Search Results (200)

The concept of “more is better” has long dominated cancer treatment, emphasizing aggressive therapies despite their toxicity. However, the rise of personalized medicine has fostered treatment de-escalation strategies aimed at minimizing toxicity, improving quality of life, and reducing costs. This position paper highlights key applications of de-escalation in medical oncology, with a primary focus on breast cancer and notable examples in colorectal, head and neck, ovarian, lung, and prostate cancers. Various approaches, including dose reduction, treatment duration shortening, and regimen optimization, have demonstrated efficacy without compromising clinical outcomes. Advances in molecular diagnostics, such as Oncotype Dx in breast cancer and circulating tumor DNA (ctDNA) analysis in colorectal cancer, have facilitated patient selection for de-escalation. While these strategies present promising results, challenges remain, particularly in balancing treatment intensity with oncologic control. The review underscores the need for further prospective trials to refine de-escalation approaches and ensure their safe integration into standard oncologic care. Full article

Conventional chemotherapy continues to form the backbone of treatment for many pediatric central nervous system (CNS) tumors. Advances have been made especially in the molecular underpinning of certain pediatric CNS tumors, allowing for advancement and consideration in incorporating this molecular information in molecular targeted therapy or appropriate de-escalation or escalation of therapy. In very young children with embryonal CNS tumors, intensive high-dose chemotherapy approaches have been used with varied increased survival in medulloblastoma, atypical teratoid rhabdoid tumor (ATRT), and rare embryonal subtypes, but there are certain molecular risk groups that require new therapies, such as the ATRT MYC subtype. Some CNS tumors remain resistant or refractory to conventional chemotherapy, especially in relapsed disease. Strategies to explore combination therapies with chemotherapy, novel agents, and novel approaches are needed to improve survival in this population in the future. Full article

Background: Kawasaki disease (KD) is a systemic vasculitis and the leading cause of acquired heart disease in children. Early identification of coronary artery abnormalities (CAAs) is crucial to guide treatment and improve outcomes. While transthoracic 2D echocardiography (TTE) remains the first-line imaging modality, it has limitations, particularly in visualizing distal coronary artery segments and detecting thrombi. Computed tomography coronary angiography (CTCA) offers enhanced visualization, but its role at initial presentation of KD remains underexplored. Methods: We reviewed the records of 71 children with KD who underwent CTCA at their initial presentation at a tertiary center between November 2013 and December 2024. The CTCA findings were compared with those of TTE. CTCA was performed after stabilization using radiation-minimized protocols. Results: Of 71 patients, 62 had CAAs on baseline TTE. CTCA confirmed CAAs in 39 patients, identified additional lesions in 23, and detected distal aneurysms and coronary branch involvement missed by TTE. In 20 patients with initially abnormal TTE, CTCA demonstrated normal coronaries, facilitating treatment de-escalation. CTCA identified coronary thrombi missed on TTE in two patients and congenital coronary anomalies in three patients. CTCA findings led to modification of therapy in multiple cases. Conclusions: CTCA is a valuable adjunct to TTE in evaluating coronary artery involvement at the time of initial presentation of children with KD. Given its superior visualization of the entire length of coronary arteries, CTCA has a vital role in therapeutic decision-making in KD. Full article

Objective: This study aimed to assess the effect of antibiotic de-escalation on 30-day mortality, duration of intravenous (IV) antibiotic therapy and length of hospital stay (LOS) in severe community-acquired pneumonia (sCAP). Methods: We performed a retrospective analysis of prospectively collected data from a cohort of adults diagnosed with sCAP and microbiologically confirmed etiology between 1995 to 2022. Two distinct time points of the de-escalation were analyzed: 3 and 6 days post-admission, corresponding, respectively, to the availability of microbiological results and the median time to clinical stability. Inverse propensity score-weighted binary logistic regression was used to adjust for potential confounders. Results: A total of 398 consecutive cases of sCAP were analyzed. No significant differences were observed between the de-escalation and non-de-escalation groups in terms of age, sex, comorbidities, or severity-related variables (such as impaired consciousness, shock, respiratory failure, or multilobar pneumonia). Patients in the de-escalation group had lower rates of leukopenia, bacteremia and empyema, and less need for mechanical ventilation, with variations depending on the timing of de-escalation. After adjusting for confounding factors in an inverse propensity score-weighted analysis, de-escalation within 3 or 6 days after admission was not associated with increased mortality risk (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 0.29–7.4; p = 0.63, and aOR 0.57, 95% CI 0.14–2.31, p = 0.43, respectively). Similar findings were observed for prolonged LOS. However, antibiotic de-escalation was related to a lower risk of prolonged IV antibiotic. Conclusions: Antibiotic de-escalation in microbiologically confirmed sCAP did not negatively impact clinical outcomes, supporting the safety of this strategy for optimizing antibiotic use in this serious infection. Full article

