Transmission dynamics, complications and mitigation strategies of the current mpox outbreak: A comprehensive review with bibliometric study.

As the mankind counters the ongoing COVID-19 pandemic by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), it simultaneously witnesses the emergence of mpox virus (MPXV) that signals at global spread and could potentially lead to another pandemic. Although MPXV has existed for more than 50 years now with most of the human cases being reported from the endemic West and Central African regions, the disease is recently being reported in non-endemic regions too that affect more than 50 countries. Controlling the spread of MPXV is important due to its potential danger of a global spread, causing severe morbidity and mortality. The article highlights the transmission dynamics, zoonosis potential, complication and mitigation strategies for MPXV infection, and concludes with suggested 'one health' approach for better management, control and prevention. Bibliometric analyses of the data extend the understanding and provide leads on the research trends, the global spread, and the need to revamp the critical research and healthcare interventions. Globally published mpox-related literature does not align well with endemic areas/regions of occurrence which should ideally have been the scenario. Such demographic and geographic gaps between the location of the research work and the endemic epicentres of the disease need to be bridged for greater and effective translation of the research outputs to pubic healthcare systems, it is suggested.

Current approaches in smart nano-inspired drug delivery: A narrative review.

Background and Aim: The traditional drug delivery approach involves systemic administration of a drug that could be nonspecific in targeting, low on efficacy, and with severe side-effects. To address such challenges, the field of smart drug delivery has emerged aiming at designing and developing delivery systems that can target specific cells, tissues, and organs and have minimal off-target side-effects. Methods: A literature search was done to collate papers and reports about the currently available various strategies for smart nano-inspired drug delivery. The databases searched were PubMed, Scopus, and Google Scholar. Based on selection criteria, the most pertinent and recent items were included. Results: Smart drug delivery is a cutting-edge revolutionary intervention in modern medicines to ensure effective and safe administration of therapeutics to target sites. These hold great promise for targeted and controlled delivery of therapeutic agents to improve the efficacy with reduced side-effects as compared to the conventional drug delivery approaches. Current smart drug delivery approaches include nanoparticles, liposomes, micelles, and hydrogels, each with its own advantages and limitations. The success of these delivery systems lies in engineering and designing them, and optimizing their pharmacokinetics and pharmacodynamics properties. Conclusion: Development of drug delivery systems that can get beyond various physiological and clinical barriers, as observed in conventionally administered chemotherapeutics, has been possible through recent advancements. Using multifunctional targeting methodologies, smart drug delivery tries to localize therapy to the target location, reduces cytotoxicity, and improves the therapeutic index. Rapid advancements in research and development in smart drug delivery provide wider and more promising avenues to guarantee a better healthcare system, improve patient outcomes, and achieve higher levels of effective medical interventions like personalized medicine.

Premastectomy Radiotherapy and Immediate Breast Reconstruction: A Randomized Clinical Trial.

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR). Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR. Design, Setting, and Participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible. Intervention: This trial evaluated outcomes after PreMRT followed by mastectomy and IMBR. Patients were randomized to receive either hypofractionated (40.05 Gy/15 fractions) or conventionally fractionated (50 Gy/25 fractions) RNI. Main Outcome and Measures: The primary outcome was reconstructive failure, defined as complete autologous flap loss. Demographic, treatment, and outcomes data were collected, and associations between multiple variables and outcomes were evaluated. Analysis was performed on an intent-to-treat basis. Results: Fifty patients were enrolled. Among 49 evaluable patients, the median age was 48 years (range, 31-72 years), and 46 patients (94%) received neoadjuvant systemic therapy. Twenty-five patients received 50 Gy in 25 fractions to the breast and 45 Gy in 25 fractions to regional nodes, and 24 patients received 40.05 Gy in 15 fractions to the breast and 37.5 Gy in 15 fractions to regional nodes, including internal mammary lymph nodes. Forty-eight patients underwent mastectomy with IMBR, at a median of 23 days (IQR, 20-28.5 days) after radiotherapy. Forty-one patients had microvascular autologous flap reconstruction, 5 underwent latissimus dorsi pedicled flap reconstruction, and 2 had tissue expander placement. There were no complete autologous flap losses, and 1 patient underwent tissue expander explantation. Eight of 48 patients (17%) had mastectomy skin flap necrosis of the treated breast, of whom 1 underwent reoperation. During follow-up (median, 29.7 months [range, 10.1-65.2 months]), there were no locoregional recurrences or distant metastasis. Conclusions and Relevance: This randomized clinical trial found PreMRT and RNI followed by mastectomy and microvascular autologous flap IMBR to be feasible and safe. Based on these results, a larger randomized clinical trial of hypofractionated vs conventionally fractionated PreMRT has been started (NCT05774678). Trial Registration: ClinicalTrials.gov Identifier: NCT02912312.

