bluuebunny/crossref_metadata_2025 huggingface dataset:
Intensive care management of a patient with necrotizing fasciitis due to non-O1/O139 Vibrio cholerae after traveling to Taiwan: a case report
Authors: Tsuruta Keisuke , Ueyama Toru , Watanabe Tomoo , Nakano Kenichi , Uno Kenji , Fukushima Hidetada
Published: August 2020

Background

Vibrio cholerae are oxidase-positive bacteria that are classified into various serotypes based on the O surface antigen. V. cholerae serotypes are divided into two main groups: the O1 and O139 group and the non-O1/non-O139 group. O1 and O139 V. cholerae are related to cholera infection, whereas non-O1/non-O139 V. cholerae (NOVC) can cause cholera-like diarrhea. A PubMed search revealed that only 16 cases of necrotizing fasciitis caused by NOVC have been recorded in the scientific literature to date. We report the case of a Japanese woman who developed necrotizing fasciitis caused by NOVC after traveling to Taiwan and returning to Japan.

Case presentation

A 63-year-old woman visited our hospital because she had experienced left knee pain for the past 3 days. She had a history of colon cancer (Stage IV: T3N3 M1a) and had received chemotherapy. She had visited Taiwan 5 days previously, where she had received a massage. She was diagnosed with septic shock owing to necrotizing fasciitis. She underwent fasciotomy and received intensive care. She recovered from the septic shock; however, after 3 weeks, she required an above-knee amputation for necrosis and infection. Her condition improved, and she was discharged after 22 weeks in the hospital.

Conclusions

With the increase in tourism, it is important for clinicians to check patients’ travel history. Clinicians should be alert to the possibility of necrotizing fasciitis in patients with risk factors. Necrotizing fasciitis caused by NOVC is severe and requires early fasciotomy and debridement followed by intensive postoperative care.
Complete remission of nephrotic syndrome in a young woman with anti-LRP2 nephropathy after immunosuppressive therapy
Authors: Zhu Xiaoye , Tu Lingxue , Liu Shaojun , You Huaizhou , Xue Jun , Hao Chuanming
Published: August 2020

Background

Anti-low density lipoprotein receptor-related protein 2 (LRP2) nephropathy/anti-brush border antibody (ABBA) disease is a disorder characterized by acute tubulointerstitial injury associated with circulating antibodies to kidney proximal tubular brush border protein LRP2/megalin. Patients are typically elderly and present with acute kidney injury and subnephrotic proteinuria. They progress to end-stage renal disease with poor response to immunosuppressive therapies.

Case presentation

We report a case of a 29-year-old Chinese woman, who presented with nephrotic syndrome with normal kidney function. Kidney biopsy showed no obvious tubular injury or interstitial inflammation. Positive immunoglobulin G (IgG) staining was revealed along the brush border of proximal tubular cells. Anti-LRP2 antibody was identified in serum, consistent with a diagnosis of anti-LRP2 nephropathy. The patient achieved complete remission after receiving prednisone and cyclophosphamide.

Conclusions

Anti-LRP2 nephropathy can also present as nephrotic syndrome in young patients and complete remission from nephrotic syndrome may be achieved after immunosuppressive therapy.
Quality assurance assessment of a specialized perinatal mental health clinic
Authors: Caropreso Luisa , Saliba Sarah , Hasegawa Lindsay , Lawrence Jack , Davey Caitlin J. , Frey Benicio N.
Published: August 2020

Background

Mood and anxiety issues are the main mental health complaints of women during pregnancy and the postpartum period. Services targeting such women can reduce perinatal complications related to psychiatric difficulties. This quality assurance project aimed to examine changes in mood and anxiety symptoms in pregnant and postpartum women referred to the Women’s Health Concerns Clinic (WHCC), a specialized outpatient women’s mental health program.

Methods

We extracted patient characteristics and service utilization from electronic medical records of women referred between 2015 and 2016. We also extracted admission and discharge scores on the Edinburgh Postnatal Depression Scale (EPDS) and the Generalized Anxiety Disorder-7 (GAD-7) scale.

Results

Most patients accessed the WHCC during pregnancy (54%), had a diagnosis of major depressive disorder (54.9%), were prescribed a change in their medication or dose (61.9%), and accessed psychotherapy for perinatal anxiety (30.1%). There was a significant decrease in EPDS scores between admission and discharge (t(214) = 11.57; p = .000; effect size d = .86), as well as in GAD-7 scores (t(51) = 3.63; p = .001; effect size d = .61). A secondary analysis showed that patients with more severe depression and anxiety symptoms demonstrated even greater effect sizes.

