De-escalation Of Therapy Research Articles

Breast cancer related lymphoedema: a review of contemporary preventive strategies.

Secondary lymphoedema remains an incurable long-term complication of breast cancer treatment. Prevention is our best chance against this debilitating condition. Strategies for selective de-escalation of oncological therapies have continued to evolve over the last few decades to reduce the incidence of this feared complication. In this manuscript we first review the current strategies in de-escalation of axillary treatment. We then review the current evidence for immediate lymphatic reconstruction in those high-risk patients who cannot be spared from more aggressive axillary management.

Abstract B023: Cell-free HPV-DNA dynamics during induction chemotherapy and response-stratified de-escalation in viral-mediated oropharyngeal cancer

Abstract Background: Cell-free HPV-DNA (cfHPV-DNA) in plasma represents a promising biomarker to grade treatment response and monitor for persistence/recurrence. We evaluated the dynamic changes of cfHPV-DNA during induction chemotherapy followed by response-stratified de-escalation in HPV associated (HPV+) oropharyngeal squamous cell cancer (OPSCC). Methods: A prospective biomarker clinical trial of response-stratified de-escalation therapy was conducted. Eligible patients had loco-regional HPV+ OPSCC and received induction chemotherapy with carboplatin and paclitaxel for three cycles followed by risk and response-stratified de-escalation with transoral robotic surgery (TORS), de-escalated radiation (RT) to 50Gy with or without cisplatin, or standard RT to 70Gy with cisplatin. Patients with deep response (>=50% tumor shrinkage per RECIST 1.1) qualified for de-escalated therapy. Cell-free HPV-DNA was measured using a CLIA-certified HPV-SEQ assay that utilizes NGS technology to detect and quantify HPV16 and HPV18 DNA in plasma at baseline, after each cycle of induction chemotherapy, during radiation, and post-treatment surveillance at 3, 6, 9, 12, 18, and 24 months following treatment. Results: Forty-six eligible patients were enrolled, with 464 cfHPV-DNA plasma samples analyzed (median 10 samples per patient). There were five recurrences (10.9%), all detected by HPV-SEQ. Baseline cfHPV-DNA was detected in 44/46 patients (96%). Patients with rapid early cfHPV-DNA clearance after one 3-week cycle of induction (>=95% clearance) predicted deep radiographic response following induction therapy (p=0.003). The detection of cfHPV-DNA at 3 months or later after treatment was associated with worse progression free survival (PFS), with 2-year PFS of 25% (95% CI 0.012-0.65) compared with patients without detectable cfHPV-DNA of 100% (95% CI 1.0-1.0); p<0.001). The longest lead-time from positive cfHPV-DNA to developing recurrent disease was 25 months. Conclusion: Rapid early clearance of cfHPV-DNA during induction has utility in predicting response to treatment. Detectable cfHPV-DNA following treatment is strongly associated with worse PFS. A subsequent trial using cfHPV-DNA to select patients for treatment de-escalation is ongoing. Clinicaltrials.gov ID: NCT04572100 Citation Format: Ari Rosenberg, Evgeny Izumchenko, John Cursio, Augustin Vannier, Aditya Juloori, Rohan Katipally, Rifat Hasina, Frederick Jones, Anna Starus, Elizabeth Blair, Daniel J. Haraf, Alexander T. Pearson, Everett E. Vokes, Nishant Agrawal. Cell-free HPV-DNA dynamics during induction chemotherapy and response-stratified de-escalation in viral-mediated oropharyngeal cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B023.

Temporal modulation (early escalation and late de-escalation) of antiplatelet therapy in patients undergoing complex high-risk PCI: rationale and design of the TAILORED-CHIP trial.

