bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P6-08-26: Outcomes and prognostic factors in 2000 patients with TNBC: Long-term results covering 10 years
Authors: Morante Z , Pinto J , Enriquez D , Araujos J , Luque R , Eyzaguirre E , Saavedra A , Fuentes H , Neciosup S , Gomez H
Published: February 2018

Background: Triple-negative breast cancer (TNBC) is characterized by being a heterogeneous disease with different risk factors and poor survival rates. TNBC have a higher prevalence in the Peruvian population (21.3%) than in Caucasian groups. Our study aims to determine the outcome and identify prognostic factors in Peruvian women with TNBC.

Methods: We retrospectively analyzed TNBC patients treated at the “Instituto Nacional de Enfermedades Neoplasicas” between 2000 and 2014. Survival rates and differences were calculated by the Kaplan-Meier method and Log-rank test, respectively. With the Cox regression, in univariate and multivariate analysis, we identified prognostic factors in for our TNBC population.

Results: In total, 2007 patients were diagnosed.The mean age was 50 years (range: 19-95 years); 44.8% were premenopausal and 26.2% had obesity at diagnosis. A family history of breast and/or ovarian cancer was present in 266 (28.9%) patients. Regarding the clinical-pathological features, 1860 (93.5%) had ductal invasive carcinoma and 1024 (51.6%) patients were in Stage (S) III. Local relapse and distant metastasis affected to 34.5% and 51.4% of our patients, respectively. Lung (14.5%) and bone (9.7%) were the most frequent sites of metastasis. The median follow-up was 9 years. The 5 and 10 yrs DFS/OS rates are shown in table 1. In the multivariate analysis, adjuvant chemotherapy (ACT) (HR: 0.60, 95%CI: 0.44-0.82, p=0.001) and radiotherapy (RT) (HR:0.72, 95%CI:0.55-0.93, p=0.014) were associated with a reduced risk of recurrence, while nodal involvement were associated to a high recurrence risk. Factors associated to a reduction in the risk of death were ACT (HR:0.73, 95%CI:0.61-0.88, p=0.001), RT (HR: 0.70, 95%CI: 0.60-0.92, p<0.001), and Neoadjuvant CT (HR: 0.61, 95%CI: 0.51-0.73, p<0.001); in contrast, a NLR≥3 (HR:1.60,95%CI: 1.36-1.87, p<0.001), N stage were associated with a higher risk of death.

Conclusions: Sociodemographic features of Peruvian patients with TNBC resemble other populations; however, our population is diagnosed at more advanced clinical stages, hence DFS and OS were lower than international reports while prognostic factors were similar to previous studies.

Table 1. 5- and 10-years DFS/OS ratesClinical StageIIIIIIIVTotalp (value)DFS (%)     <0.0015-years837540-63 10-years696429-52 OS (%)     <0.0015-years938239655 10-years837532550 

Citation Format: De la Cruz-Ku G, Morante Z, Pinto J, Enriquez D, Araujos J, Luque R, Eyzaguirre E, Saavedra A, Fuentes H, Neciosup S, Gomez H. Outcomes and prognostic factors in 2000 patients with TNBC: Long-term results covering 10 years [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-26.
Abstract P6-09-02: Associations between hereditary cancer panel predisposition genes and breast cancer histological subtypes
Authors: Lilyquist J , Laduca H , Hu C , Na J , Polley EC , Hart SN , Pesaran T , Tippin-Davis B , Goldgar DE , Dolinsky JS , Couch FJ
Published: February 2018

Background: Clinical panel testing has become routine practice for patients that are diagnosed with breast cancer at a young age and/or have a personal or family history of cancer. Associations with known breast cancer genes and breast cancer subtypes have been previously identified, such as BRCA1 associations with estrogen receptor negative (ER-) and triple negative (ER-/PR-/HER2-) breast cancers. However, the cancer predisposition genes associated with each of the four clinical subtypes of breast cancer have not been fully defined. We evaluated 24,901 Caucasian female breast cancer cases receiving clinical panel testing for 23 cancer predisposition genes and assessed associations between mutations in each gene and breast cancer subtypes.

Methods: Germline hereditary cancer multigene panel testing results for cancer predisposition genes were obtained for 24,901 Caucasian female breast cancer cases evaluated by a clinical testing laboratory. Information on tumor histology, personal and family history of cancer, age at diagnosis, and previous genetic testing was provided by clinical care providers of patients receiving clinical cancer genetic testing. Breast cancer cases were classified into clinical breast cancer subtypes based on estrogen/progesterone hormone receptor status (HR) and HER2 status: Luminal A (HR+/HER2-), Luminal B (HR+/HER2-), HER2 subtype (HR-/HER2+), and Triple Negative (HR-/HER2-). The frequency of pathogenic or likely pathogenic mutations observed in each subtype was compared against the Exome Aggregation Consortium (ExAC) non-TCGA non-Finnish European population to estimate risks.

Results: ATM was associated with moderate risks (odds ratio (OR)>2.0) of Luminal A, Luminal B, and HER2 subtypes of breast cancer, but was not associated with the Triple Negative subtype. PALB2 was associated with moderate risk for Luminal B subtype, but high risk (OR>5.0) for Luminal A, HER2, and triple negative subtypes. TP53 was associated with high risks for Luminal B and HER2 tumors. NBN, MRE11A, and RAD50 were not associated with any subtype of breast cancer.

Conclusions: Identifying associations between inherited mutations (odds ratio (OR)>2.0) and breast cancer subtypes can inform clinical risk management, treatment options, and therapeutic development efforts.

