX and ATRX was assessed using fully quantitative digital immunohistochemistry. Overall, DAXX exhibited consistently higher expression than ATRX across benign and malignant samples from the prostate and bladder. DAXX and ATRX expression demonstrated a positive correlation across all prostate (ρ = 0.692, p < 0.05) and bladder (ρ = 0.488, p < 0.05) samples, suggesting coordinated regulation. They displayed organ-specific expression patterns: prostate carcinomas showed increased expression of both proteins compared with non-malignant prostate tissues. In contrast, in the bladder, expression declined with increasing tumour aggressiveness (p < 0.05). Our findings provide new insights into the potential of DAXX and ATRX as bi-omarkers, offering new insights into their clinical relevance in dogs.

Abstract: Background: Fermentation is among the oldest and most versa-tile food processing techniques, enhancing not only shelf life but also nutritional and functional value. While Asian and Western fermented foods are extensively studied, traditional Eastern European fermentations—such as sauerkraut, kefir, bryndza, kvass, and sourdough—remain underexplored, despite their enduring cultural and dietary importance. These foods combine spontaneous or mixed-culture fermentations, diverse substrates, and unique microbial consortia that may yield distinct bioactive pro-files with potential health benefits. Methods: This narrative review synthesizes data from scientific articles, regional reports, and ethnographic sources retrieved from PubMed, Scopus, and Google Scholar up to 2025. Studies were selected for relevance to composition, microbiology, bioactive compounds, and human or experimental health outcomes related to Eastern European fermented foods. Results: Evidence indicates that traditional fermented dairy, ce-real, and vegetable products contain bioactive peptides, poly-phenols, vitamins, organic acids, and live or non-viable micro-organisms contributing to antioxidant, antihypertensive, immunomodulatory, and metabolic effects. Mechanistic studies support the generation of ACE-inhibitory peptides, microbial vitamins, and prebiotic/postbiotic compounds. However, variability in artisanal production and the scarcity of standardized human trials limit definitive conclusions. Conclusions: Eastern European fermented foods represent a culturally unique yet scientifically under characterized component of functional nutrition. Their complex microbial ecosystems and diverse substrates offer valuable models for studying diet–microbe interactions. Further omics-based and clinical research is warranted to clarify bioavailability, mechanisms of action, and their potential integration into evidence-based dietary strategies.

Abstract: Background: Histologic healing is increasingly recognized as a sensitive marker of disease remission in ulcerative colitis (UC). However, the dynamics of mucosal T lymphocytes and pro-inflammatory cytokines during healing remain incompletely understood. Methods: In this observational, cross-sectional study, paired colonic biopsies from 20 adult UC patients were analyzed during active inflammation and subsequent histologic healing. Immunohistochemistry was performed for CD3, CD4, CD8, and IL-6. Lymphocyte densities were quantified in intraepithelial and lamina propria compartments, while IL-6 expression was scored semi-quantitatively. Histologic activity was assessed using the Geboes score. Results: Intraepithelial CD4⁺ T cells significantly decreased during histologic healing (mean 6.8 → 3.75 cells/HPF, p < 0.05), whereas lamina propria CD4⁺ cells remained variably persistent, suggesting ongoing immune regulation. Intraepithelial CD8⁺ cells increased during remission, indicating a potential reparative or surveillance role. IL-6 expression markedly declined in epithelial and stromal compartments during healing, reflecting resolution of mucosal inflammation. Correlation analyses revealed enhanced coordination between CD4⁺ and CD8⁺ cells in the healing phase, consistent with immune homeostasis. Conclusions: Histologic healing in UC involves compartment-specific shifts in T lymphocyte populations and a marked reduction of IL-6 expression, reflecting coordinated immune regulation beyond clinical remission. These findings highlight the potential of combined cellular and cytokine biomarkers to monitor mucosal healing and guide immunomodulatory therapies.

Abstract:

Background and Objectives: With more than 1.9 million new cases and 0.9 million deaths in 2020, colorectal cancer (CRC) was the third most common cancer and the second most common cause of cancer mortality worldwide. The adenoma detection rate as a precursor to the formation of CRC is directly related to the degree of bowel preparation for colonoscopy.Materials and Methods: This is a retrospective single-center study on a total number of 4835 colonoscopies performed in a period of 34 months during the global COVID-19 pandemic.The main goal of the research was related to the emergence of differences in cleaning in relation to gender, age, days of preparation, the type of cleaning agent.Results: There is no signification difference between gender. Compared to younger respondents, older respondents had a lower likelihood of having adequate bowel preparation. Compared to PEG, other solutions had a lower probability of adequate bowel preparation.Conclusions: Better cooperation between patients and medical staff is needed, as well as public health campaigns that raise awareness of the importance of good preparation for colonoscopy.

