Ductal carcinoma in situ and cause-specific mortality among younger and older postmenopausal women: the Women's Health Initiative.

BACKGROUND: Whether DCIS is associated with higher breast cancer-specific and all-cause mortality is unclear with few studies in older women. Therefore, we examined DCIS and breast cancer-specific, cardiovascular (CVD)-specific, and all-cause mortality among Women's Health Initiative (WHI) Clinical Trial participants overall and by age (< 70 versus ≥ 70 years). METHODS: Of 68,132 WHI participants, included were 781 postmenopausal women with incident DCIS and 781 matched controls. Serial screening mammography was mandated with high adherence. DCIS cases were confirmed by central medical record review. Adjusted multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Kaplan Meier (KM) plots were used to assess 10-year and 20-year mortality rates. RESULTS: After 20.3 years total, and 13.2 years median post-diagnosis follow-up, compared to controls, DCIS was associated with higher breast cancer-specific mortality (HR 3.29; CI = 1.32-8.22, P = 0.01). The absolute difference in 20-year breast cancer mortality was 1.2% without DCIS and 3.4% after DCIS, log-rank P = 0.026. Findings were similar by age (< 70 versus ≥ 70 years) with no interaction (P interaction = 0.80). Incident DCIS was not associated with CVD-specific mortality (HR 0.77; CI-0.54-1.09, P = 0.14) or with all-cause mortality (HR 0.96; CI = 0.80-1.16, P = 0.68) with similar findings by age. CONCLUSIONS: In postmenopausal women, incident DCIS was associated with over three-fold higher breast cancer-specific mortality, with similar findings in younger and older postmenopausal women. These finding suggest caution in using age to adjust DCIS clinical management or research strategies.

Randomized trials of estrogen-alone and breast cancer incidence: a meta-analysis.

PURPOSE: In the Women's Health initiative (WHI) randomized clinical trial, conjugated equine estrogen (CEE)-alone significantly reduced breast cancer incidence (P = 0.005). As cohort studies had opposite findings, other randomized clinical trials were identified to conduct a meta-analysis of estrogen-alone influence on breast cancer incidence. METHODS: We conducted literature searches on randomized trials and: estrogen, hormone therapy, and breast cancer, and searches from a prior meta-analysis and reviews. In the meta-analysis, for trials with published relative risks (RR) and 95% confidence intervals (CI), each log-RR was multiplied by weight = 1/V, where V = variance of the log-RR, and V was derived from the corresponding 95% CI. For smaller trials with only breast cancer numbers, the corresponding log-RR = (O - E)/weight, where O is the observed case number in the oestrogen-alone group and E the corresponding expected case number, E = nP. RESULTS: Findings from 10 randomized trials included 14,282 participants and 591 incident breast cancers. In 9 smaller trials, with 1.2% (24 of 2029) vs 2.2% (33 of 1514) randomized to estrogen-alone vs placebo (open label, one trial) (RR 0.65 95% CI 0.38-1.11, P = 0.12). For 5 trials evaluating estradiol formulations, RR = 0.63 95% CI 0.34-1.16, P = 0.15. Combining the 10 trials, 3.6% (262 of 7339) vs 4.7% (329 of 6943) randomized to estrogen-alone vs placebo (overall RR 0.77 95% CI 0.65-0.91, P = 0.002). CONCLUSION: The totality of randomized clinical trial evidence supports a conclusion that estrogen-alone use significantly reduces breast cancer incidence.

Processing complementary foods to reduce mycotoxins in a medium scale Tanzanian mill: A hazard analysis critical control point (HACCP) approach.

Designing and implementing processing procedures for producing safe complementary foods in dynamic and unregulated food systems where common food staples are frequently contaminated with mycotoxins is challenging. This paper presents lessons about minimizing aflatoxins (AF) in groundnut flour and AF and/or fumonisins (FUM) in maize and groundnut pre-blended flour for complementary feeding in the context of a dietary research intervention in rural Tanzania. The flours were processed in collaboration with Halisi Products Limited (Halisi), a medium scale enterprise with experience in milling cereal-based flours in Arusha, Tanzania. Using a hazard analysis critical control point (HACCP) approach for quality assurance, two critical control points (CCPs) for AF in processing the pre-blended flour were identified: 1) screening maize before procurement, and 2) blending during the processing of each constituent flour. Blending of maize flour was also identified as a CCP for FUM. Visual inspection during screening and sorting were identified as important control measures for reducing AF, but these steps did not meet the criteria for a CCP due to lack of objective measurement and verifiable standards for AF. The HACCP approach enabled the production of low AF (<5 µg/kg) and FUM (<2 µg/g) flours with low rejection rates for the final products. The paper presents practical lessons that could be of value to a range of commercial processors in similar low- and middle-income contexts who are keen on improving food quality.