Citation Format: Lilyquist J, Laduca H, Hu C, Na J, Polley EC, Hart SN, Pesaran T, Tippin-Davis B, Goldgar DE, Dolinsky JS, Couch FJ. Associations between hereditary cancer panel predisposition genes and breast cancer histological subtypes [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-09-02.
Abstract P6-11-07: Effectiveness and adverse events of DigniCap® scalp cooling system
Authors: Traub L , Brandi C , Khandan F , Thill M
Published: February 2018

Background

Chemotherapy-induced alopecia (CIA) is able to affect a patient's self-image and confidence negatively. A decade ago scalp cooling failed to avoid chemotherapy- induced hairloss in women who underwent chemotherapy as only thermal packs were used.

The DigniCap® scalp cooling system consists of a silicon cap that includes two sensor controlled cooling cycles. These cycles regulate the scalp temperature to lead to a continuous vasoconstriction in the scalp. Thus, it is indicated to reduce the likelihood of CIA.

Reduced temperature results in a reduced blood flow to the scalp area so that less chemotherapy reaches the hair cells. Therefore, these are not exposed to the full dose of chemotherapy and may be able to survive the treatment.

The purpose of this study was to evaluate the effectiveness and adverse events of DigniCap® scalp cooling system.

Patients and Methods

Since October 2015, 48 of 60 planned breast cancer patients undergoing chemotherapy were prospectively included in a unicentric cohort study in the certified breast cancer center at AGAPLESION Markus Hospital, Frankfurt, Germany. The average age of the women was 52.7 years (range 33 – 76).

The chemotherapy regimen included 4x EC q3w -> 12x paclitaxel q1w (60.4%), 4x TC q3w (8.3%), 6x carboplatin plus paclitaxel q3w (8.3%), 6x docetaxel, carboplatin, trastuzumab (TCbH) q3w + pertuzumab (4.1%), 4x nab-paclitaxel m 3 q4 (2.1%), 4x paclitaxel q2w -> 4x EC q2w (2.1%), 18x paclitaxel q1w (2.1%), 18x paclitaxel q1w plus myocet q1w (2.1%), eribulin d1, 8 q3 (2.1%), 4x EC q3w -> 12x paclitaxel q1w plus trastuzumab plus pertuzumab (2.1%), 6x carboplatin plus paclitaxel q3w plus bevacizumab (2.1%), 4x nab-paclitaxel3 q4 plus bevacizumab (2.1%), 4x nab-paclitaxel 3 q4 -> 4x EC q3w (2.1%).

Our aim was to quantify the grade of alopecia, satisfaction and side effects of the scalp cooling system. Alopecia quantification was done by a standardized questionnaire and photo documentation. Final results of the whole cohort of 60 patients will be presented at SABCS 2017.

Results

The interim analysis showed a success rate of complete hair loss avoidance of 8.0%. Hair loss of less than 20% was documented in 60.0% (29 patients). In 19/ 48 patients (39.6%) adverse reactions caused by the DigniCap® Scalp Cooling System, like headache (12.5%) or CIA (27.1%) were reported.

Conclusion

Our evaluation shows that DigniCap® Scalp Cooling Systemhas a minimal rate of adverse events (39.6%) and reduces the likelihood of chemotherapy-induced alopecia (< 20% hair loss)effectively by 60.0%, even in anthracycline-based regimen.

Citation Format: Traub L, Brandi C, Khandan F, Thill M. Effectiveness and adverse events of DigniCap® scalp cooling system [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-11-07.
Abstract P6-12-03: Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer related lymphedema
Authors: Kaufman D , Shah C , Vicini F
Published: February 2018

Background: With improved breast cancer outcomes, an increasing focus on sequelae of treatment as part of survivorship has emerged. Breast cancer related lymphedema (BCRL) represents one such sequelae. Increasing data and recent NCCN guidelines support the use of prospective BCRL surveillance to allow for early detection and intervention as a method to reduce chronic, irreversible BCRL. Therefore, this study was performed to evaluate the impact early detection and treatment of BCRL in breast cancer patients undergoing prospective surveillance with bioimpedance spectroscopy (BIS).

Methods: From 8/2010 through 12/2016, 206 patients were evaluated with BIS as part of a prospective surveillance program.The protocol included pre-operative assessment with BIS as well as post-operative assessments with BIS at regular intervals. Patients with L-Dex readings increasing by more than 10 from baseline were considered to have subclinical BCRL and treated with a compression sleeve for 4 weeks. For the purpose of this analysis, high-risk was defined as receipt of ALND, regional nodal irradiation, or taxane chemotherapy. Chronic BCRL was defined as the need for complex decongestive physiotherapy.

Results: A total of 206 patients were analyzed, with a mean age of 61 years old and a median follow up of 25.9 months. Overall, 17% of patients had least one high-risk feature, 8% had two factors, and 7% had all three factors. A total of 21 patients (9.8%) were diagnosed with subclinical BCRL. Increased rates of subclinical BCRL were seen in patients undergoing ALND (23% vs. 7%, p=0.01) with ALND and receipt of RNI associated with development of subclinical BCRL. At last follow-up, no patients had persistent, chronic BCRL following early, conservative intervention measures.

Conclusions: The results of this study support prospective surveillance and early treatment utilizing BIS. Intervention triggered by subclinical BCRL detection with an elevated L-Dex score was associated with a very low rate of chronic BCRL.

