Search Results (1,008)

Metastatic pancreatic ductal adenocarcinoma (PDAC) is typically treated with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel (GnP), but the choice between regimens remains largely empirical. This narrative review summarizes biomarkers with potential to inform first-line selection in metastatic PDAC, emphasizing genomic and transcriptomic correlates of differential benefit. Recent head-to-head trials, particularly Pancreatic Adenocarcinoma Signature Stratification for Treatment (PASS-01) and GENERATE (Japan Clinical Oncology Group [JCOG] 1611), indicate that modified FOLFIRINOX (mFOLFIRINOX) is not uniformly superior to GnP, strengthening the rationale for biomarker-guided selection. The strongest evidence favoring platinum-based/FOLFIRINOX strategies involves homologous recombination repair deficiency (HRD), especially alterations in germline breast cancer gene 1/2 (BRCA1/2) or partner and localizer of BRCA2 (PALB2), as well as broader genomic scar signatures. Transcriptomic subtype and GATA-binding protein 6 (GATA6) expression are promising but remain unsettled because retrospective data favor classical/GATA6-high disease for FOLFIRINOX, whereas PASS-01 suggested better outcomes with GnP in classical tumors. Candidate biomarkers favoring GnP include high human equilibrative nucleoside transporter 1 (hENT1), low class III β-tubulin (TUBB3) expression, and exploratory phosphatidylinositol 3-kinase (PI3K)/KIT/NOTCH pathway mutation signals. Comprehensive molecular profiling also identifies actionable alterations that may redirect patients to targeted therapy or clinical trials rather than standard chemotherapy alone. Importantly, no biomarker has yet been prospectively validated in a biomarker-stratified randomized trial with regimen selection as the primary endpoint; all biomarker-regimen associations described in this review should therefore be considered hypothesis-generating rather than practice-defining. Nevertheless, the convergence of genomic, transcriptomic, and organoid-based approaches makes biologically informed first-line selection increasingly feasible in metastatic PDAC. Full article

Background/Objective: Respiratory syncytial virus (RSV) is an often under-recognized cause of respiratory illness in older adults. Clinical overlap with bacterial infections and delayed virologic confirmation may lead to the unnecessary prescription of antibiotics and antimicrobial resistance (AMR). This systematic review was conducted to assess antibiotic prescription in older adults with RSV and the factors influencing these decisions. Methods: This systematic review was preregistered in PROSPERO (CRD42024586905) and reported according to PRISMA guidelines. PubMed/MEDLINE, Embase, Web of Science, Cochrane CENTRAL, and Scopus were searched for studies published between January 2000 and August 2025. Eligible studies were those including adults aged ≥60 or ≥65 years with RSV infection and reporting antibiotic use. Data on antibiotic prescription, confirmed bacterial infection, hospitalization, length of stay (LOS), and prescribing indications were extracted. Results: Eight observational studies across inpatient, outpatient, emergency, and primary-care settings were included. Antibiotic prescribing ranged from 40.0% to 97.7%, whereas confirmed bacterial infection did not exceed 20% in any study. Antibiotic prescribing was associated with diagnostic uncertainty, radiologic findings, inflammatory markers, respiratory distress, delayed RSV testing, and multimorbidity rather than microbiological confirmation. Hospitalization rates varied across settings, and the LOS ranged from 3.5 to 11 days. None of the studies reported antibiotic discontinuation following RSV confirmation. Conclusions: Older adults with RSV frequently receive antibiotics despite low rates of confirmed bacterial infection, indicating substantial empirical prescribing. Improved rapid diagnostics, reassessment of therapy, and strengthened antimicrobial stewardship may help reduce unnecessary antibiotic use. RSV vaccination may be a promising strategy for reducing severe disease and hospitalization, with a potential indirect effect on antibiotic use, although these effects remain hypothetical. Full article

