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Simple Summary: Radiotherapy (RT) is a cornerstone in the adjuvant treatment of breast cancer. Continuous technical improvements allow better sparing of organs at risk compared to the past with a potential reduction of RT-related toxicity. Whereas prior trials focused on histopathological criteria, mainly T- and N-stage, biological parameters like endocrine responsiveness and proliferation helped to identify a low-risk subgroup in which omission of RT is an option. Ongoing trials are incorporating molecular markers and the response to neoadjuvant systemic therapy for additional risk stratification. De-escalation regarding volume (partial breast irradiation only—PBI) can be used in selected cases. Hypofractionated regimens should be standard. In contrast, the omission of axillary dissection in node-positive disease led to an escalation of regional RT, and RT for oligometastatic disease is becoming increasingly popular. Studies are ongoing to test if any axillary treatment can be omitted and which oligometastatic patients do really benefit from RT. Postoperative radiotherapy (RT) is recommended after breast-conserving surgery and mastectomy (with risk factors). Consideration of pros and cons, including potential side effects, demands the optimization of adjuvant RT and a risk-adapted approach. There is clear de-escalation in fractionation—hypofractionation should be considered standard. For selected low-risk situations, PBI only or even the omission of RT might be appropriate. In contrast, tendencies toward escalating RT are obvious. Preoperative RT seems attractive for patients in whom breast reconstruction is planned or for defining the tumor location more precisely with the potential of giving ablative doses. Dose escalation by a (simultaneous integrated) boost or the combination with new compounds/systemic treatments may increase antitumor efficacy but also toxicity. Despite low evidence, RT for oligometastatic disease is becoming increasingly popular. The omission of axillary dissection in node-positive disease led to an escalation of regional RT. Studies are ongoing to test if any axillary treatment can be omitted and which oligometastatic patients do really benefit from RT. Besides technical improvements, the incorporation of molecular risk profiles and also the response to neoadjuvant systemic therapy have the potential to optimize the decision-making concerning if and how local and/or regional RT should be administered. [ABSTRACT FROM AUTHOR]

Police encounters with suspects may produce unfortunate outcomes, particularly when defiance of authority leads to usage of force. Application of excessive force may be interrupted, or obviated by the actions of bystander officers who become intervening officers. This study evaluated officer and supervisor perceptions of a training program which taught intervention strategies and tactics to help officers intervene with other officers to prevent harm. Data were collected very early in program implementation and approximately one year later. Survey data were collected with officers and qualitative focus groups were conducted with officers and supervisors. Findings indicate a marked change in perceptions by officers. Both quantitative and qualitative findings collected in early phase indicate a high degree of officer resistance. Late phase data indicate significantly higher endorsement of officer intervention strategies and participants reported higher frequencies of intervening with other officers. Findings suggest officer-based de-escalation and intervention training warrants implementation consideration from agency decision makers. [ABSTRACT FROM AUTHOR]

After an acute coronary syndrome (ACS) it is imperative to balance the bleeding vs. the ischemic risk given the similar prognostic impact of the two events. Since the post-discharge bleeding risk is substantially stable over time whereas the ischemic risk accumulates in the first weeks to months, a strategy of de-escalation of antithrombotic treatment, consisting in the reduction of either the duration (i.e., early interruption of one antiplatelet agent) or the intensity (i.e., switching from the more potent P2Y12-inhibitors prasugrel or ticagrelor to clopidogrel) of dual antiplatelet therapy (DAPT), has been proposed. Reducing the intensity of DAPT can be carried out as a default strategy (unguided approach) or based on the results of either platelet function tests or genetic tests (guided approach). Overall, all de-escalation strategies have shown to consistently decrease bleeding events with no apparent increase in ischemic events as compared to 12-month standard-of-care DAPT. Owing however to several limitations and weaknesses of the available evidence, de-escalation strategies are currently not recommended as a routine, but should rather be considered for selected ACS patients, such as those at increased risk of bleeding. [ABSTRACT FROM AUTHOR]

Purpose of Review: To describe current research regarding omission of sentinel lymph node biopsy (SLNB) in breast cancer patients. Recent Findings: Results from a recent clinical trial, the SOUND trial, with results pending from trials such as NAUTILUS, INSEMA and BOOG 2013–08, suggest that the omission of SLNB in patients with T1-2 N0 invasive breast cancer is oncologically safe and has noninferior 5-year distant disease-free survival compared to those who underwent SLNB ± ALND. Best practice guidelines do recommend omitting SLNB for older patients with estrogen receptor invasive breast cancers and for most patients undergoing surgery for ductal carcinoma in situ. Summary: Axillary surgery continues to evolve over time to less surgery in the axilla for patients with both invasive and noninvasive disease. Changes in adjuvant therapy, increased use of genomic testing and axillary US have all impacted this trend. [ABSTRACT FROM AUTHOR]

Purpose: The randomized phase 2 Neo-peaks study examined usefulness of neoadjuvant trastuzumab emtansine + pertuzumab (T-DM1 + P) following docetaxel + carboplatin + trastuzumab + pertuzumab (TCbHP) as compared with the standard TCbHP regimen. We previously reported that pCR rate after neoadjuvant therapy tended to be higher with TCbHP followed by T-DM1 + P. We conducted an exploratory analysis of prognosis 5 years after surgery. Methods: Neoadjuvant treatment with TCbHP (6 cycles; group A), TCbHP (4 cycles) followed by T-DM1 + P (4 cycles; group B), and T-DM1 + P (4 cycles; group C, + 2 cycles in responders) were compared. Group C non-responders after 4 cycles were switched to an anthracycline-based regimen. We evaluated 5-year disease-free survival (DFS), distant DFS (DDFS), and overall survival (OS). Results: Data from 203 patients (50, 52, and 101 in groups A–C, respectively) were analyzed. No significant intergroup differences were found for DFS, DDFS, or OS. The 5-year DFS rates (95% CI) were 91.8% (79.6–96.8%), 92.3% (80.8–97.0%), and 88.0% (79.9–93.0%) in groups A–C, respectively. TCbHP followed by T-DM1 + P and T-DM1 + P with response-guided addition of anthracycline therapy resulted in similar long-term prognosis to that of TCbHP. Conclusions: In patients who achieved pCR after neoadjuvant therapy with T-DM1 + P, omission of adjuvant anthracycline may be considered, whereas treatment should be adjusted for non-pCR patients with residual disease. T-DM1 + P with response-guided treatment adjustment may be useful for minimizing toxicity. Trial registration number and date of registration: UMIN-CTR, UMIN000014649, prospectively registered July 25, 2014. Some of the study results were presented as a Mini Oral session at the ESMO Breast Cancer 2023 (Berlin, Germany, 11–13 May 2023). [ABSTRACT FROM AUTHOR]

In light of increasing concerns about use of force, one of the most prominent recommendations for improving policing is ‘de-escalation’. However, despite the hype surrounding de-escalation, a clear definition still is lacking. At the same time, debates about de-escalation have not been grounded in, or informed by, police practice. The lack of a solid definition is problematic in practice, as police struggle with potentially conflicting considerations. This study utilizes interviews with use of force experts and a survey of frontline officers to produce a better understanding of de-escalation. The results highlight the importance of nuance in police-public interactions, which are highly variable. In particular, de-escalation cannot be conceptualized as a one-size-fits-all solution capable of solving all elevated police-citizen interactions. A practical definition of de-escalation must also acknowledge that force may sometimes be required. The perspective that use of force is incompatible with de-escalation does not reflect the realities of policing. [ABSTRACT FROM AUTHOR]