Citation Format: Kaufman D, Shah C, Vicini F. Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer related lymphedema [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-03.
Abstract P6-12-22: Sexual health in long-term breast cancer survivors
Authors: Soldera SV , Ennis M , Lohmann AE , Goodwin PJ
Published: February 2018

Background Significant sexual dysfunction is reported in women with breast cancer (BC) in the years following diagnosis. It is unclear whether symptoms persist over time in BC survivors (BCS) as long-term data compared to healthy controls is lacking. We compared sexual functioning in long-term BCS to controls and explored the impact of adjuvant therapy on sexual health. Methods A cohort of women with localized BC recruited from 1989 to 1996 was prospectively followed as previously described. BCS without recurrence and controls without BC were contacted between 2005 and 2007 and answered self-reported quality of life questionnaires. Sexual health was measured with the Sexual Activity Questionnaire (SAQ). Vasomotor, gynecological and bladder symptoms were scored using the Menopausal Symptom Scale (scale ranges 0-4) based on the Breast Cancer Prevention Trial Symptom Checklist. Regression analysis was used to compare groups, with and without adjustment for age (quadratic) and menopausal status. P values <0.05 were considered significant. Results 248 of 285 BCS and 159 of 167 controls completed the SAQ. The median time from diagnosis of BCS was 12.5 years. BCS were slightly older (61.9 vs 59.1 years, p=0.0004) and somewhat more likely to be post-menopausal (94.4 vs 85.5%, p=0.0025) than controls. Overall, fewer BCS were sexually active than controls (45.2 vs 59.7%, p=0.0041). This difference was no longer significant when adjusted for age and menopausal status (odds ratio 0.68, p=0.075). In those sexually active, no significant differences were noted on the SAQ Pleasure and Discomfort scales.Differences in adjuvant treatment were not significantly associated with being sexually active or the SAQ subscales. BCS scored higher (worse) on the gynecological and bladder symptom scale than controls (0.66 vs 0.43, p=0.0036, adjusted difference 0.24, p=0.0029; 0.60 vs 0.41, p=0.02, adjusted difference 0.18, p=0.029 respectively), but no difference was seen in vasomotor scores. Gynecological symptom scores were greatest in BCS who received adjuvant chemotherapy. Conclusion Despite more frequent long-term gynecological and bladder symptoms, sexual health is similar in BCS and controls. Adjuvant chemotherapy is associated with persistent gynecological symptoms and interventions aimed at improving these could improve quality of life.

Citation Format: Soldera SV, Ennis M, Lohmann AE, Goodwin PJ. Sexual health in long-term breast cancer survivors [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-22.
Abstract P6-12-23: Not presented
Authors: Lugo L , Sánchez A , Cabrera-Galeana P , Muñoz-Montaño W , Vazquez-Romo R , Esparza N , Robles C , Bargallo-Rocha E
Published: February 2018

This abstract was not presented at the symposium.
Abstract P6-15-02: Withdrawn
Authors:   I-SPY 2 TRIAL Investigators
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P6-15-03: Outcome after neoadjuvant chemotherapy in elderly breast cancer patients – a pooled analysis of individual patient data from eight prospectively randomized controlled trials
Authors: von Waldenfels G , Loibl S , Furlanetto J , Anna M , Lederer B , Denkert C , Hanusch C , Huober J , Jackisch C , Kümmel S , von Minckwitz G , Schneeweiss A , Untch M , Rhiem K , Fasching PA , Blohmer JU
Published: February 2018

Introduction: Recent studies showed the high and independent impact of age (<40 years) on pathologic complete remission (pCR) and prognosis for patients undergoing neoadjuvant chemotherapy (NACT). Some physicians might not consider elderly patients (>65 years) for NACT due to poor prognosis or higher toxicity. The aim of this analysis is to help selecting appropriately elderly women who would benefit from NACT. Secondly, survival parameters will be investigated in several clinical and histological subgroups.

Methods: From 1998 to 2010, eight prospectively randomized German Breast Group (GBG) trials of anthracycline- and taxane-based NACT were performed and analyzed in this study.

Results: Compared to the overall average, women older than 65 years had significant larger tumors and more overall lymph node involvement. Also, compared to patients younger than 51 years, they had more lobular invasive tumors. Histologically, they had more G2 tumors, more estrogen-receptor positive tumors. PCR (ypT0 ypN0) was strongly associated with age: >65y: 11.7%; 51-65y: 14.1%; 40-50y: 17.3%; <40y: 20.9%. The multivariable logistic regression analysis of clinical parameters showed that young age, clinical stage T4, invasive ductal cancer and poor differentiated breast cancer are predictive for high pCR. The multivariate analyses of molecular subgroups also showed that age >65years is a predictor of significant (p<0.05) lower pCR in TNBC and HR positive/HER2- breast cancers. Nonetheless, in this cohort, HER2+ patients showed pCR rates as high - and for HR+/HER2+ even higher - pCR rates compared to younger patients.

Discussion: This study underlines the unfavorable impact of higher age on pCR, but it shows nevertheless a realistic chance for pCR if NACT is applied - especially for HER2+ patients. Furthermore, elderly patients in this analysis with non-TNBC have a good prognosis (comparable to younger patients) regarding OS, even if they do not have pCR.

Citation Format: von Waldenfels G, Loibl S, Furlanetto J, Anna M, Lederer B, Denkert C, Hanusch C, Huober J, Jackisch C, Kümmel S, von Minckwitz G, Schneeweiss A, Untch M, Rhiem K, Fasching PA, Blohmer JU. Outcome after neoadjuvant chemotherapy in elderly breast cancer patients – a pooled analysis of individual patient data from eight prospectively randomized controlled trials [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-03.
Abstract P6-15-07: Not presented
Authors: Somlo G , Waisman J , Yuan Y , Li M , Kruper L , Jones V , Treece T , Frankel P , Yim J , Tumyan L , Schmolze D , Menghi F , Liu ET , Hurria A , Yeon C , Mortimer J
Published: February 2018

This abstract was not presented at the symposium.
Abstract PD2-12: Molecular imaging for early identification of patients who benefit from palbociclib in addition to letrozole
Authors: Venema CM , de Vries EFJ , Glaudemans AWJM , Hospers GAP , Schröder CP
Published: February 2018