Despite the use of conventional dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI), the risk of adverse events remains high among patients with increased thrombotic risk. Until recently, the optimal antiplatelet strategy to balance the ischaemic and bleeding risks in patients who are undergoing complex high-risk PCI has been unclear. The TAILored Versus COnventional AntithRombotic StratEgy IntenDed for Complex HIgh-Risk PCI (TAILORED-CHIP) trial is an investigator-initiated, multicentre, prospective randomised trial to evaluate the efficacy and safety of a time-dependent tailored antiplatelet therapy with an early (<6 months post-PCI) escalation (low-dose ticagrelor at 60 mg twice daily plus aspirin) and a late (>6 months post-PCI) de-escalation (clopidogrel monotherapy) in patients undergoing complex high-risk PCI as compared with standard DAPT (clopidogrel plus aspirin for 12 months). Eligible patients had to have at least one high-risk anatomical or procedural feature or clinical characteristic associated with an increased risk of ischaemic or thrombotic events. The primary endpoint was the net clinical outcome, a composite of death from any cause, myocardial infarction, stroke, stent thrombosis, urgent revascularisation, or clinically relevant bleeding (Bleeding Academic Research Consortium type 2, 3, or 5) at 12 months after randomisation. (ClinicalTrials.gov: NCT03465644).

Assessment of postoperative therapy de-escalation for early-stage, intermediate-risk cervical cancer: Japanese Gynecologic Oncology Group study

Assessment of postoperative therapy de-escalation for early-stage, intermediate-risk cervical cancer: Japanese Gynecologic Oncology Group study

Impact of procedural and patient-related risks on 1-year outcomes for patients with 1-month DAPT followed by P2Y12 inhibitor monotherapy after biodegradable-polymer drug-eluting stent implantation

Abstract Background While early de-escalation of dual antiplatelet therapy (DAPT) and P2Y12 inhibitor monotherapy following short DAPT are becoming standard treatments for patients after percutaneous coronary intervention (PCI), the impact of procedural and patient-related risks on clinical outcomes of PCI for patients receiving the above DAPT regimen has never been established. Purpose To evaluate the impact of procedural and patient-related risk factors on 1-year cardiovascular and bleeding outcomes in patients with 1-month DAPT followed by P2Y12 inhibitor monotherapy after biodegradable-polymer drug-eluting stent (BP-DES) implantation. Methods Using data from the multi-centre regional-wide REIWA registry, we assessed clinical outcomes according to each risk factor and compared between patients with and without either procedural or patient-related risk factors. The primary end point was net adverse clinical events (NACE), defined as a composite of cardiovascular outcomes (cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic or hemorrhagic stroke) and bleeding outcomes (TIMI major or minor bleeding), which was same with that for STOPDAPT-2 trial. Procedural risk was defined as a factor of complex PCI which was previously published and included the follows: treatment of three vessels, three or more lesions, three or more stents, bifurcation with two stents, long stenting (total stent length &amp;gt;60 mm) and target of chronic total occlusion. Additionally, patient-related risk factors were defined as chronic kidney disease, anaemia, peripheral vascular disease, heart failure and advanced age (≧75 years). Results Among 1,202 patients treated BP-DES with 1-month DAPT, 276 patients (23.0%) had at least one procedural factors and 510 patients (42.4%) had one or more patient-related risks. Compared with each risk factor, patients with patient-related risk factor were more likely to have higher NACE rates, whereas low NACE rates were observed in patients with each procedural risk factor (Figure 1). In addition, during 1-year follow-up, patients with patient-related risk factors had a significantly higher incidence of NACE compared with patients without such risks (4.90 % vs. 1.73 %, p = 0.002) (Figure 2). However, no significant differences in NACE rates was observed between patients with and without procedural risk factors (2.54% vs. 3.24%, p = 0.555). Conclusion In patients undergoing BP-DES implantation and 1 month DAPT followed by P2Y12 inhibitor monotherapy, patient-related risk factors had an impact on 1-year clinical outcomes, while procedural risk factors no longer had small impact on those outcomes.

Triple Therapy De-Escalation and Withdrawal of Inhaled Corticosteroids to Dual Bronchodilator Therapy in Patients with Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis.

