Polygenic risk score-based prediction of breast cancer risk in Taiwanese women with dense breast using a retrospective cohort study.

Mammographic screening has contributed to a significant reduction in breast cancer mortality. Several studies have highlighted the correlation between breast density, as detected through mammography, and a higher likelihood of developing breast cancer. A polygenic risk score (PRS) is a numerical score that is calculated based on an individual's genetic information. This study aims to explore the potential roles of PRS as candidate markers for breast cancer development and investigate the genetic profiles associated with clinical characteristics in Asian females with dense breasts. This is a retrospective cohort study integrated breast cancer screening, population genotyping, and cancer registry database. The PRSs of the study cohort were estimated using genotyping data of 77 single nucleotide polymorphisms based on the PGS000001 Catalog. A subgroup analysis was conducted for females without breast symptoms. Breast cancer patients constituted a higher proportion of individuals in PRS Q4 (37.8% vs. 24.8% in controls). Among dense breast patients with no symptoms, the high PRS group (Q4) consistently showed a significantly elevated breast cancer risk compared to the low PRS group (Q1-Q3) in both univariate (OR = 2.25, 95% CI 1.43-3.50, P < 0.001) and multivariate analyses (OR: 2.23; 95% CI 1.41-3.48, P < 0.001). The study was extended to predict breast cancer risk using common low-penetrance risk variants in a PRS model, which could be integrated into personalized screening strategies for Taiwanese females with dense breasts without prominent symptoms.

Is minimal-accessed (endoscopic- or robotic-assisted) nipple-sparing mastectomy contraindicated for large breasts?

BACKGROUND: In the developmental stage of minimal-accessed nipple-sparing mastectomy (MA-NSM), selecting patients with small to medium-sized breasts was common for better cosmetic outcomes and oncological safety. However, the suitability of MA-NSM for large, ptotic breasts remained uncertain. This retrospective study aim to assess MA-NSM outcomes in patients with large breasts. MATERIALS AND METHODS: This retrospective study included patients receiving conventional NSM (C-NSM) and MA-NSM from January 2011 to September 2022, at a single institution. We analyzed perioperative parameters and clinical outcomes based on breast specimen size, classified as small (≤300 g), medium (>300-450 g), large (>450-600 g), and very large (>600 g). RESULTS: A total of 728 patients was enrolled. C-NSM was performed in 51% (371/728) of cases, while MA-NSM was done in 49% (357/728). The overall complication rate of MA-NSM was comparable to C-NSM (p = 0.573), but severe complications (Clavien-Dindo, CD III) was significantly reported more following C-NSM, regardless of breast size. During a median follow-up of 52 months, no significant difference in oncological outcomes was observed. Comparing MA-NSM and C-NSM outcomes in large-very large breasts (>450 g), MA-NSM demonstrated significantly less blood loss (p = 0.036) and lower incidence of severe complications (CD ≥ III) compared to C-NSM (p = 0.002). CONCLUSION: MA-NSM is feasible for large breasts and offers benefits by reducing blood loss and decreasing the incidence of severe complications (CD ≥ III) in this patient group.

Scarless totally implantable venous access port (TIVAP) implantation: Surgical technique, preliminary results, learning curve, and patients-reported outcome in 125 breast cancer patients.

BACKGROUND: Minimal-access (endoscopic or robotic-assisted) breast surgery has been increasingly performed and shown better cosmetic results. However, location of totally implantable venous access port (TIVAP) for systemic treatment at anterior chest may compromise its aesthetic benefits. Therefore, we proposed a new scarless technique for TIVAP implantation, and reported the preliminary results, learning curve, and patients-surveyed outcome. METHODS: Surgical technique of the new "scarless" TIVAP implantation was proposed. Patients receiving this procedure in a single institution were included. The preliminary results of the scarless TIVAP implantation, learning curve, and patient-reported outcome were analyzed and reported. RESULTS: A total of 125 breast cancer patients received scarless TIVAP procedures were enrolled. The primary success rate of the scarless TIVAP implantation was 100%. Mean operative time was 46 ± 14 min. Mean amount of blood loss was 8.5 ± 3.2 ml. The cumulative sum plot showed operation time significantly decreased after 24th cases. In the initial learning phase, the mean operative time was 55 ± 17 min, and decreased to 43 ± 12 min in the later mature phase (P = 0.003). There were 5 (4%) complications detected, which included 1 (0.8%) seroma formation, 2 (1.6%) revisions, and 2 (1.6%) unplanned explantations. From patients-evaluated questionnaires, more than 90% of responders were satisfied with aesthetic results, experience during surgery, and application of scarless TIVAP for systemic therapy. CONCLUSIONS: The scarless TIVAP implantation is a safe & reliable procedure with high patients-reported aesthetic satisfaction, and could be an alternative TIVAP procedure for patients requiring chemotherapy and desiring a less noticeable scar.

