Expanding Access to Immediate Lymphatic Reconstruction Through an Axillary Surgery Referral Program: A 6-Year Single-Center Experience.

BACKGROUND: Recent advances in breast cancer have progressed toward less aggressive axillary surgery. However, axillary lymph node dissection (ALND) remains necessary in specific cases and can increase the risk of lymphedema. Performing ALND with immediate lymphatic reconstruction (ILR) can help lower this risk. This report outlines the implementation of an Axillary Surgery Referral Program (ASRP) to broaden access to ILR, providing insights for institutions considering similar initiatives. METHODS: A retrospective study analyzed patients referred to the ASRP at Beth Israel Deaconess Medical Center (BIDMC) between 6 January 2017 and 10 December 2022. Patients were identified from a prospective registry, with data subsequently extracted from electronic medical records. This analysis specifically centered on patients referred from external institutions to undergo ALND with ILR. RESULTS: The program received referrals for 131 patients from institutions across five different states. Annual referrals steadily increased over time. The primary indication for referral was residual axillary disease after neoadjuvant chemotherapy (41.2%). Among the referrals, 20 patients (15.3%) no longer required ALND due to axillary pathologic complete response to neoadjuvant therapy. Care coordination played a crucial role in streamlining the patient care process for both efficiency and effectiveness. CONCLUSION: The ASRP expands access to ILR for patients with breast cancer, the majority referred for surgical management of residual disease after chemotherapy. The program provides a model for health care institutions aiming to establish similar specialized referral services. Continued program evaluation will be instrumental in refining axillary surgery referral practices and ensuring optimal patient care.

Reliability of artificial intelligence chatbot responses to frequently asked questions in breast surgical oncology.

INTRODUCTION: Artificial intelligence (AI)-driven chatbots, capable of simulating human-like conversations, are becoming more prevalent in healthcare. While this technology offers potential benefits in patient engagement and information accessibility, it raises concerns about potential misuse, misinformation, inaccuracies, and ethical challenges. METHODS: This study evaluated a publicly available AI chatbot, ChatGPT, in its responses to nine questions related to breast cancer surgery selected from the American Society of Breast Surgeons' frequently asked questions (FAQ) patient education website. Four breast surgical oncologists assessed the responses for accuracy and reliability using a five-point Likert scale and the Patient Education Materials Assessment (PEMAT) Tool. RESULTS: The average reliability score for ChatGPT in answering breast cancer surgery questions was 3.98 out of 5.00. Surgeons unanimously found the responses understandable and actionable per the PEMAT criteria. The consensus found ChatGPT's overall performance was appropriate, with minor or no inaccuracies. CONCLUSION: ChatGPT demonstrates good reliability in responding to breast cancer surgery queries, with minor, nonharmful inaccuracies. Its answers are accurate, clear, and easy to comprehend. Notably, ChatGPT acknowledged its informational role and did not attempt to replace medical advice or discourage users from seeking input from a healthcare professional.

Axillary de-escalation after neoadjuvant chemotherapy for advanced lymph node involvement in breast cancer.

INTRODUCTION: Sentinel lymph node biopsy reduces morbidity in patients with clinically node-positive breast cancer who achieve axillary pathologic complete response following neoadjuvant therapy (NACT). De-escalation trials primarily addressed cN1 disease, with underrepresentation of cN2 disease. This study evaluates the role of de-escalation in patients with cN2 breast cancer. METHODS: A retrospective analysis of the National Cancer Database (2013-2020) included women over 18 with T1-2 invasive breast cancer and clinical N2 disease who received NACT followed by ALND or SLNB then ALND. The primary outcome was pathologic nodal status post-NACT. RESULTS: Of 5852 cN2 patients treated, 18.15 â€‹% achieved ypN0, 0.97 â€‹% had isolated tumor cells, 19.14 â€‹% were ypN1, 49.64 â€‹% were ypN2, and 12.20 â€‹% were ypN3 following NACT. Achieving ypN0 was associated with pCR in the breast, HER2-positive and triple-negative receptor status, cT2 tumors, and younger age. CONCLUSION: Despite some patients with cN2 disease achieving ypN0, most exhibited residual axillary disease post-NACT. These findings indicate that axillary de-escalation may not be feasible for most patients with cN2 disease, underscoring the importance of meticulous patient selection and assessment.