Recurrent pericarditis (RP) remains challenging, especially in tuberculosis (TB)-endemic regions where empirical anti-TB therapy is often unnecessarily prolonged. We report a 35-year-old woman with three RP episodes over six months, presenting with pleuritic chest pain, elevated inflammatory markers, and moderate-to-large pericardial effusion. Extensive infectious (including TB), autoimmune, and malignancy workups were negative. Cardiac magnetic resonance revealed persistent pericardial late gadolinium enhancement despite clinical remission. Whole-exome sequencing identified a heterozygous MEFV c.442G>C (p.Glu148Gln) variant, suggesting an autoinflammatory predisposition. Although the patient finally achieved sustained symptom-free status for six months on a standardized low-dose colchicine regimen, still over 10% of patients have recurrent symptoms receiving colchicine in addition to conventional anti-inflammatory therapy with aspirin or ibuprofen. This case highlights the shifting paradigm from an infection-centered to an autoinflammatory framework for RP in TB-endemic countries, underscores the role of MEFV variants in idiopathic recurrent pericarditis, and illustrates the real-world gap between genetic insights and therapeutic accessibility to IL-1 inhibitors in resource-limited settings. Full article

Background: Necrotizing fasciitis (NF) is a rapidly progressive, life-threatening soft tissue infection characterized by fascial necrosis, with mortality rates of 20–30%. Despite its rarity, NF is increasingly encountered due to the rising prevalence of predisposing factors. Data from Southern European tertiary centers remain scarce. Methods: We retrospectively reviewed all patients ≥18 years with radiological and/or surgical diagnosis of NF managed at IRCCS Policlinico San Matteo, Pavia, Italy, between November 2018 and August 2023. Clinical, microbiological, and treatment data were extracted from electronic medical records. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score was calculated retrospectively. The Charlson Comorbidity Index was computed for each patient. Given the small sample size, we adopted a purely descriptive analytical approach without inferential testing. Results: Thirteen patients met inclusion criteria (median age 58 years, IQR 44.5–79.5; 69.2% male). The most common comorbidities were diabetes mellitus (6/13, 46.2%), renal failure (4/13, 30.8%), and chronic liver disease (4/13, 30.8%). The age-adjusted Charlson Index ranged from 0 to 11 (median 4). Lower limbs were the most frequently affected anatomic site (5/13, 38.5%), followed by the perineal/genital region (Fournier gangrene, 4/13, 30.8%). Type II (monomicrobial) NF predominated (9/13, 69.2%). Microbiological cultures were positive in 8/13 patients (61.5%): Gram-positive cocci were isolated in 5/8 (62.5%) and mixed aerobic/anaerobic flora in 3/8 (37.5%). Empirical antibiotic regimens included a piperacillin–tazobactam backbone in 6/12 (50.0%) patients and a meropenem-based combination in 5/12 (41.7%); 6/12 patients underwent targeted de-escalation after culture results. Two patients (15.4%) died in hospital, both with Fournier gangrene and Type I infection (mortality 2/4, 50.0% in Type I vs. 0/9 in Type II). The median length of stay was 26 days (IQR 17–28.5). All patients had LRINEC ≥6 at admission, with 9/13 (69.2%) classified as high risk (≥8). Conclusions: In this small retrospective Italian cohort, NF was most frequently associated with diabetes and high comorbidity burden. Type I (polymicrobial) infections, predominantly involving the perineal region, showed worse outcomes than Type II infections. The clinical experience accumulated during this study period subsequently informed the development of an institutional empirical antimicrobial protocol for skin and soft tissue infections at our hospital. Full article

Rising antimicrobial resistance has reduced the effectiveness of empirical eradication regimens for Helicobacter pylori (H. pylori) infection, particularly those containing clarithromycin. Local resistance surveillance and identification of clinical predictors of resistance are essential to guide treatment strategies. This study evaluated antimicrobial resistance patterns and clinical determinants of resistance in a real-world tertiary-care cohort. A retrospective observational study was performed, which included 352 adult patients with confirmed H. pylori infection managed between November 2022 and November 2025. Of these, 168 patients underwent culture and antibiotic susceptibility testing, while 184 received empirical therapy. Resistance rates were calculated according to the number of isolates tested for each antimicrobial agent (available-case analysis). Multivariable logistic regression analysis was used to identify independent predictors of resistance. Among susceptibility-tested patients, resistance to at least one antimicrobial agent was detected in 44.6%. Clarithromycin resistance was most frequent (42.5%), followed by metronidazole (36.4%) and levofloxacin (14.0%), whereas amoxicillin resistance remained low (2.4%). Multidrug resistance (MDR) based on available susceptibility data was observed in 12.5% of cases, most commonly involving dual clarithromycin–metronidazole resistance. Prior eradication therapy was independently associated with resistance (adjusted Odds Ratio aOR 2.41; 95% Confidence Interval CI 1.29–4.51; p = 0.006), while demographic factors were not. Clarithromycin resistance substantially exceeds recommended thresholds for empirical triple therapy in this setting. Prior eradication therapy is the principal predictor of resistance, supporting resistance-informed and stewardship-oriented management strategies. Full article