Molecular methods allow for a rapid identification of the main causative agents of pneumonia along with the most frequent resistance genes. Prolonged broad-spectrum antibiotic therapy without microbiological evidence of infection drives antimicrobial resistance. We evaluated if the result provided by the molecular method is helpful for antimicrobial de-escalation. All respiratory samples collected and directly processed via Real-Time PCR from patients with suspected pneumonia, of whom clinical data were available, were included in this study. In 82 patients out of a total of 174 (47.1%), antimicrobial therapy was modified after the molecular test, and in 28/82 (34.1%), antimicrobial de-escalation was carried out. Among the 92 patients in whom therapy was not modified, 33 (35.9%) were did not receive any antimicrobial therapy before the molecular test and no antibiotics were prescribed after the test. Therefore, in 61 (28 + 33) out of the 174 (35%) patients, unnecessary antimicrobials were discontinued or avoided. The syndromic panel used at our institution can be of help in better choosing when empiric antibiotic de-escalation therapy could be feasible. Full article

Background and Objectives: This study aimed to assess the prevalence of colistin prescriptions among patients with multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa) infections admitted to a tertiary teaching hospital in Jordan. Additionally, the study evaluated the appropriateness of colistin prescriptions and assessed resistance levels of this strain. Materials and Methods: In this retrospective study, adult patients who were infected with MDR P. aeruginosa and were admitted to Jordan University Hospital between January 2018 and March 2024 were included. Data on demographics, clinical characteristics, sources of infection, antibiotic therapy, and clinical outcomes were collected. Results: Out of the 85 patients who met the inclusion criteria for having MDR P. aeruginosa, colistin was administered to 16 patients (18.8%). Notably, approximately two-thirds (68.7%) of the isolates from patients who received colistin were classified as extensively drug-resistant (XDR). Among the isolates, 15 out of 16 (93.8%) were resistant to both ciprofloxacin and imipenem. Among the patients requiring colistin, five (31.3%) discontinued therapy, while two (12.5%) remained on colistin despite the availability of safer alternatives. No significant difference was observed in 30-day all-cause mortality between patients treated with colistin (0%) and those who were not (4.3%, p = 1.00). Similarly, the incidence of acute kidney injury did not differ significantly between the colistin group (0%) and the non-colistin group (p = 1.00). No significant difference was found in the hospital stay between colistin-treated patients (median 10.5 days, IQR [5.0–14.0]) and those not treated with colistin (median 13.0 days, IQR [7.0–21.0]), (p = 0.22). Conclusions: This study demonstrated that colistin was selectively initiated in high-risk patients, particularly those with XDR P. aeruginosa. However, its inappropriate continuation despite safer alternatives, as well as its discontinuation when no other options existed, raise concerns about antibiotic de-escalation practices. Interestingly, no significant differences in mortality or acute kidney injury were observed between patients who were treated with colistin and those who were not. These findings emphasize the need for antimicrobial stewardship programs and highlight the importance of large-scale trials to evaluate colistin’s efficacy and safety in MDR infections. Full article