Background: De-escalation is often advocated to reduce harm associated with violence and use of restrictive interventions, but there is insufficient understanding of factors that influence de-escalation behaviour in practice. For the first time, using behaviour change and implementation science methodology, this paper aims to identify the drivers that will enhance de-escalation in acute inpatient and psychiatric intensive care mental health settings. Methods: Secondary analysis of 46 qualitative interviews with ward staff (n = 20) and patients (n = 26) informed by the Theoretical Domains Framework. Results: Capabilities for de-escalation included knowledge (impact of trauma on memory and self-regulation and the aetiology and experience of voice hearing) and skills (emotional self-regulation, distress validation, reducing social distance, confirming autonomy, setting limits and problem-solving). Opportunities for de-escalation were limited by dysfunctional risk management cultures/ relationships between ward staff and clinical leadership, and a lack of patient involvement in safety maintenance. Motivation to engage in de-escalation was limited by negative emotion associated with moral formulations of patients and internal attributions for behaviour. Conclusion: In addition to training that enhances knowledge and skills, interventions to enhance de-escalation should target ward and organisational cultures, as well as making fundamental changes to the social and physical structure of inpatient mental health wards. Psychological interventions targeting negative emotion in staff are needed to increase motivation. This paper provides a new evidence-based framework of indicative changes that will enhance de-escalation in adult acute mental health inpatient and PICU settings. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with locoregional head and neck cancer often receive radiation and/or surgery with curative intent. Chemotherapy is often used as a radiation sensitizer or adjunctively to improve treatment effect. However, these modalities are often associated with significant and potentially debilitating adverse events, which negatively impacts quality of life. HPV-associated oropharyngeal head and neck cancer has been shown to be more responsive to treatment compared to HPV-negative disease. Therefore, various de-escalation strategies have been under investigation in hopes of optimizing therapeutic response while also minimizing toxicity from treatment. The incidence of HPV-related oropharyngeal cancers has increased in recent decades. While cure rates exceed those of HPV-negative head and neck cancers, both acute and long-term sequelae of chemotherapy, radiation and surgery have led to clinical investigation into de-escalation of treatment. De-escalation trials have sought to reduce long-term treatment-related morbidity by altering or omitting chemotherapy, reducing radiation, or incorporating less invasive surgical resection through transoral surgery. More recent approaches include the use of novel agents such as immunotherapy in place of cisplatin. With the advent of tumor-tissue-modified HPV DNA detection and monitoring in blood, new strategies incorporating this biomarker are being developed. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Merkel cell carcinoma (MCC) presents challenges in surveillance due to varied recurrence rates and uncertain follow‐up protocols, especially in late recurrent cases. These cases need personalized monitoring strategies beyond traditional timelines, such as clinical and molecular factors, in order to optimize patient outcomes. Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with neuroendocrine differentiation with a propensity for recurrence following initial treatment. Surveillance strategies for MCC patients lack specificity, and the duration of surveillance remains uncertain, posing challenges in identifying appropriate follow‐up intervals. Therefore, we present a 94‐year‐old woman, with history of stage IA MCC in her left nasal wall 21 years prior, that presented with a dome‐shaped eroded nodule on her left fifth finger. Biopsy showed characteristic MCC features with positive immunohistochemistry for CD56, synaptophysin, and CK20 (perinuclear dotting). The patient opted against further imaging or lymph node biopsy and underwent Mohs micrographic surgery. To date, there has not been any evidence of recurrence at previous sites or development of new primary lesions. This case underscores the need for ongoing surveillance despite long disease‐free intervals. It also stands out as the case demonstrating the longest latency/recurrence‐free interval following the initial diagnosis of MCC in the literature. While most recurrences occur within the first few years post‐diagnosis, our case highlights the exceptional nature of late recurrences and prompts reevaluation of surveillance protocols. Current guidelines recommend surveillance for up to 3 years post‐treatment, but factors, such as patient demographics and tumor characteristics, may warrant extended monitoring periods. Emerging biomarkers, such as Merkel cell polyomavirus status and circulating tumor DNA, show promise in predicting and monitoring recurrences, but their utility in late recurrence detection requires further investigation. [ABSTRACT FROM AUTHOR]

Lymphatic metastasis is the dominant route of initial spread for most solid tumors. For many such malignancies, including melanomas, surgical treatment previously included removal of all potentially draining regional lymph nodes (elective node dissection). The advent of lymphatic mapping and sentinel lymph node (SLN) biopsy allowed accurate pathologic assessment of the metastatic status of regional nodes and spared patients full dissection if their SLN was clear. In melanoma, recent clinical research has demonstrated that complete lymph node dissection is not clinically beneficial, even for patients with sentinel node metastases and that patients with high-risk primary melanomas benefit from adjuvant systemic immunotherapy, even without nodal disease. These two changes in the standard of care have led to some interest in abandoning surgical nodal staging via the sentinel lymph node biopsy procedure. However, this appears to be premature and potentially detrimental to optimal patient management. The ongoing value of sentinel node biopsy stems from its ability to provide critically important prognostic information as well as durable regional nodal disease control for most patients with nodal metastases, even in the absence of complete dissection of the basin. It also provides an opportunity to identify novel prognostic and predictive immunologic and molecular biomarkers. While it is certainly possible that additional changes in melanoma therapy will make sentinel lymph node biopsy obsolete in the future, at present it remains a minimally invasive, low morbidity means of improving both staging and outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Patients with clinically node-negative breast cancer have a negative sentinel lymph node status (pN0) in approximately 75% of cases and the necessity of routine surgical nodal staging by sentinel lymph node biopsy (SLNB) has been questioned. Previous prediction models for pN0 have included postoperative variables, thus defeating their purpose to spare patients non-beneficial axillary surgery. We aimed to develop a preoperative prediction model for pN0 and to evaluate the contribution of mammographic breast density and mammogram features derived by artificial intelligence for de-escalation of SLNB. Materials and methods: This retrospective cohort study included 755 women with primary breast cancer. Mammograms were analyzed by commercially available artificial intelligence and automated systems. The additional predictive value of features was evaluated using logistic regression models including preoperative clinical variables and radiological tumor size. The final model was internally validated using bootstrap and externally validated in a separate cohort. A nomogram for prediction of pN0 was developed. The correlation between pathological tumor size and the preoperative radiological tumor size was calculated. Results: Radiological tumor size was the strongest predictor of pN0 and included in a preoperative prediction model displaying an area under the curve of 0.68 (95% confidence interval: 0.63-0.72) in internal validation and 0.64 (95% confidence interval: 0.59-0.69) in external validation. Although the addition of mammographic features did not improve discrimination, the prediction model provided a 21% SLNB reduction rate when a false negative rate of 10% was accepted, reflecting the accepted false negative rate of SLNB. Conclusion: This study shows that the preoperatively available radiological tumor size might replace pathological tumor size as a key predictor in a preoperative prediction model for pN0. While the overall performance was not improved by mammographic features, one in five patients could be omitted from axillary surgery by applying the preoperative prediction model for nodal status. The nomogram visualizing the model could support preoperative patient-centered decision-making on the management of the axilla. [ABSTRACT FROM AUTHOR]

