Identification of circular RNA circVPS33A as a modulator in house dust mite-induced injury in human bronchial epithelial cells.

BACKGROUND: House dust mite has been well documented as a major source of allergen in asthma. Circular RNAs (circRNAs) vacuolar protein sorting 33A (circVPS33A, circ_0000455) is overexpressed in a murine asthma model. Herein, we sought to identify its critical action in Dermatophagoides pteronyssinus peptidase 1 (Der p1)-induced dysfunction of BEAS-2B cells. METHODS: The levels of circVPS33A, microRNA (miR)-192-5p, and high-mobility group box 1 (HMGB1) were assessed by quantitative real-time PCR (qRT-PCR) or western blot. Actinomycin D treatment and Ribonuclease R (RNase R) assay were used to characterize circVPS33A. Cell viability, proliferation, apoptosis, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and transwell assays, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to quantify interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and IL-6. Direct relationship between miR-192-5p and circVPS33A or HMGB1 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assay. RESULTS: CircVPS33A was highly expressed in asthma plasma and Der p1-treated BEAS-2B cells. Knocking down circVPS33A suppressed Der p1-induced injury in BEAS-2B cells. CircVPS33A targeted miR-192-5p. MiR-192-5p directly targeted HMGB1, and miR-192-5p-mediated repression of HMGB1 alleviated Der p1-driven cell injury. Furthermore, circVPS33A modulated HMGB1 expression through miR-192-5p. CONCLUSION: Our findings demonstrated that circVPS33A regulated house dust mite-induced injury in human bronchial epithelial cells at least partially depending on the modulation of the miR-192-5p/HMGB1 axis.

Complications of clavicle fracture surgery in patients with concomitant chest wall injury: a retrospective study.

BACKGROUND: The impact of associated chest wall injuries (CWI) on the complications of clavicle fracture repair is unclear to date. This study aimed to investigate the complications after surgical clavicle fracture fixation in patients with and without different degrees of associated CWI. METHODS: A retrospective review over a four-year period of patients who underwent clavicle fracture repair was conducted. A CWI and no-CWI group were distinguished, and the CWI group was subdivided into the minor-CWI (three or fewer rib fractures without flail chest) and complex-CWI (flail chest, four or more rib fractures) subgroup. Demographic data, classification of the clavicle fracture, number of rib fractures, and associated injuries were recorded. Overall complications included surgery-related complications and unplanned hospital readmissions. Univariate analysis and stepwise backward multivariate logistic regression were used to identify potential risk factors for complications. RESULTS: A total of 314 patients undergoing 316 clavicle fracture operations were studied; 28.7% of patients (90/314) occurred with associated CWI. Patients with associated CWI showed a significantly higher age, body mass index, and number of rib fractures. The overall and surgical-related complication rate were similar between groups. Unplanned 30-day hospital readmission rates were significantly higher in the complex-CWI group (p = 0.02). Complex CWI and number of rib fractures were both independent factor for 30-day unplanned hospital readmission (OR 1.59, 95% CI: 1.00-2.54 and OR 1.33, 95% CI: 1.06-1.68, respectively). CONCLUSION: CWI did not affect surgery-related complications after clavicle fracture repair. However, complex-CWI may increase 30-day unplanned hospital readmission rates.

Diagnosis and management of a trapped lung or diaphragm by fractured ribs: analysis of patients undergoing rib fracture repair.

BACKGROUND: There are few reports regarding a lung or diaphragm trapped by a fractured rib. This study aimed to describe the clinical presentations, diagnosis, and management of these intrathoracic pathologies. METHODS: We retrospectively reviewed the database at our institute for patients with rib fractures who underwent thoracoscope-assisted surgical stabilization of rib fracture (SSRF). We analyzed the demographic data, mechanism of trauma, presentations, operative findings, and subsequent management strategies. RESULTS: A total of 38 consecutive patients who underwent SSRF were analyzed. Three patients had a trapped lung and one had a trapped diaphragm. Abnormal radiographic findings were observed in 50% of cases. The median waiting time for surgery was 25 days. Surgery was indicated for intractable dynamic pain following conservative treatment. A definitive diagnosis was made during thoracoscopic exploration. Thoracoscopic repair and resection were used for trapped lungs and thoracoscopic release for a trapped diaphragm. We subsequently performed SSRF for unhealed rib fractures. CONCLUSION: As per our analysis, the incidence of a trapped lung or diaphragm was 10.5%. If a patient presents with persistent intractable dynamic pain, thoracoscopic exploration with concurrent SSRF may be a feasible and effective treatment option.

