OncotypeDX Testing Does Not Benefit Patients with Estrogen and Progesterone Receptor Positive Grade 1 Breast Cancers: A TAILORx Validated Study.

BACKGROUND & OBJECTIVES: We previously described a predictive AAMC model that identifies patients (grade 1, hormonepositive) who would not benefit from OncotypeDX testing. The purpose of this study was to validate the AAMC model by assessing distant recurrence-free interval (DRFI) and invasive disease-free survival (IDFS) using TAILORx clinical trial data. MATERIALS & METHODS: We retrospectively analyzed TAILORx trial data and categorized patients based on the AAMC model. AAMC low-risk patients are those with grade 1 and hormone-positive tumors. Kaplan-Meier curves examined DRFI and IDFS. RESULTS: Of the 9195 cases, 2246 (24.4%) were identified by AAMC as low-risk. Among these AAMC low-risk patients, 55.2% had Recurrence Score (RS) 0-15, 42.3% had RS 15-25, and 2.4% had RS > 25. The 10-year DRFI did not differ for those who received adjuvant chemotherapy versus those who did not (98% vs. 96%, log-rank p = 0.46). Similarly, IDFS was comparable between those who received adjuvant chemotherapy and those that did not (86% vs. 86%, log-rank p = 0.66). Only 2.4% of AAMC low-risk patients were categorized as high-risk (RS > 25). A sensitivity analysis of this discordant group, wherein those with RS > 25 were re-classified into the no-chemotherapy group and assumed to have experienced recurrences at the rate expected without chemotherapy, did not find any difference in DRFI between those who received adjuvant chemotherapy and those who did not (log-rank p = 0.16). CONCLUSION: OncotypeDX testing does not benefit AAMC low-risk patients with hormone-positive grade 1 tumors. Based on these data, 1 in 4 TAILORx participants would not need OncotypeDX testing.

Outcomes of Nipple-sparing Mastectomy with Reconstruction after Recent Oncoplastic Wise-pattern Reduction.

For patients with large and/or ptotic breasts, a planned staged approach to nipple-sparing mastectomy (NSM) has been described. Less is known about surgical outcomes of unplanned staged NSM for management of positive margins after partial mastectomy with oncoplastic reduction. It is not clear from earlier studies whether an interval of less than 10 weeks between oncoplastic reduction and NSM is feasible, when a shorter interval is important for oncologic reasons. Methods: This is a single institution analysis of patients from 2018 to 2021 with a diagnosis of invasive cancer or ductal carcinoma in situ who underwent NSM after oncoplastic breast reduction for positive margins or nodes. The primary endpoint measured was nipple loss. Secondary outcomes were need for operative re-intervention and wound complications. Results: Nine patients (14 breasts) underwent partial mastectomy with oncoplastic Wise-pattern breast reduction, followed by NSM. Three patients underwent intersurgery chemotherapy. The average interval between oncoplastic reduction and NSM was 11.3 weeks when excluding patients undergoing chemotherapy (range 8-13 weeks). Thirteen breasts (93%) underwent pre-pectoral direct-to-implant reconstruction. One breast (7%) received autologous reconstruction. One breast required reoperation for seroma. The rate of partial or total nipple loss was 0%, with an average follow-up of 1.6 years. Conclusions: Our experience demonstrates excellent outcomes from NSM after oncoplastic breast reduction, with the majority of patients undergoing single-stage pectoral direct-to-implant breast reconstruction. Overall, patients had a shorter intersurgery interval, compared with prior studies, with no cases of nipple loss. An intersurgery interval of 8 weeks may be feasible when avoiding delays is important for oncologic reasons.