Reliability of predicting low-burden (≤ 2) positive axillary lymph nodes indicating sentinel lymph node biopsy in primary operable breast cancer - a retrospective comparative study with PET/CT and breast MRI.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in early breast cancer patients with low-burden axillary metastasis (≤ 2 positive nodes). This study aimed to determine the diagnostic performances of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and breast magnetic resonance imaging in detecting axillary lymph node (ALN) metastases and the reliability to predict ALN burden. METHODS: A total of 275 patients with primary operable breast cancer receiving preoperative PET/CT and upfront surgery from January 2001 to December 2022 in a single institution were enrolled. A total of 244 (88.7%) of them also received breast MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT and breast MRI were assessed. The predictive values to determine ALN burden were evaluated using radio-histopathological concordance. RESULTS: PET/CT demonstrated a sensitivity of 53.4%, specificity of 82.1%, PPV of 65.5%, NPV of 73.5%, and accuracy of 70.9% for detecting ALN metastasis, and the corresponding values for MRI were 71.8%, 67.8%, 56%, 80.8%, and 69.2%, respectively. Combining PET/CT and MRI showed a significantly higher PPV than MRI (72.7% vs 56% for MRI alone, p = 0.037) and a significantly higher NPV than PET/CT (84% vs 73.5% for PET/CT alone, p = 0.041). For predicting low-burden axillary metastasis (1-2 positive nodes), the PPVs were 35.9% for PET/CT, 36.7% for MRI, and 55% for combined PET/CT and MRI. Regarding patients with 0-2 positive ALNs in imaging, who were indicated for SLNB, the predictive correctness was 96.1% for combined PET/CT and MRI, 95.7% for MRI alone, and 88.6% for PET/CT alone. CONCLUSIONS: PET/CT and breast MRI exhibit high predictive values for identifying low-burden axillary metastasis in patients with operable breast cancer with ≦ 2 positive ALNs on imaging.

Associations between paraben exposure, thyroid capacity, homeostasis and pituitary thyrotropic function in the general Taiwanese: Taiwan Environmental Survey for Toxicants (TEST) 2013.

Several studies have suggested that some endocrine disruptors such as synthetic phenols, parabens and phthalates may disrupt thyroid hormone signaling and associated negative feed-backs with the central hypothalamic-pituitary-thyroid (HPT) axis. Therefore, we investigated urinary paraben and blood thyroid hormone levels in the Taiwanese population. Our sample comprised 264 adults (aged 18-97 years) and 75 minors (aged 7-17 years) from Taiwan Environmental Survey for Toxicants 2013. Urinary levels of methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) were assessed. Hormones of particular interest include: thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). We sought integrated parameters to describe the transfer of thyroid hormones in homeostatic models. The geometric mean urinary paraben levels of the adults were higher than those of the minors (adults vs. minors; MeP: 383 vs. 62.4 ng/mL; PrP: 109 vs. 8.00 ng/mL; EtP: 39.5 vs. 2.38 ng/mL, and BuP: 6.36 vs. 2.13 ng/mL). In the male adults, we discovered that 0.253% (p = 0.032), 0.256% (p = 0.041) and 0.257% (p = 0.037) decreases in the TSH, TSH/T4 and TSH/FreeT4 ratio was associated with 1% EtP increases, respectively. In the female minors, 0.093% (p = 0.044), 0.072% (p = 0.047) and 0.156 (p = 0.004) increases in the TSH ratios were associated with a 1% MeP, EtP and BuP increase, respectively. Moreover, 0.151% (p = 0.008) and 0.177% (p = 0.001) increases in TSH/T4 and TSH/free T4 ratios were associated with a BuP 1% increase, respectively. Finally, EtP was positively associated with SPINA-GT (ß: 15.66, p = 0.036) in the male adults. By contrast, EtP were positively associated with Jostel's TSH index and sTSHI (ß: 0.072, p = 0.049; ß: 0.107, p = 0.049) in the female minors. The Taiwanese population is commonly exposed to parabens, which can potentially lead to alteration of thyroid hormone homeostasis.