Immune Checkpoint Inhibitor Induced Supraglottitis: A Case Series.

OBJECTIVE: To report a series of two cases of unusual airway complications with immunotherapy. METHOD: Case series and review of literature. RESULTS: We report two cases of significant supraglottitis in patients treated with immunotherapy. The first patient is a 62-year-old male receiving treatment for a stage 4 melanoma with Nivolumab and Relatlimab. He presented in Otolaryngology clinic for subacute dysphonia and dysphagia. Flexible laryngoscopy showed significant airway edema, mucopurulent secretions, and inflammation. He was admitted inpatient and treated with high dose systemic steroids and intravenous antibiotics. Daily airway examination with flexible laryngoscopy showed improvement with this medical management. The patient was discharged with antibiotics and a steroid taper. Treatment with immunotherapy was held due to this severe and potentially life-threatening complication. The second patient is a 76-year-old male with bladder cancer treated with Pembrolizumab. Four months after beginning treatment, he experienced hoarseness and throat discomfort. His laryngoscopic examination showed diffuse supraglottic swelling. He was treated inpatient with high dose systemic steroids, intravenous antibiotics, and antifungals, which resulted in improvement of supraglottic swelling. He remained on his immunotherapy treatment. Repeat examination demonstrated persistent supraglottic swelling without airway obstruction. Regarding airway-related complications with immunotherapy, the literature reports three other cases of tracheitis related to immune checkpoint inhibitors. CONCLUSION: This is the first case series of supraglottitis in patients treated with immune checkpoint inhibitors. This adds to the emerging literature of the potential respiratory implications of these medications. Laryngoscope, 2024.

The effect of food deserts on gynecologic cancer survival.

Objective: Living in a food desert is a known negative health risk, with recent literature finding an associated higher mortality in patients with cancers. Gynecologic cancers have not specifically been studied. We aimed to describe patients with gynecologic cancers who live in a food desert and determine if there is an association between living in a food desert and gynecologic cancer mortality. Methods: The 2013-2019 California Cancer Registry (CCR) was used to identify patients with endometrial, ovarian, or cervical cancers. Patient residential census tract was linked to food desert census tracts identified by the 2015 United States Department of Agriculture Food Access Research Atlas. Comorbidity data were obtained from the California Office of Statewide Health Planning and Development database (OSHPD). Treatment, diagnosis, and survival outcomes were obtained from the CCR's variables and compared by food desert status. Five-year disease-specific survival was analyzed by applying Cox proportional hazards analysis. Results: 40,340 gynecologic cancer cases were identified. 60.1 % had endometrial cancer, 23.2 % had ovarian cancer, and 15.9 % had cervical cancer. The average age of the cohort was 59.4 years, 48.0 % was non-Hispanic White, 50.3 % was privately insured, and 6.8 % of lived in a food desert. Living in a food desert was associated with higher disease-specific mortality for patients with gynecologic cancers (endometrial cancer HR 1.43p < 0.001 95 % CI 1.22-1.68; ovarian cancer HR 1.47p < 0.001 95 % CI 1.27-1.69; cervical cancer HR 1.24p = 0.045 95 % CI 1.01-1.54). Conclusion: Patients living in food deserts had worse disease-specific survival, making access to food a modifiable risk factor that may result in mitigating gynecologic cancer disparities.

Laser Versus Cold Steel for Endoscopic Management of Subglottic Stenosis.

OBJECTIVE: Endoscopic management of subglottic stenosis (SGS) includes a wide range of techniques. This 17-year review compares treatment outcomes between carbon dioxide (CO2) laser and cold steel. STUDY DESIGN: Retrospective chart review. SETTING: Single tertiary care center. METHODS: A chart review was performed for all patients undergoing endoscopic treatment of SGS at Cleveland Clinic between July 12, 2000 and September 1, 2017. Data collected included demographics, stenosis etiology, stenosis severity, comorbidities, treatment modality, and airway procedure history. The primary endpoint was repeated treatment-free survival (RTFS) within 2 years using a Kaplan-Meier analysis and Cox proportional hazard model. RESULTS: A total of 139 patients (median [interquartile range] aged 48.7 [37.8, 57.0] years; 83.4% female) were included in the analysis, with etiologies including idiopathic (56.8%), granulomatosis with polyangiitis (25.2%), and intubation (16.5%). All patients underwent either cold steel (107 patients) or CO2 laser (32 patients) lysis of stenosis with concurrent dilation. RTFS within 2 years was 50.2% for CO2 laser and 31.9% for cold steel (hazard ratio [HR] and 95% confidence interval [CI]: 1.69, 0.96-2.97, P = .07). In patients with no prior airway procedures, there was no difference in RTFS between laser and cold knife (P = .41). However, in patients with prior airway procedures, RTFS was significantly greater in the laser group, even after adjusting for age, smoking history, and stenosis etiology (50.0% vs 16.8%, adjusted HR and CI: 2.82, 1.14-6.98, P = .025). CONCLUSION: Endoscopic lysis of SGS with CO2 laser should be considered in revision cases.