ThermoPCD: a database of molecular dynamics trajectories of antibody-antigen complexes at physiologic and fever-range temperatures.

Progression of various cancers and autoimmune diseases is associated with changes in systemic or local tissue temperatures, which may impact current therapies. The role of fever and acute inflammation-range temperatures on the stability and activity of antibodies relevant for cancers and autoimmunity is unknown. To produce molecular dynamics (MD) trajectories of immune complexes at relevant temperatures, we used the Research Collaboratory for Structural Bioinformatics (RCSB) database to identify 50 antibody:antigen complexes of interest, in addition to single antibodies and antigens, and deployed Groningen Machine for Chemical Simulations (GROMACS) to prepare and run the structures at different temperatures for 100-500 ns, in single or multiple random seeds. MD trajectories are freely available. Processed data include Protein Data Bank outputs for all files obtained every 50 ns, and free binding energy calculations for some of the immune complexes. Protocols for using the data are also available. Individual datasets contain unique DOIs. We created a web interface, ThermoPCD, as a platform to explore the data. The outputs of ThermoPCD allow the users to relate thermally-dependent changes in epitopes:paratopes interfaces to their free binding energies, or against own experimentally derived binding affinities. ThermoPCD is a free to use database of immune complexes' trajectories at different temperatures that does not require registration and allows for all the data to be available for download. Database URL: https://sites.google.com/view/thermopcd/home.

Rheumatoid arthritis autoantibodies benefit from inflammation temperatures.

BACKGROUND: Symptoms of rheumatoid arthritis are associated with local inflammation and may include low-grade fever. OBJECTIVE: To establish the role of fever/inflammation temperatures (38℃-39℃) on the activity of autoantibodies and therapeutic antibodies relevant for rheumatoid arthritis. METHODS: Through the use of molecular dynamics and free energy calculations, we investigated the role of temperature on the formation of pertinent immune complexes. RESULTS: Rheumatoid arthritis autoantibodies bind with higher affinity at febrile/inflammation temperatures. CONCLUSIONS: Fever may modulate binding affinity of autoantibodies relevant for rheumatoid arthritis.

Society of Surgical Oncology Breast Disease Site Working Group Statement on Contralateral Mastectomy: Indications, Outcomes, and Risks.

Rates of contralateral mastectomy (CM) among patients with unilateral breast cancer have been increasing in the United States. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, risks, and benefits of CM since the society's 2017 statement. We held a virtual meeting to outline key topics and then conducted a literature search using PubMed to identify relevant articles. We reviewed the articles and made recommendations based on group consensus. Patients consider CM for many reasons, including concerns regarding the risk of contralateral breast cancer (CBC), desire for improved cosmesis and symmetry, and preferences to avoid ongoing screening, whereas surgeons primarily consider CBC risk when making a recommendation for CM. For patients with a high risk of CBC, CM reduces the risk of new breast cancer, however it is not known to convey an overall survival benefit. Studies evaluating patient satisfaction with CM and reconstruction have yielded mixed results. Imaging with mammography within 12 months before CM is recommended, but routine preoperative breast magnetic resonance imaging is not; there is also no evidence to support routine postmastectomy imaging surveillance. Because the likelihood of identifying an occult malignancy during CM is low, routine sentinel lymph node surgery is not recommended. Data on the rates of postoperative complications are conflicting, and such complications may not be directly related to CM. Adjuvant therapy delays due to complications have not been reported. Surgeons can reduce CM rates by encouraging shared decision making and informed discussions incorporating patient preferences.

Resuscitation With Vitamin C, Hydrocortisone, and Thiamin in Children With Septic Shock: A Multicenter Randomized Pilot Study.