Background: Strongyloides stercoralis is a soil-transmitted helminth capable of establishing chronic infection through an autoinfective cycle, with the potential to progress to life-threatening hyperinfection, particularly in immunocompromised individuals. Case Presentation: We report the case of a 70-year-old man from an endemic region in Colombia with metastatic urothelial carcinoma who developed hyperinfection syndrome following corticosteroid therapy for spinal cord compression. The patient presented with progressive respiratory failure and diffuse alveolar hemorrhage. Chest imaging showed bilateral ground glass opacities, and bronchoalveolar lavage revealed numerous larvae consistent with S. stercoralis, confirming the diagnosis. Despite supportive care and broad-spectrum antimicrobial therapy, the patient experienced rapid clinical deterioration and died. Conclusions: This case highlights the importance of considering strongyloidiasis in the differential diagnosis of diffuse alveolar hemorrhage in endemic settings, particularly in patients receiving corticosteroids. Early recognition and timely treatment are essential to reduce the high associated mortality. Preventive strategies, including targeted screening or empiric ivermectin administration prior to immunosuppression, should be considered in high-risk populations. Full article

Immunotherapy with immune checkpoint inhibitors (ICIs) has profoundly transformed the therapeutic landscape of lung cancer. Although ICIs are generally associated with a more favorable toxicity profile compared with traditional chemotherapy, rare and potentially severe immune-related adverse events (irAEs) may occur, sometimes posing significant diagnostic challenges. We report a case of macrophage activation syndrome (MAS) following a single administration of the anti-PD-L1 antibody atezolizumab in a patient with advanced non-small-cell lung cancer (NSCLC). A 62-year-old woman was diagnosed in February 2024 with stage IIIB NSCLC according to the 8th TNM classification. The patient was deemed ineligible for radiotherapy because of previous thoracic irradiation for breast cancer. First-line therapy with carboplatin plus pemetrexed was administered from March to June 2024, resulting in stable disease; this was followed by pemetrexed maintenance from July to October 2024, at which time thoracic disease progression was documented. Second-line treatment with atezolizumab was initiated in November 2024. Ten days after the first infusion, the patient was admitted to the emergency department for fever and confusion. Laboratory investigations revealed markedly elevated C-reactive protein and hyperferritinemia. Despite empirical antibiotic therapy, fever and thrombocytopenia persisted. Bone marrow biopsy demonstrated findings consistent with MAS. Corticosteroid therapy with prednisone at 1 mg/kg was promptly initiated under rheumatologic supervision, leading to a rapid clinical and biochemical improvement. During tapering, inflammatory markers relapsed when prednisone was reduced to below 12.5 mg/day. Given the occurrence of a grade 4 (CTCAE v5.0) immune-related adverse event, atezolizumab was permanently discontinued. The patient remains in follow-up without radiological evidence of disease progression. This case highlights the diagnostic challenge of MAS secondary to ICIs, which may initially present with nonspecific symptoms such as fever, confusion, and elevated inflammatory markers. Early recognition and timely initiation of high-dose corticosteroids were essential for effective management and full recovery. Clinicians should maintain a high index of suspicion for MAS among rare but severe hematologic irAEs during immunotherapy. Full article