Background/Objectives: Antimicrobial stewardship programs (ASPs) optimize antimicrobial use, improving outcomes and reducing resistance. This study assessed the impact of a ward-specific ASP. Methods: A pre/post quasi-experimental study was conducted in an internal medicine ward at a tertiary hospital in Padua, Italy. During the intervention year (September 2023–August 2024), a multidisciplinary team (infectious disease consultants, pharmacists, microbiologists, nurses, and hygienists) held bi-weekly ward-based audits, reviewing antimicrobial prescriptions and performing bedside assessments. Therapy adjustments followed guidelines and local epidemiology. Educational sessions and infection prevention and control (IPC) protocols were also reinforced. Outcomes were compared to the previous year, considering patient characteristics. The primary outcome was antimicrobial consumption (DDD/100 patient days, DDD/100PD); secondary outcomes included cost savings, length of stay (LOS), and mortality. Results: Fifty audits assessed 1074 patients and 1401 antimicrobial treatments. Patient characteristics were similar. Antibiotic suspension or de-escalation occurred in 37.9% and 22% of patients, respectively. AWARE ACCESS class use increased (+17.5%), while carbapenem (−54.4%) and fluoroquinolone (−42.0%) use significantly declined (p < 0.05). IPC and microbiological culture guidance were provided in 12.1% of cases. Antimicrobial consumption dropped from 107.7 to 84.4 DDD/100PD (p < 0.05). No significant changes in LOS or mortality were observed. Antimicrobial costs fell by 48.8% (with EUR 57,100 saved). Conclusions: ASP reduced antimicrobial consumption, improved prescription quality, and cut costs without compromising patient outcomes. Multidisciplinary collaboration, audits, and education proved essential. Future studies should assess long-term resistance trends and integrate rapid diagnostics for enhanced stewardship. Full article

Background: Quality of life (QoL) is a critical indicator in assessing the success of oncological treatments for head and neck malignancies, reflecting their impact on physiological functions and psychosocial well-being beyond mere survival. Treatments (surgery, radiotherapy, chemotherapy) pose multiple functional and emotional challenges, and recent advancements underscore the necessity of evaluating post-treatment QoL. Objective: This literature review investigates the impact of oncological treatment on the QoL of patients with malignant head and neck cancers (oral, oropharyngeal, hypopharyngeal, laryngeal) and identifies factors influencing their QoL index. Methodology: Using a PICO framework, studies from PubMed Central were analyzed, selected based on inclusion (English publications, full text, PROM results) and exclusion criteria. The last research was conducted on 6 April 2025. From 231 identified studies, 49 were included after applying filters (MeSH: “Quality of Life,” “laryngeal cancer,” “oral cavity cancer,” etc.). Data were organized in Excel, and the methodology adhered to PRISMA standards. Results: Treatment Impact: Oncological treatments significantly affect QoL, with acute post-treatment declines in functions such as speech, swallowing, and emotional well-being (anxiety, depression). Partial recovery depends on rehabilitative interventions. Influencing Factors: Treatment type, disease stage, socioeconomic, and demographic contexts influence QoL. De-escalated treatments and prompt rehabilitation improve recovery, while complications like trismus, dysphagia, or persistent hearing issues reduce long-term QoL. Assessment Tools: Standardized PROM questionnaires (EORTC QLQ-C30, QLQ-H&N35, MDADI, HADS) highlighted QoL variations. Studies from Europe, North America, and Asia indicate regional differences in outcomes. Limitations: Retrospective designs, small sample sizes, and PROM variability limit generalizability. Multicentric studies with extended follow-up are recommended. Conclusions: Oncological treatments for head and neck malignancies have a complex impact on QoL, necessitating personalized and multidisciplinary strategies. De-escalated therapies, early rehabilitation, and continuous monitoring are essential for optimizing functional and psychosocial outcomes. Methodological gaps highlight the need for standardized research. Full article

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Good overall survival rates of about 90% are the result of improvements in risk stratification and risk-adapted therapy, intensive chemotherapy regimens, hematopoietic stem cell transplantation, and better supportive care. Background and Objectives: The aim of this study is to review the epidemiology, prognostic factors, and causes of death in pediatric ALL patients treated at a tertiary care center, and to identify risk factors influencing clinical outcomes. Materials and Methods: A retrospective study was conducted at the Department of Pediatric Hematology and Oncology, University Hospital Centre Zagreb, including 302 children (0–18 years) diagnosed with ALL between January 2001 and December 2015. Results: Two hundred fifty-one children survived (5-year overall survival 83%). Relapse occurred in 13.6% of patients. Relapse rates were higher for B-cell precursor (Bcp)-ALL than for T-cell ALL (14.3% vs. 10.4%), and no patient with relapsed T-cell ALL survived. The main causes of death were refractory/relapsed disease (43% of patients), followed by infections (35%) and GVHD (8%). The most frequent causes of infectious death were Pseudomonas aeruginosa and Aspergillus fumigatus. The most critical treatment periods were the induction and reinduction phases, especially the de-escalation of corticosteroids. The time of relapse and risk group were independent factors in predicting the outcome. Conclusions: Relapse and infections were the leading causes of death in children with ALL, with the highest mortality observed during induction and reinduction phases. Survival was significantly influenced by relapse timing and risk group, with no survivors among relapsed T-ALL patients. Full article