Abstract Background De-escalation is often advocated to reduce harm associated with violence and use of restrictive interventions, but there is insufficient understanding of factors that influence de-escalation behaviour in practice. For the first time, using behaviour change and implementation science methodology, this paper aims to identify the drivers that will enhance de-escalation in acute inpatient and psychiatric intensive care mental health settings. Methods Secondary analysis of 46 qualitative interviews with ward staff (n = 20) and patients (n = 26) informed by the Theoretical Domains Framework. Results Capabilities for de-escalation included knowledge (impact of trauma on memory and self-regulation and the aetiology and experience of voice hearing) and skills (emotional self-regulation, distress validation, reducing social distance, confirming autonomy, setting limits and problem-solving). Opportunities for de-escalation were limited by dysfunctional risk management cultures/ relationships between ward staff and clinical leadership, and a lack of patient involvement in safety maintenance. Motivation to engage in de-escalation was limited by negative emotion associated with moral formulations of patients and internal attributions for behaviour. Conclusion In addition to training that enhances knowledge and skills, interventions to enhance de-escalation should target ward and organisational cultures, as well as making fundamental changes to the social and physical structure of inpatient mental health wards. Psychological interventions targeting negative emotion in staff are needed to increase motivation. This paper provides a new evidence-based framework of indicative changes that will enhance de-escalation in adult acute mental health inpatient and PICU settings.

To date, the literature offers multiple suggestions for how to recover from service failures, albeit without explicitly addressing customers' negative, high-arousal states evoked by the failure. The few studies that do address ways to improve negative emotions after failures focus on face-to-face interactions only. Because many customers today prefer to complain on social media, firms must learn how to effectively de-escalate negative, high-arousal emotions through text-based exchanges to achieve successful service recoveries. With three field studies using natural language processing tools and three preregistered controlled experiments, the current research identifies ways to mitigate negative arousal in text-based social media complaining, specifically, active listening and empathy. In detail, increasing active listening and empathy in the firm response evokes gratitude among customers in high-arousal states, even if the actual failure is not (yet) recovered. These findings provide a new theoretical perspective on the role of customer arousal in service failures and recoveries as well as managerially relevant implications for dealing with public social media complaints. [ABSTRACT FROM AUTHOR]

Abstract Antimicrobial/antibiotic de-escalation (ADE) is a key feature of antimicrobial stewardship programs (ASP) that relies mainly on individual panels for determining ADE events based on subjective ranking of antibiotics’ spectrum activity. The lack of consensus among ASP experts leads to reproducibility issues in the measure of this clinical outcome, making difficult to assess its real impact on patient care. The S3 score (Simplified Spectrum Score) app was developed to allow an objective ranking of antibiotics. Ranking was achieved by developing a database harboring pairs of bacteria-antibiotics for which each molecule was assigned a score based on published and clinically validated data from a recognized international committee. S3 score shows a strong correlation relationship and substantial agreement to a clinically validated spectrum score, and its framework enables any person to use it for ADE detection without assuming prior knowledge or training. In addition, its design enables regular updates and sustainability.

Objectives: To evaluate the impact of clinical pharmacist practitioner (CPP) management on potentially inappropriate use of inhaled corticosteroids (ICS) in the ambulatory care setting. Design: Multicenter, prospective quality assurance/improvement (QA/QI) project. Setting: Erie Veterans Affairs Medical Center (VAMC) and surrounding Ashtabula, Crawford, and Venango County Community-Based Outpatient Clinics (CBOCs). Participants: Thirty-five participants with chronic obstructive pulmonary disease (COPD) who met inclusion criteria were included in the project. Interventions: Participants were contacted to schedule an initial sixty-minute telephone visit with a CPP. Exacerbation history, rescue inhaler use, and symptom burden were assessed using the COPD Assessment Test (CAT) and Modified Medical Research Counsel Breathlessness Scale (mMRC) scales. Medication regimens were optimized based on guideline recommendations with an emphasis on appropriate use of ICS. Participants were scheduled for follow-up telephone visits with the CPP every 4 weeks. Main Outcome Measures: The primary project outcome was potentially inappropriate use of ICS without a long-acting muscarinic antagonist (LAMA)/long-acting beta agonist (LABA). Secondary project outcomes included ICS de-escalation, vaccinations, and smoking cessation. Results: The primary outcome of reducing use of ICS without a LAMA/LABA was achieved in thirty-one (88.6%) participants. ICS de-escalation was achieved in twenty-three (65.7%) participants. Rates of recommended vaccinations and smoking cessation with nicotine replacement therapy increased as a result of pharmacist intervention. Conclusion: Pharmacist management of COPD in the ambulatory care setting was associated with a decrease in potentially inappropriate use of ICS and an increase in preventative care measures. [ABSTRACT FROM AUTHOR]

The serum (1,3)-beta- d -glucan (BDG) assay gives quicker results and has higher sensitivity than blood cultures, therefore it is advised for early diagnosis of invasive candidemia and/or discontinuation of empirical therapy. Its sensitivity may depend on different factors. The aim of our study was to analyse the in vitro and in vivo BDG levels in clinical isolates of three species of Candida responsible for candidemia. C. albicans, C. parapsilosis, and C. auris strains were collected from blood cultures of patients who had a concurrent (–1 to +3 days) serum BDG test (Fungitell assay). Supernatants of all strains were tested in quadruplicate for BDG levels. Twenty-two C. auris , 14 C. albicans, and ten C. parapsilosis strains were included. The median BDG levels in supernatants were 463 pg/mL (interquartile range [IQR] 379–648) for C. auris , 1080 pg/mL (IQR 830–1276) for C. albican s, and 755 pg/mL (IQR 511–930) for C. parapsilosis , with the significant difference among the species (p < 0.0001). Median serum BDG levels (IQR) were significantly lower in case C. auris and C. parapsilosis vs. C. albicans (p < 0.0001), respectively, 50 pg/mL (IQR 15–161) and 57 pg/mL (IQR 18–332), vs. 372 pg/mL (IQR 102–520). Sensitivity of serum BDG was 39% (95% confidence interval [CI], 18–64) in case of C. auris , 30% (95% CI, 8–65) C. parapsilosis and 78% (95% CI, 49–94) C. albicans candidemia. In our centre C. auris and C. parapsilosis strains have lower BDG content as compared with C. albicans , with a potential impact on serum BDG performance for the diagnosis of candidemia. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance and excessive antibiotic usage are a growing public health concern. Antimicrobial Stewardship Programs (ASPs) aim to optimize antibiotic use and curb resistance. This retro-respective study evaluated the impact of an ASP at Madinat Zayed Hospital, Abu Dhabi (January 2021-December 2022). It analyzed electronic health records to assess the ASP's impact on antibiotic consumption, resistance patterns, and economic outcomes. Patients from intensive care units, medical wards, and outpatient settings were included, though patients admitted to obstetrics/gynaecology, paediatrics, neonatal intensive care, and surgical wards were excluded. The primary objective of this study was to report on the ASP experience and measure the prescribing appropriateness percentage of empirical antibiotic therapy along with the de-escalation of broad-spectrum antimicrobials, after ASP implementation at Madinat Zayed Hospital in Al Dhafra Region, United Arab Emirates. The secondary objectives were to reflect on the rate of Multidrug-Resistant Organisms (MDROs), total utilization using defined daily dose, and the total direct cost of antibiotics. Descriptive analysis, proportions, mean values, and percentage changes were employed for data analysis. The ASP achieved high compliance rates with restricted antibiotics (>90%) and approved guidelines (inpatient 97-100%, outpatient 93-98%). Antibiotic de-escalation rates were also high (>80%). Significant reductions in use were observed for cefixime (91.3%), levofloxacin (46.3%), and several others. Notably, cefepime use increased (1137.5%). Direct antibiotic expenditure decreased by 2% (saving Dhs2.6 million), and resistance decreased in some bacteria. However, a concerning rise in ceftazidime resistance against Pseudomonas aeruginosa was identified. This study concluded that the implementation of a new Antimicrobial Stewardship Program at Madinat Zayed Hospital demonstrated effectiveness in promoting responsible antibiotic use. The program achieved high compliance with restricted antibiotic use and approved guidelines, leading to significant reductions in overall antibiotic consumption. [ABSTRACT FROM AUTHOR]

