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Background: To restore sensation after breast reconstruction, a modified surgical approach was employed by identifying the cut fourth intercostal lateral cutaneous branch, elongating it with intercostal nerve grafts, and coapting it to the innervating nerve of the flap or by using direct neurotization of the spared nipple/skin. Methods: This was a retrospective case–control study including 56 patients who underwent breast neurotization surgery. Breast operations included immediate reconstruction after nipple-sparing mastectomy (36 patients), skin-sparing mastectomy (8 patients), and delayed reconstruction with nipple preservation (7 patients) or without nipple preservation (5 patients). Patients who underwent breast reconstruction without neurotization were included as the non-neurotization negative control group. The contralateral normal breasts were included as positive controls. Results: The mean(s.d.) monofilament test values were 0.07(0.10) g for the positive control breasts and 179.13(143.31) g for the breasts operated on in the non-neurotization group. Breasts that underwent neurotization had significantly better sensation after surgery, with a mean(s.d.) value of 35.61(92.63) g (P < 0.001). The mean(s.d.) sensory return after neurotization was gradual; 138.17(143.65) g in the first 6 months, 59.55(116.46) g at 7–12 months, 14.54(62.27) g at 13–18 months, and 0.37(0.50) g at 19–24 months after surgery. Two patients had accidental rupture of the pleura, which was repaired uneventfully. One patient underwent re-exploration due to a lack of improvement 1.5 years after neurotization. Conclusion: Using the lateral cutaneous branch of the intercostal nerve as the innervating stump and elongating it with intercostal nerve grafts is a suitable technique to restore sensation after mastectomy. This method effectively innervates reconstructed breasts and spares the nipple/skin with minimal morbidity. Using an intercostal nerve as the donor and direct suture to the base of the nipple is an efficient and effective method for breast and nipple neurotization. [ABSTRACT FROM AUTHOR]

Germline pathogenic variants of BRCA1 or BRCA2 cause hereditary breast and ovarian cancer syndromes. The present study investigated the participants' understanding and awareness of germline BRCA1/2 pathogenic variants before genetic counseling, the expectations and obstacles for genetic testing from the perspective of participants and their families, and their attitudes towards genetic testing after counseling. In this single‐country, multicenter, non‐interventional, patient‐reported outcome study, untested cancer patients and their families who visited genetic counseling clinics or who wanted to receive pre‐test genetic counseling were eligible to fill in the questionnaire after pre‐test counseling for germline BRCA1/2 testing. Demographic information, clinical characteristics, and information collected from the questionnaires, including the understanding of BRCA1/2 pathogenic variants before genetic counseling, understanding of BRCA1/2 pathogenic variants and feelings after genetic counseling, willingness to share results of genetic testing with family, and willingness to receive genetic testing, were summarized using descriptive statistics. A total of 88 participants were enrolled. The proportion of slight understanding of BRCA1/2 pathogenic variants increased from 11.4% to 67.0%, and the proportion of full understanding increased from 0% to 8.0%. After genetic counseling, most participants were willing to undergo genetic testing (87.5%) and share the results with their families (96.6%). The main factors that may affect participants' willingness to undergo BRCA1/2 testing were management (61.2%) and testing costs (25.9%). After pre‐test counseling, there was a high acceptance of BRCA1/2 testing and in‐family information sharing in Taiwanese patients with cancer and their families, which may serve as a reference for implementing genetic counseling in Taiwan. [ABSTRACT FROM AUTHOR]

Using higher order factor models, this article illustrates latent curve analysis for the purpose of modeling longitudinal change directly in a latent construct. Provides examples with simultaneous estimation of covariance and mean structures for a single-group and two-group structure. (SLD)

Closed-incision negative-pressure wound therapy (iNPWT) is known to enhance wound healing and tissue regeneration. The main aim of the present study is to investigate its effectiveness on enhancing wound healing under tension. An animal study was designed using a swine model by removing a skin flap to create a wound that could be closed primarily under tension, and iNPWT was applied. The enhancement of angiogenesis, lymphangiogenesis, collagen deposition, and tissue proliferation with reduced inflammation by iNPWT was confirmed by histology. The effect of iNPWT was further verified in patients receiving a profunda artery perforator (PAP) free flap for breast reconstruction. iNPWT was applied on the transversely designed donor site in continuous mode for 7 days, in which the wound was always closed under tension. A significant improvement in off-bed time was noted with the application of iNPWT (4.6 ± 1.1st and 5.5 ± 0.8th postoperative days in the iNPWT and control groups, respectively, p = 0.028). The control group (without iNPWT treatment) presented more cases of poor wound healing in the acute (23.1% vs. 0%) and wound breakdown in the late (23.1% vs. 8.3%) stages. The treatment of closed incisions under tension with iNPWT clinically enhances wound healing and tissue regeneration and with histological evidence. [ABSTRACT FROM AUTHOR]