Background/Objectives: The interpretation of evidence on the de-escalation of triple therapy with the withdrawal of inhaled corticosteroids (ICSs) to dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA) in patients with chronic obstructive pulmonary disease (COPD) is conflicting. We evaluated the efficacy and safety of ICS discontinuation from LABA-LAMA-ICS triple therapy compared to its continuation. Methods: We searched PubMed, Embase, Scopus, Web Of Science, clinicaltrial.gov, and CENTRAL for RCTs and observational studies from inception to 22 March 2024, investigating the effect of triple therapy de-escalation with the withdrawal of ICSs to dual therapy on the risk of COPD exacerbation, pneumonia, and lung function. This study was registered with PROSPERO, CRD42024527942. Results: A total of 3335 studies was screened; 3 RCTs and 3 real-world non-interventional studies were identified as eligible. The analysis of the time to the first moderate or severe exacerbation showed a pooled HR of 0.96 (95% CI, 0.80-1.15; I2 = 77%) for ICS withdrawal compared to triple therapy continuation. The analysis according eosinophil levels showed that COPD subjects with ≥300 eosinophils/µL had a significant increase in the incidence of moderate or severe exacerbations when de-escalated to LABA/LAMA (pooled HR: 1.35, 95% CI: 1.00-1.82; I2: 56%). ICS withdrawal did not significantly affect the risk of mortality and pneumonia. Conclusions: The de-escalation of triple therapy with ICS withdrawal does not affect the main outcomes evaluated (moderate or severe exacerbations, change in trough FEV1). COPD patients with high blood eosinophils (≥2% or ≥300 cells/µL) are most likely to benefit from continuing triple therapy.

A multicenter evaluation of a novel microfluidic rapid AST assay for Gram-negative bloodstream infections.

Increasing antimicrobial resistance underscores the need for new diagnostic solutions to guide therapy, but traditional antimicrobial susceptibility testing (AST) is often inadequate in time-critical diseases such as sepsis. This work presents a novel and rapid AST system with a rapid turnaround of results, which may help reduce the time to guided therapy, possibly allowing early de-escalation of broad-spectrum empirical therapy as well as rapid adjustments to treatments when coverage is lacking.

De-Escalating Treatment Strategies for Patients with Human Epidermal Growth Factor Receptor-2 (HER2)-Positive Early-Stage Breast Cancer.

Almost one-fifth of breast cancer cases express Human Epidermal Growth Factor-2 (HER2), and such expression is associated with highly proliferative tumors and poor prognosis. The introduction of anti-HER2 therapies has dramatically changed the natural course of this aggressive subtype of breast cancer. However, anti-HER2 therapy can be associated with substantial toxicities, mostly cardiac, and high cost. Over the past few years, there has been growing interest in de-escalation of anti-HER2 therapies to minimize adverse events and healthcare costs, while maintaining the efficacy of treatment. Data from clinical observations and single-arm studies have eluted to the minimal impact of anti-HER2 therapy in low-risk patients, like those with node-negative and small tumors. Though single-arm, the APT trial, in which patients with node-negative, small tumors received single-agent paclitaxel for 12 cycles plus trastuzumab for 1 year, was a practice-changing study. Several other recently published studies, like the PERSEPHONE trial, have shown more convincing data that 6 months of trastuzumab is not inferior to 12 months, in terms of disease-free survival (DFS), suggesting that de-escalating strategies with shorter treatment may be appropriate for some low-risk patients. Other de-escalating strategies involved an adaptive, response-directed approach, and personalized therapy that depends on tumor genomic profiling.

Role of Immunotherapy in Conjunction With the Surgical Treatment of Breast Cancer: Preoperative and Postoperative Applications.

Breast cancer is one of the most common cancers in the world. Since the appearance of molecular medicine, the perspective of breast cancer treatment has changed, making it more successful in comparison with the treatment during previous years. Numerous ongoing trials are exploring the capacity of immunotherapy, mainly in immune checkpoint inhibitors (ICIs), in conjunction with conventional therapies or with antibody-drug conjugates (ADCs). The current narrative review discusses the advantages and limitations of immunotherapy in breast cancer treatment in conjunction with the surgical options available. Going through the modern capacity of surgery treatment and how the use of immunotherapy in conjunction with it has emerged as a transformative approach to breast cancer and listing the main complications and adverse effects caused by ICIs. We searched Google Scholar, PubMed, MEDLINE, and EMBASS. Fourteen different articles showed that the use of cytokines and cancer vaccines revealed new possibilities to treat breast cancer with antibodies against PD-1/PD-L1 (pembrolizumab), PI3K/Akt/mTOR (alpelisib and everolimus), CAR T-cell (chimeric antigen receptor), PARP (poly ADP-ribose polymerase), and CTLA4 (cytotoxic T-lymphocyte-associated protein 4), and with representative relevance of changing in tumor microenvironment. Immunotherapy made it possible to reduce recurrences, after radiotherapy and surgery. Estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) targets show also a high effectivity. In recent years, the release of new strategies has become promising, for changing the microenvironment and de-escalation of therapy based on tumor biology, novel biomarkers, and tumor spread.