Conclusions

Changes in EPDS and GAD-7 scores indicate that the WHCC is effective in reducing mood and anxiety symptoms associated with the perinatal period. This project highlights the importance of quality assurance methods in evaluating the effectiveness of clinical services targeting perinatal mental health, in order to inform policy and funding strategies.
OTX1 exerts an oncogenic role and is negatively regulated by miR129-5p in laryngeal squamous cell carcinoma
Authors: Tu Xiu-Ping , Li Hao , Chen Liang-Si , Luo Xiao-Ning , Lu Zhong-Ming , Zhang Si-Yi , Chen Shao-Hua
Published: August 2020

Background

Orthodenticle homeobox 1 (OTX1) is a transcription factor that plays an important role in various human cancers. However, the function of OTX1 in laryngeal squamous cell carcinoma (LSCC) is largely unknown. We aimed to explore the roles of OTX1 in LSCC and its possible molecular mechanism.

Methods

The expression levels of OTX1 were assessed in LSCC cell lines and tissue samples. We further examined the effect of OTX1 on LSCC progression. The upstream regulator of OTX1 was identified using a computer algorithm and confirmed experimentally.

Results

OTX1 was highly expressed in 70.7% (70/99) of LSCC tissue samples. The OTX1 expression in LSCC was significantly correlated with lymph node metastasis. High OTX1 expression in patients with LSCC was correlated with poor prognosis. Knockdown of OTX1 inhibited proliferation, colony formation, migration and invasion in LSCC cells. Knockdown of OTX1 inhibited tumor growth in a xenograft mouse model. Mechanistically, OTX1 might act as a direct target of miR-129-5p. OTX1 enhanced tumorigenicity and tumor growth both in vitro and in vivo.

Conclusions

Our findings support that OTX1 is an oncogene in LSCC tumorigenesis and progression. Furthermore, OTX1 is a direct target of miR-129-5p in LSCC cells. Taken together, OTX1 is a promising diagnostic and therapeutic marker for LSCC.
Sphingomyelin(d35:1) as a novel predictor for lung adenocarcinoma recurrence after a radical surgery: a case-control study
Authors: Takanashi Yusuke , Funai Kazuhito , Sato Shumpei , Kawase Akikazu , Tao Hong , Takahashi Yutaka , Sugimura Haruhiko , Setou Mitsutoshi , Kahyo Tomoaki , Shiiya Norihiko
Published: August 2020

Background

To improve the postoperative prognosis of patients with lung cancer, predicting the recurrence high-risk patients is needed for the efficient application of adjuvant chemotherapy. However, predicting lung cancer recurrence after a radical surgery is difficult even with conventional histopathological prognostic factors, thereby a novel predictor should be identified. As lipid metabolism alterations are known to contribute to cancer progression, we hypothesized that lung adenocarcinomas with high recurrence risk contain candidate lipid predictors. This study aimed to identify candidate lipid predictors for the recurrence of lung adenocarcinoma after a radical surgery.

Methods

Frozen tissue samples of primary lung adenocarcinoma obtained from patients who underwent a radical surgery were retrospectively reviewed. Recurrent and non-recurrent cases were assigned to recurrent (n = 10) and non-recurrent (n = 10) groups, respectively. Extracted lipids from frozen tissue samples were subjected to liquid chromatography-tandem mass spectrometry analysis. The average total lipid levels of the non-recurrent and recurrent groups were compared. Candidate predictors were screened by comparing the folding change and P-value of t-test in each lipid species between the recurrent and non-recurrent groups.

Results

The average total lipid level of the recurrent group was 1.65 times higher than that of the non-recurrent group (P < 0.05). A total of 203 lipid species were increased (folding change, ≥2; P < 0.05) and 4 lipid species were decreased (folding change, ≤0.5; P < 0.05) in the recurrent group. Among these candidates, increased sphingomyelin (SM)(d35:1) in the recurrent group was the most prominent candidate predictor, showing high performance of recurrence prediction (AUC, 9.1; sensitivity, 1.0; specificity, 0.8; accuracy, 0.9).

Conclusion

We propose SM(d35:1) as a novel candidate predictor for lung adenocarcinoma recurrence. Our finding can contribute to precise recurrence prediction and qualified postoperative therapeutic strategy for lung adenocarcinomas.