Spinal infections in general, and infectious spondylodiscitis in particular, are increasingly diagnosed in the Western world, in recent decades. This rise in incidence is associated with an ageing population and with an increased availability of accurate diagnostic modalities. Even so, due to the non-specific nature of clinical manifestations, and of the implicated blood and serum markers, there is a risk of underdiagnosis or misdiagnosis of the disease in its initial stages. Ionizing radiation methods, such as plain radiography (X-ray) and computed tomography (CT), are also not reliable in the early stages of the diseases, and the golden standard of imagistic diagnosis, magnetic resonance imaging (MRI), is not always available or requested. Still, MRI remains the most reliable method in most cases where there is a need for differential diagnosis with other pathologies, namely Andersson lesions, destructive spondyloarthropathy, erosive osteochondritis, micro-crystalline spondylitis, Modic 1 lesion, Charcot spinal arthropathy, osteoporotic fractures, SAPHO syndrome with spinal involvement, and Schmorl’s nodes. Infectious spondylodiscitis is caused by bacteria, and, less frequently, by fungi. Rare cases of parasitic causes have also been reported in the literature. Infectious spondylodiscitis of bacterial causes may be pyogenic, more frequently caused by Staphylococcus spp. or Streptococcus spp., or granulomatous, usually caused by Mycobacterium tuberculosis complex (MTBC) or from classical brucellosis. In all these cases, therapy may be conservative, with antibiotics, or surgical, when the former fails or in patients with significant spinal instability or other neurological manifestations. There are various surgical approaches, each with its own drawbacks, and usually used according to the preference of the attending physician. Even in cases of surgical treatment, antibiotic administration is prolonged, and it is important for a proper scheme to be selected based on antimicrobial susceptibility testing. However, given that in many cases, the causative agent cannot be identified, empirical treatment must be initiated. Finally, newer approaches, including the incorporation of antimicrobial substances, may offer better solutions for improving treatment and rehabilitation outcomes. Full article

Background/Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKp) remains a critical driver of antimicrobial resistance (AMR) in hospital settings worldwide. Methods: This study examined trends in CRKp bloodstream infections over a seven-year period (2019–2025) in a tertiary care hospital in Greece, with particular attention given to resistance patterns and patient outcomes, including the impact of the COVID-19 pandemic. Results: A total of 671 non-duplicate CRKp isolates were analyzed and classified into three groups: KPC producers (67.4%), dual carbapenemase producers (dual CP) (17.4%), and single metallo-β-lactamase (MBL) producers (15.2%). Overall incidence showed a slight but non-significant increase over time. KPC-producing strains rose significantly until 2022 (p < 0.001), followed by a marked decline (p < 0.001). In contrast, dual CPs—mainly KPC combined with VIM or NDM—and single-MBL producers, particularly NDM, increased steadily, indicating a notable epidemiological shift. Resistance to aminoglycosides and tigecycline increased around 2021, followed by partial declines, whereas colistin resistance demonstrated a continuous upward trend throughout the study period. Despite phenotypic differences, overall mortality remained high, with no statistically significant differences between groups (p = 0.37), likely reflecting either the severity of patients’ clinical condition or inadequate empirical antibiotic therapy. Conclusions: This study highlights a dynamic evolution in CRKp epidemiology with decreasing KPC dominance and increasing prevalence of MBL- and dual CP strains. This transition, which became evident during and after the COVID-19 pandemic, underscores ongoing epidemiological adaptation and the urgent need for improved antimicrobial stewardship, rapid diagnostics, and broader access to effective therapies. Full article

Background/Objectives: Acanthamoeba keratitis (AK) is a rare but sight-threatening corneal infection. This study reviews the clinical profile, diagnostic pathways, treatment strategies, and outcomes of AK cases managed over a 34-year period. Methods: We conducted a retrospective analysis of 52 microbiologically AK cases from 1983 to 2017. Results: The mean age at presentation was 27.7 ± 9.4 years, with a female predominance (63.5%). The majority (82.7%) were contact lens users, almost exclusively soft lens wearers, with documented risk behaviors such as poor hygiene and sleeping with lenses. 44.2% were initially misdiagnosed as nonspecific microbial keratitis. Common clinical findings included epithelial defects (30.8%), ring infiltrates (44.2%), superficial infiltrates (53.8%), hypopyon (30.8%), and corneal thinning (13.5%). Diagnosis was confirmed by culture/stain in 61.5% of cases, while others required confocal microscopy or corneal biopsy. Co-infections with bacteria were noted in ~20%. Prior to referral, 82.7% of patients had received empirical topical therapy. At KKESH, all received dual anti-Acanthamoeba therapy, and 69.2% underwent surgical intervention, including tectonic PKP (46.2%) and optical PKP (19.2%). Visual acuity improved from a mean logMAR of 1.51 at presentation to 0.87 at last follow-up. Anti-Acanthamoeba therapy was discontinued in 95.9% of patients by the end of follow-up, with steroid use tapering from 61.5% at 3 months to 16.3% at final visit. Conclusions: Acanthamoeba keratitis in Saudi Arabia predominantly affects young female contact lens users and often presents with diagnostic delays and misclassification as herpetic or bacterial keratitis. Despite aggressive medical and surgical therapy, visual outcomes remain suboptimal in many cases. Full article