Urinary excretion after transcaval renal penetration of a fragmented Bird's Nest filter.

Permanent inferior vena cava (IVC) filters are used to prevent venous thromboembolic events in select populations of patients. The Bird's Nest filter (BNF; Cook Medical, Bloomington, Ind) is an IVC filter that has been associated with various complications including filter strut fractures, migration, caval wall perforation, visceral perforation, and vascular injury. We report a case of a BNF that eroded transmurally through the IVC into the right kidney parenchyma. The patient underwent operative intervention with removal of the BNF with an uncomplicated postoperative course. In patients with symptoms and local filter perforations, we advocate for safe filter removal when possible to avoid long-term damage.

Circulating microRNA Signatures in Rodent Models of Pain.

MicroRNAs (miRNAs) remain stable in circulation and have been identified as potential biomarkers for a variety of conditions. We report miRNA changes in blood from multiple rodent models of pain, including spinal nerve ligation and spared nerve injury models of neuropathic pain; a complete Freund's adjuvant (CFA) model of inflammatory pain; and a chemotherapy-induced model of pain using the histone deacetylase inhibitor JNJ-26481585. The effect of celecoxib, a cyclooxygenase-2-selective nonsteroidal anti-inflammatory drug, was investigated in the CFA model as proof of principle for assessing the utility of circulating miRNAs as biomarkers in determining treatment response. Each study resulted in a unique miRNA expression profile. Despite differences in miRNAs identified from various models, computational target prediction and functional enrichment have identified biological pathways common among different models. The Wnt signaling pathway was affected in all models, suggesting a crucial role for this pathway in the pathogenesis of pain. Our studies demonstrate the utility of circulating miRNAs as pain biomarkers and suggest the potential for rigorous forward and reverse translational approaches. Evaluating alterations in miRNA fingerprints under different pain conditions and after administering therapeutic agents may be beneficial in evaluating clinical trial outcomes, predicting treatment response, and developing correlational outcomes between preclinical and human studies.

Effect of histone deacetylase inhibitor JNJ-26481585 in pain.

Recent studies have shown that histone deacetylase (HDAC) inhibitors can alleviate inflammatory and neuropathic pain. We investigated the effects of JNJ-26481585, a pan-HDAC inhibitor on basal mechanical sensitivity. Unlike previous reports for HDAC inhibitors, JNJ-26481585 induced mechanical hypersensitivity in mice. This effect was reversible with gabapentin. Voltage-dependent calcium channel subunit alpha-2/delta-1, one of the putative targets for gabapentin, was upregulated in the spinal cord from JNJ-26481585-treated mice. Transcriptional profiling of spinal cord from JNJ-26481585-treated mice showed significant alterations in pathways involved in axon guidance, suggesting overlap in mechanisms underlying neurotoxicity caused by other known chemotherapeutic agents. To investigate the mechanisms underlying the development of pain, RAW 264.7 mouse macrophage cells were treated with JNJ-26481585. There was a dose- and time-dependent activation of nuclear factor-kappaB and interleukin-1ß increase. Thus, alterations in the axon guidance pathway, increase in voltage-dependent calcium channel alpha(2)delta-1 subunit, and the induction of proinflammatory mediators by JNJ-26481585 could all contribute to increased mechanical sensitivity. Our data indicate that the effect of HDAC inhibitors may be unique to the compound studied and highlights the potential to develop chemotherapy-induced peripheral neuropathy with the use of a pan-HDAC inhibitor for cancer treatment, and this pain may be alleviated by gabapentin.

Purification and microRNA profiling of exosomes derived from blood and culture media.

