Intensive care unit (ICU) patients are at high risk for colonization with multidrug-resistant organisms (MDROs) and Candida species, which frequently precedes invasive infections. However, the longitudinal acquisition dynamics and time-dependent relationship between colonization and subsequent clinical infection remain incompletely defined. We conducted a prospective longitudinal cohort study including 290 adult ICU patients. Patients were followed throughout their ICU stay with serial weekly surveillance cultures. Active surveillance screened for four major organism groups: carbapenem-resistant or extended-spectrum beta-lactamase (CR/ESBL)-producing Gram-negative bacteria (GNB), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Candida species. Prior colonization was modeled as a time-varying exposure. The association between colonization and subsequent infection was evaluated using time-dependent Cox proportional hazards models with a one-week lag period. The mean ICU length of stay was 23.4 +/- 19.1 days. Overall cumulative colonization rates were 37.6% (n = 109) for CR/ESBL-producing GNB, 25.5% (n = 74) for VRE, 16.6% (n = 48) for Candida species, and 16.2% (n = 47) for MRSA. Although VRE was the second most common colonizer, zero clinical VRE infection events occurred during ICU follow-up, precluding its inclusion in multivariable infection risk modeling. In time-dependent Cox regression analyses, prior colonization significantly increased the hazard of subsequent clinical infection across all evaluable pathogen groups: CR/ESBL-producing GNB (adjusted hazard ratio [aHR] 2.89, 95% confidence interval [CI] 1.82-4.59, P < 0.001), MRSA (aHR 4.02, 95% CI 1.37-11.79, P = 0.011), and Candida species (aHR 3.99, 95% CI 1.78-8.92, P = 0.001). Prolonged ICU stay and pre-acquisition broad-spectrum antimicrobial exposure were consistent independent predictors of colonization acquisition. Prolonged ICU stay is associated with progressive cumulative acquisition of MDRO and Candida colonization, which was independently associated with an increased hazard of subsequent infection. Although VRE colonization was relatively frequent, no transition to clinical infection was observed during ICU follow-up. Given the observational design of our study, this finding should be interpreted cautiously as a reflection of sample size constraints rather than a measure of infection-control efficacy.
Breast cancer is the most common malignancy in women, and pharmacotherapy is the cornerstone of multidisciplinary care. However, drug resistance severely impairs therapeutic efficacy and patient prognosis. Circular RNAs (circRNAs) have become a key focus in breast cancer chemoresistance due to their high stability and specific expression profiles. This review classifies circRNA functions according to breast cancer molecular subtypes, elucidating their regulatory mechanisms underlying drug resistance via RNA-RNA crosstalk, RNA-protein binding, and translational regulation. We systematically summarize the core signaling cascades through which circRNAs modulate downstream biological events, including drug efflux and DNA damage repair, to drive resistance, and highlight the vital function of exosomal circRNAs in propagating systemic drug resistance. We integrate existing research evidence into a comprehensive landscape of subtype-specific circRNA regulatory networks in breast cancer drug resistance.
Cancer treatment is difficult, there are many issues regarding cancer treatment because Protein Kinase Inhibitors (PKIs) are unable to control tumors that are resistant to them. Resistance to drugs starts with changes in genetic code and continues with fresh changes, routes and alterations in the tumour. When treating cancer with imatinib or osimertinib, PKIs can correct faulty signals, yet patients generally become resistant swiftly and this resistance can include unpleasant side effects. Reviewing Epidermal Growth Factor Receptor (EGFR) T790M and BCR::ABL1 T315I mutations reveals that the important interactions and binding sites are removed or obstructed with the drug. This is how researchers design second- and third-generation drug inhibitors. In addition, the use of single-cell sequencing, CRISPR screens and liquid biopsies helps researchers and doctors to accurately fight resistance in cancer patients. For cancer treatments to succeed, systems to reduce drug costs and make them available, fresh ideas, global experts and equitable healthcare laws should be implemented.