Background  Robotic-assisted techniques are a tremendous revolution in modern surgery, and the advantages and indications were well discussed in different specialties. However, the use of robotic technique in plastic and reconstructive surgery is still very limited, especially in the field of peripheral nerve reconstruction. This study aims to identify current clinical applications for peripheral nerve reconstruction, and to evaluate the advantages and disadvantages to establish potential uses in the future. Methods  A review was conducted in the literatures from PubMed focusing on currently published robotic peripheral nerve intervention techniques. Eligible studies included related animal model, cadaveric and human studies. Reviews on robotic microsurgical technique unrelated to peripheral nerve intervention and non-English articles were excluded. The differences of wound assessment and nerve management between robotic-assisted and conventional approach were compared. Results  Total 19 studies including preclinical experimental researches and clinical reports were listed and classified into brachial plexus reconstruction, peripheral nerve tumors management, peripheral nerve decompression or repair, peripheral nerve harvesting, and sympathetic trunk reconstruction. There were three animal studies, four cadaveric studies, eight clinical series, and four studies demonstrating clinical, animal, or cadaveric studies simultaneously. In total 53 clinical cases, only 20 (37.7%) cases were successfully approached with minimal invasive and intervened robotically; 17 (32.1%) cases underwent conventional approach and the nerves were intervened robotically; 12 (22.6%) cases converted to open approach but still intervened the nerve by robot; and 4 (7.5%) cases failed to approach robotically and converted to open surgery entirely. Conclusion  Robotic-assisted surgery is still in the early stage in peripheral nerve surgery. We believe the use of the robotic system in this field will develop to become popular in the future, especially in the fields that need cooperation with other specialties to provide the solutions for challenging circumstances. [ABSTRACT FROM AUTHOR]

Abstract Background Mometasone furoate/formoterol (MF/F) is a novel combination therapy for treatment of persistent asthma. This noninferiority trial compared the effects of MF/F and fluticasone propionate/salmeterol (FP/S) combination therapies on pulmonary function and onset of action in subjects with persistent asthma. Methods Following a 2- to 4-week run-in period with MF administered via a metered-dose inhaler (MDI) 200 μg (delivered as 2 inhalations of MF-MDI 100 μg) twice daily (BID), subjects (aged ≥12 y) were randomized to MF/F-MDI 200/10 μg BID (delivered as 2 inhalations of MF/F-MDI 100/5 μg) or FP/S administered via a dry powder inhaler (DPI) 250/50 μg (delivered as 1 inhalation) BID for 12 weeks. The primary assessment was change from baseline to week 12 in area under the curve for forced expiratory volume in 1 second measured serially for 0-12 hours postdose (FEV1 AUC0-12 h). Secondary assessments included onset of action (change from baseline in FEV1 at 5 minutes postdose on day 1) and patient-reported outcomes. Results 722 subjects were randomized to MF/F-MDI (n = 371) or FP/S-DPI (n = 351). Mean FEV1 AUC0-12 h change from baseline at week 12 for MF/F-MDI and FP/S-DPI was 3.43 and 3.24 L × h, respectively (95% CI, -0.40 to 0.76). MF/F-MDI was associated with a 200-mL mean increase from baseline in FEV1 at 5 minutes postdose on day 1, which was significantly larger than the 90-mL increase for FP/S-DPI (P < 0.001). The overall incidence of adverse events during the 12-week treatment period that were considered related to study therapy was similar in both groups (MF/F-MDI, 7.8% [n = 29]; FP/S-DPI, 8.3% [n = 29]). Conclusions The results of this 12-week study indicated that MF/F improves pulmonary function and asthma control similar to FP/S with a superior onset of action compared with FP/S. Both drugs were safe, improved asthma control, and demonstrated similar results for other secondary study endpoints. Trial registration ClinicalTrials.gov: NCT00424008