Associations of the Transforming Growth Factor ß/Smad Pathway, Body Mass Index, and Physical Activity With Breast Cancer Outcomes: Results From the Shanghai Breast Cancer Study.

The transforming growth factor ß (TGF-ß) pathway plays an important role in breast cancer progression and in metabolic regulation and energy homeostasis. The prognostic significance of TGF-ß interaction with obesity and physical activity in breast cancer patients remains unclear. We evaluated the expression of TGF-ß type II receptor and pSmad2 immunohistochemically in breast cancer tissue from 1,045 patients in the Shanghai Breast Cancer Study (2002-2005). We found that the presence of nuclear pSmad2 in breast cancer cells was inversely associated with overall and disease-free survival, predominantly among participants with lower body mass index (BMI; weight (kg)/height (m)2) and a moderate level of physical activity. However, the test for multiplicative interaction produced a significant result only for BMI (for disease-free survival and overall survival, adjusted hazard ratios were 1.79 and 2.05, respectively). In 535 earlier-stage (T1-2, N0) invasive cancers, nuclear pSmad2 was associated with improved survival among persons with higher BMI (overall survival: adjusted hazard ratio = 0.27, 95% confidence interval: 0.09, 0.86). The cytoplasmic pattern of TGF-ß type II receptor expression in cancer cells was significantly associated with a lower survival rate but was not modified by BMI or physical activity. Our study suggests that the TGF-ß pathway in tumor cells is involved in breast cancer prognosis and may be modified by BMI through pSmad2.

Body mass index and weight change in relation to triple-negative breast cancer survival.

The aim of this study was to evaluate the influence of body mass index (BMI), weight change on triple-negative breast cancer (TNBC) prognosis in a population-based prospective cohort study. The current analysis included 518 participants diagnosed with TNBC in Shanghai Breast Cancer Survival Study. Weight at 1 year prior to cancer diagnosis, at diagnosis, and at 6, 18 and 36 months after cancer diagnosis and height at 6 months after cancer diagnosis were assessed. Disease-free survival (DFS) and overall survival (OS) were evaluated in relation to BMI and weight change using Cox proportional hazard models. Obesity (BMI ≥ 28.0 kg/m(2)) at 1-year pre-diagnosis was associated with higher risk of total mortality and recurrence/disease-specific mortality, with multivariate hazard ratios (HRs) of 1.79 (95 % CI 1.06-3.03) and 1.83 (95 % CI 1.05-3.21), respectively. The associations between BMI and TNBC prognosis attenuated over time from pre-diagnosis to post-diagnosis. Compared with stable weight (change within 5 %), weight loss ≥5 % at 18- or 36-month post-diagnosis was related with higher risk of total mortality and recurrence/disease-specific mortality. Respective multivariate HRs were 2.08 (95 % CI 1.25-3.46) and 1.42 (95 % CI 0.77-2.63) for OS, and 2.50 (95 % CI 1.45-4.30) and 2.17 (95 % CI 1.14-4.12) for DFS. However, the association of weight loss and OS/DFS attenuated after excluding patients whose weight was measured after recurrence. Weight gain ≥5 % at 18- or 36-month post-diagnosis was associated with a non-significant increased risk of death. The results showed that obesity pre-diagnosis and weight loss post-diagnosis was inversely associated with TNBC prognosis. Emphasis on maintaining stable weight after cancer diagnosis for TNBC patients may be considered.

Increased pSmad2 expression and cytoplasmic predominant presence of TGF-ßRII in breast cancer tissue are associated with poor prognosis: results from the Shanghai Breast Cancer Study.