Acute chest syndrome (ACS) is a common pulmonary complication in children with sickle cell disease, defined by a new pulmonary infiltrate on imaging accompanied by fever and/or respiratory symptoms. ACS pathophysiology is multifactorial and incompletely understood, involving vaso-occlusion, pulmonary infarction, inflammation, hypoventilation, and infection—the latter being a frequent trigger in children. While most pediatric cases are mild, ACS can be life-threatening and requires prompt diagnosis and management to prevent progression into respiratory failure. Mild cases are managed with pain control, IV hydration, empiric antibiotics, incentive spirometry, and supplemental oxygen when needed. More severe cases may require simple or exchange transfusion to reduce hemoglobin S levels and limit further vaso-occlusion. ACS is associated with neurologic events and long-term pulmonary complications, making prevention a clinical priority. Disease-modifying therapies include hydroxyurea and chronic transfusion. This review summarizes current evidence on the pathophysiology, risk factors, clinical presentation, diagnosis, acute management, and preventative therapies for ACS in children. Full article

Background: Infection following total knee arthroplasty (TKA) is a challenging complication. Optimal empirical antibiotic therapy and surgical management hinge on up-to-date knowledge of local pathogen distribution and resistance patterns. However, few studies have examined whether geographical factors, specifically rural versus urban residence, influence the microbiology or clinical outcomes of periprosthetic joint infection (PJI) within integrated healthcare systems. The goal of this study was to assess the temporal evolution of bacterial species and antimicrobial resistance in knee PJI over an 11-year period. As a secondary objective, we wanted to evaluate the potential impact of patient residence on microbiological trends and treatment success. Methods: We conducted a retrospective analysis of all patients diagnosed with knee PJI who underwent surgical treatment between 2013 and 2023 at our center. Infections were classified as acute postoperative, acute hematogenous, or chronic. Patient residence was categorized as rural (<5000 inhabitants) or urban. Temporal trends were modeled using Poisson regression, and comparisons between subgroups were performed using Fisher’s exact test and Student’s t-test. Results: A total of 98 patients were analyzed, with 99 microorganisms identified. Gram-positive organisms predominated (72.3%), with Staphylococcus aureus (33.3%) and Coagulase-negative Staphylococci (CoNS) (29.3%) as the most frequent isolates. Resistance to vancomycin was not detected in S. aureus isolates. However, CoNS demonstrated high resistance to fluoroquinolones (55.2%) and rifampicin (20.7%). No significant annual shifts were observed for Gram-positive (IRR = 0.94; 95% CI: 0.86–1.03; p = 0.413) or Gram-negative cases (IRR = 0.75; 95% CI: 0.53–1.05; p = 0.086). Comparing rural versus urban populations, no differences were found in microbiological profiles (Fisher’s exact test, all p > 0.05). Furthermore, clinical treatment success rates were comparable (Rural 69.4% vs. Urban 63.0%, p = 0.500), despite a significantly higher prevalence of diabetes mellitus in rural patients (34.7% vs. 10.2%, p = 0.007). Conclusions: The microbiological landscape of knee PJI has remained stable, with no emergence of multidrug-resistant S. aureus. In our setting, standardized management protocols appeared to be equally effective regardless of patient residence. However, given the single-center nature and sample size of this study, broader multicenter validation is required before these findings can be generalized. Full article