Actualización en el diagnóstico de la encefalitis / Update on the diagnosis of encephalitis

Las encefalitis autoinmunes son procesos inflamatorios cerebrales que se clasifican en dos grandes grupos según el mecanismo patogénico subyacente: las mediadas por anticuerpos vs. antígenos intracelulares (paraneoplásicas) y las mediadas por anticuerpos frente a los antígenos extracelulares o de superficie neuronal. Las manifestaciones clínicas son muy variadas y poco específicas. Las pruebas complementarias incluidas en el diagnóstico clínico de la encefalitis autoinmune incluyen, entre otras, la determinación de anticuerpos en suero o en líquido cefalorraquídeo y la resonancia magnética (RM). La RM puede presentar patrones característicos como la afectación mesial del temporal, aunque en determinados casos puede ser normal. La imagen de tomografía por emisión de positrones (PET/TC) con 18F-Fluorodeoxiglucosa (18F-FDG PET/TC) puede ser de gran utilidad en los casos de encefalitis autoinmunes paraneoplásicas para encontrar el tumor primario. En los casos de encefalitis autoinmunes mediadas por anticuerpos frente a los antígenos extracelulares, la 18F-FDG PET/TC presenta unos patrones que pueden ayudar al diagnóstico clínico. Esta colaboración especial pretende presentar de forma clara y de fácil comprensión las características clínicas de la encefalitis autoinmune, las dificultades en el diagnóstico clínico y los patrones observados en la RM y en la 18F-FDG PET/TC (AU)

Autoimmune encephalitis are brain inflammatory processes that are classified into two main groups according to the underlying pathogenic mechanism: antibodies to intracellular antigens (paraneoplastic) and antibodies to extracellular or neuronal surface antigens. The clinical manifestations of autoimmune encephalitis are very varied and non-specific. Complementary tests included in its clinical diagnosis include determination of antibodies in serum or cerebrospinal fluid and magnetic resonance imaging (MRI). MRI may show characteristic patterns such as mesial temporal involvement, although in some cases it may be normal or non-specific. 18F-Fluorodeoxyglucose PET/CT (18F-FDG PET/CT) imaging may be helpful in cases of paraneoplastic autoimmune encephalitis to find the primary tumor. In autoimmune encephalitis mediated by antibodies to extracellular antigens, 18F-FDG PET/CT shows distinctive patterns that can aid clinical diagnosis. This special collaboration aims to present in a clear and easy-to-understand way, the clinical features of autoimmune encephalitis, the difficulties in clinical diagnosis and the patterns seen on MRI and 18F-FDG PET/CT (AU)

Recurrence Score Testing Does not Appear to Benefit Patients With Grade 1, Progesterone Receptor-Positive Breast Cancers: An Opportunity to Eliminate Overtreatment and Decrease Testing Costs.

BACKGROUND: We previously described a risk prediction model (Anne Arundel Medical Center [AAMC] model) based on pathology which may eliminate the need for recurrence score (RS) testing in select early-stage breast cancers. There is a concern that patients in discordant risk prediction groups (AAMC vs. RS) may be overtreated or undertreated if RS testing were omitted. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) database for all breast cancer patients between 2004 and 2015. AAMC low-risk was defined as Grade 1 and progesterone receptor-positive (PR + ) tumors, while AAMC high-risk was defined as Grade 3 or estrogen-negative tumors. RS low-risk group was defined as RS < 16 and age ≤ 50 years, or RS ≤ 25 and age > 50 years. RS high-risk group was defined as RS > 25. RESULTS: A total of 71,212 cases were analyzed. Of these, 590 were AAMC low-risk/RS high-risk discordant, while 5,596 were AAMC high-risk/RS low-risk discordant. For AAMC low-risk/RS high-risk discordant, 10-year breast cancer-specific survival (BCSS) did not differ for patients who received adjuvant chemotherapy versus those who did not (93% chemotherapy vs. 99% unknown/no chemotherapy, p = .12). Overall survival (OS) was also comparable (92% chemotherapy vs. 91% unknown/no chemotherapy, p = .42). In the AAMC high-risk/RS low-risk discordant group, 10-year BCSS (92% chemotherapy vs. 96% unknown/no chemotherapy, p = .06) and OS (87% chemotherapy vs. 90% unknown/no chemotherapy, p = .52) did not differ between adjuvant chemotherapy and unknown/no chemotherapy groups. CONCLUSIONS: Adjuvant chemotherapy in the AAMC low-risk/RS high-risk and AAMC high-risk/RS low-risk discordant groups did not improve survival. This supports consideration of omission of RS testing in Grade 1, PR + tumors. Patients with Grade 3 tumors do benefit from RS testing.