Perturbations of transforming growth factor-beta (TGF-ß) signaling are pivotal to tumorigenesis and tumor progression through their effects on cell proliferation and cell invasion. This study aims to evaluate the association of TGF-ßRII and pSmad2 protein expressions in breast tissue with clinicopathological factors and prognosis of breast cancer. Expression of the TGF-ßRII and pSmad2 proteins was assessed in breast tissue of 1,045 breast cancer cases in the Shanghai Breast Cancer Study using a double immunofluorescence staining method, which was validated with standard single immunostains. TGF-ßRII expression intensity was positively associated with younger age at diagnosis (P = 0.03), pre-menopausal status (P = 0.03), and lower TNM stage (P = 0.04). Cytoplasmic predominant expression pattern of TGF-ßRII was associated with older age at diagnosis (P = 0.04) and invasive histological type (P = 0.03). Increased pSmad2 expression was associated with higher breast cancer grade (P < 0.01). Higher pSmad2 expression [HR (95 % CI):1.48 (1.07-2.04), P = 0.02] and cytoplasmic predominant TGF-ßRII expression [HR (95 % CI): 1.80 (1.08-3.00), P = 0.02] were significantly associated with reduced cancer-free survival. Our data suggest that TGF-ßRII and pSmad2 expressions are associated with certain clinical and pathologic features of breast cancer. A cytoplasmic predominant TGF-ßRII expression pattern and a higher pSmad2 expression were associated with decreased breast cancer survival. Our study provides additional evidence to support the important role of TGF-ß signaling in breast cancer prognosis.

Tumor tissue microRNA expression in association with triple-negative breast cancer outcomes.

We evaluated suggested metastasis-related microRNAs (miRNAs) for their associations with disease-free survival (DFS) and overall survival (OS) of triple-negative breast cancer (TNBC). In a cohort of 456 TNBC cases, we systematically evaluated 57 previously reported metastasis-related miRNAs in tumor tissue using the NanoString nCounter assay. Cox regression was applied to evaluate miRNA expression in association with DFS and OS. In vitro assays using the TNBC cell line MDA-MB-231 were also conducted to validate epidemiological study findings. During a median follow-up of 5.3 years, 112 deaths and 97 recurrences were documented. High levels of miR-374b-5p, miR-218-5p, or miR-126-3p, or low levels of miR-27b-3p were independently associated with a favorable TNBC outcome (P < 0.01 for all). A composite score based on the levels of these four miRNAs was associated with DFS, with hazard ratios (95 % confidence interval) of 0.70 (0.43-1.15), 0.51 (0.29-0.90), and 0.18 (0.09-0.37) for the second, third, and fourth compared to the lowest quartile. Incorporating the miRNA score with known TNBC outcome predictors, i.e., age at diagnosis, tumor stage, and basal-like subtype, increased the C-index for predicting DFS from 0.68 to 0.74. Additionally, miR-126-3p was correlated with basal-like breast cancer, and miR-374b-5p modified the therapeutic effects of 5-Fluorouracil and Cyclophosphamide treatments in basal-like breast cancer patients. Restoring miR-126-3p, miR-218-5p, or miR-374b-5p, or inhibiting miR-27b-3p in MDA-MB-231 cells reduced cell proliferation. miR-374b-5p suppressed cell invasion and miR-218-5p inhibited colonization. This study provides strong evidence that the expression levels of miR-374b-5p, miR-27b-3p, miR-126-3p, and miR-218-5p in tumor tissues predict TNBC outcomes.

Dual specificity phosphatase 4 gene expression in association with triple-negative breast cancer outcome.

Triple-negative breast cancer (TNBC) is an aggressive cancer with limited treatment options. Dual specificity phosphatase 4 (DUSP4) has recently been suggested as a potential marker of chemotherapy resistance for TNBC. DUSP4 gene expression levels were measured in breast cancer tissue from 469 TNBC patients aged 20-75 years who participated in the Shanghai Breast Cancer Survival Study, and their association with recurrence/breast cancer mortality and total mortality was evaluated. Information on breast cancer diagnosis, treatment, and disease progression was collected via medical chart review and multiple in-person follow-up surveys. A Cox regression model was applied in the data analyses. Over a median follow-up of 5.3 years (range: 0.7-8.9 years), 100 deaths and 92 recurrences/breast cancer deaths were documented. Expression levels of transcript variant 1 (NM_001394) and transcript variant 2 (NM_057158) of the DUSP4 gene were studied and were highly correlated (r = 0.76). Low DUSP4 expression levels, particularly of variant 1, were associated with both increased recurrence/breast cancer mortality and increased overall mortality. Hazard ratios with adjustment for age at diagnosis and TNM stage associated with below versus above the median expression level were 1.97 (95 % confidence interval (CI): 1.27-3.05) for recurrence/breast cancer mortality and 2.09 (95 % CI: 1.38-3.17) for overall mortality. Additional adjustment for expression levels of MKI67 and TP53, common treatment types, breast cancer subtype, and grade did not materially alter the observed associations. Low DUSP4 expression levels predict recurrence and mortality in TNBC patients independently from known clinical and molecular predictors.