Background: Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with radiation-based therapy suffer from short- and long-term toxicities that affect quality of life (QOL). Transoral robotic surgery (TORS) has an established role in the management of early OPSCC but adjuvant treatment is often indicated postoperatively due to the high incidence of nodal metastasis associated with advanced human papillomavirus (HPV)-related OPSCC. To overcome the need for adjuvant radiation therapy (RT), neoadjuvant chemotherapy followed by TORS and neck dissection (ND) is proposed. This study aimed to assess if QOL in HPV-associated OPSCC receiving neoadjuvant chemotherapy followed by TORS and ND returns to baseline within 12 months of completing treatment. Methods: A 12 month longitudinal study was carried out at McGill University Health Centre in Montreal, Canada, among a convenience sample of patients with American Joint Committee on Cancer Seventh Edition stage III and IVa HPV-related OPSCC who were treated with neoadjuvant chemotherapy followed by TORS and ND. QOL data were obtained pretreatment and at 1, 3, 6, and 12 months following treatment completion using the European Organisation for Research and Treatment of Cancer Core and Head and Neck extension modules. Paired t tests and mixed models for repeated measures analysis were used to assess changes in QOL from baseline to 12 months postoperatively and over time, respectively. Results: Nineteen of 23 patients (median age 58 years) who received the study treatment fulfilled the eligibility criteria. OPSCC subsites were palatine tonsil (n = 12) and base of tongue (n = 7). All 19 patients were treated per protocol and none required adjuvant RT as per pathology review and protocol requirements at a postoperative multidisciplinary team tumor board discussion. No significant differences were found when comparing 12 month QOL follow-up scores to pretreatment scores in measures that would likely be affected by RT [eg, swallowing (P =.7), social eating (P =.8), xerostomia (P =.9)]. Conclusion: In HPV-related OPSCC, neoadjuvant chemotherapy followed by TORS and ND as definitive treatment is associated with excellent QOL outcomes. Postoperative QOL scores returned to baseline by 3 months and were maintained for all measures, indicating a return to normal function. [ABSTRACT FROM AUTHOR]

The landscape of treating metastatic prostate cancer has evolved with the addition of Androgen Receptor pathway inhibitor (ARPI) to Androgen Deprivation Therapy (ADT), significantly improving survival rates. However, prolonged use of these therapies introduces notable side effects, prompting a need to revisit intermittent treatment duration. The EORTC 2238 De-Escalate trial is a pragmatic trial seeking to reassess the role of intermittent therapy in patients undergoing maximal androgen blockade (MAB) for metastatic hormone naïve prostate cancer (mHNPC), i.e., the combination of ADT with an ARPI, with the aims of reducing side effects, enhancing Quality of Life (QoL) and optimizing resource usage, while maintaining oncological benefits. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) presents unique challenges and opportunities for treatment, particularly regarding de-escalation strategies to reduce treatment morbidity without compromising oncological outcomes. This paper examines the role of Transoral Robotic Surgery (TORS) as a de-escalation strategy in managing HPV-related OPSCC. We conducted a comprehensive literature review from January 2010 to June 2023, focusing on studies exploring TORS outcomes in patients with HPV-positive OPSCC. These findings highlight TORS's potential to reduce the need for adjuvant therapy, thereby minimizing treatment-related side effects while maintaining high rates of oncological control. TORS offers advantages such as precise tumor resection and the ability to obtain accurate pathological staging, which can guide the tailoring of adjuvant treatments. Some clinical trials provide evidence supporting the use of TORS in specific patient populations. The MC1273 trial demonstrated promising outcomes with lower doses of adjuvant radiotherapy (RT) following TORS, showing high locoregional tumor control rates and favorable survival outcomes with minimal side effects. ECOG 3311 evaluated upfront TORS followed by histopathologically directed adjuvant therapy, revealing good oncological and functional outcomes, particularly in intermediate-risk patients. The SIRS trial emphasized the benefits of upfront surgery with neck dissection followed by de-escalated RT in patients with favorable survival and excellent functional outcomes. At the same time, the PATHOS trial examined the impact of risk-adapted adjuvant treatment on functional outcomes and survival. The ongoing ADEPT trial investigates reduced-dose adjuvant RT, and the DART-HPV study aims to compare standard adjuvant chemoradiotherapy (CRT) with a reduced dose of adjuvant RT in HPV-positive OPSCC patients. These trials collectively underscore the potential of TORS in facilitating treatment de-escalation while maintaining favorable oncological and functional outcomes in selected patients with HPV-related OPSCC. The aim of this scoping review is to discuss the challenges of risk stratification, the importance of HPV status determination, and the implications of smoking on treatment outcomes. It also explores the evolving criteria for adjuvant therapy following TORS, focusing on reducing radiation dosage and volume without compromising treatment efficacy. In conclusion, TORS emerges as a viable upfront treatment option for carefully selected patients with HPV-positive OPSCC, offering a pathway toward treatment de-escalation. However, selecting the optimal candidate for TORS-based de-escalation strategies is crucial to fully leverage the benefits of treatment de-intensification. [ABSTRACT FROM AUTHOR]

Antimicrobial/antibiotic de-escalation (ADE) is a key feature of antimicrobial stewardship programs (ASP) that relies mainly on individual panels for determining ADE events based on subjective ranking of antibiotics' spectrum activity. The lack of consensus among ASP experts leads to reproducibility issues in the measure of this clinical outcome, making difficult to assess its real impact on patient care. The S3 score (Simplified Spectrum Score) app was developed to allow an objective ranking of antibiotics. Ranking was achieved by developing a database harboring pairs of bacteria-antibiotics for which each molecule was assigned a score based on published and clinically validated data from a recognized international committee. S3 score shows a strong correlation relationship and substantial agreement to a clinically validated spectrum score, and its framework enables any person to use it for ADE detection without assuming prior knowledge or training. In addition, its design enables regular updates and sustainability. [ABSTRACT FROM AUTHOR]