De-escalation of Radiation Therapy in the Treatment Plan of Patients with Stage I-IIV Breast Cancer after Subcutaneous/Skin-Sparing Mastectomies with Immediate Reconstruction

Introduction. Indications for radiation therapy after mastectomies with/without reconstruction at T1­2N0­1M0 remain unclear; treatment standards contain references to the possible administration of radiation therapy for factors that increase breast cancer recurrence. Materials and methods. A retrospective single­center, non­randomized study enrolled 984 breast cancer patients treated at P.A. Gertsen Moscow Cancer Research Institute from 2014 to 2022. Patients were divided into 2 groups: a radiotherapy group and a non­radiotherapy group. Results and discussion. The paper presents an analysis of patients’ age, the histological structure of the tumor, immunohistochemical characteristics, tumor grade, multicentricity, presence of lymphovascular invasion, tumor cells, the state of R1 and R0 margins, and the tumor stage at risk of recurrence. Overall survival in the recurrence group accounted for 95.1%, in the non­recurrence group – 98.4%. In the radiotherapy group (group I), the overall survival comprised 98.4%; metastases were diagnosed in 4.9% of cases. In thenon­radiotherapy group (group II), the overall survival amounted to 98.2%; metastases were revealed in 5.9% of cases. Conclusion. Univariate analysis in the study groups showed that radiation therapy reduced the risk of relapse by 3.5%. In case of positive R1 margin, radiotherapy is recommended, which was confirmed in our study, the difference accounted for 14.5%, and in the presence of R1, radiotherapy is claimed to be necessary in the postoperative period. When analyzing the stage of breast cancer and the risk of recurrence, the statistical difference was revealed only at stage IIA (T1N1M0); radiation therapy reduced the risk of breast cancer recurrence. The statistical difference in groups I and II was detected at Grade 2 tumor, Ki­67 level less than 50%, presence of tumor embolism and age of patients under 40 years. Radiation therapy after subcutaneous/skin­sparing mastectomy reduces the recurrence risk by 3.2%; however, the overall survival in group I and group II accounted for 98.4 and 98.2%, respectively; the difference is not statistically significant. In our study, the criteria for prescribing radiation therapy in the postoperative period include: young age of the patients, R1 resection margin, luminal/non­luminal HER2 positive type, cN1, presence of tumor embolism.

Plasma Cell-free DNA Metagenomic Next-Generation Sequencing in Immunocompromised Children

Abstract Background Plasma cell-free DNA metagenomic next-generation sequencing (mNGS) is a novel diagnostic tool for infectious diseases [1]. Data suggests that plasma mNGS may be useful in immunocompromised adults, changing management in up to 60% of the patients [2]. A prospective study evaluating utility of plasma mNGS for pneumonia in immunocompromised adults concluded that mNGS provided an additive diagnostic value of 12.1% [3]. A similar study in adults with febrile neutropenia reported a sensitivity and specificity of 85 and 100%, respectively [4]. However, there is limited data evaluating the utility of mNGS in immunocompromised children. Methods We retrospectively reviewed all pediatric immunocompromised patients who had plasma mNGS testing performed from December 2018 to July 2023 at St. Jude Children’s Research Hospital. Electronic medical records were reviewed to extract relevant clinical data and microbiologic data including results of mNGS, contemporaneous cultures, and related antimicrobial treatment. Descriptive statistics are presented as frequencies and medians (interquartile range, IQR). Comparisons were performed using Fisher’s exact test or Wilcoxon rank-sum test, as appropriate, using R version 3.6.3. Results A total of 18 immunocompromised children underwent plasma mNGS testing. Acute lymphoblastic leukemia was the most common malignancy (33.3%), followed by acute myeloid leukemia (22.2%). Two patients (11.1%) had undergone hematopoietic cell transplant, both allogeneic. At the time of testing, 16 patients (88.9%) had fever and 10 (55.6%) had an absolute neutrophil count of &amp;lt;500/mm3. All except one were on antimicrobial therapy at the time of testing, with a median duration of 8 days (IQR=12.25). Only 9 (50%) patients had a positive mNGS result. A positive mNGS resulted in broadening or extending antibiotics course in 4 patients (22.2%); negative mNGS results did not lead to changes in management in any of the cases. There were no significant differences in age, sex, days of fever, neutropenia, gastrointestinal (GI) symptoms, and days of fever before testing between those with positive versus negative results. However, a higher frequency of GI symptoms at the time of testing among those with positive results was observed. Clinical characteristics and impact on management in patients with positive and negative results are summarized in Table 1. Conclusion Plasma mNGS had a limited impact on the management of immunocompromised children at our institution. Negative results did not lead to de-escalation of therapy, and positive results led to additional exposure to antibiotics. Further research is needed to determine the role of mNGS in this population, and the interpretation of positive testing in the setting of gastrointestinal disease.