OBJECTIVES: Adjunctive therapy with vitamin C, hydrocortisone, and thiamin has been evaluated in adults, but randomized controlled trial (RCT) data in children are lacking. We aimed to test the feasibility of vitamin C, hydrocortisone, and thiamin in PICU patients with septic shock; and to explore whether the intervention is associated with increased survival free of organ dysfunction. DESIGN: Open-label parallel, pilot RCT multicenter study. The primary endpoint was feasibility. Clinical endpoints included survival free of organ dysfunction censored at 28 days and nine secondary outcomes, shock reversal, and two proxy measures of intervention efficacy. SETTING: Six PICUs in Australia and New Zealand. PATIENTS: Children of age between 28 days and 18 years requiring vasoactive drugs for septic shock between August 2019 and March 2021. INTERVENTIONS: Patients were assigned 1:1 to receive 1 mg/kg hydrocortisone every 6 hours (q6h), 30 mg/kg ascorbic acid q6h, and 4 mg/kg thiamin every 12 hours (n = 27), or standard septic shock management (n = 33). MEASUREMENTS AND MAIN RESULTS: Sixty of 77 (78%) eligible patients consented with 91% of approached parents providing consent. The median time from randomization to intervention was 44 (interquartile range [IQR] 29-120) min. Seventy of seventy-seven (28%) patients had received IV steroids before randomization. Median survival alive and free of organ dysfunction was 20.0 (0.0-26.0) days in the intervention and 21.0 (0.0-25.0) days in the standard care group. Median PICU length of stay was 5.3 (2.5-11.3) days in the intervention group versus 6.9 (3.0-11.5) days in the control group. Shock reversal occurred at a median of 35.2 (14.6-101.2) hours in the intervention group versus 47.3 (22.4-106.8) hours in the standard care group (median difference -12 hr; 95% CI, -56.8 to 32.7 hr). CONCLUSIONS: In children requiring vasopressors for septic shock, a protocol comparing adjunctive treatment with high-dose vitamin C, hydrocortisone, and thiamin versus standard care was feasible. These findings assist in making modifications to the trial protocol to enable a better-designed larger RCT.

Does Neoadjuvant Chemotherapy in Clinical T1-T2 N0 Triple-Negative Breast Cancer Increase the Extent of Axillary Surgery?

BACKGROUND: Current management strategies for early-stage triple-negative breast cancer (TNBC) include upfront surgery to determine pathologic stage to guide chemotherapy recommendations, or neoadjuvant chemotherapy (NAC) to de-escalate surgery, elucidate tumor response, and determine the role of adjuvant chemotherapy. However, patients who receive NAC with residual pathological nodal (pN) involvement require axillary lymph node dissection (ALND) as they are Z11/AMAROS ineligible. We aimed to evaluate the impact of NAC compared with upfront surgery on pN status and ALND rates in cT1-2N0 TNBC. METHODS: The National Cancer Database (NCDB) was queried for women with operable cT1-2N0 TNBC from 2014 to 2019. Demographic, clinicopathologic, and treatment data were collected. Multivariable linear regression analysis was performed to assess the odds of pN+ disease and undergoing ALND. RESULTS: Overall, 55,624 women were included: 26.9% (n = 14,942) underwent NAC and 73.1% (n = 40,682) underwent upfront surgery. The NAC cohort was younger (mean age 52.9 vs. 61.3 years; p < 0.001) with more cT2 tumors (71.6% vs. 31.0%; p < 0.001), and had lower ALND rates (4.3% vs. 5.5%; p < 0.001). The upfront surgery cohort was more likely to have one to three pathologically positive nodes (12.1% vs. 6.5%; odds ratio [OR] 2.37, 95% confidence interval (CI) 2.17-2.58; p < 0.001) but there was no difference in the likelihood of ALND (OR 1.1, 95% CI 0.99-1.24; p = 0.08). CONCLUSION: Patients who underwent upfront surgery were more likely to be pN+; however, ALND rates were similar between the two cohorts. Thus, the use of NAC does not result in a higher odds of ALND and the decision for NAC should be individualized and based on modern guidelines and systemic therapy benefits.

National trends in neoadjuvant chemotherapy utilization in patients with early-stage node-negative triple-negative breast cancer: the impact of the CREATE-X trial.