Single-port three-dimensional (3D) endoscopic-assisted breast surgery-preliminary results and patient-reported satisfaction in 145 breast cancer and gynecomastia cases.

BACKGROUND: Minimal-accessed (robotic and endoscopic) breast cancer surgery is increasingly performed due to better cosmetic results and acceptable oncological outcomes. This study aims to demonstrate the clinical safety and patient-reported cosmetic satisfaction of single-port three-dimensional endoscopic-assisted breast surgery (S-P 3D EABS), which is our new endoscopic surgical innovation, in both malignant and benign breast conditions. METHODS: Patients who underwent S-P 3D EABS from 1 August 2018 to 31 July 2022 in a single institution were enrolled. Clinical outcomes of this procedure were retrospectively reviewed, and the patient-reported cosmetic satisfaction was evaluated by a questionnaire and reported herein. RESULTS: During the study period, 145 patients underwent 164 procedures of S-P 3D EABS. One hundred fifty (91.5%) procedures were endoscopic-assisted nipple-sparing mastectomy (S-P 3D E-NSM; 117 therapeutic procedures for breast cancer, 13 prophylactic mastectomies, 20 procedures for gynecomastia). Fourteen (8.5%) procedures of endoscopic-assisted breast-conserving surgery (S-P 3D E-BCS) were performed (12 S-P 3D E-BCS, 2 S-P 3D E-BCS with 3D videoscope-assisted partial breast reconstruction, which was 1 case of latissimus dorsi flap and 1 case of omental flap). The mean operative time was 245 ± 110 min in S-P 3D E-NSM and 260 ± 142 min in S-P 3D E-BCS. The mean intraoperative blood loss was 49.7 ± 46.9 ml in S-P 3D E-NSM and 32.8 ± 17.5 ml in S-P 3D E-BCS. Subnipple biopsy showed positive malignancy in 3 (2.6%) S-P 3D E-NSM patients. None of the S-P 3D E-BCS patients found margin involvement; however, 3 (2.6%) reported margin involvement in S-P 3D E-NSM patients. Thirty-two complications were found (24.6%): 7 (5.3%) transient nipple-areolar complex (NAC) ischemia, 7 (5.3%) partial NAC necrosis, 1 (0.7%) total NAC necrosis, and 1 (0.7%) implant loss. During the mean follow-up time of 34 months, there were 2 (1.5%) patients with locoregional recurrence, 9 (6.9%) distant metastasis, and 2 (1.5%) mortality. 78.6% (77/98) of patients answering the cosmetic-evaluated questionnaire reported good and excellent overall satisfaction. CONCLUSIONS: S-P 3D EABS is a novel surgical innovation, which is able to perform safely in either malignant or benign breast conditions and offer promising cosmetic results.

Exposure and risk assessment of urinary trans, trans-Muconic acid in school-age children in the vicinity of a petrochemical complex in Central Taiwan.