Trial registration

This retrospective study was registered at the UMIN Clinical Trial Registry (UMIN000039202) on 21st January 2020.
Correction to: Effectiveness of mobile SMS based counselling intervention in improving knowledge, attitude and practices of HIV/AIDS patients enrolled in hospitals/NGOs in Terengganu, Malaysia: a mixed mode study protocol
Authors: Hossain Md Mosharaf , Min Ruhani Mat , Muhammad Zikri , Mani Kulanthayan K. C.
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Experiences of sexual health in persons with hip and knee osteoarthritis: a qualitative study
Authors: Nilsing Strid Emma , Ekelius-Hamping Marie
Published: August 2020

Background

Osteoarthritis (OA) is the world’s most common form of arthritis and a common cause of musculoskeletal pain and disability. Persons living with chronic diseases often have affected sexual health because of pain and limited function. Osteoarthritis is a chronic disease but there is scarce knowledge about how sexual health is experienced. The aim of this study was to explore the experience of sexual health in persons who have seen a physiotherapist for their hip and/or knee OA.

Methods

This study has a qualitative design. Participants were recruited from the Swedish Quality Register Better Management of Patients with Osteoarthritis (BOA). To reach a variety of experiences and strengthen credibility, a purposeful sampling strategy based on age, sex and hip and knee OA was used. Semi-structured telephone interviews were held with 20 persons with hip and/or knee OA. Data were analysed with qualitative content analysis and inductive category development was applied.

Results

The analysis resulted in two main categories. The first category, Individual differences in how sexual health is affected by hip and knee OA, comprises of two sub categories: Pain limits sexual health; and Strategies for sexual health in the relationship. The second main category, Varying needs for communication about sexual health, is supported by the sub categories: Physiotherapists do not ask about sexual health; and Relevance of communicating about sexual health.

Conclusions

Painful hip and knee OA limit sexual health to varying degrees, and individuals make adjustments or develop strategies to maintain sexual life. Sexual health is not talked about during consultations with physiotherapists or other health care professionals, indicating that patients with OA may have unmet needs regarding their sexual health. Further research is needed on how to provide support and information about sexual health in OA.
Collaborative advance care planning in advanced cancer patients: col-ACP –study – study protocol of a randomised controlled trial
Authors: Seifart Carola , Koch Martin , Leppin Nico , Nagelschmidt Katharina , Knorrenschild Jorge Riera , Timmesfeld Nina , Rief Winfried , von Blanckenburg Pia
Published: August 2020

Background

To assure patient-centred end-of-life care, palliative interventions need to account for patients’ preferences. Advance care planning (ACP) is a structured approach that allows patients, relatives and physicians to discuss end-of-life decisions. Although ACP can improve several patient related outcomes, the implementation of ACP remains difficult. The col-ACP-study (collaborative advance care planning) will investigate a new ACP procedure (col-ACP-intervention (German: Hand-in-Hand Intervention)) in palliative cancer patients and their relatives that addresses individual values and targets barriers of communication before an ACP process.

Methods

In a randomised controlled trial, 270 cancer patients without curative treatment options and their relatives will receive either 1) col-ACP 2) a supportive intervention (active control group) or 3) standard medical care (TAU). col-ACP comprises two steps: a) addressing various barriers of patients and relatives that discourage them from discussing end-of-life issues followed by b) a regular, structured ACP procedure. The col-ACP-intervention consists of 6 sessions. Primary endpoint is the patients’ quality of life 16 weeks after randomisation. Secondary endpoints include measurements of distress; depression; communication barriers; caregivers’ quality of life; existence of ACP or advance directives; the consistence of end of life care; and others. Patients will be followed up for 13 months. Multivariate analyses will be carried out. Qualitative evaluation of the intervention will be conducted.

Discussion

Augmentation of a regular ACP program by a structured psycho-oncological intervention is an innovative approach to target barriers of communication about end-of-life issues. Study findings will help to understand the value of such a combined intervention in palliative care.

Trial registration

ClinicalTrials.gov Identifier: NCT03387436 (Date of registration: 01/02/2018, retrospectively registered.
A prospective study evaluating the integration of a multifaceted evidence-based medicine curriculum into early years in an undergraduate medical school
Authors: Kumaravel B. , Jenkins H. , Chepkin S. , Kirisnathas S. , Hearn J. , Stocker C. J. , Petersen S.
Published: August 2020

Background

The importance of ensuring medical students are equipped with the skills to be able to practice evidence-based medicine (EBM) has been increasingly recognized in recent years. However, there is limited information on an effective EBM curriculum for undergraduate medical schools. This study aims to test the feasibility of integrating a multifaceted EBM curriculum in the early years of an undergraduate medical school. This was subsequently evaluated using the validated Fresno test and students’ self-reported knowledge and attitudes as they progressed through the curriculum.