Procalcitonin Level Monitoring in Antibiotic De-Escalation and Stewardship Program for Patients with Cancer and Febrile Neutropenia

Objective: Serial procalcitonin (PCT) monitoring has been adopted to supplement clinical judgement and help guide antibiotic therapy as part of antimicrobial stewardship programs. PCT levels peak 24 to 48 h after infection onset and decline with infection resolution. We explored the role of PCT as an infection biomarker for guiding antibiotic therapy in cancer patients hospitalized for febrile neutropenia. Design: Prospective randomized study. Methods: Patients were enrolled between October 2021 and August 2023 and received empiric intravenous broad-spectrum antibiotics (IVBSA) for at least 48 h. PCT was measured at baseline and 48–72 h after IVBSA initiation. PCT drop 48–72 h after IVBSA initiation was defined as a reduction of 30% from baseline or a PCT level &lt; 0.25 ng/mL. De-escalation was defined as a switch from IVBSA to oral or simplified once-daily IV therapy. Results: Of the 89 patients with available PCT levels, 53 (60%) had a PCT drop, most of whom (79%) underwent IVBSA de-escalation. Compared with patients without a PCT drop, patients with a PCT drop had a higher de-escalation rate at 72 h (71% vs. 45%; p = 0.003) and a shorter median antibiotic duration (55 h vs. 98 h; p = 0.004). Patients with bacteremia had a significantly higher median PCT level than those without bacteremia (2.35 ng/mL vs. 0.370 ng/mL, p = 0.013). Conclusions: In patients with cancer and febrile neutropenia, a PCT drop was associated with earlier therapy de-escalation and shorter antibiotic duration. PCT monitoring may be useful in antimicrobial stewardship initiatives in this patient population. Clinical trials identifier: NCT04983901.

Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer.

Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a 'low-ctDNA-shedding' and 'less-aggressive' subgroup. ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722). After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2-0.8, Cohort#2: OR: 0.7, 95%CI: 0.5-0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3-1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4-1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1-0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2-0.6). Our study suggests that asymptomatic patients are enriched for a 'low-ctDNA-shedding-low-recurrence-risk' subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients.

The Evolving Role of Genomics in Colorectal Cancer

Approximately 75% of colorectal cancers (CRCs) harbour an identifiable driver mutation, 5% of these being heritable. These drivers have recognised implications for prognosis and therapy selection. In addition, potential germline mutations require investigations to inform testing of relatives, as well as surveillance for other malignancies. With increasing numbers of targeted drugs being approved, judicious testing is required to ensure sufficient tumour is available for testing and at the right point in the cancer pathway. Liquid biopsy with circulating tumour DNA (ctDNA) in the blood presents an exciting adjunct to tumour tissue testing for molecular drivers, as well as escalation and de-escalation of therapy. We review the most frequent molecular alterations in CRC, how genomic testing should be integrated into the treatment pathway for CRC, and sources of further education.

S566 Patriot Clinic Proton-Pump Inhibitor Review and Therapy De-Escalation (PCP-PIRATE) at the Orlando VA Healthcare System

S566 Patriot Clinic Proton-Pump Inhibitor Review and Therapy De-Escalation (PCP-PIRATE) at the Orlando VA Healthcare System

The cost of doing business: Drug costs in federally sponsored cancer clinical trials.