Simple Summary: We aimed to develop a Bayesian Network model to predict treatment outcomes and quality of life. Conditional probabilities and disability weights for radiotherapy-related benefit and risk were collected from nationwide expert survey. Overall disease burden (ODB) was defined as sum of conditional probabilities multiplied by disability weights. A Bayesian network model to predict ODB for (y)pN1 breast cancer was constructed. This model evaluated ongoing prospective trials for (y)pN1 breast cancer such as the Alliance A011202, PORT-N1, RAPCHEM, and RT-CHARM trials, validating reported results and assumptions. Background: We aimed to construct an expert knowledge-based Bayesian network (BN) model for assessing the overall disease burden (ODB) in (y)pN1 breast cancer patients and compare ODB across arms of ongoing trials. Methods: Utilizing institutional data and expert surveys, we developed a BN model for (y)pN1 breast cancer. Expert-derived probabilities and disability weights for radiotherapy-related benefit (e.g., 7-year disease-free survival [DFS]) and toxicities were integrated into the model. ODB was defined as the sum of disability weights multiplied by probabilities. In silico predictions were conducted for Alliance A011202, PORT-N1, RAPCHEM, and RT-CHARM trials, comparing ODB, 7-year DFS, and side effects. Results: In the Alliance A011202 trial, 7-year DFS was 80.1% in both arms. Axillary lymph node dissection led to higher clinical lymphedema and ODB compared to sentinel lymph node biopsy with full regional nodal irradiation (RNI). In the PORT-N1 trial, the control arm (whole-breast irradiation [WBI] with RNI or post-mastectomy radiotherapy [PMRT]) had an ODB of 0.254, while the experimental arm (WBI alone or no PMRT) had an ODB of 0.255. In the RAPCHEM trial, the radiotherapy field did not impact the 7-year DFS in ypN1 patients. However, there was a mild ODB increase with a larger irradiation field. In the RT-CHARM trial, we identified factors associated with the major complication rate, which ranged from 18.3% to 22.1%. Conclusions: The expert knowledge-based BN model predicted ongoing trial outcomes, validating reported results and assumptions. In addition, the model demonstrated the ODB in different arms, with an emphasis on quality of life. [ABSTRACT FROM AUTHOR]

Background and purpose: The volume treated with postoperative radiation therapy (PORT) in patients with oral cavity squamous cell carcinoma (OCSCC) is a mediator of toxicity affecting quality of life. Current guidelines only allow for very limited reduction of PORT volumes. This study investigated the safety and efficacy of de-intensified PORT for patients with OCSCC by refined compartmentalization of the treatment volume. Materials and methods: This retrospective cohort study identified 103 OCSCC patients treated surgically from 2014 to 2019 with a loco-regional risk profile qualifying for PORT according to guidelines. PORT was administered only to the at-risk compartment and according to a refined compartmentalization concept (CC). Oncological outcome of this CC cohort was compared to a historical cohort (HC) of 98 patients treated before the CC was implemented. Results: Median follow-up time was 4.5 and 4.8 years in the CC and HC cohorts, respectively. In the CC cohort, a total of 72 of 103 patients (70%) had a pathological risk profile that allowed for further compartmentalization and, hence, received a reduced treatment volume or omission of PORT altogether. Loco-regional control at 3 and 5 years was 77% and 73% in the CC cohort versus 78% and 73% in the HC (p = 0.93), progression-free survival was 72% and 64% versus75% and 68% (p = 0.58), respectively. Similarly, no statistically significant difference was seen in other outcome measures. Conclusions: De-intensified PORT limiting the treatment volume to the at-risk compartment or avoiding PORT altogether for low-risk patients with OCSCC does not seem to compromise disease control in this retrospective comparison. Based on these hypothesis-generating findings, a prospective study is being planned. [ABSTRACT FROM AUTHOR]

Background: Patients with hematologic malignancies frequently develop febrile neutropenia (FN) and subsequently receive long courses of broad-spectrum antibiotics. Limited data is available on de-escalation strategies. Methods : This was a retrospective observational cohort study of adult patients with a hematologic malignancy, FN, and positive culture results from June 2017 to June 2020. A conventional group (patients who remained on empiric, broad-spectrum agents) was compared to a de-escalation group (patients whose antibiotic therapy was de-escalated based on culture results). The primary outcome was the incidence of recurrent fever or antibiotic escalation due to infection while neutropenic. Results: Of the 123 patients included, the composite primary outcome occurred in 35.3% in the de-escalation group and 39.3% in the conventional group (P =.83). For secondary outcomes, median time to recurrent fever was 7 days in the de-escalation group and 7 days in the conventional group (P =.73). Incidence of Clostridioides difficile was 5.9% in the de-escalation group and 6.7% in the conventional group (P = 1.00). Development of multidrug resistant pathogens during hospital admission was 20.6% in the de-escalation group and 14.6% in the conventional group (P =.59). Median length of broad-spectrum antibiotics was 3 days in the de-escalation group and 8 days in the conventional group (P <.001). All-cause mortality within 30 days was 0 in the de-escalation group and 5.6% in the conventional group (P =.32). Conclusion: In a small sample of patients with a hematologic malignancy and FN, de-escalating antibiotics based on positive cultures decreased the duration of antibiotic therapy without increasing the rate of antibiotic failure. [ABSTRACT FROM AUTHOR]

Observational studies in adults suggest nasal methicillin-resistant Staphylococcus aureus (MRSA) swabs have a high negative predictive value (NPV) for ruling out MRSA pneumonia, however, pediatric data are limited. This retrospective study of 505 pediatric patients found a 99.8% NPV among children with suspected respiratory infections. [ABSTRACT FROM AUTHOR]

Background: De‐escalation strategies for newly‐diagnosed p16‐positive oropharyngeal squamous cell carcinoma (p16+ OPSCC), aim to reduce treatment‐related morbidity without compromising disease control. One strategy is neoadjuvant cisplatin and docetaxel chemotherapy (NAC + S) before transoral robotic surgery, with pathology‐based risk‐adapted adjuvant treatment. Methods: We examined the recurrence‐free survival (RFS) for patients who received NAC + S. Results: Comparing outcomes in 103 patients between 2008 and 2023, 92% avoided adjuvant treatment and showed significantly higher 2‐year recurrence‐free survival (RFS) compared to those with adjuvant treatment (95.9% vs. 43.8%, p = 0.0049) Conclusion: Our findings suggest that pathology‐based risk‐adapted omission of adjuvant treatment following NAC + S does not appear to elevate recurrence risk and that NAC may identify patients with favorable tumor biology, yielding a 2‐year RFS probability exceeding 95% without adjuvant treatment. Further, the study identifies a patient subset experiencing disease recurrence despite triple modality therapy. Despite limitations, including a retrospective design and modest sample size, the data advocate for controlled NAC + S studies. [ABSTRACT FROM AUTHOR]