Ozone Pollution and Acute Exacerbation of Asthma in Residents of China: An Ecological Study.

Purpose: The evidence for a causal relationship between high-level ozone (O3) exposure and acute exacerbation of asthma among adults is limited, and the conclusions are less definitive. Patients and methods: Here we collected the daily data on asthma cases, O3 exposure, and meteorological factors from 2010 to 2016 in Shijiazhuang, China. We investigated the risk of asthma exacerbation associated with high-level ozone exposure using a polynomial distributed lag model (PDLM). Using a generalized additive model (GAM), we estimated the interactive effects between O3 and other pollutants as well as meteorological factors on asthma exacerbation. Results: A total of 7270 patients with asthma were enrolled from 22 governmental hospitals in 13 counties. Each 10 µg/m3 increase in O3 concentration on the exacerbation of asthma was associated with a 1.92% (95% CI = 0.80-3.03%) higher risk of asthma exacerbation on day lag 7. The cumulative risk of O3 on asthma exacerbation increased by 18.9% (95% CI = 12.8-25.4%) on the 14th day. High consecutive levels of O3 increase the risk of asthma exacerbation, and the interactive effect of O3 and sulfur dioxide (SO2) appears before the exacerbation onset. Conclusion: These findings suggested that O3 should be an important risk factor for asthma exacerbation, and health benefits in reducing asthma exacerbation risk would be gained with continued efforts to improve the air quality in China.

Nonalcoholic Fatty Liver Disease Is Associated With Decreased Bone Mineral Density in Adults: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to investigate the effect of nonalcoholic fatty liver disease (NAFLD) on bone mineral density (BMD) and the risk of osteoporosis and osteoporotic fracture in adults. We searched PubMed, MEDLINE, Embase, CINAHL, Web of Science, Cochrane Library, and Scopus for observational studies published from inception to January 2023 that reported adjusted effect sizes of NAFLD on BMD, osteopenia/osteoporosis, and osteoporotic fracture. The data were synthesized using multilevel and random-effects models. A total of 19 studies were included; of these, nine (21,294 participants) evaluated the effect of NAFLD on BMD, six (133,319 participants) investigated the risk of osteoporosis, and five (227,901 participants) assessed the risk of osteoporotic fracture. This meta-analysis showed that NAFLD was associated with decreased BMD (mean difference -0.019 g/cm2 , 95% confidence interval [CI] -0.036 to -0.002, I2 = 93%) and increased risks of osteoporosis (adjusted risk ratio [RR] = 1.28, 95% CI 1.08 to 1.52, I2 = 84%) and osteoporotic fractures (adjusted RR = 1.17, 95% CI 1.00 to 1.37, I2 = 67%). Subgroup analyses revealed that NAFLD had a significantly detrimental effect on BMD in men and on the BMD of the femoral neck and total hip. Stratified analyses by ethnicity demonstrated that NAFLD was not associated with BMD, osteoporosis, or osteoporotic fracture in non-Asian populations. The publication bias of all included studies was low; however, there was considerable heterogeneity among the studies, warranting a careful interpretation of the findings. Overall, our results suggest that NAFLD is associated with decreased BMD and an increased risk of osteoporosis or osteoporotic fractures. Male sex and the BMD of the femoral neck and total hip may be potential risk factors for decreased BMD in adults with NAFLD. Additionally, ethnic disparities were observed between Asian and non-Asian populations regarding BMD and osteoporotic fractures. © 2023 American Society for Bone and Mineral Research (ASBMR).

Fruit, vegetable, and animal food intake and breast cancer risk by hormone receptor status.