PURPOSE: Neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) allows for assessment of tumor pathological response and has survival implications. In 2017, the CREATE-X trial demonstrated survival benefit with adjuvant capecitabine in patients TNBC and residual disease after NAC. We aimed to assess national rates of NAC for cT1-2N0M0 TNBC before and after CREATE-X and examine factors associated with receiving NAC vs adjuvant chemotherapy (AC). METHODS: A retrospective cohort study of women with cT1-2N0M0 TNBC diagnosed from 2014 to 2019 in the National Cancer Database (NCDB) was performed. Variables were analyzed via ANOVA, Chi-squared, Fisher Exact tests, and a multivariate linear regression model was created. RESULTS: 55,633 women were included: 26.9% received NAC, 52.4% AC, and 20.7% received no chemotherapy (median ages 53, 59, and 71 years, p < 0.01). NAC utilization significantly increased over time: 19.5% in 2014-15 (n = 3,465 of 17,777), 27.1% in 2016-17 (n = 5,140 of 18,985), and 33.6% in 2018-19 (n = 6,337 of 18,871, p < 0.001). On multivariate analysis, increased NAC was associated with younger age (< 50), non-Hispanic white race/ethnicity, lack of comorbidities, cT2 tumors, care at an academic or integrated-network cancer program, and diagnosis post-2017 (p < 0.05 for all). Patients with government-provided insurance were less likely to receive NAC (p < 0.01). Women who traveled > 60 miles for treatment were more likely to receive NAC (p < 0.01). CONCLUSION: From 2014 to 2019, NAC utilization increased for patients with cT1-2N0M0 TNBC. Racial, socioeconomic, and access disparities were observed in who received NAC vs AC and warrants interventions to ensure equitable care.

Long-Term Outcomes and Predictors of Response in Breast Cancer Patients with Advanced Nodal Involvement.

BACKGROUND: Advanced nodal disease is associated with poor prognosis. However, modern neoadjuvant systemic therapy (NST) regimens have resulted in higher pathologic complete response (pCR) rates, which are associated with improved survival. We sought to assess contemporary outcomes in patients with advanced nodal involvement and response to NST. STUDY DESIGN: We conducted a single-institution, retrospective study of 521 patients with cN2-3 primary nonmetastatic breast cancer treated with NST followed by surgery and radiation from 2012 to 2018. Descriptive statistics, multivariate Cox regression, and Kaplan-Meier analyses were performed. RESULTS: The mean age was 50.5 years, and median follow-up was 61 (4.7 to 197) months. The majority of patients had hormone receptor-positive (HR+)/HER2-negative tumors (HER2-; n = 242, 47.8%). Most were cT2 (n = 243; 46.6%) or cT3 (n = 139; 26.7%) and 73.3% (n = 382) had cN3 disease. Rate of axillary pCR was 34.2%, and breast and axillary pCR was 19.4% (n = 101). Event-free survival (EFS) at 5 years was 75.1% (95% CI, 0.71 to 0.79). Rate of locoregional recurrence was 6.7%; distant metastatic rate was 29.4%. Axillary pCR with or without breast pCR was significantly associated with longer EFS (p = 0.001). Achieving breast/axillary pCR was an independent predictor of improved EFS (hazard ratio 0.22, p < 0.0001). Having triple-negative disease was associated with worse EFS (hazard ratio 1.74, p = 0.008). CONCLUSIONS: In a high-risk cohort of patients with cN2-3 disease, trimodality therapy was effective in achieving durable EFS. Approximately one-third of patients achieved axillary pCR, which was associated with improved survival. Further studies are needed to accurately determine axillary response in cN2-3 breast cancer after NST in order to develop de-escalation strategies to reduce morbidity associated with axillary surgery.

Lobular Neoplasia Diagnosed by MRI-Guided Breast Biopsy: Identifying Upgrade Rate to Malignancy and Outcomes of Clinical and Surgical Management.