Abstract: Resistant hypertension (HTN) affects up to 20% of patients who fail to achieve blood pressure (BP) control despite standard triple-drug therapy. As pharmacological treatments remain inadequate for these patients, baroreflex activation therapy (BAT) has emerged as a promising nonpharmacological alternative. By electrically stimulating baroreceptors in the carotid sinus, BAT restores autonomic balance through increased parasympathetic and reduced sympathetic activity, resulting in substantial BP reductions. Modern implantable devices such as the Rheos® and BAROSTIM NEO® systems have demonstrated significant and sustained decreases in both systolic and diastolic BP in treatment-resistant HTN, as well as clinical benefits in heart failure and end-stage renal disease. Despite these advances, BAT remains limited by its surgical invasiveness, adverse effects, and narrow patient eligibility. Ongoing research aims to develop less invasive stimulation methods and refine patient selection criteria. Large-scale, randomized, double-blind trials are still needed to establish BAT’s long-term safety, efficacy, and clinical applicability. Overall, BAT represents an innovative, device-based therapeutic strategy for managing resistant hypertension.

Abstract: Background/Objectives: Cabozantinib is widely used as a subsequent-line therapy after immune checkpoint inhibitor (ICI) treatment in metastatic renal cell carcinoma (mRCC), yet reliable on-treatment biomarkers are lacking. This study evaluated the prognostic value of a composite score combining early changes in serum albumin (ΔAlb) and the systemic immune–inflammation index (ΔSII) during cabozantinib therapy. Methods: We retrospectively analyzed 40 patients with mRCC who received cabozantinib after prior ICI therapy. Alb and SII were measured at baseline and 6 weeks after initiation. Patients were classified into three categories according to the ΔAlb + ΔSII composite: both favorable, either unfavorable, or both unfavorable. Progression-free survival (PFS) was analyzed using Kaplan–Meier and Cox regression models. Results: Among 38 evaluable patients, PFS significantly differed across composite categories (p for trend < 0.05). Patients with both favorable changes achieved notably longer PFS, while those with both unfavorable changes experienced the shortest. Compared with the both-favorable group, the “either” and “both unfavorable” groups had shorter PFS (HR = 1.83, 95% CI 0.61–5.46; HR = 6.27, 95% CI 1.61–24.49). Conclusions: Early on-treatment changes in Alb and SII (ΔAlb + ΔSII composite) were associated with prognosis in ICI-pretreated mRCC treated with cabozantinib, warranting prospective validation.

Abstract: Inborn errors of amino acid metabolism (IEAAMs) are a heterogeneous group of genetic disorders caused by defects in enzymes, cofactors, or transporters of amino acid catabolism, biosynthesis, or transport. These defects result in toxic metabolite accumulation and/or deficiency of essential metabolites. This review aims to provide an updated overview of diagnosis, clinical implications, management, and evolving therapeutic approaches across major IEAAMs. A narrative review of recent literature was undertaken, focusing on established and novel therapeutic strategies for key IEAAMs, including phenylketonuria, alkaptonuria, tyrosinemia, homocystinuria, and maple syrup urine disease. Key management strategies include amino acid-restricted diets/restriction of natural protein with restriction of dietary precursors, dietary supplementations, including disease-specific amino acid supplements, medications to reduce formation of offending metabolites, pharmacotherapies, enzyme/cofactor replacement or pharmacological chaperones, enhancing residual enzyme activity and promoting alternative path-ways/accessory pathways. Emergency therapy is essential in severe types and focuses on promoting anabolism, limiting catabolism, reducing formation, and enhancing clearance of toxic metabolites. Other treatment options include organ transplantation, and new emerging modalities, such as mRNA therapies and gene therapies/in vivo gene editing offer potential for definitive interventions. Despite advancements in therapy and close monitoring, many IEAAMs remain associated with significant comorbidities. Future research is essential to optimise current treatment standards, particularly neuroprotective and metabolic regulatory features. While an in-depth discussion of innovative person-alised therapies is beyond the scope of this article, we believe that collective experiences will thrust future research in this field and expand access to innovative personalised therapies.

Abstract: The diagnosis and management of UAD require an integrated, multidisciplinary approach. Diagnostic strategies combine clinical evaluation, imaging (CT), allergy testing, biomarker measurement (such as FeNO, blood eosinophils, IgE), and pulmonary function testing (spirometry, IOS) to phenotype the disease. Therapeutic management is stratified and aims to control inflammation and symptoms in both compartments. Cornerstones include topical corticosteroids (intranasal and inhaled) and saline irrigations. For severe forms, especially T2-high, targeted biologic therapies (anti-IL-5/IL-5R, anti-IL-4R, anti-TSLP) have revolutionized treatment, reducing dependence on oral corticosteroids and the need for surgical interventions (like endoscopic sinus surgery, ESS). Adopting a "treatable traits" approach is emerging as a key strategy for precision medicine in UAD.