Introduction Biologic therapy is an effective treatment for inflammatory bowel disease [IBD]. However due to cost and safety concerns, dose de-escalation strategies after achieving remission have been suggested. Aim To critically review available data on dose de-escalation of biologics [or other advanced therapies] in IBD. We will focus on studies evaluating de-escalation to standard dosing in patients initially optimised, and also on studies assessing de-escalation from standard dosing. Methods A systematic bibliographic search was performed. Results The mean frequency of de-escalation after previous dose intensification [12 studies, 1,474 patients] was 34%. The corresponding frequency of de-escalation from standard dosing [five studies, 3,842 patients] was 4.2%. The relapse rate of IBD following anti-tumour necrosis factor [TNF] de-escalation to standard dosing in patients initially dose-escalated [10 studies, 301 patients] was 30%. The corresponding relapse rate following anti-TNF de-escalation from standard dosing [nine studies, 494 patients] was 38%. The risk of relapse was lower for patients in clinical, biologic, and endoscopic/radiological remission at the time of de-escalation. A role of anti-TNF therapeutic drug monitoring in the decision to dose de-escalate has been demonstrated. In patients relapsing after de-escalation, re-escalation is generally effective. De-escalation is not consistently associated with a better safety profile. The cost-effectiveness of the de-escalation strategy remains uncertain. Finally, there is not enough evidence to recommend dose de-escalation of biologics different from anti-TNFs or small molecules. Conclusions Any consideration for de-escalation of biologic therapy in IBD must be tailored, taking into account the risks and consequences of a flare and patients' preferences. [ABSTRACT FROM AUTHOR]

Background: Coping with complex behaviour in mental health care is a challenging but integral part of a caregiver's job. De-escalation can prevent violence as it aims to stop the progress of violent cycles. Skill stations show promising results when testing and learning social competence in real-life scenarios, and develop the theoretical competencies of hospital staff. Objective: To transform research-based knowledge of de-escalation into a skill station. Method: Together with stakeholders, and across psychiatric and somatic hospitals, the skill station was designed, tested and disseminated. Evaluation was done through surveys and focus groups. Results: Staff found the skill station helpful. Team learning provided knowledge of how to cope with complex behavior among patients and relatives, leading to an increase in the means of preventing aggression and violence in general hospital units. Conclusion: Skill stations in de-escalation can apply a way of learning which is familiar to clinical staff and may replace classroom teaching. [ABSTRACT FROM AUTHOR]

In recent years, Virtual Reality (VR) has emerged as a promising tool for enhancing training responses in high-stress professions, notably among police officers. This study investigates the psychophysiological responses and subjective user experience of active police officers undergoing Mental Health Crisis Response (MHCR) training using an immersive full-body VR system. A total of 10 active police officers with Special Weapons and Tactics (SWAT) training participated in our controlled study. Officers independently took part in one VR training session lasting 7–12 min involving an avatar in crisis portrayed by an actor. Officers wore integrated cardiovascular and electrodermal activity measurement devices for physiological monitoring. VR user experience aspects such as induced symptoms or game mechanics were investigated upon completing the training, aiming to evaluate the officer’s perceptions of the technology. We used the DePICT™ scale to evaluate the de-escalation skills of officers, coded by a research professional. Our findings revealed significant differences in heart rate and heart rate variability responses between baseline and VR scenario immersion, suggesting heightened stress regulation during the MHCR simulation using full-body VR. Arousal measurements also revealed measurable responses during the training in VR. Additionally, the user experience assessment indicated a positive reception to the VR training, with minimal VR-induced symptoms. A “Defensive-Dynamics-Dichotomy” was revealed highlighting dominant autonomic responses linked to defensive actions (e.g., officers who drew a weapon; those who kept their weapons holstered) and their respective implications for stress management and cognitive function. A unique constellation of de-escalation skills was revealed among officers who relied on weapons relative to those who did not, to resolve the scenario. The study highlighted the perceived utility of physiological monitoring technologies in enhancing police training outcomes. In conclusion, our research underscores the potential of VR as an effective tool for de-escalation training following MHCR simulated scenarios among active police officers, offering insights into its psychophysiological impact and user experience. The findings contribute to improving our understanding of the physiology associated with decision-making in police officers to draw a weapon, emphasizing the role of advanced simulation and physiological monitoring technology in developing evidence-based training programs for public safety.

Key Clinical Message Merkel cell carcinoma (MCC) presents challenges in surveillance due to varied recurrence rates and uncertain follow‐up protocols, especially in late recurrent cases. These cases need personalized monitoring strategies beyond traditional timelines, such as clinical and molecular factors, in order to optimize patient outcomes. Abstract Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with neuroendocrine differentiation with a propensity for recurrence following initial treatment. Surveillance strategies for MCC patients lack specificity, and the duration of surveillance remains uncertain, posing challenges in identifying appropriate follow‐up intervals. Therefore, we present a 94‐year‐old woman, with history of stage IA MCC in her left nasal wall 21 years prior, that presented with a dome‐shaped eroded nodule on her left fifth finger. Biopsy showed characteristic MCC features with positive immunohistochemistry for CD56, synaptophysin, and CK20 (perinuclear dotting). The patient opted against further imaging or lymph node biopsy and underwent Mohs micrographic surgery. To date, there has not been any evidence of recurrence at previous sites or development of new primary lesions. This case underscores the need for ongoing surveillance despite long disease‐free intervals. It also stands out as the case demonstrating the longest latency/recurrence‐free interval following the initial diagnosis of MCC in the literature. While most recurrences occur within the first few years post‐diagnosis, our case highlights the exceptional nature of late recurrences and prompts reevaluation of surveillance protocols. Current guidelines recommend surveillance for up to 3 years post‐treatment, but factors, such as patient demographics and tumor characteristics, may warrant extended monitoring periods. Emerging biomarkers, such as Merkel cell polyomavirus status and circulating tumor DNA, show promise in predicting and monitoring recurrences, but their utility in late recurrence detection requires further investigation.

Carcinosarcomas are high-grade endometrial cancers which enclose mesenchymal and epithelial differentiated components. The vast majority of these cancers belong to the p53 abnormal molecular subgroup and usually come with an unfavorable prognosis. POLE mutant carcinosarcomas are a rarity and only make up about 5% of this histologic subtype. Recent literature even suggests that this number is still an overestimation and the result of misclassification of undifferentiated or dedifferentiated endometrial cancers.Here we present a case of a 56-years old patient diagnosed with carcinosarcoma of the uterus. Hysterectomy, bilateral salpingo-oophorectomy with pelvic lymph node staging was performed and complete molecular workup of the tumor revealed an abnormal p53 expression as well as a pathologic POLE mutation. NGS was performed separately on the epithelial and mesenchymal component of this high-grade cancer and both components shared two identical POLE mutations, a known pathologic mutation, and a variant of unknown significance (VUS). This finding hints to a clonal origin of both histologic components of this tumor and supports conversion theory as mechanism of carcinosarcoma emergence. The cancer was correctly staged as FIGO 2023 Stage IAmPOLEmut and according to ESGO-ESTRO-ESP guidelines adjuvant chemotherapy no longer considered and our patient entered follow-up after a detailed discussion.