The effects of diet on breast cancer are controversial and whether the effects vary with hormone receptor status has not been well investigated. This study evaluated the associations of dietary factors with risk for breast cancer overall and by the hormone receptor status of tumors among Chinese women. The Shanghai Breast Cancer Study, a large, population-based, case-control study, enrolled 3,443 cases and 3,474 controls in 1996-1998 (phase I) and 2002-2005 (phase II); 2676 cases had estrogen receptor (ER) and progesterone receptor (PR) data. Dietary intake was assessed using a validated, quantitative, food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from multivariate, polychotomous, unconditional logistic regression models. Total vegetable intake was inversely related to breast cancer risk, with an adjusted OR for the highest quintile of 0.80 (95% CI = 0.67-0.95; P trend = 0.02). Reduced risk was also related to high intake of allium vegetables (P trend = 0.01) and fresh legumes (P trend = 0.0008). High intake of citrus fruits and rosaceae fruits were inversely associated with breast cancer risk (P trend = 0.003 and 0.004, respectively), although no consistent association was seen for total fruit intake. Elevated risk was observed for all types of meat and fish intake (all P trend < 0.05), whereas intakes of eggs and milk were associated with a decreased risk of breast cancer (both P trend <0.05). There was little evidence that associations with dietary intakes varied across the 4 tumor subtypes or between ER+/PR+ and ER-/PR- tumors (P for heterogeneity >0.05). Our results suggest that high intake of total vegetables, certain fruits, milk, and eggs may reduce the risk of breast cancer, whereas high consumption of animal-source foods may increase risk. The dietary associations did not appear to vary by ER/PR status.

Association between waist circumference change and incident chronic obstructive pulmonary disease among Chinese adults: a 10-year cohort study.

The aim of our study was to investigate waist circumference (WC) change and the risk of incident chronic obstructive pulmonary disease (COPD) among Chinese adults. A total of 8164 participants aged > 18 years who attended health examinations with repeat measurements of WC and lung function [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1)] from 2010 to 2019 were recruited. WC change was categorized as ≤ - 2.5%, - 2.5 to 2.5%, 2.5% to 5% and > 5% according to sex. Modified Poisson regression models were used to assess the association of WC gain and the risk of COPD. During the 10-year follow-up, a total of 917 COPD cases were identified. From baseline to follow-up, the mean FEV1 decreased from 3.20 to 2.79L among male participants and 2.28-1.95L among female participants. Compared with participants who did not have abdominal obesity, at either, baseline or follow-up, participants with abdominal obesity of both sexes after the follow-up were associated with a greater risk of COPD regardless of abdominal obesity at baseline. The risk of incident COPD increased 19% among male participants (RR = 1.19, 95%CI = 1.04-1.48) and 14% among female participants (RR = 1.14, 95%CI = 1.01-1.40) when WC gain increased > 5% during the 10-year follow-up. The COPD risk decreased 18% among male participants with a WC change ≤ - 2.5% (RR = 0.82, 95%CI = 0.67-0.99). The risk of incident COPD was positively associated with increasing WC among Chinese adults of both sexes.

Surgical stabilization of rib fractures versus nonoperative treatment in patients with multiple rib fractures following cardiopulmonary resuscitation: An international, retrospective matched case-control study.

BACKGROUND: The presence of six or more rib fractures or a displaced rib fracture due to cardiopulmonary resuscitation (CPR) has been associated with longer hospital and intensive care unit (ICU) length of stay (LOS). Evidence on the effect of surgical stabilization of rib fractures (SSRF) following CPR is limited. This study aimed to evaluate outcomes after SSRF versus nonoperative management in patients with multiple rib fractures after CPR. METHODS: An international, retrospective study was performed in patients who underwent SSRF or nonoperative management for multiple rib fractures following CPR between January 1, 2012, and July 31, 2020. Patients who underwent SSRF were matched to nonoperative controls by cardiac arrest location and cause, rib fracture pattern, and age. The primary outcome was ICU LOS. RESULTS: Thirty-nine operatively treated patient were matched to 66 nonoperatively managed controls with comparable CPR-related characteristics. Patients who underwent SSRF more often had displaced rib fractures (n = 28 [72%] vs. n = 31 [47%]; p = 0.015) and a higher median number of displaced ribs (2 [P 25 -P 75 , 0-3] vs. 0 [P 25 -P 75 , 0-3]; p = 0.014). Surgical stabilization of rib fractures was performed at a median of 5 days (P 25 -P 75 , 3-8 days) after CPR. In the nonoperative group, a rib fixation specialist was consulted in 14 patients (21%). The ICU LOS was longer in the SSRF group (13 days [P 25 -P 75 , 9-23 days] vs. 9 days [P 25 -P 75 , 5-15 days]; p = 0.004). Mechanical ventilator-free days, hospital LOS, thoracic complications, and mortality were similar. CONCLUSION: Despite matching, those who underwent SSRF over nonoperative management for multiple rib fractures following CPR had more severe consequential chest wall injury and a longer ICU LOS. A benefit of SSRF on in-hospital outcomes could not be demonstrated. A low consultation rate for rib fixation in the nonoperative group indicates that the consideration to perform SSRF in this population might be associated with other nonradiographic or injury-related variables. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Surgical stabilization versus nonoperative treatment for flail and non-flail rib fracture patterns in patients with traumatic brain injury.