Candidemia is a significant cause of morbidity and mortality among critically ill patients. Early-onset candidemia is characterized by occurring within the first seven days after admission to the Intensive Care Unit and presents several important challenges regarding its management. Risk factors may vary among patients with early- and late-onset infection, while clinical manifestations are generally non-specific and covered by the underlying disease and co-morbidities. Diagnosis and appropriate therapy are frequently delayed, with a high risk of progression to invasive, deep-seated infections, leading to rapid clinical deterioration. Management strategies to optimize the approach for patients with early-onset candidemia include the use of both conventional and novel diagnostic techniques, the initiation of appropriate antifungal therapy, administration of an adequate dose, daily evaluation of clinical response, de-escalation treatment whenever possible, and early discontinuation. Incorporating an antifungal stewardship program in clinical practice is essential in order to achieve the best clinical outcomes. Based on a review and analysis of the available literature, this article provides a thorough update on the risk factors, clinical characteristics, diagnostic methods, and management of early-onset candidemia in adult critically ill patients. Full article

Background: In patients with curatively resected pancreatic adenocarcinoma who have undergone neoadjuvant chemotherapy (NACT), evidence supporting the benefit of additional adjuvant chemotherapy (ACT) remains limited. We aim to identify favorable factors contributing to survival benefits in resected pancreatic adenocarcinoma after NACT. Methods: This is a retrospective cohort study of pancreatic adenocarcinoma patients who underwent NACT followed by curative surgical resection between 2008 and 2023 at a single academic institution. Univariate and multivariable analyses were conducted to identify factors contributing to disease-free survival (DFS) and overall survival (OS). Results: A total of 230 patients with a median age of 68 years (IQR, 62–72 years) were included. All patients underwent curative surgical resection. Of these, 42% received neoadjuvant modified (m) FOLFIRINOX (96/230), 15% received gemcitabine plus nab-paclitaxel (GEM-NAB) (34/230), and 43% received gemcitabine, docetaxel, and capecitabine (GTX) (100/230). In univariate analysis, lower College of American Pathologists (CAP) tumor regression grade (TRG) (0–1 vs. 2–3, median DFS: 29.8 vs. 14.2 months, p = 0.0081) and receipt of ACT (Yes vs. No, median DFS: 22.2 vs. 12.4 months, p < 0.0001) demonstrated significant associations with superior DFS. Multivariable analysis identified receipt of ACT as an independent predictor of superior DFS (HR 0.55, 95% CI: 0.39–0.78, p = 0.0007) and OS (HR 0.49, 95% CI: 0.33–0.71, p = 0.0002). However, the NACT regimen (mFOLFIRINOX vs. GEM-NAB) and the transition between neoadjuvant and adjuvant therapy (de-escalation vs. continuation vs. change) did not correlate with DFS or OS. The duration of perioperative chemotherapy showed a trend toward improved survival outcomes, though not statistically significant (6 months vs. <6 months: DFS, 19.4 vs. 16.2 months, p = 0.1448; OS, 49.6 vs. 30.4 months, p = 0.0623). In the following subgroup analyses, receipt of ACT provided DFS/OS benefits in patients who did not achieve a major pathologic response, pN0, or R0 resection (DFS: p = 0.0003; OS: p < 0.0001). However, it did not provide DFS/OS benefits in those who achieved a major pathologic response with pN0/R0 to NACT (DFS: p = 0.8036; OS: p = 0.1877). Conclusions: In resected pancreatic adenocarcinoma following NACT, receiving ACT was associated with favorable survival outcomes. Additional ACT appears to benefit patients who did not achieve a major pathologic response (pN0 or R0) to neoadjuvant therapy, with limited benefit for those who achieved a major response with pN0/R0. The specific NACT regimen (mFOLFIRINOX vs. GEM-NAB) and changes in ACT from NACT did not significantly influence survival outcomes in our cohort. Full article

