Nodal Response and Survival After Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive Breast Cancer: 20-Year Experience from a Single Institution.

INTRODUCTION: Axillary response to neoadjuvant endocrine therapy (NET) for the treatment of hormone receptor-positive breast cancer (HR+ BC) is not well-described. This study was designed to characterize nodal response after NET. METHODS: Patients receiving NET followed by curative intent surgery at a comprehensive cancer center from 1998 to 2022 in a prospectively collected registry were included. Patients with distant metastasis were excluded. Primary outcome was nodal pathologic complete response (pCR). Downstaging was defined as post-NET decrease in category. RESULTS: We included 123 patients; the majority were cT2 (n = 59) or cT3 (n = 35), and cN0 (n = 81). Median age was 70.0 years (interquartile range 62.1-76.0). Forty-two patients (34.1%) were clinically node-positive. After NET, 73 (59.8%) underwent breast-conserving surgery. All patients underwent sentinel lymph node biopsy, and 12 (9.8%) underwent completion axillary lymph node dissection. In-breast downstaging was achieved in 51 (41.5%) patients, 1 (0.8%) had breast pCR, and 14 (11.4%) had breast upstaging. Axillary downstaging was achieved in 10 (23.8%), 6 patients (14.3%) had nodal pCR, and 14 (33.3%) had axillary upstaging. At 10-year follow-up, local recurrence was 1% and distant recurrence was 14%, while disease-free survival was 82%. After adjusting for demographic and clinical factors, age was the only characteristic associated with mortality (hazard ratio 1.07, 95% confidence interval 1.01-1.13). CONCLUSIONS: In HR+ BC treated with NET, long-term disease-free survival is good, although nodal pCR is uncommon for cN+ patients. Future studies are needed to elucidate optimal neoadjuvant systemic therapy and to delineate oncologically safe strategies to deescalate axillary management for residual microscopic disease.

Validation of an international classification of disease, tenth revision, clinical modification (ICD-10-CM) algorithm in identifying severe hypoglycaemia events for real-world studies.

AIM: The transition to the ICD-10-CM coding system has reduced the utility of hypoglycaemia algorithms based on ICD-9-CM diagnosis codes in real-world studies of antidiabetic drugs. We mapped a validated ICD-9-CM hypoglycaemia algorithm to ICD-10-CM codes to create an ICD-10-CM hypoglycaemia algorithm and assessed its performance in identifying severe hypoglycaemia. MATERIALS AND METHODS: We assembled a cohort of Medicare patients with DM and linked electronic health record (EHR) data to the University of North Carolina Health System and identified candidate severe hypoglycaemia events from their Medicare claims using the ICD-10-CM hypoglycaemia algorithm. We confirmed severe hypoglycaemia by EHR review and computed a positive predictive value (PPV) of the algorithm to assess its performance. We refined the algorithm by removing poor performing codes (PPV ≤0.5) and computed a Cohen's κ statistic to evaluate the agreement of the EHR reviews. RESULTS: The algorithm identified 642 candidate severe hypoglycaemia events, and we confirmed 455 as true severe hypoglycaemia events, PPV of 0.709 (95% confidence interval: 0.672, 0.744). When we refined the algorithm, the PPV increased to 0.893 (0.862, 0.918) and missed <2.42% (<11) true severe hypoglycaemia events. Agreement between reviewers was high, κ = 0.93 (0.89, 0.97). CONCLUSIONS: We translated an ICD-9-CM hypoglycaemia algorithm to an ICD-10-CM version and found its performance was modest. The performance of the algorithm improved by removing poor performing codes at the trade-off of missing very few severe hypoglycaemia events. The algorithm has the potential to be used to identify severe hypoglycaemia in real-world studies of antidiabetic drugs.

The Effect of Sodium Glucose Cotransporter-2 Inhibitors on Hemoglobin A1c Variability and Acute Kidney Injury: A Causal Mediation Analysis.