School-age children living near large petrochemical factories may be at high risk of exposure to benzene released during manufacturing processes. We aimed to investigate the urinary concentrations of trans, trans-muconic acid (t,t-MA) in school-age children living near a petrochemical complex and to estimate their cumulative risk of benzene exposure. We examined an established cohort (Taiwan Petrochemical Complex Cohort for Children, TPE3C) of school-age children (aged 6-13 years) who lived near large petrochemical factories in central Taiwan between October 2013 and September 2014. The cohort comprised 297 children from five elementary schools, namely S.-C. Branch (n = 63, school A, ~0.9 km), F.-A. (n = 51, school B, ~2.7 km), C.-T. (n = 63, school C, ~5.5 km), M.-L. (n = 54, school D, ~6.9 km), and L.-F. (n = 66, school E, ~8.6 km). We analyzed the urinary t,t-MA levels of each participant and estimated their daily intake of benzene. We also performed multiple regression analysis to investigate potential risk factors for a high urinary t,t-MA level in the study cohort. The median urinary t,t-MA levels and median estimated benzene daily intake of the children from each school were as follows: school A, 64.07 ng/mL, 11.13 µg/kg/day; school B, 61.01 ng/mL, 15.32 µg/kg/day; school C, 59.38 ng/mL, 14.81 µg/kg/day; school D, 42.35 ng/mL, 11.67 µg/kg/day; school E, undetected, 0.14 µg/kg/day. The distance between a school and a petrochemical complex (greater distance: ß = -0.26, 95% confidence interval [CI] = -0.52 to 0.00, p = 0.053), and the age of the children (older age: ß = -3.44, 95% CI = -5.90 to -1.46, p < 0.001) were identified as potential risk factors. After confounders were adjusted for, the creatinine adjusted urinary t,t-MA levels of the school-age children tended to be lower when the distance between their school and a petrochemical complex was greater.

A binary module for microbiota-mediated regulation of γδ17 cells, hallmarked by microbiota-driven expression of programmed cell death protein 1.

Little is known about how microbiota regulate innate-like γδ T cells or how these restrict their effector functions within mucosal barriers, where microbiota provide chronic stimulation. Here, we show that microbiota-mediated regulation of γδ17 cells is binary, where microbiota instruct in situ interleukin-17 (IL-17) production and concomitant expression of the inhibitory receptor programmed cell death protein 1 (PD-1). Microbiota-driven expression of PD-1 and IL-17 and preferential adoption of a PD-1high phenotype are conserved for γδ17 cells across multiple mucosal barriers. Importantly, microbiota-driven PD-1 inhibits in situ IL-17 production by mucosa-resident γδ17 effectors, linking microbiota to their simultaneous activation and suppression. We further show the dynamic nature of this microbiota-driven module and define an inflammation-associated activation state for γδ17 cells marked by augmented PD-1, IL-17, and lipid uptake, thus linking the microbiota to dynamic subset-specific activation and metabolic remodeling to support γδ17 effector functions in a microbiota-dense tissue environment.

Use of Magnetic Resonance Imaging for Evaluating Residual Breast Tissue After Robotic-Assisted Nipple-Sparing Mastectomy in Women With Early Breast Cancer.

OBJECTIVE: Prospective studies on postoperative residual breast tissue (RBT) after robotic-assisted nipple-sparing mastectomy (R-NSM) for breast cancer are limited. RBT presents an unknown risk of local recurrence or the development of new cancer after curative or risk-reducing mastectomies. This study investigated the technical feasibility of using magnetic resonance imaging (MRI) to evaluate RBT after R-NSM in women with breast cancer. MATERIALS AND METHODS: In this prospective pilot study, 105 patients, who underwent R-NSM for breast cancer at Changhua Christian Hospital between March 2017 and May 2022, were subjected to postoperative breast MRI to evaluate the presence and location of RBT. The postoperative MRI scans of 43 patients (age, 47.8 ± 8.5 years), with existing preoperative MRI scans, were evaluated for the presence and location of RBT. In total, 54 R-NSM procedures were performed. In parallel, we reviewed the literature on RBT after nipple-sparing mastectomy, considering its prevalence. RESULTS: RBT was detected in 7 (13.0%) of the 54 mastectomies (6 of the 48 therapeutic mastectomies and 1 of the 6 prophylactic mastectomies). The most common location for RBT was behind the nipple-areolar complex (5 of 7 [71.4%]). Another RBT was found in the upper inner quadrant (2 of 7 [28.6%]). Among the six patients who underwent RBT after therapeutic mastectomies, one patient developed a local recurrence of the skin flap. The other five patients with RBT after therapeutic mastectomies remained disease-free. CONCLUSION: R-NSM, a surgical innovation, does not seem to increase the prevalence of RBT, and breast MRI showed feasibility as a noninvasive imaging tool for evaluating the presence and location of RBT.