Summary: Background: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC. Methods: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II–III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154). Findings: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3–67.6) and 41 of 70 (58.6%, 95% CI 46.2–70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1–2). Interpretation: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation. Funding: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

IntroductionPatients with clinically node-negative breast cancer have a negative sentinel lymph node status (pN0) in approximately 75% of cases and the necessity of routine surgical nodal staging by sentinel lymph node biopsy (SLNB) has been questioned. Previous prediction models for pN0 have included postoperative variables, thus defeating their purpose to spare patients non-beneficial axillary surgery. We aimed to develop a preoperative prediction model for pN0 and to evaluate the contribution of mammographic breast density and mammogram features derived by artificial intelligence for de-escalation of SLNB.Materials and methodsThis retrospective cohort study included 755 women with primary breast cancer. Mammograms were analyzed by commercially available artificial intelligence and automated systems. The additional predictive value of features was evaluated using logistic regression models including preoperative clinical variables and radiological tumor size. The final model was internally validated using bootstrap and externally validated in a separate cohort. A nomogram for prediction of pN0 was developed. The correlation between pathological tumor size and the preoperative radiological tumor size was calculated.ResultsRadiological tumor size was the strongest predictor of pN0 and included in a preoperative prediction model displaying an area under the curve of 0.68 (95% confidence interval: 0.63–0.72) in internal validation and 0.64 (95% confidence interval: 0.59–0.69) in external validation. Although the addition of mammographic features did not improve discrimination, the prediction model provided a 21% SLNB reduction rate when a false negative rate of 10% was accepted, reflecting the accepted false negative rate of SLNB.ConclusionThis study shows that the preoperatively available radiological tumor size might replace pathological tumor size as a key predictor in a preoperative prediction model for pN0. While the overall performance was not improved by mammographic features, one in five patients could be omitted from axillary surgery by applying the preoperative prediction model for nodal status. The nomogram visualizing the model could support preoperative patient-centered decision-making on the management of the axilla.

Conflict de-escalation in police-citizen encounters is an under-researched topic despite increased focus from the public and the media. This paper aims to increase the understanding of how police officers attempt to de-escalate conflict through detailed accounts of actual conflicts. The study is based on seven qualitative interviews with Norwegian police officers and has a case-control-inspired design. The informants were asked to describe three ordinary encounters: one verbal conflict, one conflict involving threats, and one physical conflict involving force or violence. The interviews put specific focus on the behaviors the informants reported doing. The analysis revealed three ways de-escalation can be performed to manage conflicts. First, the informants emphasize verbal and nonverbal communication in three ways: calming, autonomy-enhancing, and commanding. Secondly, they describe how they reduce physical opportunities in order to de-escalate, by either delimiting physical space or by the use of force. Lastly, the informants also report on ways to prevent a conflict from escalating in the first place. These accounts highlight the informantsʼ understanding of de-escalation and are useful to understand how officers de-escalate conflicts in action. I discuss the relevance of the findings as well as the fruitfulness of the case-control-inspired interview technique.

Norihiro Saito,1– 3 Junichiro Tsuchiya,1,3 Masamichi Itoga,1,2 Yuji Okamura,1,4 Hiromasa Tsuyama,1,4 Masahiko Kimura,1,3 Fumio Inoue,1,3 Toshiyuki Kimura,1 Hiromi Ozaki,1 Yuka Tono,1,4 Satoko Minakawa,1,3 Hirofumi Tomita2,3,5 1Division of Infection Control and Prevention, Hirosaki University Hospital, Hirosaki, Aomori, Japan; 2Department of Clinical Laboratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan; 3Division of Clinical Laboratory, Hirosaki University Hospital, Hirosaki, Aomori, Japan; 4Division of Pharmacy, Hirosaki University Hospital, Hirosaki, Aomori, Japan; 5Department of Cardiology and Nephrology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, JapanCorrespondence: Norihiro Saito, Division of Infection Control and Prevention, Hirosaki University Hospital, 53 Hon-cho, Hirosaki, Aomori, 036-8563, Japan, Tel +81-172-33-5111, Email norihiro@hirosaki-u.ac.jpObjective: This study aimed to identify factors that should be focused on by the antimicrobial stewardship team for treating patients with sepsis, by investigating the mortality of patients with sepsis within 30 days and the mortality-related factors in our hospital over a 10-year period from the perspective of appropriate antimicrobial use.Methods: Factors associated with 30-day mortality were investigated using hierarchical multiple logistic regression in 1406 patients with pathogen-identified sepsis in Hirosaki University Hospital. These factors were clinical data, microbiological data, antimicrobials used in empiric and definitive therapies, presence/absence of ineffective use, underdosing as evaluated using Monte Carlo simulation, and practice of de-escalation.Results: The ineffective use of antimicrobials in empiric therapy and the underdosing and ineffective use in definitive therapy were significantly associated with 30-day mortality (odds ratio [OR] = 2.70, 3.72, and 3.65, respectively). Multiple blood culture sampling was inversely associated with these inappropriate antimicrobial uses. Every year, the 30-day mortality rate has been decreasing, in line with the increase in multiple blood culture sampling and de-escalation; the inappropriate use of antimicrobials has also decreased.Conclusion: Multiple blood culture sampling, proper choice of antimicrobial, and using an adequate dose in definitive therapy could decrease the 30-day mortality rate in patients with sepsis and these factors could be supported by the antimicrobial stewardship team.Keywords: sepsis, antimicrobial stewardship, Monte Carlo simulation, de-escalation

BackgroundThere is significant interest in treatment de-escalation for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) patients given the generally favourable prognosis. However, 15-30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to risk stratify HPV+ OPSCC patients.MethodsWe created an immune score (UWO3) associated with survival outcomes in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes.FindingsA three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival compared to the immune desert (HR = 9.0, 95% CI: 3.2-25.5, P = 3.6 × 10-5) and mixed (HR = 6.4, 95% CI: 2.2-18.7, P = 0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two small treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation.InterpretationWith additional prospective validation, the UWO3 score could enable biomarker-driven clinical decision-making for patients with HPV+ OPSCC based on robust outcome prediction across six independent cohorts. Prospective de-escalation and intensification clinical trials are currently being planned.FundingCIHR, European Union, and the NIH.

Simple Summary: Neoadjuvant therapy (NAT) has transformed the treatment of advanced breast cancer (BC), making previously inoperable tumors operable and allowing for the direct observation of treatment response. This approach reduces the need for extensive surgery, making breast-conserving surgery (BCS) a viable option for more patients. Despite the shift towards less-invasive surgery, the decision between BCS and mastectomy remains complex, influenced by numerous factors. Our study specifically looked at patients with cT3-4 BC treated with NAT, aiming to identify independent factors that predict the likelihood of undergoing BCS and to compare long-term oncological outcomes between BCS and mastectomy. We found that the absence of vascular invasion, smaller tumor size post-NAT, and achieving a complete response of the primary tumor were key predictors for breast conservation. Our results indicate that BCS post-NAT does not negatively impact long-term oncological outcomes, supporting its use as a safe option for patients with cT3-4 BC. Background: Neoadjuvant therapy (NAT) has become increasingly employed for the treatment of cT3-4 breast cancer (BC), enabling breast-conserving surgery (BCS) in cases traditionally considered for mastectomy. This study aims to identify predictors for breast conservation post-NAT and to evaluate whether BCS influences long-term oncological outcomes. Methods: We retrospectively analyzed data from patients with cT3-4 BC who received NAT at the Breast Unit of IRCCS Humanitas Research Hospital, Milan, Italy, from October 2009 to April 2020. Surgical outcomes and long-term oncological results, such as disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), and BC-specific survival (BCSS), were compared between the BCS and mastectomy groups. Results: Among 114 patients analyzed, 37 (32.5%) underwent BCS, and 77 (67.5%) had a mastectomy. The key predictors for opting for BCS included absence of vascular invasion, reduced tumor size post-NAT, and achieving ypT0 status. No significant differences in DFS, DDFS, OS, and BCSS were observed between the two surgical groups (log-ranks, p = 0.520, p = 0.789, p = 0.216, p = 0.559, respectively). Conclusions: BCS after NAT is a feasible and safe option for patients with cT3-4 BC, without adversely affecting long-term oncological outcomes. Identifying predictors of breast conservation can guide surgical decision-making, ensuring that patients receive optimal treatment. [ABSTRACT FROM AUTHOR]