PURPOSE: The role of lower hemoglobin A1c (HbA1c) variability in the effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on acute kidney injury (AKI) remains unclear. We compared AKI risk between SGLT2i and dipeptidyl peptidase 4 inhibitors (DPP4i) initiators. Additionally, we aimed to explore the extent to which SGLT2i's influence on AKI risk is mediated by reducing long-term HbA1c variability. METHODS: Using 2018-2022 year data in Yinzhou Regional Health Care Database, we included adult, type 2 diabetes patients who were new users of SGLT2i or DPP4i. The effect of SGLT2i versus DPP4i on AKI, HbA1c variability, and AKI through HbA1c variability was compared using inverse probability of treatment weighted Cox proportional hazards models, median regression models, and causal mediation analysis. RESULTS: With a median follow-up of 1.76 years, 19 717 adults (for SGLT2i, n = 6008; for DPP4i, n = 13 709) with type 2 diabetes were included. The adjusted hazard ratio for SGLT2i versus DPP4i was 0.79 (95% confidence interval [CI] 0.64-0.98) for AKI. The adjusted differences in median HbA1c variability score (HVS) and HbA1c reduction were -16.67% (95% CI: -27.71% to -5.62%) and -1.98% (95% CI: -14.34% to 10.38%), respectively. Furthermore, lower AKI risk associated with SGLT2i was moderately mediated (22.77%) through HVS. The results remained consistent across various subgroups and sensitivity analyses. CONCLUSIONS: Compared to DPP4i, lower AKI risk associated with SGLT2i is moderately mediated through HbA1c variability. These findings enhance our understanding of the effect of SGLT2i on AKI and underscore the importance of considering HbA1c variability in diabetes treatment and management.

Bariatric surgery: trends in utilization, complications, conversions and revisions.

BACKGROUND: Sleeve gastrectomy (SG) increased in popularity after 2010 but recent data suggest it has concerning rates of gastroesophageal reflux and need for conversions. This study aims to evaluate recent trends in the utilization of bariatric procedures, associated complications, and conversions using an administrative claims database in the United States. METHODS: We included adults who had bariatric procedures from 2000 to 2020 with continuous enrollment for at least 6 months in the MarketScan Commercial Claims and Encounters database. Index bariatric procedures and subsequent revisions or conversions were identified using CPT codes. Baseline comorbidities and postoperative complications were identified with ICD-9-CM and ICD-10 codes. Cumulative incidences of complications were estimated at 30-days, 6-months, and 1-year and compared with stabilized inverse probability of treatment weighted Kaplan-Meier analysis. RESULTS: We identified 349,411 bariatric procedures and 5521 conversions or revisions. The sampled SG volume appeared to begin declining in 2018 while Roux-en-Y gastric bypass (RYGB) remained steady. Compared to RYGB, SG was associated with lower 1-year incidence [aHR, (95% CIs)] for 30-days readmission [0.65, (0.64-0.68)], dehydration [0.75, (0.73-0.78)], nausea or vomiting [0.70, (0.69-0.72)], dysphagia [0.55, (0.53-0.57)], and gastrointestinal hemorrhage [0.43, (0.40-0.46)]. Compared to RYGB, SG was associated with higher 1-year incidence [aHR, (95% CIs)] of esophagogastroduodenoscopy [1.13, (1.11-1.15)], heartburn [1.38, (1.28-1.49)], gastritis [4.28, (4.14-4.44)], portal vein thrombosis [3.93, (2.82-5.48)], and hernias of all types [1.36, (1.34-1.39)]. There were more conversions from SG to RYGB than re-sleeving procedures. SG had a significantly lower 1-year incidence of other non-revisional surgical interventions when compared to RYGB. CONCLUSIONS: The overall volume of bariatric procedures within the claims database appeared to be declining over the last 10 years. The decreasing proportion of SG and the increasing proportion of RYGB suggest the specific complications of SG may be driving this trend. Clearly, RYGB should remain an important tool in the bariatric surgeon's armamentarium.