Pediatric central nervous system (CNS) tumor survivors are highly susceptible to long-term toxicity due to tumor location and also the treatment received. Advancements in treatment techniques, risk-adapted approaches to therapy with adjustments to treatment regimens—including de-escalation when feasible—along with the addition of supportive therapy and surveillance in these survivors, serve to minimize and manage late effects of therapy. Full article

Background: Neoadjuvant therapy (NAT) plays a crucial role in breast cancer (BC) management by enabling tumor and nodal downstaging. While axillary lymph node dissection (ALND) remains the standard for patients with residual nodal disease after NAT, its prognostic benefit is debated. Identifying predictors of high-burden residual axillary disease may guide treatment intensification and surgical de-escalation strategies. Methods: We retrospectively analyzed 262 BC patients treated with NAT followed by ALND between 2006 and 2023. Patients were stratified into low- (ypN0-mi-1) and high-burden (ypN2-3) residual axillary disease groups. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of high-burden residual disease. Results: High-burden residual axillary disease was observed in 35.9% of patients. Baseline cN+ status (OR = 7.697, p = 0.013), HR+/HER2− subtype (OR = 3.945, p = 0.003), and larger post-NAT tumor size (OR = 1.043, p < 0.001) were independent predictors. Conclusions: Identifying patients at risk of high-burden residual axillary disease is essential to optimize neoadjuvant strategies. Increasing axillary pathological complete response may reduce the need for ALND, minimizing surgical morbidity without compromising oncological outcomes. Full article

Antibiotic de-escalation (ADE) is important to help optimize antibiotic use and balance the positive and negative effects of antimicrobial therapy. ADE should be performed promptly, and infections should be treated with the shortest course of antimicrobials as clinically feasible to avoid unnecessary use of broad-spectrum antimicrobials. Several tools have been developed to increase efficient ADE, including rapid diagnostic tests (ex. multiplex PCR), MRSA nasal PCR/culture, and biomarkers. Multiplex PCR and MRSA nasal PCR/culture have been associated with reductions in inappropriate antibiotic use. Procalcitonin, a biomarker, has been associated with shorter antimicrobial durations in some studies; however, widespread use may be limited by lack of specificity for bacterial infections, cost, and lack of set cut-off points. Additional biomarkers such as IL-6, HMGB1, presepsin, sTREM-1, CD64, PSP, proadrenomedullin, and pentraxin-3 are currently being studied. As technology improves, additional tools may be leveraged to better optimize ADE even better, such as antimicrobial spectrum scoring tools and artificial intelligence (AI). Spectrum scores, which quantify antibiotic activity using specific numeric values, could be incorporated into electronic health records to identify patients on unnecessarily broad antibiotics. AI modeling has the potential to predict personal antibiograms or provide the probability that an empiric regimen may cover a particular infection, among other potential applications. This review will discuss the literature associated with ADE in the ICU, selected tools to help guide ADE, and perspectives on how to implement ADE into clinical practice. Full article

Triple-negative breast cancer (TNBC) continues to present a therapeutic challenge due to the fact that by definition, these cancer cells lack the expression of targetable receptors. Current treatment options include cytotoxic chemotherapy, antibody–drug conjugates (ADC), and the PD-1 checkpoint inhibitor, pembrolizumab. Due to high rates of recurrence, current guidelines for early-stage TNBC recommend either multi-agent chemotherapy or chemo–immunotherapy in all patients other than those with node-negative tumors < 0.5 cm. This approach can lead to significant long-term effects for TNBC survivors, driving a growing interest in de-escalating therapy where appropriate. Tumor infiltrating lymphocytes (TILs) represent a promising prognostic and predictive biomarker for TNBC. These diverse immune cells are present in the tumor microenvironment and within the tumor itself, and multiple retrospective studies have demonstrated that a higher number of TILs in early-stage TNBC portends a favorable prognosis. Research has also explored the potential of TIL scores to predict the response to immunotherapy. However, several barriers to the widespread use of TILs in clinical practice remain, including logistical and technical challenges with the scoring of TILs and lack of prospective trials to validate the trends seen in retrospective studies. This review will present the current understanding of the role of TILs in TNBC and discuss the future directions of TIL research. Full article