PURPOSE: Literature on outcomes after SSRF, stratified for rib fracture pattern is scarce in patients with moderate to severe traumatic brain injury (TBI; Glasgow Coma Scale ≤ 12). We hypothesized that SSRF is associated with improved outcomes as compared to nonoperative management without hampering neurological recovery in these patients. METHODS: A post hoc subgroup analysis of the multicenter, retrospective CWIS-TBI study was performed in patients with TBI and stratified by having sustained a non-flail fracture pattern or flail chest between January 1, 2012 and July 31, 2019. The primary outcome was mechanical ventilation-free days and secondary outcomes were in-hospital outcomes. In multivariable analysis, outcomes were assessed, stratified for rib fracture pattern. RESULTS: In total, 449 patients were analyzed. In patients with a non-flail fracture pattern, 25 of 228 (11.0%) underwent SSRF and in patients with a flail chest, 86 of 221 (38.9%). In multivariable analysis, ventilator-free days were similar in both treatment groups. For patients with a non-flail fracture pattern, the odds of pneumonia were significantly lower after SSRF (odds ratio 0.29; 95% CI 0.11-0.77; p = 0.013). In patients with a flail chest, the ICU LOS was significantly shorter in the SSRF group (beta, - 2.96 days; 95% CI - 5.70 to - 0.23; p = 0.034). CONCLUSION: In patients with TBI and a non-flail fracture pattern, SSRF was associated with a reduced pneumonia risk. In patients with TBI and a flail chest, a shorter ICU LOS was observed in the SSRF group. In both groups, SSRF was safe and did not hamper neurological recovery.

Association of hormone-related characteristics and breast cancer risk by estrogen receptor/progesterone receptor status in the shanghai breast cancer study.

Etiologic differences between subtypes of breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status are not well understood. The authors evaluated associations of hormone-related factors with breast cancer subtypes in a population-based case-control study involving 1,409 ER-positive (ER+)/PR-positive (PR+) cases, 712 ER-negative (ER-)/PR-negative (PR-) cases, 301 ER+/PR- cases, 254 ER-/PR+ cases, and 3,474 controls aged 20-70 years in Shanghai, China (phase I, 1996-1998; phase II, 2002-2005). Polytomous logistic regression and Wald tests for heterogeneity across subtypes were conducted. Breast cancer risks associated with age at menarche, age at menopause, breastfeeding, age at first livebirth, waist-to-hip ratio, and oral contraceptive use did not differ by hormone receptor status. Among postmenopausal women, higher parity (≥2 children vs. 1) was associated with reduced risk (odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.52, 0.91) and higher body mass index (BMI; weight (kg)/height (m)(2)) with increased risk (highest quartile: OR = 2.40, 95% CI: 1.65, 3.47) of the ER+/PR+ subtype but was unrelated to the ER-/PR- subtype (for parity, P(heterogeneity) = 0.02; for BMI, P(heterogeneity) < 0.01). Hormone replacement therapy (OR = 2.25, 95% CI: 1.40, 3.62) and alcohol consumption (OR = 1.59, 95% CI: 1.01, 2.51) appeared to be preferentially associated with the ER+/PR- subtype. These findings indicate that BMI, parity, hormone replacement therapy, and alcohol consumption may play different roles in subtypes of breast cancer. More research is needed to better understand the etiology of 2 relatively rare subtypes, ER+/PR- tumors and ER-/PR+ tumors.

Distinct distribution and prognostic significance of molecular subtypes of breast cancer in Chinese women: a population-based cohort study.