Stable miRNAs are present in all body fluids and some circulating miRNAs are protected from degradation by sequestration in small vesicles called exosomes. Exosomes can fuse with the plasma membrane resulting in the transfer of RNA and proteins to the target cell. Their biological functions include immune response, antigen presentation, and intracellular communication. Delivery of miRNAs that can regulate gene expression in the recipient cells via blood has opened novel avenues for target intervention. In addition to offering a strategy for delivery of drugs or RNA therapeutic agents, exosomal contents can serve as biomarkers that can aid in diagnosis, determining treatment options and prognosis. Here we will describe the procedure for quantitatively analyzing miRNAs and messenger RNAs (mRNA) from exosomes secreted in blood and cell culture media. Purified exosomes will be characterized using western blot analysis for exosomal markers and PCR for mRNAs of interest. Transmission electron microscopy (TEM) and immunogold labeling will be used to validate exosomal morphology and integrity. Total RNA will be purified from these exosomes to ensure that we can study both mRNA and miRNA from the same sample. After validating RNA integrity by Bioanalyzer, we will perform a medium throughput quantitative real time PCR (qPCR) to identify the exosomal miRNA using Taqman Low Density Array (TLDA) cards and gene expression studies for transcripts of interest. These protocols can be used to quantify changes in exosomal miRNAs in patients, rodent models and cell culture media before and after pharmacological intervention. Exosomal contents vary due to the source of origin and the physiological conditions of cells that secrete exosomes. These variations can provide insight on how cells and systems cope with stress or physiological perturbations. Our representative data show variations in miRNAs present in exosomes purified from mouse blood, human blood and human cell culture media. Here we will describe the procedure for quantitatively analyzing miRNAs and messenger RNAs (mRNA) from exosomes secreted in blood and cell culture media. Purified exosomes will be characterized using western blot analysis for exosomal markers and PCR for mRNAs of interest. Transmission electron microscopy (TEM) and immunogold labeling will be used to validate exosomal morphology and integrity. Total RNA will be purified from these exosomes to ensure that we can study both mRNA and miRNA from the same sample. After validating RNA integrity by Bioanalyzer, we will perform a medium throughput quantitative real time PCR (qPCR) to identify the exosomal miRNA using Taqman Low Density Array (TLDA) cards and gene expression studies for transcripts of interest. These protocols can be used to quantify changes in exosomal miRNAs in patients, rodent models and cell culture media before and after pharmacological intervention. Exosomal contents vary due to the source of origin and the physiological conditions of cells that secrete exosomes. These variations can provide insight on how cells and systems cope with stress or physiological perturbations. Our representative data show variations in miRNAs present in exosomes purified from mouse blood, human blood and human cell culture media.

The characterization of a unique Trypanosoma brucei ß-hydroxybutyrate dehydrogenase.

A putative ß-hydroxybutyrate dehydrogenase (ßHBDH) ortholog was identified in Trypanosoma brucei, the unicellular eukaryotic parasite responsible for causing African Sleeping Sickness. The trypanosome enzyme has greater sequence similarity to bacterial sources of soluble ßHBDH than to membrane-bound Type I ßHBDH found in higher eukaryotes. The ßHBDH gene was cloned from T. brucei genomic DNA and active, recombinant His-tagged enzyme (His(10)-TbßHBDH) was purified to approximate homogeneity from E. coli. ßHBDH catalyzes the reversible NADH-dependent conversion of acetoacetate to D-3-hydroxybutyrate. In the direction of D-3-hydroxybutyrate formation, His(10)-TbßHBDH has a k(cat) value of 0.19 s(-1) and a K(M) value of 0.69 mM for acetoacetate. In the direction of acetoacetate formation, His(10)-TbßHBDH has a k(cat) value of 11.2 s(-1) and a K(M) value of 0.65 mM for D-3-hydroxybutyrate. Cofactor preference was examined and His(10)-TbßHBDH utilizes both NAD(H) and NADP(H) almost equivalently, distinguishing the parasite enzyme from other characterized ßHBDHs. Furthermore, His(10)-TbßHBDH binds NAD(P)(+) in a cooperative fashion, another unique characteristic of trypanosome ßHBDH. The apparent native molecular weight of recombinant His(10)-TbßHBDH is 112 kDa, corresponding to tetramer, as determined through size exclusion chromatography. RNA interference studies in procyclic trypanosomes were carried out to evaluate the importance of TbßHBDH in vivo. Upon knockdown of TbßHBDH, a small reduction in parasite growth was observed suggesting ßHBDH has an important physiological role in T. brucei.