The increasing number of female breast cancer (FBC) incidences in the East predominated by Chinese language speakers has generated concerns over women's medicare. To minimize the mortality rate associated with FBC in the region, governments and health experts are jointly encouraging women to undergo mammography screening at the earliest suspicion of FBC symptoms. However, studies show that a huge number of women affected by FBC tend to delay medical consultation at its early stage as a result of factors such as complacency due to unawareness of FBC symptoms, procrastination due to lifestyle, and the feeling of embarrassment in discussing private matters especially with medical personnel of the opposite gender. To address these issues, we propose a symptomatic assessment chatbot (SAC) based on artificial intelligence (AI) designed to prescreen women for FBC symptoms via a textual question-and-answer (Q&A) approach. The purpose of our chatbot is to assist women in engaging in communication regarding FBC symptoms, so as to subsequently initiate formal medical consultations for early FBC diagnosis and treatment. We implemented the SAC systematically with some of the latest natural language processing (NLP) techniques suitable for Chinese word segmentation (CWS) and trained the model with real-world FBC Q&A data obtained from a major hospital in Taiwan. The results from our experiments showed that the SAC achieved very high accuracy in FBC assessment scoring in comparison to FBC patients' screening benchmark scores obtained from doctors. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy (NACT) was initially applied to locally advanced breast cancer to convert advanced lesions to an operable status. Currently, its application has been expanded to enhance overall oncological results, especially in patients with triple-negative or HER-2-positive breast cancer. With more NACT being applied, the role and impact of this approach on breast reconstruction needs to be determined. This study aimed to perform a complete reconstructive outcome analysis of patients receiving NACT who underwent immediate breast reconstruction.Methods: A retrospective review of a single reconstructive surgeon's immediate breast reconstructions performed from July 2008 to December 2018 was undertaken. The results were stratified by the use of NACT. Patient demographics, delivery of NACT, adjuvant treatment, incidence of surgical complications, and postoperative photographs were analyzed.Results: A total of 269 patients were included. The mean follow-up was 46.3 months. Forty-six out of 269 patients received NACT and were included in the NACT group. The other patients were included in the non-NACT group. When implant-based reconstruction was planned, the NACT group had a higher rate of two-stage tissue expander-implant reconstruction than direct-to-implant reconstruction (p < 0.001). The requirement for postmastectomy radiotherapy was higher in the NACT group (p < 0.001). The surgical complication rates were similar between groups after adjusting for confounding factors. The objective aesthetic outcomes assessed by 6 plastic surgeons were also similar between groups.Conclusions: Immediate breast reconstruction is a safe and reliable procedure, with an acceptable reconstructive complication rate and satisfactory aesthetic outcomes, for patients treated with NACT. [ABSTRACT FROM AUTHOR]

Objective We undertook this phase III study to evaluate baricitinib, an orally administered JAK-1/JAK-2 inhibitor, as monotherapy or combined with methotrexate (MTX) compared to MTX monotherapy in patients with active rheumatoid arthritis (RA) who had received no or minimal conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and who were naive to biologic DMARDs. Methods A total of 588 patients were randomized 4:3:4 to receive MTX monotherapy (once weekly), baricitinib monotherapy (4 mg once daily), or the combination of baricitinib and MTX for 52 weeks. The primary end point assessment was a noninferiority comparison of baricitinib monotherapy to MTX monotherapy based on the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 24. Results The study met its primary objective. Moreover, baricitinib monotherapy was found to be superior to MTX monotherapy at week 24, with a higher ACR20 response rate (77% versus 62%; P ≤ 0.01). Similar results were observed for combination therapy. Compared to MTX monotherapy, significant improvements in disease activity and physical function were observed for both baricitinib groups as early as week 1. Radiographic progression was reduced in both baricitinib groups compared to MTX monotherapy; the difference was statistically significant for baricitinib plus MTX. The rates of serious adverse events (AEs) were similar across treatment groups, while rates of some treatment-emergent AEs, including infections, were increased with baricitinib plus MTX. Three deaths were reported, all occurring in the MTX monotherapy group. Malignancies, including nonmelanoma skin cancer, were reported in 1 patient receiving MTX monotherapy, 1 receiving baricitinib monotherapy, and 4 receiving baricitinib plus MTX. Conclusion Baricitinib alone or in combination with MTX demonstrated superior efficacy with acceptable safety compared to MTX monotherapy as initial therapy for patients with active RA. [ABSTRACT FROM AUTHOR]