OBJECTIVE: The aim of this study was to determine surgical and clinical outcomes of lobular neoplasia (LN) diagnosed by magnetic resonance imaging (MRI) biopsy, including upgrade to malignancy, and to assess for characteristics associated with upgrade. METHOD: A single-institution retrospective study, between 2013 and 2022, of patients with histopathological findings of LN via MRI-guided biopsy was performed using an institutional database and review of the electronic medical records. Decision for excision or surveillance was made by a multidisciplinary team per institutional practice. Patient demographics and imaging characteristics were summarized using descriptive analyses. Upgrade was defined as upgrade to cancer on surgical pathology for patients treated with excision or the development of cancer at the biopsy site during surveillance. The Wilcoxon rank-sum test and Fisher's exact test were used to compare features of the upgraded cohort with the remainder of the group. RESULTS: Ninety-four MRI biopsies diagnosing LN were included. Median age was 57 years (range 37-78 years). Forty-six lesions underwent excision while 48 lesions were surveilled. The upgrade rate was 7.4% (7/94). Upgrades in the excised cohort consisted of pleomorphic lobular carcinoma in situ (LCIS; n = 1), ductal carcinoma in situ (DCIS; n = 3) and invasive lobular carcinoma (ILC; n = 2), while one interval development of DCIS was observed at the site of biopsy in the surveillance cohort. No MRI or patient variables were associated with upgrade. CONCLUSIONS: In this contemporary cohort of MRI-detected LNs, the upgrade rate was low. Omission of surgery for MRI-detected LNs in carefully selected patients may be considered in a shared decision-making capacity between the patient and the treatment team. Larger cohorts are needed to determine factors predictive of upgrade risk.

Ethnomedicinal values of Boerhaavia diffusa L. as a panacea against multiple human ailments: a state of art review.

Ethnopharmacological relevance: Therapeutic botanicals (plants and derivatives) are in use since antiquity for various health ailments. The ethnic community is the repository of the information, the multifactorial therapeutic applications of which may often need scientific validation. The spreading hogweed or Boerhaavia diffusa L., also known as Punarnava, is a reassuring medicinal herb with diverse pharmacological benefits. It is used in Ayurveda in Asia and Africa as a rejuvenator or "Rasayan" for its excellent antiaging and antioxidant properties. Aim: The study aimed at compiling the state-of-art knowledge of the medicinal benefits of Boerhaavia diffusa L. and unraveling the unexplored commercially useful bioactive constituents by establishing their possible pharmacological benefits. Methods: The data from published literature, confined to pharmacological manifestations of various phytocomponents of Boerhaavia diffusa L. or its parts like root, leaf and stem were extracted from scientific databases, Google, Science Direct, PubMed, etc. using its antifungal, antibacterial, anticancer, anti-inflammatory, antidiabetic, hepatoprotective, cardioprotective, renoprotective, antifertility benefits and molecular docking study as search strings and keywords. Further, the reported in silico studies for bioactivity and bioavailability are detailed. Results: The botanicals possess numerous bioactive compounds, the most widely reported ones being phenolic (punarnavoside, trans-caftaric acid, boerhavic acid), rotenoid (boeravinones A-J), flavonoid (borhaavone, quercetin, kaempferol), isoflavonoid (2'-O-methyl abronisoflavone), alkaloid (punarnavine), steroid (boerhavisterol, ß-Ecdysone), anthracenes and lignans (liriodendrin, syringaresinol mono-ß-D-glucoside). Some of the reported reassuring benefits of their purified forms or even the crude extracts are antidiabetic, antimicrobial, anticancer, antioxidant, anti-inflammatory, hepatoprotective, renoprotective, cardioprotective, antifertility, etc. Conclusion: The article provides an extensive study on such pharmacological utility to support the ethnomedicinal use of Boerhaavia diffusa L. and propose possible mechanism of the various bioactive compounds in optimising metabolic dysfunctions, healing and protecting vital body organs, often related to the magnificent antioxidant property of this ayurvedic panacea. Further, establishing specific roles of its yet-to-explore bioactive constituents for diverse pharmacological applications is suggested.

REstrictive versus StandarD FlUid Management in Mechanically Ventilated ChildrEn Admitted to PICU: study protocol for a pilot randomised controlled trial (REDUCE-1).