Diagnostic accuracy of pre-operative breast magnetic resonance imaging (MRI) in predicting axillary lymph node metastasis: variations in intrinsic subtypes, and strategy to improve negative predictive value-an analysis of 2473 invasive breast cancer patients.

BACKGROUND: The value and utility of axillary lymph node (ALN) evaluation with MRI in breast cancer were not clear for various intrinsic subtypes. The aim of the current study is to test the potential of combining breast MRI and clinicopathologic factors to identify low-risk groups of ALN metastasis and improve diagnostic performance. MATERIAL AND METHODS: Patients with primary operable invasive breast cancer with pre-operative breast MRI and post-operative pathologic reports were retrospectively collected from January 2009 to December 2021 in a single institute. The concordance of MRI and pathology of ALN status were determined, and also analyzed in different intrinsic subtypes. A stepwise strategy was designed to improve MRI-negative predictive value (NPV) on ALN metastasis. RESULTS: 2473 patients were enrolled. The diagnostic performance of MRI in detecting metastatic ALN was significantly different between intrinsic subtypes (p = 0.007). Multivariate analysis identified tumor size and histologic type as independent predictive factors of ALN metastases. Patients with HER-2 (MRI tumor size ≤ 2 cm), or TNBC (MRI tumor size ≤ 2 cm) were found to have MRI-ALN-NPV higher than 90%, and these false cases were limited to low axillary tumor burden. CONCLUSION: The diagnostic performance of MRI to predict ALN metastasis varied according to the intrinsic subtype. Combined pre-operative clinicopathologic factors and intrinsic subtypes may increase ALN MRI NPV, and further identify some groups of patients with low risks of ALN metastasis, high NPV, and low burdens of axillary disease even in false-negative cases.

Factors associated with alteration of nipple or skin sensation and impact of duration of time following nipple-sparing mastectomy (NSM): an analysis of 460 cases with comparison of conventional versus endoscopic- or robotic-assisted NSM.

BACKGROUND: The current study aims to evaluate the nipple and skin sensation following nipple-sparing mastectomy (NSM) and identify patient-, surgical-, or treatment-related factors affecting nipple or skin sensation in this cohort. METHODS: Patients who received NSM with postoperative nipple and skin sensation test evaluation at a single institution over the past 10 years were retrospectively retrieved from a prospectively collected breast cancer surgery database. RESULTS: A total of 460 NSM procedures were included in this current study, with the mean age of 48.3 ± 9.1. Three-hundred eighty-three (83.3%) patients had breast reconstructions. One-hundred seventy-four (37.8%) received conventional NSM (C-NSM), 195 (42.4%) endoscopic-assisted NSM (E-NSM), and 91 (19.8%) robotic-assisted NSM (R-NSM) procedures. For nipple sensation assessment, 15 (3.3%) were grade 0, 83 (18.2%) grade I, 229 (49.7%) grade II, and 133 (28.9%) grade III (normal sensation), respectively, with mean grade score of 2.1 ± 0.7. The preserved (grade III) nipple sensation rate was 36.2% (63/174) in the C-NSM group, 26.7% (52/195) in the E-NSM group, and 19.7% (18/91) in the R-NSM group (P = 0.06). The "time since surgery to last evaluation" was significantly longer in the C-NSM group (45.6 ± 34 months) or E-NSM group (44.7 ± 35.8 months) as compared to R-NSM group (31.8 ± 16 months, P < 0.01). In multivariate analysis, peri-areolar incision showed higher grade of nipple sensation (OR: 2.1, P = 0.02) compared to upper outer quadrant incision, and longer follow-up time post-NSM showed significant improvement of nipple or skin sensation (> 60 months vs. ≦ 12 months: nipple odds ratio (OR) = 5.75, P < 0.01; skin, OR = 1.97, P < 0.05). CONCLUSION: Our current analysis showed some factors to be related to postoperative nipple or skin sensation, and longer "time after surgery" was associated with significant improvement of nipple and skin sensation in patients who received NSM, regardless of the surgical approaches. SYNOPSIS: Our current analysis showed a significant portion of patients with decrease or loss of nipple or skin sensation after nipple-sparing mastectomy (NSM). Several factors associated with preserved nipple or skin sensation were identified, including age, surgical methods, surgical wound location, and association of time from surgery showing that improvement of partial nipple or skin sensation was evident after a longer follow-up.

