This cross-sectional study of National Health and Nutrition Examination Survey data sets evaluates the feasibility of reidentifying accelerometer-measured physical activity data that have had protected health information removed, using support vector machines and random forest methods from machine learning.

The objective of this study was to assess the clinical and histopathological relationship between pulmonary fibrosis and type 1 diabetes. We examined clinical pulmonary function parameters and transbronchial lung biopsies to assess associated histopathological changes in 12 type 1 diabetic patients presenting with dyspnea. Lung CT images pulmonary function tests from 12 diabetic patients without dyspnea and from 12 matched normal subjects served as controls. A similar histopathological analysis, including cytokine levels and pro-fibrotic markers, was performed on lung tissues in mice after the induction of experimental diabetes in an attempt to strengthen the link between diabetes and pulmonary fibrosis. Pulmonary function parameters (FVC, FEV1, TLC, and DLco/VA) were significantly reduced in diabetic patients with dyspnea and without dyspnea, compared to controls. Both patient groups also had increased lung CT scores and symptoms compared to normal controls, though the greatest increases were in the diabetic patients with dyspnea. Chronic hyperglycemia induced in mice led to histopathological changes in the lungs that were similar to those found in the human diabetic subjects and included alveoli compression by hyperplastic interstitium infiltrated with inflammatory cells and fibrotic in nature. Two inflammatory related genes, TNF-α and PAI-1, and two fibrosis-related genes, CTGF and fibronectin, demonstrated increased mRNA and protein expression in diabetic mouse lungs. In conclusion, there were significant clinical and histopathological correlations between pulmonary fibrosis and the presence of type 1 diabetes. Diabetes was clinically associated with pulmonary fibrosis and dysfunction in humans, and diabetes induction led to a similar pulmonary fibrosis in an experimental model. These clinical and non-clinical data suggest that diabetes is an independent risk factor for pulmonary fibrosis.

Diabetic patients have a high risk of pulmonary disorders that are usually associated with restrictive impairment of lung function, suggesting a fibrotic process (van den Borst B, Gosker HR, Zeegers MP, Schols AM. Chest 138: 393-406, 2010; Ehrlich SF, Quesenberry CP Jr, Van Den Eeden SK, Shan J, Ferrara A. Diabetes Care 33: 55-60, 2010). The present study was undertaken to define whether and how diabetes causes lung fibrosis. Lung samples from streptozotocin-induced type 1 diabetic mice, spontaneously developed type 1 diabetic OVE26 mice, and their age-matched controls were investigated with histopathological and biochemical analysis. Signaling mechanism was investigated with cultured normal human lung fibroblasts in vitro. In both diabetes models, histological examination with Sirius red and hemotoxylin and eosin stains showed fibrosis along with massive inflammatory cell infiltration. The fibrotic and inflammatory processes were confirmed by real-time PCR and Western blotting assays for the increased fibronectin, CTGF, PAI-1, and TNFα mRNA and protein expressions. Diabetes also significantly increased NADPH oxidase (NOX) expression and protein nitration along with upregulation of angiotensin II (Ang II) and its receptor expression. In cell culture, exposure of lung fibroblasts to Ang II increased CTGF expression in a dose- and time-dependent manner, which could be abolished by inhibition of superoxide, NO, and peroxynitrite accumulation. Furthermore, chronic infusion of Ang II to normal mice at a subpressor dose induced diabetes-like lung fibrosis, and Ang II receptor AT1 blocker (losartan) abolished the lung fibrotic and inflammatory responses in diabetic mice. These results suggest that Ang II plays a critical role in diabetic lung fibrosis, which is most likely caused by NOX activation-mediated nitrosative damage.

ImportanceGiven conflicting results regarding the prognosis of erb-b2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)–low breast cancer, a large-scale, nationally applicable comparison of ERBB2-low vs ERBB2-negative breast cancer is needed.ObjectiveTo investigate whether ERBB2-low breast cancer is a clinically distinct subtype in terms of epidemiological characteristics, prognosis, and response to neoadjuvant chemotherapy.Design/Participants/SettingThis retrospective cohort study was conducted using the National Cancer Database, including 1 136 016 patients in the US diagnosed with invasive breast cancer from January 1, 2010, to December 31, 2019, who had ERBB2-negative disease and had immunohistochemistry results available. ERBB2-low tumors were classified as having an immunohistochemistry score of 1+, or 2+ with a negative in situ hybridization test. Data were analyzed from November 1, 2021, through November 30, 2022.ExposuresStandard therapy according to routine clinical practice.Main Outcomes and MeasuresThe primary outcomes were overall survival (OS), reported as adjusted hazard ratios (aHRs), and pathologic complete response, reported as adjusted odds ratios (aORs), for ERBB2-negative vs ERBB2-low breast cancer, controlling for age, sex, race and ethnicity, Charlson-Deyo Comorbidity Index score, treatment facility type, tumor grade, tumor histology, hormone receptor status, and cancer stage.ResultsThe study identified 1 136 016 patients (mean [SD] age, 62.4 [13.1] years; 99.1% female; 78.6% non-Hispanic White), of whom 392 246 (34.5%) were diagnosed with ERBB2-negative and 743 770 (65.5%) with ERBB2-low breast cancer. The mean (SD) age of the ERBB2-negative group was 62.1 (13.2) years and 62.5 (13.0) years for the ERBB2-low group. Higher estrogen receptor expression was associated with increased rates of ERBB2-low disease (aOR, 1.15 per 10% increase). Compared with non-Hispanic White patients, of whom 66.1% were diagnosed with ERBB2-low breast cancer, fewer non-Hispanic Black (62.8%) and Hispanic (61.0%) patients had ERBB2-low disease, although in non-Hispanic Black patients this was mediated by differences in rates of triple-negative disease and other confounders. A slightly lower rate of pathologic complete response was seen in patients with ERBB2-low disease vs patients with ERBB2-negative disease on multivariable analysis (aOR, 0.89; 95% CI, 0.86-0.92; P < .001). ERBB2-low status was also associated with small improvements in OS for stage III (aHR, 0.92; 95% CI, 0.89-0.96; P < .001) and stage IV (aHR, 0.91; 95% CI, 0.87-0.96; P < .001) triple-negative breast cancer, although this amounted to only a 2.0% (stage III) and 0.4% (stage IV) increase in 5-year OS.Conclusions and RelevanceThis large-scale retrospective cohort analysis found minimal prognostic differences between ERBB2-low and ERBB2-negative breast cancer. These findings suggest that, moving forward, outcomes in ERBB2-low breast cancer will be driven by ERBB2-directed antibody-drug conjugates, rather than intrinsic differences in biological characteristics associated with low-level ERBB2 expression. These findings do not support the classification of ERBB2-low breast cancer as a unique disease entity.