10 Background: Federally sponsored cancer clinical trials (FS-CCTs) address a broad set of clinical cancer research questions that are avoided by industry sponsors, including combining treatment modalities, examining whether approved drugs may work in other cancers, or examining de-escalation therapy. FS-CCTs routinely extend the lives of patients with cancer and inform treatment guidelines. However, FS-CCTs must often be conducted in partnership with industry sponsors since the cost of drugs is high and cannot be paid for by the government. This limits the independence of FS-CCTs. We aimed to examine the drug costs for trials with federal sponsorship. Methods: We included all US-based cancer treatment trials registered in ClinicalTrials.gov that examined pharmaceuticals and/or biological products and started from 2018-2022. Trials with any NIH or other federal sponsorship (as the sole, lead, or other sponsor) were included. Drug names and number of enrollments per arm and drug were extracted from ClinicalTrials.gov and study protocols. The Wholesale Acquisition Cost (WAC) was obtained from IBM Micromedex RED BOOK (2023) by matching the product name, dose strength and administration route. The product acquisition cost (“cost”) per trial was computed by summing the WAC for each drug and multiplying by the number of enrollments. Results: Overall, N=1020 trials were examined (phase I = 343, phase II = 611, phase III = 66). The mean (median) drug costs were $53.9 million (m) ($7.4m) overall, including $73.8m ($19.8m), $47.2m ($8.7m), and $44.7m ($5.8m) for trials solely sponsored, led by, or with secondary/tertiary participation by federal sponsors, respectively. Trial-level drug costs were $19.2m ($3.6m), $51.9m ($9.4m), and $244.9m ($38.8m) for phase I, II, and III trials, respectively. Drug costs were much greater for trials involving immune and/or targeted therapies ($60.1m [$11.4m]) than those with conventional chemotherapies ($30.8m [$1.5m]). In the subset of n=128 phase 2 or 3 comparative trials, drug costs were $97.7m ($21.8m) for experimental arms and $24.1m ($1.4m) for control arms. Conclusions: The costs for drugs in FS-CCTs were very high, especially for the experimental arms, highlighting the necessity for federally sponsored researchers to collaborate with industry partners to conduct trials. Drug costs for immune and/or targeted therapies were higher yet, suggesting that the cost burden to conduct trials for federal sponsors may continue to increase. These findings also suggest that systemwide costs for cancer drugs in clinical practice will continue to increase substantially. These results have implications for how FS-CCTs are designed and conducted, since the necessity of collaboration between federal and industry sponsors likely limits the independence of federal research. Future public policy efforts should focus on mechanisms for independent investigation of new pharmacologic agents.

The effect of allergen immunotherapy in patients with central compartment atopic disease post-surgery.

To assess the effect of allergen immunotherapy (AIT) on patients with central compartment atopic disease (CCAD) and house dust mite (HDM) sensitization post-surgery. A retrospective cohort of surgically treated, HDM-sensitized CRSwNP patients phenotyped as CCAD was assessed. Patients were divided into two groups based on whether they had AIT commenced as part of their surgical care. All AIT patients started immunotherapy prior to their surgery. The primary endpoint was reformation of middle turbinate (MT) edema 12 months postsurgery. Secondary endpoints were corticosteroid irrigation use (<4 times/week vs. ≥4 times/week, %) and the rhinologic domain of the 22-item sino-nasal outcome test (SNOT-22). Demographic characteristics, concomitant asthma, smoking status, history of aspirin-exacerbated respiratory disease, conjunctival symptoms, polysensitization, serum eosinophils (cell×109/L), tissue eosinophilia (%>100/HPF), and serum IgE (kU/L) were also recorded. Eighty-six CCAD patients were assessed (41±14yrs, 64% female). AIT was applied in 37% (n=32). Baseline features were similar apart from greater conjunctival symptoms (72 vs. 45%, p=0.02) in the AIT group. At 12 months post-surgery, the AIT group has less MT edema (%≥diffuse 15.6 vs. 52.9, p<0.01). Patients on AIT also had less pharmacotherapy requirements at 12 months (%≥4/week, 37.5 vs. 79.6%, p<0.01). The rhinologic symptoms were similar (21.1±17.1 vs. 20.1±21.6, p=0.83). Surgery and pharmacotherapy are effective in managing CCAD, but the addition of AIT improved allergic phenomenon and allowed de-escalation of topical therapy. Longer term studies are required to demonstrate further immunomodulation.