Evaluating the safety of bariatric surgery as a bridge to kidney transplant: a retrospective cohort study.

BACKGROUND: Bariatric surgery has been proven safe in end-stage kidney disease (ESKD); however, few studies have evaluated whether a history of bariatric surgery impacts transplant-specific outcomes. We hypothesize that a history of bariatric surgery at the time of transplant does not adversely impact transplant-specific outcomes. METHODS: The IBM MarketScan Commercial Claims and Encounters database was queried for patients with a history of kidney transplant between 2000 and 2021. Patients were stratified into three groups based on bariatric surgery status and body mass index (BMI) at the time of transplant: patients with obesity (O), patients without obesity (NO), and patients with a history of bariatric surgery (BS). Inverse probability of treatment weighting was used to control for confounding. Adjusted hazard ratios (aHRs) describing the risk of transplant-specific and postoperative outcomes were estimated using weighted Kaplan-Meier curves. Primary outcomes included 30-day and 1-year risk of transplant-specific outcomes. Secondary outcomes included 30-day and 1-year postoperative complications and 30-day and 1-year risk of wound-related complications. RESULTS: We identified 14,806 patients; 128 in the BS group, 1572 in the O group, and 13,106 in the NO group. There was no difference in 30-day or 1-year risk of transplant-specific complications between the BS and NO group or the O and NO group. Patients with obesity (O) were more likely to experience wound infection (aHR 1.49, 95% CI 1.12-1.99), wound dehiscence (aHR 2.2, 95% CI 1.5-3.2), and minor reoperation (aHR 1.52, 95% CI 1.23-1.89) at 1 year. BS patients had increased risk of wound infection at 1 year (aHR 2.79, 95% CI 1.26-6.16), but were without increase in risk of minor or major reoperation. CONCLUSION: A history of bariatric surgery does not adversely affect transplant-specific outcomes after kidney transplant. Bariatric surgery can be safely utilized to improve the transplant candidacy of patients with obesity with CKD and ESKD.

An Institutional Guide for Formulary Decisions of Biosimilars.

Biologics have changed the landscape for the management of many debilitating chronic diseases but account for a significant expenditure of medications globally. Fortunately, advances in technology paved the way for the introduction of biosimilars, which are highly similar to the originator biologics. In the quest to reduce the budget impact of biologics, organizations have begun to adopt biosimilars. Institutions evaluating biosimilars for inclusion in the hospital formulary must make informed formulary decisions by conducting a thorough review of key elements for evaluation of biosimilars and address the multidimensional aspects during the selection process of different biosimilar products. Therefore, we aim to present an institutional guide of these elements to inform formulary decisions. These key elements include biosimilar evaluation for formulary addition; regulatory approval; substitution, interchangeability, and switching; extrapolation; product characteristics, manufacturing, and supply chain issues; pharmacoeconomic evaluations; traceability, nomenclature, and coding; education; and pharmacovigilance.

The impact of the implementation of computerized insulin order sets for the control of hyperglycemia in hospitalized cardiac patients.