BACKGROUND: Molecular classification of breast cancer is an important prognostic factor. The distribution of molecular subtypes of breast cancer and their prognostic value has not been well documented in Asians. METHODS: A total of 2,791 breast cancer patients recruited for a population-based cohort study were evaluated for molecular subtypes of breast cancer by immunohistochemical assays. Data on clinicopathological characteristics were confirmed by centralized pathology review. The average follow-up of the patients was 53.4 months. Overall and disease-free survival by molecular subtypes of breast cancer were evaluated. RESULTS: The prevalence of the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and triple-negative subtypes were 48.6%, 16.7%, 13.7%, and 12.9%, respectively. The luminal A subtype was more likely to be diagnosed in older women (P = 0.03) and had a stronger correlation with favorable clinicopathological factors (smaller tumor size, lower histologic grade, and earlier TNM stage) than the triple-negative or HER2 subtypes. Women with triple-negative breast cancer had a higher frequency of family history of breast cancer than women with other subtypes (P = 0.048). The 5-year overall/disease-free survival percentages for the luminal A, luminal B, HER2, and triple-negative subtypes were 92.9%/88.6%, 88.6%/85.1%, 83.2%/79.1%, and 80.7%/76.0%, respectively. A similar pattern was observed in multivariate analyses. Immunotherapy was associated with improved overall and disease-free survival for luminal A breast cancer, but reduced disease-free survival (HR = 2.21, 95% CI, 1.09-4.48) for the HER2 subtype of breast cancer. CONCLUSIONS: The triple-negative and HER2 subtypes were associated with poorer outcomes compared with the luminal A subtype among these Chinese women. The HER2 subtype was more prevalent in this Chinese population compared with Western populations, suggesting the importance of standardized HER2 detection and anti-HER2 therapy to potentially benefit a high proportion of breast cancer patients in China.

Outcome after surgical stabilization of rib fractures versus nonoperative treatment in patients with multiple rib fractures and moderate to severe traumatic brain injury (CWIS-TBI).

BACKGROUND: Outcomes after surgical stabilization of rib fractures (SSRF) have not been studied in patients with multiple rib fractures and traumatic brain injury (TBI). We hypothesized that SSRF, as compared with nonoperative management, is associated with favorable outcomes in patients with TBI. METHODS: A multicenter, retrospective cohort study was performed in patients with rib fractures and TBI between January 2012 and July 2019. Patients who underwent SSRF were compared to those managed nonoperatively. The primary outcome was mechanical ventilation-free days. Secondary outcomes were intensive care unit length of stay and hospital length of stay, tracheostomy, occurrence of complications, neurologic outcome, and mortality. Patients were further stratified into moderate (GCS score, 9-12) and severe (GCS score, ≤8) TBI. RESULTS: The study cohort consisted of 456 patients of which 111 (24.3%) underwent SSRF. The SSRF was performed at a median of 3 days, and SSRF-related complication rate was 3.6%. In multivariable analyses, there was no difference in mechanical ventilation-free days between the SSRF and nonoperative groups. The odds of developing pneumonia (odds ratio [OR], 0.59; 95% confidence interval [95% CI], 0.38-0.98; p = 0.043) and 30-day mortality (OR, 0.32; 95% CI, 0.11-0.91; p = 0.032) were significantly lower in the SSRF group. Patients with moderate TBI had similar outcome in both groups. In patients with severe TBI, the odds of 30-day mortality was significantly lower after SSRF (OR, 0.19; 95% CI, 0.04-0.88; p = 0.034). CONCLUSION: In patients with multiple rib fractures and TBI, the mechanical ventilation-free days did not differ between the two treatment groups. In addition, SSRF was associated with a significantly lower risk of pneumonia and 30-day mortality. In patients with moderate TBI, outcome was similar. In patients with severe TBI a lower 30-day mortality was observed. There was a low SSRF-related complication risk. These data suggest a potential role for SSRF in select patients with TBI. LEVEL OF EVIDENCE: Therapeutic, level IV.

Light-emitting diode photobiomodulation therapy for non-specific low back pain in working nurses: A single-center, double-blind, prospective, randomized controlled trial.

BACKGROUND: Low back pain (LBP) affects approximately 51% to 57% of hospital nurses and nurses' aides in Europe. New high-risk groups include home- and long-term-care nurses and physiotherapists. A number of European countries are experiencing a shortage of healthcare workers. Light therapy has been shown to be an effective treatment for various musculoskeletal disorders, including lateral epicondylitis, temporomandibular joint pain, carpal tunnel syndrome, and delayed-onset muscle soreness. A systematic review and meta-analysis demonstrated that low-level laser therapy is an effective method for relieving non-specific chronic low back pain (NSCLBP). However, the efficacy of light-emitting diode (LED) therapy for NSCLBP is disputed. This study aims to evaluate the effect of LED therapy on NSCLBP. METHODS AND ANALYSIS: We conducted a prospective, double-blind, randomized placebo-controlled trial of 148 patients with NSCLBP. The patients were randomly assigned to 2 groups: intervention group, where patients received LED photobiomodulation therapy 3 times a week for 2 weeks, and the sham group, where patients had sham therapy 3 times a week for 2 weeks. Primary outcome measures included the visual analog scale for pain, lumbar active range of motion assessments, and chair-rising times. Secondary outcome measures included a multidimensional fatigue inventory, fear-avoidance beliefs questionnaire, and the Oswestry disability index. The outcome measures were assessed before therapy and 2weeks, 4 weeks, 8 weeks, 12 weeks, and 6 months after the first interventions were completed. DISCUSSION: This study is a prospective, single-center, double-blind, randomized, controlled study. This study aims to research the efficacy of a 2-week LED program for NSCLBP working nurse. Our results will be useful for patients, working nurses, nurses' aides, and other healthcare workers with chronic low back pain. TRIAL REGISTRATION NUMBER: NCT04424823.