Explainable Machine Learning Model to Preoperatively Predict Postoperative Complications in Inpatients With Cancer Undergoing Major Operations.

PURPOSE: Preoperative prediction of postoperative complications (PCs) in inpatients with cancer is challenging. We developed an explainable machine learning (ML) model to predict PCs in a heterogenous population of inpatients with cancer undergoing same-hospitalization major operations. METHODS: Consecutive inpatients who underwent same-hospitalization operations from December 2017 to June 2021 at a single institution were retrospectively reviewed. The ML model was developed and tested using electronic health record (EHR) data to predict 30-day PCs for patients with Clavien-Dindo grade 3 or higher (CD 3+) per the CD classification system. Model performance was assessed using area under the receiver operating characteristic curve (AUROC), area under the precision recall curve (AUPRC), and calibration plots. Model explanation was performed using the Shapley additive explanations (SHAP) method at cohort and individual operation levels. RESULTS: A total of 988 operations in 827 inpatients were included. The ML model was trained using 788 operations and tested using a holdout set of 200 operations. The CD 3+ complication rates were 28.6% and 27.5% in the training and holdout test sets, respectively. Training and holdout test sets' model performance in predicting CD 3+ complications yielded an AUROC of 0.77 and 0.73 and an AUPRC of 0.56 and 0.52, respectively. Calibration plots demonstrated good reliability. The SHAP method identified features and the contributions of the features to the risk of PCs. CONCLUSION: We trained and tested an explainable ML model to predict the risk of developing PCs in patients with cancer. Using patient-specific EHR data, the ML model accurately discriminated the risk of developing CD 3+ complications and displayed top features at the individual operation and cohort level.

Dietary Intervention Favorably Influences Physical Functioning: The Women's Health Initiative Randomized Dietary Modification Trial.

BACKGROUND: In the Women's Health Initiative Dietary Modification randomized trial, the dietary intervention reduced breast cancer mortality by 21% (P = .02) and increased physical activity as well. OBJECTIVE: Therefore, the aim was to examine whether or not these lifestyle changes attenuated age-related physical functioning decline. DESIGN: In a randomized trial, the influence of 8 years of a low-fat dietary pattern intervention was examined through 20 years of cumulative follow-up. PARTICIPANTS AND SETTING: From 1993 to 1998, 48,835 postmenopausal women, ages 50 to 79 years with no prior breast cancer and negative baseline mammogram were randomized at 40 US clinical centers to dietary intervention or usual diet comparison groups (40 out of 60). The intervention significantly reduced fat intake and increased vegetable, fruit, and grain intake. MAIN OUTCOME MEASURES: In post hoc analyses, physical functioning, assessed using the RAND 36-Item Short Form Health Survey, evaluated quality or limitations of 10 hierarchical physical activities. Longitudinal physical functioning, reported against a disability threshold (when assistance in daily activities is required) was the primary study outcome. STATISTICAL ANALYSES PERFORMED: Semiparametric linear mixed effect models were used to contrast physical functioning trajectories by randomization groups. RESULTS: Physical functioning score, assessed 495,317 times with 11.0 (median) assessments per participant, was significantly higher in the intervention vs comparison groups through 12 years of cumulative follow-up (P = .001), representing a reduction in age-related functional decline. The intervention effect subsequently attenuated and did not delay time to the disability threshold. Among women in the dietary intervention vs comparison groups, aged 50 to 59 years, who were physically inactive at entry, a persistent, statistically significant, favorable influence on physical functioning with associated delay in crossing the disability threshold by approximately a year was seen (P value for interaction = .007). CONCLUSIONS: In the Women's Health Initiative Dietary Modification randomized trial, a dietary intervention that significantly reduced breast cancer mortality also significantly reduced age-related functional decline through 12 years, which was attenuated with longer follow-up.