Background: Mometasone furoate/formoterol (MF/F) is a novel combination therapy for treatment of persistent asthma. This noninferiority trial compared the effects of MF/F and fluticasone propionate/salmeterol (FP/S) combination therapies on pulmonary function and onset of action in subjects with persistent asthma. Methods: Following a 2- to 4-week run-in period with MF administered via a metered-dose inhaler (MDI) 200 µg (delivered as 2 inhalations of MF-MDI 100 µg) twice daily (BID), subjects (aged ≥12 y) were randomized to MF/FMDI 200/10 µg BID (delivered as 2 inhalations of MF/F-MDI 100/5 µg) or FP/S administered via a dry powder inhaler (DPI) 250/50 µg (delivered as 1 inhalation) BID for 12 weeks. The primary assessment was change from baseline to week 12 in area under the curve for forced expiratory volume in 1 second measured serially for 0-12 hours postdose (FEV1 AUC0-12 h). Secondary assessments included onset of action (change from baseline in FEV1 at 5 minutes postdose on day 1) and patient-reported outcomes. Results: 722 subjects were randomized to MF/F-MDI (n = 371) or FP/S-DPI (n = 351). Mean FEV1 AUC0-12 h change from baseline at week 12 for MF/F-MDI and FP/S-DPI was 3.43 and 3.24 L × h, respectively (95% CI, -0.40 to 0.76). MF/F-MDI was associated with a 200-mL mean increase from baseline in FEV1 at 5 minutes postdose on day 1, which was significantly larger than the 90-mL increase for FP/S-DPI (P < 0.001). The overall incidence of adverse events during the 12-week treatment period that were considered related to study therapy was similar in both groups (MF/F-MDI, 7.8% [n = 29]; FP/S-DPI, 8.3% [n = 29]). Conclusions: The results of this 12-week study indicated that MF/F improves pulmonary function and asthma control similar to FP/S with a superior onset of action compared with FP/S. Both drugs were safe, improved asthma control, and demonstrated similar results for other secondary study endpoints. Trial registration: ClinicalTrials.gov: NCT00424008 [ABSTRACT FROM AUTHOR]

Simple Summary: Very limited studies so far have analyzed the long-term oncologic outcomes of breast cancer patients that developed metachronous isolated supraclavicular nodal metastasis (miSLNM) with no available treatment strategy for the critical issue. The study enrolled 139 miSLNM patients; 61 patients underwent selective neck dissection. In median follow-up of 73.1 months, significantly better 5-year overall survival rate was found in the neck dissection group compared to the no-dissection group (68.9% vs. 57.7%, respectively; HR, 1.77 (1.22–2.55), p = 0.003). The findings suggest surgery for miSLNM should be integrated into multimodal therapy of miSLNM, and the restaging of miSLNM as rN3c rather than M1 disease if detected earlier. We retrospectively enrolled 139 patients who developed metachronous isolated supraclavicular lymph node metastasis (miSLNM) from 8129 consecutive patients who underwent primary surgery between 1990 and 2008 at a single medical center. The median age was 47 years. The median follow-up time from date of primary tumor surgery was 73.1 months, and the median time to the date of neck relapse was 43.9 months in this study. Sixty-one (43.9%) patients underwent selective neck dissection (SND). The 5-year distant metastasis-free survival (DMFS), post-recurrence survival, and overall survival (OS) rates in the SND group were 31.1%, 40.3%, and 68.9%, respectively, whereas those of the no-SND group were 9.7%, 32.9%, and 57.7%, respectively (p = 0.001). No SND and time interval from primary tumor surgery to neck relapse ≤24 months were the only significant risk factors in the multivariate analysis of DMFS (hazard ratio (HR), 1.77; 95% confidence interval (CI), 1.23–2.56; p = 0.002 and HR, 1.76, 95% CI, 1.23–2.52; p = 0.002, respectively) and OS (HR, 1.77; 95% CI, 1.22–2.55; p = 0.003 and HR, 3.54, 95% CI, 2.44–5.16; p < 0.0001, respectively). Multimodal therapy, including neck dissection, significantly improved the DMFS and OS of miSLNM. Survival improvement after miSLNM control by intensive surgical treatment suggests that miSLNM is not distant metastasis. [ABSTRACT FROM AUTHOR]