Human biomonitoring reference values, exposure distribution, and characteristics of metals in the general population of Taiwan: Taiwan environmental survey for Toxicants (TESTs), 2013-2016.

Human biomonitoring (HBM) provides information to identify chemicals that need to be assessed regarding potential health risks to human populations. We established a population-representative sample in Taiwan, namely the Taiwan Environmental Survey for Toxicants (TESTs) in 2013-2016. In total, 1871 participants (aged 7-97 years) were recruited from throughout Taiwan. A questionnaire survey was applied to obtain individuals' demographic characteristics, and urine samples were obtained to assess metal concentrations. Inductively coupled plasma-mass spectrometry was used to determine concentrations of urinary As (total), Cd, Co, Cr, Cu, Fe, Ga, In, Mn, Ni, Pb, Se, Sr, Tl, and Zn. The purpose of this study was to establish the human urinary reference levels (RVs) for metals in the general population of Taiwan. We found that median concentrations of urinary Cu, Fe, Pb, and Zn in males were statistically significant (p < 0.05) higher than in females (Cu: 11.48 vs. 10.00 µg/L; Fe: 11.48 vs. 10.46 µg/L; Pb: 0.87 vs. 0.76 µg/L; and Zn: 448.93 vs. 348.35 µg/L). On the contrary, Cd and Co were significantly lower in males than in females (Cd: 0.61 vs. 0.64 µg/L; and Co: 0.27 vs. 0.40 µg/L). Urinary Cd levels in the ≥18-year-old group (0.69 µg/L) were significantly higher than those in the 7-17-year-old group (0.49 µg/L, p < 0.001). Among the investigated metals, most were significantly higher in the 7-17-year-old group than in the ≥18-year-old group, except for Cd, Ga, and Pb. Participants who lived in central Taiwan had higher median levels of urinary Cd, Cu, Ga, Ni, and Zn than those in other regions. Median levels of urinary As, Cd, Pb, and Se were significantly higher in participants who lived in harbor (94.12 µg/L), suburban (0.68 µg/L), industrial (0.92 µg/L), and rural (50.29 µg/L) areas, respectively, than the others who lived in other areas. RV95 percentiles of urinary metals (ng/mL) for 7-17/≥18-year-old groups were As (346.9/370.0), Cd (1.41/2.21), Co (2.30/1.73), Cr (0.88/0.88), Cu (28.02/22.78), Fe (42.27/42.36), Ga (0.13/0.12), In (0.05/0.04), Mn (3.83/2.91), Ni (8.09/6.17), Pb (8.09/5.75), Se (122.4/101.9), Sr (556.5/451.3), Tl (0.57/0.49), and Zn (1314.6/1058.8). In this study, we have highlighted the importance of As, Cd, Pb, and Mn exposure in the general population of Taiwan. The established RV95 of urinary metals in Taiwanese would be fundamental information to promote the reduction of metal exposure or policy intervention. We concluded that urinary levels of exposure to certain metals in the general Taiwanese population varied by sex, age, region, and urbanization level. References of metal exposure in Taiwan were established in the current study.

Gender differences in risk exposures for acute hepatitis C infection in Taiwan: a nationwide case-control study.

