The zinc finger protein ZFYVE21 is involved in immune signaling. Using humanized mouse models, primary human cells, and patient samples, we identified a T cell–autonomous role for ZFYVE21 in promoting chronic vascular inflammation associated with allograft vasculopathy. Ischemia-reperfusion injury (IRI) stimulated endothelial cells to produce Hedgehog (Hh) ligands, which in turn induced the production of ZFYVE21 in a population of T memory cells with high amounts of the Hh receptor PTCH1 (PTCH hi cells, CD3 + CD4 + CD45RO + PTCH1 hi PD-1 hi ), vigorous recruitment to injured endothelia, and increased effector responses in vivo. After priming by interferon-γ (IFN-γ), Hh-induced ZFYVE21 activated NLRP3 inflammasome activity in T cells, which potentiated IFN-γ responses. Hh-induced NLRP3 inflammasomes and T cell–specific ZFYVE21 augmented the vascular sequelae of chronic inflammation in mice engrafted with human endothelial cells or coronary arteries that had been subjected to IRI before engraftment. Moreover, the population of PTCH hi T cells producing high amounts of ZFYVE21 was expanded in patients with renal transplant–associated IRI, and sera from these patients expanded this population in control T cells in a manner that depended on Hh signaling. We conclude that Hh-induced ZFYVE21 activates NLRP3 inflammasomes in T cells, thereby promoting chronic inflammation.

The ability to stop an already initiated action is paramount to adaptive behavior. Most scientific debate in the field of human action-stopping currently focuses on two interrelated questions. First: Which mental and neural processes underpin the implementation of inhibitory control, and which reflect the attentional detection of salient stop-signals instead? Second: Why do physiological signatures of inhibition occur at two different latencies after stop-signals (for visual signals, either before or after ~150ms)? Here, we address both questions via two pre-registered experiments that combined transcranial magnetic stimulation, electromyography, and multi-variate pattern analysis of whole-scalp electroencephalography. Using a stop-signal task that also contained a second type of salient signal that did not require stopping, we found that both signals induced equal amounts of early-latency inhibitory activity, whereas only later signatures (after 175ms) distinguished the two. These findings resolve ongoing debates in the literature and strongly suggest a two-step model of action-stopping.

Background Machine learning is a set of models and methods that can automatically detect patterns in vast amounts of data, extract information, and use it to perform decision-making under uncertain conditions. The potential of machine learning is significant, and breast surgeons must strive to be informed with up-to-date knowledge and its applications. Methods A systematic database search of Embase, MEDLINE, the Cochrane database, and Google Scholar, from inception to December 2021, was conducted of original articles that explored the use of machine learning and/or artificial intelligence in breast surgery in EMBASE, MEDLINE, Cochrane database and Google Scholar. Results The search yielded 477 articles, of which 14 studies were included in this review, featuring 73 847 patients. Four main areas of machine learning application were identified: predictive modelling of surgical outcomes; breast imaging-based context; screening and triaging of patients with breast cancer; and as network utility for detection. There is evident value of machine learning in preoperative planning and in providing information for surgery both in a cancer and an aesthetic context. Machine learning outperformed traditional statistical modelling in all studies for predicting mortality, morbidity, and quality of life outcomes. Machine learning patterns and associations could support planning, anatomical visualization, and surgical navigation. Conclusion Machine learning demonstrated promising applications for improving breast surgery outcomes and patient-centred care. Neveretheless, there remain important limitations and ethical concerns relating to implementing artificial intelligence into everyday surgical practices.

Background: Challenges for breast reconstruction (BR) after delayed CPM relate to previous ipsilateral reconstructive procedures, adjuvant therapies and co-morbidities. The same type of BR for both sides may be impossible and use of an abdominal flap-based reconstruction for the therapeutic side precludes a similar technique for the contralateral side; an implant-based reconstruction may be difficult to size match with autologous tissue reconstruction. Alternative sites for tissue harvest are the latissimus dorsi and gluteal artery perforator flaps but these can be associated with significant donor site morbidity and poorer breast symmetry. Types of reconstruction and complications were evaluated in the context of BR and delayed CPM. Methods: A retrospective analysis examined breast cancer patients undergoing CPM either as an immediate or delayed procedure with or without breast reconstruction (BR) between January 2009 and December 2019. Clinical information was extracted from a prospectively maintained database with collection of data on demographics, timing and type of surgery, previous adjuvant treatments and complications. Patients undergoing delayed CPM were categorized into 4 groups based on BR or no BR and its timing in relation to both CPM and therapeutic mastectomy. Complications were listed according to the Clavien-Dindo system (scale of 1 – 5) with major adverse events being wound infection requiring intravenous antibiotics or drainage and explantation. Despite small numbers, complications were compared for therapeutic and prophylactic mastectomy together with the type and timing of reconstruction. Results: A total of 39 CPM patients were analyzed with 12 (31%) undergoing immediate BR at the time of cognate mastectomy, 22 (56%) choosing bilateral BR simultaneously with delayed CPM, 3(8%) opted for bilateral delayed BR following delayed CPM whilst 2 (5%) had no reconstruction. The mean patient age was 52 years (24–73) and the average interval between initial and delayed mastectomy was 2.67 years (0–22). The majority of reconstructions (28/39) were implant-based (72%) rather than exclusively autologous reconstruction and most patients had a similar type of BR for contralateral and ipsilateral sides. More than half of patients received neoadjuvant therapy and 85% had post-mastectomy radiotherapy prior to CPM. Major complications occurred in 8 patients (67%) with unilateral BR compared with 5 patients (23%) with bilateral immediate BR and 3 patients (100%) undergoing bilateral delayed BR. Small numbers and confounding factors preclude any robust statistical analysis but no statistically significant differences between the immediate and delayed BR groups were found on Fisher’s exact test. Complication rates appeared higher when immediate BR was performed after delayed CPM compared with therapeutic mastectomy. Conclusion: Potential complications and limitations of BR in the context of delayed CPM should be discussed with patients and used to inform decision-making processes for timing of CPM and associated reconstruction. There are no clear differences in rates of complications depending on laterality, type or timing of reconstruction. This study provides reassurance that reconstruction can be successfully performed either at the same time as delayed CPM (with or without BR on therapeutic side) or as a delayed procedure. Citation Format: Chien Lin Soh, Samantha Muktar, Charles M Malata, John R Benson. SURGICAL OUTCOMES FOR RECONSTRUCTION AFTER DELAYED CONTRALATERAL PROPHYLACTIC MASTECTOMY. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-05-06.

Extravasation of chemotherapy is rare with an estimated incidence of 0.01%-7% but can cause significant morbidity, delay in cancer treatment and potential mortality. We present a case of 55-year-old woman with a metastatic right axillary lymph node with no identifiable breast primary, commenced on chemotherapy as per multidisciplinary team decision. Extravasation of 25 mls of Epirubicin chemotherapy at the porta-a-cath (site) caused extensive inflammatory change in the breast parenchyma and chest wall with a necrotic ulcerating skin-defect. Even with ensuring port or peripheral catheter patency and position, extravasation can occur. This is the first case report to describe the use of MRI to help plan management, identifying the extent of the tissue damage and vascular compromise which could impair healing. In this case the necrotic ulcer was managed with surgical debridement and human ADM matrix (Matriderm dermal matrix) which has not been described in the literature previously.