Abstract: Healthcare data is experiencing one of the highest growth rates of any major data sector, driven primarily by rapid advances in genomics, medical imaging, and continuous data from wearable devices. The convergence of universal data standards in healthcare (terminologies, OpenEHR, FHIR, and OMOP) is now providing the common ground needed to translate this data into tangible medical advances through a wide array of different applications. Together with a growing ecosystem of analytics, predictive models, and advanced artificial intelligence tools, this synergy is poised to fundamentally transform the delivery of healthcare. With the maturation of health information technology and proliferation of research in the field, the pivotal challenge has shifted from technological capability to the pervasive inability to implement solutions effectively in routine practice, particularly those tailored to diabetic foot-specific needs. In the context of diabetic foot care, where the paramount goals are patients' well-being, tissue preservation, and amputation prevention, collaborative data management must be recognized as a critical treatment modality itself. “Data is tissue,” it is the foundational element that enables the timely, coordinated, and evidence-based interventions necessary for success. This paper highlights some of the opportunities presented by modern data methodologies to address the current implementation gap.

Abstract: Background/objectives: Studies evaluating the longitudinal impact (beyond a decade) of Antibiotic stewardship programs (ASP) strategies on the volume/quality of antibiotic prescriptions, as well as impact on antimicrobial resistance are lacking. Since 2008, the ASP at Singapore General Hospital had implemented various strategies in the following phases: 1) initiation; 2) expansion; 3) optimisation; and 4) innovation. In this study, we aim to evaluate the impact of ASP on the volume/quality of antibiotic prescribing and susceptibility trends of clinically significant Gram-negative bacilli (GNB). Methods: We conducted a single-center, retrospective observational study from 2011 to 2024. Antibiotic consumption, appropriateness and susceptibility trends of 6 GNBs to 7 commonly used antibiotics were analysed using Kendall tau test. Results: We demonstrated sustained improvement in appropriateness of 7 broad-spectrum IV antibiotics, accompanied by significant reductions in IV ciprofloxacin, cefepime and, ertapenem use (p &lt; 0.05). Hospital-wide susceptibility of 6 GNBs to all evaluated antibiotics improved significantly (p &lt; 0.05), except for E. coli susceptibility to ertapenem and Enterobacterales susceptibility to ciprofloxacin. Conclusion: An evolving multi-pronged antibiotic stewardship approach improved antibiotic prescribing and GNB susceptibility towards majority of the antibiotics. In a rapidly evolving healthcare landscape, ASPs must remain agile, continually refining priorities and employing innovative strategies.

Abstract: A 15-year-old female developed refractory Complex Regional Pain Syndrome (CRPS) Type I of the left hand following metacarpal fixation. Conservative therapy and hand rehabilitation failed, resulting in persistent allodynia and functional loss. She was admitted for multimodal analgesia combining subanesthetic ketamine infusion, gabapentin, and a tunneled supraclavicular continuous nerve catheter delivering ropivacaine. Pain decreased from 7/10 at rest to 0/10 within 48 hours. Allodynia has resolved, and motor function has fully recovered. The catheter was removed nine days later without complication, and pain remission persisted. This case demonstrates a safe and effective multimodal strategy for adolescent CRPS integrating central and peripheral desensitization mechanisms.

Abstract: Background/Objectives: Almost all orthopedic infections require a combination of surgi-cal debridement with targeted antimicrobial treatment. The number of debridement may vary considerably between infection episodes. The case-mix is enormous and so-called "second looks" are frequent. We investigate which bacteria are associated with second looks to achieve local infection control. Methods: We used a composite database stem-ming from three prospective randomized-controlled trials (RCTs) 2019-2025 with proto-colled surgical debridement (initial debridement). In these RCTs, we allowed additional debridement only in case of persistent (during several days) or progredient local infection. Results: Overall, 201/1,067 (18.8%) orthopedic infections required multiple debridement (median two second looks, range 2–8 surgeries). Gram-negative pathogens revealed the highest risk for "second looks" (28.2%), followed by implant-related infections (25.4%). Cutibacteria yielded the lowest risk (11.7%). In the multivariable logistic regression model, Gram-negative infections (odds ratio 2.04, 95%CI 1.20-3.47) and infected implants (OR 2.18, 95%CI 1.56-3.03) were independently associated to multiple interventions, in con-trast to Staphylococcus aureus, enterococci or streptococci. Conclusions: When analyzing orthopedic infections included in prospective RCTs, Gram-negative pathogens groups significantly associate with the need for second looks, which matches our own experience. Today findings support preoperative counseling, antibiotic stewardship, and operative planning for a staged management in infection cases with a high risk of clinical failure. Trials registrations: NCT04048304, NCT04081792, NCT05499481.