BACKGROUND: In Taiwan, medical providers are required to report all acute hepatitis C (AHC) patients to National Notifiable Disease Surveillance System (NNDSS). Identifying factors associated with AHC may inform the strategies to prevent the spread of hepatitis C virus (HCV). We used the national surveillance data to assess gender difference in risk factors associated with AHC in Taiwan and propose control measures in at-risk groups. METHODS: We conducted a nationwide case-control study using data from NNDSS and AHC case investigation questionnaires, for the period of March 6, 2014-December 31, 2016. Cases were AHC confirmed in NNDSS; controls were reported AHC with negative HCV nucleic acid test and negative serum anti-HCV antibody. We used bivariate analysis to identify characteristics and risk exposures for AHC and conducted gender stratified analyses. RESULTS: We identified 602 AHC cases (66.9% males, median age 48 years) and 90 controls. Older age, male gender (OR: 1.85, 95% CI: 1.18-2.90), history of viral hepatitis (OR: 7.93, 95% CI:1.91-32.88), history of sexually transmitted infections (OR: 21.02, 95% CI: 2.90-152.43), and having healthcare-associated risk exposures (OR: 2.02, 95% CI: 1.25-3.25) were associated with AHC. Stratified analyses showed receiving intravenous infusion, history of hepatitis B, syphilis, and human immunodeficiency virus infection were risk factors for male AHC; receiving hemodialysis was risk factor for females. CONCLUSIONS: Our study demonstrates risk factors for AHC in Taiwan with gender difference. Proper infection control practices in healthcare settings and interventions targeting male patients with HIV and other STIs, remain crucial to prevent individuals from AHC.

The National Laboratory Response to the COVID-19 Pandemic in Taiwan.

From April 23 to November 2021, a wave of COVID-19 infections caused by a new Alpha variant swept across Taiwan, resulting in 14,458 positive cases and 830 deaths among over 3.8 million people tested. To cope with the sudden increase in sample volume, as of December 14, 2021, a network of 249 laboratories with a total diagnostic capacity of 158,492 real-time reverse transcription polymerase chain reaction tests per day was established in 22 administrative regions. As of April 2022, over 9.5 million specimens were tested. Fully automated high-throughput and point-of-care nucleic acid testing, and rapid antigen testing, were simultaneously implemented to expand the country's daily diagnostic capacity. Saliva testing and sample pooling were also introduced to increase screening efficiency in certain situations. Antibody testing and genomic sequencing were also adopted for more precise epidemic investigation. Other challenges encountered and overcome include a lack of resources and interfacing of laboratory information management systems for case reporting, limited specimen allocation and delivery, and limited staff for diagnostic processing.

Are Phthalate Exposure Related to Oxidative Stress in Children and Adolescents with Asthma? A Cumulative Risk Assessment Approach.

Childhood asthma has become one of the most common chronic diseases in children and adolescents. However, few case-control studies investigating the relationship between phthalate exposure and asthma in children and adolescents have been conducted, especially in Asia. Therefore, we assessed the potential associations between phthalate exposure and asthma among children and adolescents in Taiwan. Because various demographic and environmental variables may influence the incidence and prognosis of asthma, we performed a case-control study with propensity score matching. Out of 615 Childhood Environment and Allergic Diseases Study participants, we conditionally matched 41 children with clinically diagnosed asthma with 111 controls. We then analyzed 11 phthalate metabolites by using liquid chromatography with tandem mass spectrometry. Compared with the control group, the median urinary phthalate levels for most phthalate metabolites in the case group were slightly increased, including monomethyl phthalate, mono-n-butyl phthalate, monobenzyl phthalate, monoethylhexyl phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, and mono-(2-carboxymethylhexyl) phthalate. Hence, our results suggest that phthalate exposure may be associated with the development of asthma. In addition, prenatal environmental factors, such as active or passive smoking during pregnancy, may increase the risk of asthma.

The impact of age group in breast cancer survival outcome according to neoadjuvant treatment response: A matched case-control study.

This study aimed to investigate the effectiveness of neoadjuvant chemotherapy in patients with breast cancer in different age groups and evaluate the impact of age group on survival outcome according to different treatment responses. Data were retrospectively collected from the cancer registry database of Kaohsiung Medical University Hospital in Taiwan under an approved protocol. Overall, 96 elder patients (aged >50 years) and 96 younger controls (aged ≤50 years) who received neoadjuvant chemotherapy and breast surgical treatment were examined after 1:1 matching. Logistic regression analysis was used to investigate the effectiveness of treatment response in patients of different age groups. Additionally, the Kaplan-Meier estimator and log-rank test were performed to evaluate the effect of age group and treatment response on disease-free and overall survival (OS). Although no direct significant association was found between age group and treatment response, several significant results were found in treatment response stratification analysis. Among 16 pathological complete response (pCR) patients, elder patients showed significantly greater 5-year disease-free survival (DFS) than younger patients (DFS rate, 85.7% vs. 0%, p = 0.041). However, in 176 non-pCR patients, elder patients showed poor DFS compared to younger patients (DFS rate, 16.6% vs. 32.3%; log-rank test, p = 0.031). With limited sample size and study design, our study results demonstrate that patients aged >50 years who achieved pCR after neoadjuvant chemotherapy could obtain better survival outcome than younger patients. However, the younger patients showed no survival benefits regardless of pCR status.