This study aimed to assess the therapeutic effects of implementing the BioFire® Blood Culture Identification 2 (BCID2) Panel (bioMérieux, Marcy l'Etoile, France) in the clinical practice of children with sepsis. This retrospective cross-sectional study included children from 15 days of age to 18 years old with sepsis and of whom the BCID2 Panel was studied from the positive blood culture. If the antimicrobial treatment was changed according to the results of BCID2 Panel, it was recorded and re-grouped as targeted antimicrobial therapy, de-escalation of the antimicrobial treatment and shifting to another antimicrobial drug if any antimicrobial resistance was detected. Seven-days and thirty-days mortality rate was recorded. Thirty-two patients with 36 septic episodes with positive BCID2 Panel results were included. The median age was 10 months 15 days (ranging from 15 days to 16.5 years). The mean difference between having positive results by the BCID2 Panel and conventional culture methods was 82.2 ± 45.4 h (ranging from 12.3 to 207 h). Effect of the BCID2 Panel on the antimicrobial treatment was detected in 69.4% of the episodes (n = 25). Glycopeptides were ceased at 6 patients, piperacillin/tazobactam was ceased at 6 patients, and cefotaxime was ceased at one patient and de-escalation was achieved in 13 episodes which formed the 36.1% of the initial antimicrobial treatment. Conclusion: The BCID2 Panel had an important impact on the patients care and optimization according to the principles of antimicrobial stewardship. The BCID2 Panel may be one of the key items for rapid and accurate diagnosis in children with sepsis. Blood culture is still the mainstay for especially detection of antimicrobial drug resistance, while BCID2 tests had several advantages such as speed and diagnostic accuracy as good as blood culture. What is Known: • The BioFire® Blood Culture Identification 2 (BCID2) Panel (bioMérieux, Marcy l'Etoile, France) is a well-validated assay that allows for the simultaneous identification of 43 nucleic acid targets associated with bloodstream infections within about 1 h. What is New: • BCID2 Panel had a direct impact on the patient's treatment decision at the 69.4% of the sepsis episodes. • The clinicians received the microbiological results 82.2 h earlier with BCID2 panel compared to blood culture methods with antimicrobial resistance and de-escalation of the antimicrobial drugs was achieved at 13 episodes which formed the 36.1% of the initial treatment. [ABSTRACT FROM AUTHOR]

The aim of this article is to discuss the challenges and new strategies in managing breast cancer patients, with a specific focus on radiation oncology and the importance of balancing oncologic outcomes with quality of life and post-treatment morbidity. A comprehensive literature review was conducted to identify advances in the management of breast cancer, exploring de-escalation strategies, hypofractionation schemes, predictors and tools for reducing toxicity (radiation-induced lymphocyte apoptosis, deep inspiration breath-hold, adaptive radiotherapy), enhancer treatments (hyperthermia, immunotherapy) and innovative diagnostic modalities (PET-MRI, omics). Balancing oncologic outcomes with quality of life and post-treatment morbidity is crucial in the era of personalized medicine. Radiotherapy plays a critical role in the management of breast cancer patients. Large randomized trials are necessary to generalize some practices and cost remains the main obstacle for many innovations that are already applicable. [ABSTRACT FROM AUTHOR]

The purpose of this study is to explore the guardian mindset as a means for improving police-community relations. Using data collected from 735 new officers in the USA, confirmatory factor analyses were used to evaluate the empirical validity of the guardian vs. warrior typology, and structural equation modeling was used to examine the relationships among the guardian mindset and outcomes believed to improve relations with the public. The results show that officers' attitudes about the community and communication styles, but not attitudes about the role of the police, differentiate a guardian from a warrior orientation. The results also show that a higher-order guardian factor was related to attitudes about the use of force, procedural justice, and de-escalation. The findings provide some support for the positive effects of a guardian mindset on improving police-community relations while at the same time raising important questions for further study. [ABSTRACT FROM AUTHOR]

The last decade has seen the disappearance of nationalist political violence in two minority nations of Western Europe: the (Spanish) Basque Country and Corsica. Considering the importance of violence in the politics of these two communities (since 1959 in the Basque Country and 1976 in Corsica), the 2014 announcement by the Front de libération nationale corse of its 'demilitarization' and the dissolution of Euskadi Ta Askatasuna in 2018 represented potential critical junctures in the political development of both the Basque Country and Corsica. What, then, was the impact of the end of political violence in the two communities and why did this new 'civil peace' play out differently across the two cases, if it did? This article traces the process of political development in the Basque Country and Corsica through and after the end of violence. It shows that such end led to a strengthening of nationalism and a surge of claims for increased autonomy much more in Corsica than in the Basque Country. Then, the paper looks for an explanation for this divergence. It focuses on four differences between the two cases that could logically account for the different outcomes: constitutional status (the Basque Country has legislative and fiscal autonomy whereas Corsica has neither); the configuration of political power within each community (Basque nationalists dominate Basque politics whereas non-nationalist forces controlled Corsica until recently); the ideological positioning of the nationalist parties (more divergent in the Basque Country than in Corsica); and the levels of past violence (high in the Basque Country and low in Corsica). All these factors make post-violence alliances between nationalist forces easier in Corsica than the Basque Country. [ABSTRACT FROM AUTHOR]

Cementless primary stems in revision hip arthroplasties may be conservative options to preserve bone stock and provide adequate reconstruction of the hip biomechanics. However, there is still little evidence about indications, limitations, and outcomes. This narrative review showed that conventional standard stems were adopted in different revision settings, up to Paprosky IIIA grade bone defects. In cases of acceptable metaphyseal bone stock, when a scratch fit of at least 4 cm can be achieved, a conventional cementless stem may be an adequate solution. Mid-term clinical and radiographic outcomes and survival rates were similar to long revision stems, whereas complications, surgical time, and costs were lower among conventional stems. However, unsuitable contexts for conventional stems included canal diameters larger than 18 mm and failed revision stems with cortical weakening. Even short stems can be considered in revisions, in order to preserve bone stock and stay proximal to femoral remodeling zones and bone/cement plugs. Short stems were successfully adopted up to Paprosky IIIA bone defects, achieving mid-term survival rates not inferior to long revision stems. Ageing, osteoporosis, and intraoperative femoral fractures were the main negative prognostic factors. In very select cases, a downsizing technique (from longer to shorter stems) may be adopted to simplify the procedure and reduce complications. [ABSTRACT FROM AUTHOR]