Palbociclib plus letrozole has improved both progression free survival and overall response rate in metastatic breast cancer (MBC) patients. For response to palbociclib, the best biomarker is ER expression. 16α-[18F]Fluoro-17β-estradiol (FES) -PET allows whole body ER level assessment, and provides insight in the heterogeneity of ER expression throughout the body. We hypothesized that lesions with low uptake on FES-PET are unlikely to respond to letrozole plus palbociclib. METHODS: Post-menopausal women with ER positive MBC were eligible for this pilot study. All patients were staged with fludeoxyglucose (FDG)-PET and CT scan, and in addition a FES-PET was performed at baseline. After 8 weeks treatment an FDG-PET/CT was used for response evaluation. The primary endpoint was the relation between standard uptake value (SUV) per lesion on FES-PET to response, as measured by RECIST 1.1 criteria in case of measurable disease. In case of non-measurable bone lesions, progression was defined as an increase in SUV on FDG-PET of more than 30% per lesion compared to baseline (based on PERCIST). RESULTS: 15 patients were included of which 14 were evaluable for primary endpoint. Mean age was 50 years (range 35-76). Median number of prior therapies was 1. A total of 280 lesions were detected on conventional imaging of which 50 showed low uptake (SUV<1.5) on FES-PET. 29/50 low uptake lesions showed progression based on diagnostic CT (n=9) or FDG PET (n=20). In contrast, 28/230 FES positive lesions showed progression.

 ResponseStable diseaseProgression FES uptake >1.51089428230FES uptake <1.57142950 11510857280

DISCUSSION: this pilot trial indicates negative predictive value of low FES uptake for response to letrozol plus palbociclib in ER positive MBC. The FES-PET may therefore be a biomarker for response for this combination treatment. This will have to be explored further in future clinical trials.

Citation Format: Venema CM, de Vries EFJ, Glaudemans AWJM, Hospers GAP, Schröder CP. Molecular imaging for early identification of patients who benefit from palbociclib in addition to letrozole [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD2-12.
Bullöses Pemphigoid getriggert durch Schlaganfall
Authors: Braun-Falco Markus
Published: February 2018

Background: We hypothesize that autoantibodies are induced after the blood-brain barrier is damaged by stroke and the risk of bullous pemphigoid (BP) is increased after stroke. We assess the risk of BP after first-ever stroke in a nationwide population-based cohort of first-ever stroke patients. Methods: We extracted data from the Longitudinal Health Insurance Database 2005 and identified patients with first-ever stroke as well as control patients matched for age, gender, and year of enrollment. The risk of BP in first-ever stroke patients in comparison with that in control patients was analyzed using Cox regression. Results: Of 12,607 patients with first-ever stroke, 38 (0.3%) patients developed BP in a median of 3.5 years. In the control patients, 8 persons (0.06%) had BP in a median of 3.7 years. The crude hazard ratio (HR) of BP in first-ever stroke patients was 4.83 (95% CI 2.25-10.34, p < 0.001) compared to the control group. The adjusted HR was 4.20 (95% CI 1.94-9.08, p < 0.001) after adjustments for age, gender, hypertension, diabetes, dementia, epilepsy, Parkinson disease, furosemide, and neuroleptics for stroke patients. Conclusions: The risk of BP is increased in first-ever stroke patients in a nationwide population-based cohort and this association is independent of well-known confounders of BP.
Honig stachelloser Bienen als natürliches Wundheilungsmittel: eine Übersicht
Authors: Abd Jalil Mohd Azri , Kasmuri Abdul Razak , Hadi Hazrina
Published: February 2018

Hintergrund: Die stachellose Biene ist eine auf fast allen Kontinenten vorkommende natürliche Bienenart. Ihr Honig wurde zu allen Zeiten und überall auf der Welt verwendet. Eine Besonderheit des Honigs ist, dass er von den Bienen in einem natürlichen Harzgefäß (Cerumen) gespeichert wird, was seine positiven Eigenschaften, insbesondere für die Wundheilung, unterstützt. Methoden: Der vorliegende Artikel enthält eine Übersicht verschiedener Studien zu Honig stachelloser Bienen, in denen die zahlreichen therapeutischen Profile dieses Honigs im Hinblick auf seine antioxidativen, antimikrobiellen, entzündungshemmenden und feuchtigkeitsspendenden Eigenschaften hervorgehoben werden. Alle diese therapeutischen Eigenschaften wirken wundheilungsfördernd. Ergebnisse: Die im Honig stachelloser Bienen enthaltenen Antioxidantien können freie Radikalketten unterbrechen, die sich negativ auf die Wundheilung auswirken. Darüber hinaus kann der Honig stachelloser Bienen durch seine antimikrobiellen Eigenschaften der bakteriellen Kontamination entgegenwirken und so die Heilungsrate verbessern. Ferner schützt die entzündungshemmende Wirkung dieses Honigs das Gewebe gegen hochwirksame Entzündungsmediatoren. Seine feuchtigkeitsspendenden Eigenschaften fördern die Wundheilung, da sie die Angiogenese anregen und die Sauerstoffversorgung verbessern. Schlussfolgerung: Die Anwendung von Honig zur Behandlung von Wunden ist von alters her weit verbreitet. Um die Heilungsraten in Zukunft weiter zu verbessern, ist es deshalb wichtig zu verstehen, über welchen pharmakologischen Mechanismus der Honig auf die Physiologie wunder Haut wirkt. Übersetzung aus Skin Pharmacol Physiol 2017;30:66-75 (DOI: 10.1159/000458416)
Das Cushing-Syndrom im Spiegel der Haut
Authors: Makrantonaki Evgenia
Published: February 2018