INTRODUCTION: Intravenous fluid therapy is the most common intervention in critically ill children. There is an increasing body of evidence questioning the safety of high-volume intravenous fluid administration in these patients. To date, the optimal fluid management strategy remains unclear. We aimed to test the feasibility of a pragmatic randomised controlled trial comparing a restrictive with a standard (liberal) fluid management strategy in critically ill children. METHODS AND ANALYSIS: Multicentre, binational pilot, randomised, controlled, open-label, pragmatic trial. Patients <18 years admitted to paediatric intensive care unit and mechanically ventilated at the time of screening are eligible. Patients with tumour lysis syndrome, diabetic ketoacidosis or postorgan transplant are excluded. INTERVENTIONS: 1:1 random assignment of 154 individual patients into two groups-restrictive versus standard, liberal, fluid strategy-stratified by primary diagnosis (cardiac/non-cardiac). The intervention consists of a restrictive fluid bundle, including lower maintenance fluid allowance, limiting fluid boluses, reducing volumes of drug delivery and initiating diuretics or peritoneal dialysis earlier. The intervention is applied for 48 hours postrandomisation or until discharge (whichever is earlier). ENDPOINTS: The number of patients recruited per month and proportion of recruited to eligible patients are feasibility endpoints. New-onset acute kidney injury and the incidence of clinically relevant central venous thrombosis are safety endpoints. Fluid balance at 48 hours after randomisation is the efficacy endpoint. Survival free of paediatric intensive care censored at 28 days is the clinical endpoint. ETHICS AND DISSEMINATION: Ethics approval was gained from the Children's Health Queensland Human Research Ethics Committee (HREC/21/QCHQ/77514, date: 1 September 2021), and University of Zurich (2021-02447, date: 17 March 2023). The trial is registered with the Australia New Zealand Clinical Trials Registry (ACTRN12621001311842). Open-access publication in high impact peer-reviewed journals will be sought. Modern information dissemination strategies will also be used including social media to disseminate the outcomes of the study. TRIAL REGISTRATION NUMBER: ACTRN12621001311842. PROTOCOL VERSION/DATE: V5/23 May 2023.

To Dissect or Not to Dissect: Can We Predict the Presence of Four or More Axillary Lymph Node Metastases in Postmenopausal Women with Clinically Node-Negative Breast Cancer?

BACKGROUND: Axillary lymph node (ALN) involvement is important for prognosis and guidance of multidisciplinary treatment of breast cancer patients. This study sought to identify preoperative clinicopathologic factors predictive of four or more pathologically positive ALNs in patients with cN0 disease and to develop a predictive nomogram to inform therapy recommendations. METHODS: Using an institutional prospective database, the study identified postmenopausal women with cN0 invasive breast cancer undergoing upfront sentinel lymph node biopsy (SLNB) with or without completion ALND (cALND) between 1993 and 2007. Logistic regression analyses identified factors predictive of four or more positive nodes in the cN0 population and patients with one, two, or more SLNs. RESULTS: The study identified 2532 postmenopausal women, 615 (24.3%) of whom underwent cALND. In the univariate analysis, tumor size, lymphovascular (LVI), histology, estrogen receptor (ER)-positive status, and multifocality/multicentricity were predictive of four or more positive nodes (n = 63; p < 0.05), and all except ER status were significant in the multivariate analysis. Of the 2532 patients, 1263 (49.2%) had hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, and 30 (2.4%) were found to have four or more positive nodes. Of the 130 patients with exactly one positive SLN who underwent cALND (n = 130, 5.4%), 7 had four or more positive nodes, with grade as the only predictive factor (p = 0.01). Of the 33 patients with two or more positive SLNs who underwent cALND, 9 (27.3%) had four or more positive nodes after cALND, but no factors were predictive in this subset. CONCLUSION: Postmenopausal women with early-stage cN0 HR-positive, HER2-negative breast cancer with a single positive SLN had a very low risk (5%) of having four or more positive nodes on final pathology. With such a low risk of N2 disease, limited staging with SLNB may be sufficient to guide therapy decisions for this subset of patients.

Lactation Education for Surgeons: American Society of Breast Surgeons (ASBrS) Survey Demonstrates Strong Member Interest in Expanded Training.