Physicians’ and pharmacists’ knowledge and perceptions of antibiotic resistance and antibiotic stewardship: a cross-sectional survey in a tertiary hospital

BackgroundThe WHO global action plan on antibiotic resistance (ABR) emphasises improving awareness of ABR and optimising antibiotic use.ObjectivesTo assess physicians’ and pharmacists’ knowledge and perceptions of ABR and antibiotic stewardship (AS) and hospital preparedness to implement AS.MethodsThis descriptive cross-sectional survey included 124 physicians and 61 pharmacists from the University of Uyo Teaching Hospital, Akwa Ibom State, Nigeria. Participants were given a 16-item questionnaire during their clinical/review meetings. The data were analysed with SPSS version 25.0.ResultsBoth physicians (98%) and pharmacists (97%) perceived ABR as a global and national concern. Only 47% of physicians and 53% of pharmacists accurately defined AS. More pharmacists (70%) than physicians (45%) knew that excessive antibiotic usage in agriculture and livestock causes resistance (p = 0.002) and that prompt de-escalation of empirical antibiotic therapy based on culture/sensitivity results reduces ABR (93% vs. 79%, respectively, p = 0.013). Knowledge scores varied among physicians according to position (p = 0.002), length of practice (p < 0.001), and age (p = 0.002); only pharmacists' age (p = 0.046) was associated with their knowledge level.ConclusionsParticipants demonstrated good knowledge of ABR and AS strategies but little awareness about the hospital’s intention to implement AS programmes. Hospital management should emphasise optimising antibiotic use through AS programmes.

Integrating Novel Agents Into the Clinical Management of Classic Hodgkin Lymphoma.

Classic Hodgkin lymphoma (cHL) is highly curable at all stages. Research efforts over the past few decades have largely focused on interim PET-adapted strategies for therapy de-escalation or intensification. The overarching goals have been to increase cure rates, minimize potential therapy-related effects, and optimize survivorship. Better understanding of the biology of cHL has led to the development and approval of effective novel agents including the antibody-drug conjugate brentuximab vedotin and the checkpoint inhibitor immunotherapies. In this review, we discuss recent trial results and how these agents are integrated into clinical practice with the goal of further optimizing outcomes.

Rapid de-escalation of anti-MRSA therapy guided by S. aureus nares screening for patients with pneumonia: protocol of a randomized controlled trial (SNAP study).

The current Infectious Disease Society of America and American Thoracic Society (IDSA/ATS) guidelines recommend linezolid or vancomycin as an empiric treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in hospitalized patients with specific risk factors,. A nasal PCR-assay for MRSA, with its high negative predictive value, can guide a rapid antibiotic de-escalation avoiding unnecessary anti-MRSA treatment. The indiscriminate use of these drugs has contributed to the emergence of resistant S. aureus strains leading to adverse effects without any survival benefit, increasing hospital stays and associated costs. Aim of the study is the use of this diagnostic tool to reduce empirical anti-MRSA treatment duration in pneumonia, shortening antimicrobial therapy days while measuring in-hospital mortality, length of stay and adverse drug event incidence. It is a prospective, randomized single-center controlled trial planned to be conducted in the Azienda Consorziale Policlinico di Bari. The research project will have a duration of 12 months following the approval of the Ethical Committee of the University of Bari. The minimum sample size is 38 patients per group, for a total of 76 subjects, calculated assuming a standard deviation of 10, a power of 90%, a type I error of 5% and a 10% drop-out rate. We will enroll eligible patients ensuring their evidence-based management according to guidelines, we will perform a nasal swab for MRSA in patients in the experimental group and discontinue the empirical anti-MRSA therapy if the nasal swab result is negative. For both arms, follow-up visits will be on day 2, 5, 7, 14, and 28 relatives to the enrollment visit (day 0). Data will be collected on the clinical course of pneumonia and laboratory tests. Our study will provide evidence on the duration (in days) of the antibiotic intake as a primary outcome of the study. Secondary outcome measures include in-hospital mortality, the length of stay and days of mechanical ventilation (in VAP), and the incidence of adverse events related to the administration of the therapy. https://classic.clinicaltrials.gov/ct2/show/NCT06238297, identifier NCT06238297.