Bilateral breast cancer is a strong predictor of BRCA 1/2 mutation and hence one criterion indicated for hereditary genetic testing. The purpose of this study is to assess the characteristics of synchronous bilateral breast cancer (SBBC) and its association with personal and familial cancer traits. Patients diagnosed with SBBC in our institute between 1992 and 2018 were retrospectively reviewed, and the information of clinicopathological features, personal and family cancer history were analyzed. Of the 307 SBBCs enrolled, the growing case number generally aligned with the regional breast cancer incidence after the era of population-based mammography screening. SBBC patients had similar cancer stages but worse survival outcomes than those in the standard scenario. A total of 42.0% had mixed pathological diagnoses, and 22.8% had discordant immunohistochemistry (IHC) subtypes from both sides, which contributed to treatment challenges. The correlation of SBBC with hereditary breast and ovarian cancer (HBOC) syndrome was strongly implied, as 20.7% of our SBBC patients with known familial cancer histories had HOBC-related familial cancers (breast, ovarian, or prostate cancers). These findings highlight the need for genetic counseling and germline mutation testing in patients with SBBC. Early PARP inhibitor treatment should also be considered in high-risk cases for outcome improvement. [ABSTRACT FROM AUTHOR]

Predictive metabolic biomarkers for the recurrent luminal breast cancer (BC) with hormone receptor (HR)-positive and human epidermal growth factor receptor type 2 (HER2)-negative are lacking. High levels of O-GlcNAcylation (O-GlcNAc) and pyruvate kinase isoenzyme M2 (PKM2) are associated with malignancy in BC; however, the association with the recurrence risk remains unclear. We first conduct survival analysis by using the METABRIC dataset to assess the correlation of PKM2 expression with BC clinical outcomes. Next, patients with HR+/HER2- luminal BC were recruited for PKM2/O-GlcNAc testing. Logistic regression and receiver operating characteristic curve analysis were performed to evaluate the 10-year DFS predicted outcome. Survival analysis of the METABRIC dataset revealed that high expression of PKM2 was significantly associated with worse overall survival in luminal BC. The high expression of O-GlcNAc or PKM2 was a significant independent marker for poor 10-year DFS using immunohistochemical analysis. The PKM2 or O-GlcNAc status was a significant predictor of DFS, with the combination of PKM2–O-GlcNAc status and T stage greatly enhancing the predictive outcome potential. In summary, O-GlcNAc, PKM2, and T stage serve as good prognostic discriminators in HR+/HER2− luminal BC. [ABSTRACT FROM AUTHOR]

Soil chemical and biological dynamics in mixed use landscapes are dependent on the distribution and pattern of soil moisture and water transport. In this paper we examine the effect of different grid sizes on soil water content for a spatially explicit, variable-source-area hydrology model applied to a watershed in central New York. Data on topography, soil type, and land use were input at grid sizes from 10 to 600 m. Output data consisted of runoff and spatial pattern of soil moisture. To characterize the spatial variability at different grid sizes, information theory was used to calculate the information content of the input and output variables. Simulation results showed higher average soil water contents and higher evaporation rates for large grid sizes. During a wet year, runoff was not affected by grid size, whereas during a dry year runoff was greatest for the smallest grid size. While the information content (i.e., spatial variability) of soil type and land use maps was not affected by the different grid sizes, increasing grid sizes caused the information content of the slope gradient to decrease slightly and the Laplacian (or curvature of the landscape) to decrease greatly. In other words, increasing grid cell size misrepresented the curvature of the landscape. During wet periods the decrease in information content of the soil moisture data was the same as for the Laplacian as grid size increased. During dry periods, when local fluxes such as evaporation and runoff determine the moisture content, this relation did not exist. The Laplacian can be used to provide a priori estimates of the moisture content deviations by aggregation. These deviations will be much smaller for the slowly undulating landscapes than the landscape with steep valleys simulated in this study. [ABSTRACT FROM AUTHOR]