Background: Glycemic control is crucial in managing hospitalized patients with type II diabetes (T2DM), and it presents as a clinical challenge in the cardiac population. Therefore, we aimed to evaluate the impact of computerized insulin order sets in T2DM hospitalized cardiac patients. Methods: A quasi-experimental, pre- and post-study design. We included T2DM patients who were hospitalized for at least 3 days. Patients undergoing cardiac surgery were excluded. The primary endpoint was the mean difference in random blood glucose level (BGL) before and after the implementation of insulin order sets. While the secondary endpoints were to compare the median differences in fasting BGLs and the number of hyperglycemic and hypoglycemic episodes during the first 7 days. The study consisted of three phases: pre-implementation, intervention and post-phase. In the intervention phase, insulin order sets were integrated into the electronic prescribing system, and education was provided to the cardiology department. The post-phase included the patient's post-implementations. Results: A total of 194 patients were enrolled during the study period. The mean random BGL was 11.17 mmol/L, 95% CI, 10.6-11.7 in the pre-phase and 9.5 mmol/L, 95% CI, 9-1 -9.9 mmol/L in the post-phase (P < 0.001). The median fasting BGL was 9.2 mmol/L (7.4-11.8, IQR) in the pre-phase and 8.5 mmol/L (6.6-10.3, IQR) in the post-phase (P = 0.027). The number of hypoglycemic episodes was 24 in pre-phase and 33 in post-phase (P = 0.13). Conclusion: The use of computerized insulin order sets was associated with potential improvements in random and fasting glycemic control without increasing the risk of hyperglycemia or hypoglycemia.

Clinical and Histological Response to Talimogene Laherparepvec Therapy in Advanced Melanoma: Impact on Overall Survival.

BACKGROUND: Talimogene laherparepvec (T-VEC) is an FDA-approved oncolytic herpesvirus therapy used for unresectable stage IIIB through IV metastatic melanoma. However, the correlation between clinical complete response (cCR) and pathologic complete response (pCR) in patients treated with T-VEC is understudied. STUDY DESIGN: We conducted a retrospective study from a prospectively maintained IRB-approved melanoma single-center database in patients treated with T-VEC from October 2015 to April 2022. Patients were categorized into 3 groups: cCR with pCR, cCR without pCR, and less than cCR. The primary endpoint was overall survival. We used descriptive statistics, chi-square tests, and Wilcoxon rank-sum tests to compare key covariates among exposure groups. We used survival analysis to compare survival curves and reported hazard ratio of death (95% CI) across exposure groups. RESULTS: We included 116 patients with a median overall survival (interquartile range) of 22.7 (14.8-39.3) months. The majority were men (69%) and White (97.4%), with a median age of 74.5 years. More than half of patients (n = 60, 51.6%) achieved cCR. Distribution among the groups was as follows: cCR with pCR (35.3%), cCR without pCR (16.3%), and less than cCR (48.4%). Median overall survival time (interquartile range) was 26.5 (18.6-36.0) months for cCR with pCR, 22.7 (14.4-35.5) months for cCR without pCR, and 17.8 (9.2-47.0) months for less than cCR (log-rank p value = 0.0033). CONCLUSIONS: Patients achieving cCR with pCR after T-VEC therapy have the most favorable overall survival outcomes, whereas those achieving cCR without pCR have inferior survival and those achieving less than cCR have the poorest overall survival outcomes. These findings emphasize the importance of histological confirmation and provide insights for optimizing T-VEC therapy in patients with advanced melanoma.

Copper oxide nanostructures as a potential method for control of zucchini yellow mosaic virus in squash.

BACKGROUND: Zucchini yellow mosaic virus (ZYMV) infects cucurbits and has been identified as a major limiting factor in their production. The purpose of this study was to create copper oxide nanostructures (CONS) to control ZYMV in squash plants. Protection of squash against ZYMV was assessed in terms of virus severity, ZYMV concentration, transcription of pathogenesis-related genes and growth enhancement of treated squash. RESULTS: The findings revealed that squash plants treated with CONS had a significant reduction in disease severity when compared with untreated plants. In squash plants treated with CONS, defense genes associated with the salicylic acid signaling pathway were strongly expressed compared with untreated plants. The structural characteristics of CONS, such as their small size and appropriate shape, added to their excellent anti-ZYMV efficacy. CONS-treated squash plants show significantly improved growth traits compared with untreated plants. CONCLUSION: Based on the results of this study, CONS may be a new strategy for the control of ZYMV in squash. This represents an unconventional solution to control this virus, particularly as no chemical pesticides can control viral diseases. © 2022 Society of Chemical Industry.