Cushing's syndrome is a rare endocrine disorder that comprises a large group of signs and symptoms resulting from chronic exposure to excess corticosteroids. Most cases of Cushing's syndrome are due to increased adrenocorticotropic hormone production from a pituitary adenoma, which is referred to as Cushing's disease. Most of the signs and symptoms are nonspecific and common in the general population, making a diagnosis often challenging. However, several dermatological manifestations, such as fragile skin, easy bruising, and reddish purple striae, are more discriminatory. Because uncontrolled Cushing's syndrome of any etiology is associated with substantial morbidity, including increased cardiovascular disease and mortality, it is important to make an early diagnosis. Unfortunately, median delays of 2 years to diagnosis have been reported. We report a case of a woman who had multiple dermatological findings, including facial plethora, easy bruising, violaceous striae, hirsutism, and acne, the latter 2 signs reflecting androgen excess. Of interest, our patient presented with a chief complaint of hair loss, a common complaint in the general population that occurs with a greater frequency in patients with Cushing's disease and is attributed to androgenetic alopecia, but it is rarely the presenting symptom.
Vermeidung von opportunistischen Infektionen in der Psoriasis-Behandlung mit Fumarsäureester durch engmaschige Kontrolle möglich
Authors: Philipp Sandra
Published: February 2018

Background: Fumaric acid esters (FAEs) are a broadly used therapy option for patients suffering from moderate-to-severe plaque psoriasis. Various studies in psoriasis have already shown peripheral blood lymphopenia during oral FAE therapy. Smaller studies also documented a reduction of CD4+ and CD8+ cell counts. Up to now, there are few case reports on opportunistic infections under FAE therapy - all of them associated with lymphopenia. Objective: To examine the influence of FAEs on white blood cells with special regard to leukocytes, lymphocytes, and CD4+ and CD8+ cells during psoriasis therapy. Patients and Methods: A cohort of 105 patients with diagnosed moderate-to-severe chronic plaque psoriasis was enrolled in this single-centre observational trial. For a cohort of 36 patients, T-cell subset analyses were performed. Results: Of the total, 65 patients were male (61.9%) and 40 (38.1%) female; the mean age was 43.3 years (range 16-73 years). The median lymphocyte count was significantly reduced by about 35.8% after the first 6 months of therapy. When assessing the lymphocyte count nadir over the whole period observed, 46.7% of the patients developed lymphopenia. Severe lymphopenia (<500/µL) was documented in 11.4% of the patients. The CD4+ and CD8+ cell counts were significantly reduced by about 30.2 and 45.3%, respectively. Conclusion: To the best of our knowledge this is the largest clinical investigation analysing prospectively CD4+ and CD8+ cell counts in psoriasis patients receiving FAEs. We suggest periodic monitoring of absolute lymphocyte counts as well as the establishment of the determination of T-cell subsets prior to and during therapy.
Intensity-Modulated Radiotherapy Triggers Onset of Bullous Pemphigoid in a Patient with Advanced Melanoma Treated with Nivolumab
Authors: Tanita Kayo , Fujimura Taku , Kambayashi Yumi , Tsukada Akira , Sato Yota , Hashimoto Akira , Aiba Setsuya
Published: February 2018

Since the efficacy of ipilimumab on nivolumab-resistant advanced melanoma is extremely low, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma is needed. Although several supportive therapies that enhance the antitumor immune response of anti-PD-1 antibodies have already been reported, unexpected immune-related adverse events were detected at the same time. In this report, we describe a patient with advanced melanoma treated with nivolumab followed by intensity-modulated radiotherapy, which might have triggered bullous pemphigoid (BP). Although several cases of BP developing in anti-PD-1 antibody-treated patients have already been reported, in this report, we shed light on the possible pathogenesis of BP developing in a patient treated with nivolumab through M2 macrophages.
The LncRNA EPEL Promotes Lung Cancer Cell Proliferation Through E2F Target Activation
Authors: Park Seong-Min , Choi Eun-Young , Bae Dong-Hyuck , Sohn Hyun Ahm , Kim Seon-Young , Kim Youn-Jae
Published: February 2018

Background/Aims: Recent studies have revealed that many long non-coding RNAs (lncRNAs) play oncogenic or tumor-suppressive roles in various cancers. Lung cancer is the leading cause of cancer-related death worldwide, and many lung cancer patients frequently relapse after surgery, even those in the early stages. However, the oncogenic or tumor-suppressive roles and clinical implications of lncRNAs in lung cancer have not been fully elucidated. Methods: The association between an E2F-mediated cell proliferation enhancing lncRNA (EPEL) expression and lung cancer patient survival was accessed using public microarray data with clinical information. Cancer-related phenotypes were analyzed by the siRNA knockdown of EPEL in two lung cancer cell lines. Gene set analysis of gene expression data were performed to identify pathways regulated by EPEL. RNA immunoprecipitation, RT-qPCR, and ChIP assays were performed to explore the functions of selected target genes regulated by EPEL. Results: EPEL, known as LOC90768 and MGC45800, was associated with the relapse and survival of lung cancer patients and promoted lung cancer cell proliferation through the activation of E2F target genes. EPEL knockdown specifically down-regulated the expression of cell cycle-related E2F target genes, including Cyclin B1 (CCNB1), in lung cancer cells but not that of apoptosis- or metabolism-related E2F target genes. EPEL interacted with E2F1 and regulated the expression of the E2F target genes by changing the binding efficiency of E2F1 to the E2F target promoters. Moreover, the expression levels of EPEL and CCNB1 both alone and in combination were robust prognostic markers for lung cancer. Conclusions: Considering its specific effects on cell cycle-related E2F target genes and its significant association with the prognosis of lung cancer patients, we suggest that the transcriptional regulation of EPEL through E2F target genes is potentially a target for the development of novel therapeutic strategies for lung cancer patients.
Lipid-Lowering Therapy With Ezetimibe Decreases Spontaneous Atherothrombotic Occlusions in a Rabbit Model of Plaque Erosion
Authors: Honda Katsuya , Matoba Tetsuya , Antoku Yoshibumi , Koga Jun-ichiro , Ichi Ikuyo , Nakano Kaku , Tsutsui Hiroyuki , Egashira Kensuke
Published: February 2018

Objective—

Plaque erosion is increasing its importance as one of the mechanisms of acute coronary syndromes in this statin era. However, the clinical efficacy of currently used lipid-lowering agents in the prevention of thrombotic complications associated with plaque erosion has not been clarified. Therefore, we examined the therapeutic effects of ezetimibe or rosuvastatin monotherapy on spontaneous atherothrombotic occlusion.