A 95-gene signature stratifies recurrence risk of invasive disease in ER-positive, HER2-negative, node-negative breast cancer with intermediate 21-gene signature recurrence scores.

PURPOSE: A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk. METHODS: Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included. RNA was extracted from archived formalin-fixed, paraffin-embedded samples, and 95-gene signature was calculated. RESULTS: 206 patients had RS of 11-25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was significantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81-19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coefficient r = 0.27), which might suggest that 95-gene signature reflects biological characteristics differing from what 21-gene signature shows. CONCLUSIONS: The 95-gene signature stratifies patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11-25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively accrued TAILORx population is warranted to confirm that 95-gene signature can identify patients who would benefit from adjuvant chemoendocrine therapy.

Development of a Low-Resource Operating Room and a Wide-Awake Orthopedic Surgery Program During the COVID-19 Pandemic.

Introduction. The COVID-19 pandemic resulted in significant medication, supply and equipment, and provider shortages, limiting the resources available for provision of surgical care. In response to mandates restricting surgery to high-acuity procedures during this period, our institution developed a multidisciplinary Low-Resource Operating Room (LROR) Taskforce in April 2020. This study describes our institutional experience developing an LROR to maintain access to urgent surgical procedures during the peak of the COVID-19 pandemic. Methods. A delineation of available resources and resource replacement strategies was conducted, and a final institution-wide plan for operationalizing the LROR was formed. Specialty-specific subgroups then convened to determine best practices and opportunities for LROR utilization. Orthopedic surgery performed in the LROR using wide-awake local anesthesia no tourniquet (WALANT) is presented as a use case. Results. Overall, 19 limited resources were identified, spanning across the domains of physical space, drugs, devices and equipment, and personnel. Based on the assessment, the decision to proceed with creation of an LROR was made. Sixteen urgent orthopedic surgeries were successfully performed using WALANT without conversion to general anesthesia. Conclusion. In response to the COVID-19 pandemic, a LROR was successfully designed and operationalized. The process for development of a LROR and recommended strategies for operating in a resource-constrained environment may serve as a model for other institutions and facilitate rapid implementation of this care model should the need arise in future pandemic or disaster situations.

Flunixin meglumine blocks frusemide-induced bronchodilation in horses with chronic obstructive pulmonary disease.

Six horses that developed acute airway obstruction (heaves) when housed in a barn and fed poor-quality hay were studied. Airway obstruction was verified by a maximal change in pleural pressure during tidal breathing (delta Pplmax) of at least 15 cmH2O. Frusemide (1.0 mg/kg bwt) or an equivalent volume of vehicle was then administered intravenously (iv) and lung function was measured 15, 30, 60, 120, 180, 240 and 300 mins after drug administration. The effect of frusemide on lung function was also studied after treatment of horses with the cyclooxygenase inhibitor flunixin meglumine (1.1 mg/kg every 8 h for 2 days before the experiment). Frusemide significantly reduced the delta Pplmax beginning 15 mins after drug administration. This effect persisted for 5 h. The reduction in delta Pplmax was due partly to an increase in dynamic compliance and partly to a decrease in pulmonary resistance. Tidal volume and respiratory frequency were unaffected by frusemide. Vehicle had no effect on lung function. Flunixin meglumine abolished the effect of frusemide on airway calibre but did not prevent diuresis. These results indicate that the effect of frusemide on airways of horses with heaves persists for at least 5 h, is mediated through prostanoids, and is not a result of diuresis.