BACKGROUND: The availability and extent of breastfeeding-specific surgical training has not been previously described. We aimed to survey breast surgeons on their lactation education and desire for additional knowledge. METHODS: Members of the American Society of Breast Surgeons were invited via email to anonymously complete an electronic survey from 27 October 2021 to 23 January 2022. The survey content included demographic information, sources of lactation education, and desired topics and methods for further training. Descriptive statistics were used to analyze the data. RESULTS: A total of 2698 surveys were delivered and 542 (20.1%) completed. While nearly all respondents (99%) reported treating lactating patients at least once or twice per year, 78% reported that their training was inadequate. The most frequently cited sources of lactation information were peer-to-peer informal knowledge sharing (50%) and personal experience with breastfeeding (44%). Nearly all respondents (99%) agreed that formal lactation education would benefit breast surgeons. Specific topics of interest included management of patients with complications of lactation (48%), management of lactating patients with a new diagnosis of breast cancer (47%), and counseling patients with pregnancy-associated breast cancer who desire to breastfeed (46%). The most frequently recommended educational formats included presentation at a national conference (60%), evidence-based management guidelines (58%), webinar (55%), and workshop/course (47%). CONCLUSION: Breast surgeons self-report minimal formal training in the management of benign and malignant breast disease in lactating patients and strong desire for expanded education. Development of clinical practice guidelines and additional educational content for surgeons should be considered to meet the needs of this patient population.

Enhanced binding at fever temperatures of HER2 in complex with trastuzumab and pertuzumab.

Aim: Fever follows the administration of trastuzumab and pertuzumab used in HER2-relevant immunotherapy, but is often eliminated in clinical practice. This work explores the role of temperature (37-39°C) in the formation of immune complexes between HER2 with either trastuzumab or pertuzumab or with both antibodies. Materials & methods: Using molecular dynamics simulations and free energy calculations, the binding between HER2 and these immunotherapeutic monoclonal antibodies was investigated at different temperatures. Results: Trastuzumab and pertuzumab present the highest binding free energy to HER2 at febrile temperatures (39°C), or when HER2 is in complex with both antibodies. Conclusion: Performing molecular dynamics simulations under fever temperatures may be important for delineating their role in enhancing the binding affinity of mature antibodies used in immunotherapy.

Breast cancer patients may present fever due to the cancer itself, due to treatment with chemotherapy or monoclonal antibody therapy, or after surgery. In this work, the role of febrile temperatures on the activity of two of the most commonly used monoclonal antibodies for breast cancer treatment, trastuzumab and pertuzumab, was investigated. These therapeutic agents benefit from fever in terms of binding to their tumor target, particularly when both antibodies are deployed together, mirroring the clinical benefits of their dual therapy. These results are important because, in clinical practice, fever that accompanies treatment in cancer patients is usually eliminated. As such, further investigations into the positive role of fever-range temperatures in assisting antibody therapy for breast cancer are warranted.

Changes in Surgical Management of the Axilla Over 11 Years - Report on More Than 1500 Breast Cancer Patients Treated with Neoadjuvant Chemotherapy on the Prospective I-SPY2 Trial.

BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.

Breast Conservation Surgery and Mastectomy Have Similar Locoregional Recurrence After Neoadjuvant Chemotherapy: Results From 1462 Patients on the Prospective, Randomized I-SPY2 Trial.

Neoadjuvant chemotherapy (NAC) increases rates of successful breast-conserving surgery (BCS) in patients with breast cancer. However, some studies suggest that BCS after NAC may confer an increased risk of locoregional recurrence (LRR). We assessed LRR rates and locoregional recurrence-free survival (LRFS) in patients enrolled on I-SPY2 (NCT01042379), a prospective NAC trial for patients with clinical stage II to III, molecularly high-risk breast cancer. Cox proportional hazards models were used to evaluate associations between surgical procedure (BCS vs mastectomy) and LRFS adjusted for age, tumor receptor subtype, clinical T category, clinical nodal status, and residual cancer burden (RCB). In 1462 patients, surgical procedure was not associated with LRR or LRFS on either univariate or multivariate analysis. The unadjusted incidence of LRR was 5.4% after BCS and 7.0% after mastectomy, at a median follow-up time of 3.5 years. The strongest predictor of LRR was RCB class, with each increasing RCB class having a significantly higher hazard ratio for LRR compared with RCB 0 on multivariate analysis. Triple-negative receptor subtype was also associated with an increased risk of LRR (hazard ratio: 2.91, 95% CI: 1.8-4.6, P < 0.0001), regardless of the type of operation. In this large multi-institutional prospective trial of patients completing NAC, we found no increased risk of LRR or differences in LRFS after BCS compared with mastectomy. Tumor receptor subtype and extent of residual disease after NAC were significantly associated with recurrence. These data demonstrate that BCS can be an excellent surgical option after NAC for appropriately selected patients.