Approach and Results—

Femoral arteries of Japanese white rabbits, fed a high-cholesterol diet, were injured by balloon catheter, and then angiotensin II was continuously administrated. In 94% of these arteries, spontaneous thrombotic occlusions were observed after 5 weeks (median) of balloon injury. Histochemical analyses indicated that the injured arteries had similar pathological features to human plaque erosions; (1) spontaneous thrombotic occlusion, (2) lack of endothelial cells, and (3) tissue factor expression in vascular smooth muscle cells. Ezetimibe (1.0 mg/kg per day), but not rosuvastatin (0.6 mg/kg per day), significantly decreased thrombotic occlusion of arteries accompanied with accelerated re-endothelialization and the decreases of serum oxysterols despite the comparable on-treatment serum cholesterol levels. The 7-ketocholesterol inhibited the migration of human umbilical vein endothelial cells. Both 7-ketocholesterol and 27-hydroxycholesterol increased tissue factor expression in cultured rat vascular smooth muscle cells. Tissue factor expression was also induced by serum from vehicle- or rosuvastatin-treated rabbits, but the induction was attenuated with serum from ezetimibe-treated rabbits.

Conclusions—

We have established a novel rabbit model of spontaneous atherothromobotic occlusion without plaque rupture that is feasible to test the therapeutic effects of various pharmacotherapies. Ezetimibe may decrease atherothrombotic complications after superficial plaque erosion by reducing serum oxysterols.
Inhibition of Endothelial NOTCH1 Signaling Attenuates Inflammation by Reducing Cytokine-Mediated Histone Acetylation at Inflammatory Enhancers
Authors: Poulsen Lars la Cour , Edelmann Reidunn Jetne , Krüger Stig , Diéguez-Hurtado Rodrigo , Shah Akshay , Stav-Noraas Tor Espen , Renzi Anastasia , Szymanska Monika , Wang Junbai , Ehling Manuel , Benedito Rui , Kasprzycka Monika , Bækkevold Espen , Sundnes Olav , Midwood Kim S. , Scott Helge , Collas Philippe , Siebel Christian W. , Adams Ralf H. , Haraldsen Guttorm , Sundlisæter Eirik , Hol Johanna
Published: February 2018

Objective—

Endothelial upregulation of adhesion molecules serves to recruit leukocytes to inflammatory sites and appears to be promoted by NOTCH1; however, current models based on interactions between active NOTCH1 and NF-κB components cannot explain the transcriptional selectivity exerted by NOTCH1 in this context.

Approach and Results—

Observing that Cre/Lox-induced conditional mutations of endothelial Notch modulated inflammation in murine contact hypersensitivity, we found that IL (interleukin)-1β stimulation induced rapid recruitment of RELA (v-rel avian reticuloendotheliosis viral oncogene homolog A) to genomic sites occupied by NOTCH1-RBPJ (recombination signal-binding protein for immunoglobulin kappa J region) and that NOTCH1 knockdown reduced histone H3K27 acetylation at a subset of NF-κB–directed inflammatory enhancers.

Conclusions—

Our findings reveal that NOTCH1 signaling supports the expression of a subset of inflammatory genes at the enhancer level and demonstrate how key signaling pathways converge on chromatin to coordinate the transition to an infla mmatory endothelial phenotype.
RGC-32 (Response Gene to Complement 32) Deficiency Protects Endothelial Cells From Inflammation and Attenuates Atherosclerosis
Authors: Cui Xiao-Bing , Luan Jun-Na , Dong Kun , Chen Sisi , Wang Yongyi , Watford Wendy T. , Chen Shi-You
Published: February 2018

Objective—

The objective of this study is to determine the role and underlying mechanisms of RGC-32 (response gene to complement 32 protein) in atherogenesis.

Approach and Results—

RGC-32 was mainly expressed in endothelial cells of atherosclerotic lesions in both ApoE
−/−
(apolipoprotein E deficient) mice and human patients.
Rgc
-32 deficiency (
Rgc32
−/−
) attenuated the high-fat diet–induced and spontaneously developed atherosclerotic lesions in ApoE
−/−
mice without affecting serum cholesterol concentration.
Rgc32
−/−
seemed to decrease the macrophage content without altering collagen and smooth muscle contents or lesional macrophage proliferation in the lesions. Transplantation of WT (wild type) mouse bone marrow to lethally irradiated
Rgc32
−/−
mice did not alter
Rgc32
−/−
-caused reduction of lesion formation and macrophage accumulation, suggesting that RGC-32 in resident vascular cells, but not the macrophages, plays a critical role in the atherogenesis. Of importance,
Rgc32
−/−
decreased the expression of ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) in endothelial cells both in vivo and in vitro, resulting in a decrease in TNF-α (tumor necrosis factor-α)–induced monocyte–endothelial cell interaction. Mechanistically, RGC-32 mediated the ICAM-1 and VCAM-1 expression, at least partially, through NF (nuclear factor)-κB signaling pathway. RGC-32 directly interacted with NF-κB and facilitated its nuclear translocation and enhanced TNF-α–induced NF-κB binding to ICAM-1 and VCAM-1 promoters.