Identification of Candidate Genes in Early-Stage Invasive Ductal Carcinoma Patients with High-Risk Mortality Using Genes Commonly Involved in Breast Cancer: A Retrospective Study.

INTRODUCTION: Invasive ductal carcinoma (IDC) of the breast is a heterogeneous disease characterized by multiple subtypes. IDC survival is highly impacted by tumor burden, molecular subtypes, and gene profiles. Gene mutation is a type of genomic instability regarded as having a considerable effect on IDC prognosis. Using integrated survival analysis, this study identified candidate genes and a high-risk group of patients with early-stage IDC to provide further understanding of the genetic characteristics associated with poor survival. METHODS: The gene mutation profiles, baseline demographics, clinicopathologic variables, and treatment characteristics of the early-stage IDC subpopulation were downloaded from an open access data platform. These data were analyzed for a total of 444 patients. In total, 40 genes commonly involved in IDC were listed, and the genes exhibiting significant differences (as estimated using the log-rank test) were selected as the candidate genes. RESULTS: The patients were divided into control, low-risk, and high-risk groups according to their gene mutation profiles. The 5-year overall survival rates of low-risk, control, and high-risk patients were 97.4%, 96.1%, and 73.0%, respectively. The high-risk group had a significantly higher risk of poor overall -survival (adjusted hazard ratio = 6.57, 95% confidence interval = 1.51-28.7, p = 0.012) than that of the control group, and the low-risk group did not have a significant survival difference compared with control group. CONCLUSIONS: This study proposed an integrative approach for the identification of candidate genes for risk assessment of overall survival in these patients through typical survival analysis methods. The 14 candidate genes selected are particularly involved in cell-cycle processes, deoxyribonucleic acid repair, and drug resistance; their mutations were found to be generally associated with disease progression or therapeutic resistance, which is commonly associated with poor overall survival outcomes in IDC.

Corrigendum: A Requirement of Protein Geranylgeranylation for Chemokine Receptor Signaling and Th17 Cell Function in an Animal Model of Multiple Sclerosis.

[This corrects the article DOI: 10.3389/fimmu.2021.641188.].

Th17 Immunity in the Colon Is Controlled by Two Novel Subsets of Colon-Specific Mononuclear Phagocytes.

Intestinal immunity is coordinated by specialized mononuclear phagocyte populations, constituted by a diversity of cell subsets. Although the cell subsets constituting the mononuclear phagocyte network are thought to be similar in both small and large intestine, these organs have distinct anatomy, microbial composition, and immunological demands. Whether these distinctions demand organ-specific mononuclear phagocyte populations with dedicated organ-specific roles in immunity are unknown. Here we implement a new strategy to subset murine intestinal mononuclear phagocytes and identify two novel subsets which are colon-specific: a macrophage subset and a Th17-inducing dendritic cell (DC) subset. Colon-specific DCs and macrophages co-expressed CD24 and CD14, and surprisingly, both were dependent on the transcription factor IRF4. Novel IRF4-dependent CD14+CD24+ macrophages were markedly distinct from conventional macrophages and failed to express classical markers including CX3CR1, CD64 and CD88, and surprisingly expressed little IL-10, which was otherwise robustly expressed by all other intestinal macrophages. We further found that colon-specific CD14+CD24+ mononuclear phagocytes were essential for Th17 immunity in the colon, and provide definitive evidence that colon and small intestine have distinct antigen presenting cell requirements for Th17 immunity. Our findings reveal unappreciated organ-specific diversity of intestine-resident mononuclear phagocytes and organ-specific requirements for Th17 immunity.