Background/Objectives: Biosimilars are medicinal products derived from reference biologics and designed to demonstrate a high degree of similarity in quality, efficacy, safety, and immunogenicity. Machine learning (ML) and other artificial intelligence (AI) methodologies have emerged as important tools in this field in biosimilar research and development. This systematic review identifies ML applications throughout the biosimilar lifecycle while distinguishing them from the broader AI literature and from health technology evaluation, economic, and decision-analytic studies. Methods: Following PRISMA, records were retrieved from Scopus, PubMed, and Web of Science. After applying predefined inclusion and exclusion criteria, 44 original peer-reviewed studies were selected. Only studies that implemented a data-driven ML method for a biosimilar-relevant problem were included. Results: The review mapped AI applications at different stages of biosimilar development and characterized emerging trends and the types of methods used at each stage. Evidence indicates that the most mature empirical ML applications are concentrated in manufacturing optimization and analytical comparability, where supervised learning, ensemble models, and neural networks support process control, glycan or spectral analysis, and similarity assessment. By contrast, biosimilar-specific ML applications in clinical prediction and pharmacovigilance remain comparatively limited. Conclusions: These advances support the mission of biosimilars to provide affordable and high-quality biologic therapies. Using ML, developers can reduce timelines, reduce costs, and strengthen safety and efficacy assessments through the analysis of complex datasets that are difficult to address with traditional approaches. The main contribution of this review is to provide a clearer map of methodological maturity, translational relevance, and future opportunities for data-driven biosimilar development. Full article

Background: Management of giant pyogenic liver abscesses (PLA) remains challenging, particularly in culture-negative cases, where clinical improvement may not reflect adequate local disease control. Case Description: A 65-year-old woman with well-controlled type 2 diabetes mellitus presented with several weeks of systemic symptoms, marked inflammatory response, cholestatic liver injury, and acute kidney dysfunction. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large, multiloculated hepatic lesion measuring approximately 10 cm, consistent with a giant PLA. Empirical broad-spectrum antimicrobial therapy resulted in rapid clinical and biochemical improvement; however, follow-up imaging demonstrated further enlargement of the abscess. Microbiological cultures from blood, urine, and the abscess cavity remained negative. In view of radiological progression, CT-guided percutaneous catheter drainage was performed, resulting in effective evacuation and subsequent lesion regression. Long-term follow-up confirmed complete resolution without recurrence. Conclusions: This case highlights that clinical and laboratory improvement alone may be insufficient to assess treatment response in giant, culture-negative PLA. Serial imaging plays a key role in identifying inadequate local disease control and guiding timely escalation to image-guided intervention. Full article

Background: Antimicrobial resistance in Staphylococcus pseudintermedius is an increasing concern in small animal medicine, particularly due to methicillin-resistant strains and associated multidrug resistance. This study aimed to characterize antimicrobial susceptibility patterns in clinical canine isolates, determine the prevalence of methicillin resistance, and assess the presence of mecA and mecC genes. Methods: A total of 243 clinical isolates from canine skin samples collected in Hungary between 2023 and 2025 were analyzed. Minimum inhibitory concentrations (MICs) for 24 antimicrobial agents were determined using broth microdilution in accordance with CLSI guidelines. Isolates were classified as methicillin-resistant or susceptible based on oxacillin MIC values. PCR assays targeting mecA and mecC were performed on oxacillin-resistant isolates. Results: Of the 243 isolates, 47 (19.3%) were methicillin-resistant. High resistance rates were observed for β-lactams, tetracyclines, macrolides, and lincosamides, while rifampicin, amikacin and florfenicol retained good to excellent activity. Methicillin-resistant isolates exhibited substantially higher resistance across multiple antimicrobial classes. Overall, 50.6% of all isolates were classified as multidrug-resistant (MDR) and 17.3% as extensively drug-resistant (XDR), while no pandrug-resistant (PDR) isolates were detected; all methicillin-resistant isolates were at least MDR. The mecA gene was detected in 80.9% of oxacillin-resistant isolates, while mecC was not identified. Conclusions: Methicillin resistance in canine S. pseudintermedius is closely associated with multidrug resistance, limiting therapeutic options. However, selected agents, including rifampicin, amikacin and florfenicol, retained in vitro activity. Partial discordance between phenotypic resistance and mecA detection highlights the importance of combined phenotypic and molecular approaches. These findings have direct implications for empirical antimicrobial therapy and support targeted treatment strategies, while emphasizing the importance of antimicrobial stewardship in small animal practice. Full article