Conclusions—

RGC-32 mediates atherogenesis by facilitating monocyte–endothelial cell interaction via the induction of endothelial ICAM-1 and VCAM-1 expression, at least partially, through NF-κB signaling pathway.
Endothelial Cell Autonomous Role of Akt1
Authors: Lee Monica Y. , Gamez-Mendez Ana , Zhang Jiasheng , Zhuang Zhenwu , Vinyard David J. , Kraehling Jan , Velazquez Heino , Brudvig Gary W. , Kyriakides Themis R. , Simons Michael , Sessa William C.
Published: February 2018

Objective—

The importance of PI3K/Akt signaling in the vasculature has been demonstrated in several models, as global loss of Akt1 results in impaired postnatal ischemia- and VEGF-induced angiogenesis. The ubiquitous expression of Akt1, however, raises the possibility of cell-type–dependent Akt1-driven actions, thereby necessitating tissue-specific characterization.

Approach and Results—

Herein, we used an inducible, endothelial-specific Akt1-deleted adult mouse model (Akt1iECKO) to characterize the endothelial cell autonomous functions of Akt1 in the vascular system. Endothelial-targeted ablation of Akt1 reduces eNOS (endothelial nitric oxide synthase) phosphorylation and promotes both increased vascular contractility in isolated vessels and elevated diastolic blood pressures throughout the diurnal cycle in vivo. Furthermore, Akt1iECKO mice subject to the hindlimb ischemia model display impaired blood flow and decreased arteriogenesis.

Conclusions—

Endothelial Akt1 signaling is necessary for ischemic resolution post-injury and likely reflects the consequence of NO insufficiency critical for vascular repair.
Disharmonious Patterns of Heterotaxy and Isomerism
Authors: Yim Deane , Nagata Hazumu , Lam Christopher Z. , Grosse-Wortmann Lars , Seed Mike , Jaeggi Edgar , Yoo Shi-Joon
Published: February 2018

Background—

It is advocated that heterotaxy should be segregated into right or left isomerism according to atrial appendage morphology. However, atrial situs determination is often based on the pattern of associated findings rather than on atrial morphology itself, which can be difficult to define. The objective was to assess how often concordant patterns of isomerism classified by atrial appendage morphology, bronchopulmonary pattern, and splenic status are breached using cardiac magnetic resonance or computed tomography. The secondary objective was to determine the feasibility of defining atrial appendage morphology using cardiac magnetic resonance or computed tomography.

Methods and Results—

Retrospective review of 114 pediatric patients (median, 2.4 years; range, 1 day–17.9 years) with heterotaxy who underwent cardiac magnetic resonance or computed tomography was performed to evaluate atrial appendage, bronchopulmonary, and visceral organ arrangements. Atrial appendage and splenic anatomy were not definable in 17 of 114 (15%) and 4 of 114 (3.5%) patients, respectively. In the remaining 93 patients, 39% had classic right isomerism (bilateral right atrial appendages, right bronchopulmonary pattern, and asplenia) and 40% had classic left isomerism (bilateral left atrial appendages, left bronchopulmonary pattern, and polysplenia). Classic pattern of isomerism was breached in 20 of 93 (21.5%) patients: 13 (65%) displayed incongruent abdominal situs, 5 (25%) incongruent bronchial situs, 1 (5%) had discrepant appendage morphology, and 1 (5%) incongruent situs at all levels.

Conclusions—

Atrial appendage morphology is difficult to assess and not always indicative of bronchopulmonary or abdominal situs. Discordance between bronchopulmonary branching, atrial appendage arrangement, and splenic status was identified in >20% patients with heterotaxy. Independent description of each organ system is required when arrangements are disharmonious among different organ systems.
Retroperitoneal Hemorrhage After Percutaneous Coronary Intervention
Authors: Kwok Chun Shing , Kontopantelis Evangelos , Kinnaird Tim , Potts Jessica , Rashid Muhammad , Shoaib Ahmad , Nolan James , Bagur Rodrigo , de Belder Mark A. , Ludman Peter , Mamas Mamas A.
Published: February 2018

Background—

Retroperitoneal hemorrhage (RH) is a rare bleeding complication of percutaneous coronary intervention, which can result as a consequence of femoral access or can occur spontaneously. This study aims to evaluate temporal changes in RH, its predictors, and clinical outcomes in a national cohort of patients undergoing percutaneous coronary intervention in the United Kingdom.

Methods and Results—

We analyzed RH events in patients who underwent percutaneous coronary intervention between 2007 and 2014. Multiple logistic regression models were used to identify factors associated with RH and to quantify the association between RH and 30-day mortality and major adverse cardiovascular events. A total of 511 106 participants were included, and 291 in hospital RH events were recorded (0.06%). Overall, rates of RH declined from 0.09% to 0.03% between 2007 and 2014. The strongest independent predictors of RH events were femoral access (odds ratio [OR], 19.66; 95% confidence interval [CI], 11.22–34.43), glycoprotein IIb/IIIa inhibitor (OR, 2.63; 95% CI, 1.99–3.47), and warfarin use (OR, 2.53; 95% CI, 1.07–5.99). RH was associated with a significant increase in 30-day mortality (OR, 3.59; 95% CI, 2.19–5.90) and in-hospital major adverse cardiovascular events (OR, 5.76; 95% CI, 3.71–8.95). A legacy effect was not observed; patients with RH who survived 30 days did not have higher 1-year mortality compared with those without this complication (hazard ratio, 0.97; 95% CI, 0.49–1.91).