Early versus late surgical stabilization of severe rib fractures in patients with respiratory failure: A retrospective study.

INTRODUCTION: The timing of surgical stabilization of rib fractures remains controversial. We hypothesized that early surgical stabilization (within 3 days of injury) can improve clinical outcome in patients with severe rib fractures and respiratory failure. The aim of this study was to analyze the impact of early surgical stabilization of rib fractures on the perioperative results, clinical outcomes, and medical costs of patients with severe rib fractures and respiratory failure. METHODS: This was a retrospective comparative study based on a prospectively collected database at a single institute. Patients with severe rib fractures and respiratory failure who underwent surgical stabilization were classified into early (within 3 days of injury) and late (more than 3 days after injury) groups. Outcome measures included operation time, duration of mechanical ventilation, intensive care unit stay, hospital stay, complication rate, mortality rate, and medical cost. RESULTS: A total of 33 patients were enrolled (16 and 17 in the early and late groups, respectively). The demographics, trauma mechanism, associated injuries, and severity of trauma were comparable in both groups. The early group had significantly shorter duration of mechanical ventilation (median 36 vs. 90 hours, p = 0.03), intensive care unit stay (median 123 vs. 230 hours, p = 0.004), and hospital stay (median 12 vs. 18 days, p = 0.005); and lower National Health Insurance costs (median 6,617 vs. 10,017 US dollars, p = 0.031). The early group tended to have lower rates of morbidity and mortality, but the difference was not statistically significant. CONCLUSION: Early surgical stabilization of rib fractures in selected patients may significantly shorten their duration of mechanical ventilation, and intensive care unit and hospital stays, while incurring less medical costs.

Multilayered epithelium in a rat model and human Barrett's esophagus: similar expression patterns of transcription factors and differentiation markers.

BACKGROUND: In rats, esophagogastroduodenal anastomosis (EGDA) without concomitant chemical carcinogen treatment leads to gastroesophageal reflux disease, multilayered epithelium (MLE, a presumed precursor in intestinal metaplasia), columnar-lined esophagus, dysplasia, and esophageal adenocarcinoma. Previously we have shown that columnar-lined esophagus in EGDA rats resembled human Barrett's esophagus (BE) in its morphology, mucin features and expression of differentiation markers (Lab. Invest. 2004;84:753-765). The purpose of this study was to compare the phenotype of rat MLE with human MLE, in order to gain insight into the nature of MLE and its potential role in the development of BE. METHODS: Serial sectioning was performed on tissue samples from 32 EGDA rats and 13 patients with established BE. Tissue sections were immunohistochemically stained for a variety of transcription factors and differentiation markers of esophageal squamous epithelium and intestinal columnar epithelium. RESULTS: We detected MLE in 56.3% (18/32) of EGDA rats, and in all human samples. As expected, both rat and human squamous epithelium, but not intestinal metaplasia, expressed squamous transcription factors and differentiation markers (p63, Sox2, CK14 and CK4) in all cases. Both rat and human intestinal metaplasia, but not squamous epithelium, expressed intestinal transcription factors and differentiation markers (Cdx2, GATA4, HNF1alpha, villin and Muc2) in all cases. Rat MLE shared expression patterns of Sox2, CK4, Cdx2, GATA4, villin and Muc2 with human MLE. However, p63 and CK14 were expressed in a higher proportion of rat MLE compared to humans. CONCLUSION: These data indicate that rat MLE shares similar properties to human MLE in its expression pattern of these markers, not withstanding small differences, and support the concept that MLE may be a transitional stage in the metaplastic conversion of squamous to columnar epithelium in BE.