Conclusions—

Our results suggest that RH is a rare event that is declining in the United Kingdom, related to transition to transradial access site utilization, but remains a clinically important event associated with increased 30-day mortality but no long-term legacy effect.
Bibliography of Studies on Women and Gender in China since 2008
Authors: Yates Robin D.S. , Cai Danni
Published: February 2018

This bibliography is an update of Women in China from Earliest Times to the Present: A Bibliography of Studies in Western Languages, published in 2009 by Brill. It includes more than 1500 items in multiple disciplines that have been published in Western languages, primarily English, in a wide variety of venues, in journals, monographs and edited and co-edited volumes, but generally not entries in encyclopedias or chapters in textbooks. Included are a few important items from 2008 and earlier that were missed in the previous version. It does not include online websites and databases that are becoming increasingly important resources for scholarship.
Ten Chinese Books That Changed Our View of Women’s History
Authors: Hinsch Bret
Published: February 2018

Scholars of Chinese women’s history in the West have often ignored the scholarship of their colleagues in China. For much of the twentieth century, Chinese academia was in chaos. With so little good research coming out of China, Western scholars became accustomed to ignoring the works of Chinese academics. Since the 1980s, however, Chinese scholarship has steadily improved, reaching international standards of quality. Chinese scholars remain highly influenced by their rich intellectual legacy. A post-Marxist mindset makes them extremely sensitive to the importance of social class. And the study of imperial philology has taught them the importance of textual criticism and close reading. This article discusses ten representative Chinese books covering different eras of women’s history, which exemplify the contributions that Chinese scholars are currently making to the field.
An Individual’s Endeavour to Save Sino-Japanese Relations. A Discussion of Wang Tao’s (1828-1897) Travel to Japan based on his Travel Diary
Authors: Tsui Wai
Published: February 2018

In the spring of 1879, while the relations between Japan and China was deteriorated by a series of disputes in Korea, Taiwan and the Ryukyu Islands, Wang Tao 王韜 (1828-1897), a Chinese scholar, was invited by a group of prominent Japanese intellectuals, including Kurimoto Joun 栗本鋤雲 (1822-1897), Shigeno Yasutsugu 重野安繹 (1827-1910), Nakamura Masanao 中村正直 (1832-1890), and Oka Senjin 岡千仭 (1833-1914), to travel to Japan, exchanging ideas of reform and discussing the crises of Asian countries with increasing Western invasions. Wang Tao was warmly welcomed as an expert of both Chinese Classics and international affairs. Having the objectives of finding out more about the Meiji Japan and promoting friendship and strategic relations between the two countries, Wang and his hosts inevitably started a discussion on modernization, Westernization and future development of the two neighbouring countries. This was a significant intellectual exchange among Chinese and Japanese men of letters in modern history. During his visit, Wang recorded his journey in Fusang youji 扶桑遊記 (A Travel to Japan). Upon returning to China, Wang presented his diary to Kurimoto Joun and the book was published by Yūbin Hōchi, a leading news printing press in Japan.

Although there are research outlining Wang Tao’s travel to Japan, its significance, especially Wang’s vision of the future development of Sino-Japanese relation has not been fully analysed. His travel diary, an important source to reveal Wang’s thought, has only been seen as a record of travel itinerary and personal romance. In fact, his senses of history and knowledge in current affairs have reminded him the threat of an ambitious Japan. He, therefore, endeavoured to rebuild and maintain the link between the two countries from historic, cultural and strategic aspects during his journey. This paper aims to examine how Wang Tao conveyed his messages in inoffensive but effective ways in his travel diary.
Diphyllobothrium stemmacephalum Cobbold, 1858 (Diphyllobothriidea) from common bottlenose dolphin, Tursiops truncatus (Montagu) from the Texas Gulf coast, USA
Authors: SÁNCHEZ SOPHIA M. , GOLDSTEIN LIAT Y. , DRONEN NORMAN O.
Published: February 2018

Cobbold (1858) established Diphyllobothrium Cobbold, 1858 with the description of Diphyllobothrium stemmacephalum Cobbold, 1858 from the common harbor porpoise, Phocoena phocoena (Linnaeus) (Phocoenidae), from the North Sea off Scotland. Diphyllobothrium stemmacephalum typically has been reported from a number of Phocoenidae and Delphinidae hosts from a variety of localities: common harbor porpoise from the northern Atlantic Ocean, Baltic Sea and Black sea (e.g. Cobbold, 1858; Delyamure 1955; Delyamure 1968; Delyamure 1971; Delyamure et al. 1985; Anderson, 1987); bottlenose dolphin, Tursiops truncatus (Montagu), from the Gulf of Mexico (Ward & Collins 1959), the Black sea (Delyamure et al. 1985); common harbor porpoise off Newfoundland (Brattey & Stenson 1995), the Black Sea (Krivokhizin & Birkun 1994 [see Yera et al. 2008]), off Denmark (Herreras et al. 1997); long-finned pilot whale, Globicephala melas [Traill], North Atlantic off Faroe Island (Balbuena & Raga 1993); Atlantic white-sided dolphin, Lagenorhynchus acutus [Gray], off Massachusetts (Olson & Caira 1999).
Socoflata gen. nov., described for two new planthopper species from the mountains in Socotra island (Hemiptera: Fulgoromorpha: Flatidae)
Authors: STROIŃSKI ADAM , MALENOVSKÝ IGOR , ŚWIERCZEWSKI DARIUSZ
Published: February 2018

A new genus of flatid planthoppers (Hemiptera: Fulgoromorpha: Flatidae) is described from the island of Socotra (Yemen): Socoflata gen. nov., for S. aurolineata sp. nov. and S. histrionica sp. nov. (type species). Habitus, male and female external and internal genital structures of the new species are illustrated and diagnosed. Both Socoflata species are abundant and syntopic in the evergreen montane woodland and dwarf shrubland at high elevations in the Hagher mountains in central Socotra and are likely endemics of this area.