Methods

EBM was integrated horizontally and vertically into the curriculum into the first 2 years of undergraduate medical school. First year medical students were recruited to participate in the study. The 212-point Fresno test was administered along with a locally developed questionnaire at baseline before EBM teaching in year one and at the end of EBM teaching in year two.

Results

Thirty-one students participated at baseline and 55 students participated at the end of second year EBM teaching. For the 18 students who completed the Fresno at both time points, the average score increased by 38.7 marks (p < 0.001) after EBM teaching. Students felt confident in formulating clinical questions and in critically appraising journal articles after EBM teaching. EBM was perceived to be important to their future practice as a doctor and for improving patient outcomes at both time points.

Conclusions

It has been feasible to integrate a multifaceted, EBM curriculum from the first year of an undergraduate medical program. Early evaluation of the curriculum using the Fresno test has shown a significant increase in students’ EBM knowledge. The curriculum also demonstrated an increase in students’ perceptions of the clinical relevance of EBM in their developing practice.
An empirical study on the determinants of health care expenses in emerging economies
Authors: Zhou Lulin , Ampon-Wireko Sabina , Asante Antwi Henry , Xu Xinglong , Salman Muhammad , Antwi Maxwell Opuni , Afua Tordzro Mary Norvienyo
Published: August 2020

Background

Emerging countries continue to suffer gravely from insufficient healthcare funding, which adversely affects access to quality healthcare and ultimately the health status of citizens. By using panel data from the World Development Indicators, the study examined the determinants of health care expenditure among twenty-two (22) emerging countries from the year 2000 to 2018.

Methods

The study employed cross-section dependence and homogeneity tests to confirm cross-sectional dependence and to deal with homogeneity issues. The Quantile regression technique is employed to test for the relationship between private and public health care expenses and its determinants. The Pooled mean group causality test is used to examine the causal connections among the variables.

Results

The outcome of the quantile regression test revealed that economic growth and aging population could induce healthcare costs in emerging countries. However, the impact of industrialization, agricultural activities, and technological advancement on health expenses are found to be noticeably heterogeneous at the various quantile levels. Unidirectional causality was found between industrialization and public health expenses; whereas two-way causal influence was reveled amongst public health expenditure and GDP per capita; public health expenditure and agricultural activities.

Conclusion

It is therefore suggested that effective and integrated strategies should be considered by industries and agricultural sectors to help reduce preventable diseases that will ultimately reduce healthcare costs among the emerging countries.
Total injectable anesthesia of dogs and cats for remote location veterinary sterilization clinic
Authors: Posner Lysa Pam , Applegate Jeffrey , Cannedy Allen , Deresienski Diane , Mozzachio Kristie , Serrano Maria , Lewbart Gregory
Published: August 2020

Background

Sterilization clinics often occur in remote places where anesthesia machines and compressed oxygen are unavailable. This study describes the use of total injectable anesthesia in dogs and cats presented for sterilization in a remote location.

Results

A total of 100 animals were sterilized; 26 female cats (CF), 22 male cats (CM), 28 female dogs (DF), and 24 male dogs (DM). CF were anesthetized with dexmedetomidine (20 mcg/kg), ketamine (8 mg/kg) and hydromorphone (0.1 mg/kg) IM. CM were anesthetized with dexmedetomidine (15 mcg/kg), ketamine (5 mg/kg) and hydromorphone (0.1 mg/kg) IM. Insufficient anesthesia in cats was treated with alfaxalone (1 mg/kg) IM. All cats were administered meloxicam at 0.3 mg/kg SQ. DF were anesthetized with dexmedetomidine (15 mcg/kg), ketamine (7–10 mg/kg) and hydromorphone (0.1 mg/kg) IM. DM were anesthetized with dexmedetomidine (15 mcg/kg), ketamine (5 mg/kg) and hydromorphone (0.1 mg/kg) IM. All dogs had IV catheter and endotracheal tube placed. If SpO2 < 91%, ventilation was assisted with an Ambu bag. Insufficient anesthesia in dogs was treated with alfaxalone (1 mg/kg) IV. All dogs were administered meloxicam at 0.2 mg/kg SQ. Following surgery, atipamezole (0.05–0.1 mg/kg) IM was administered to any patient that did not have voluntary movement. All patients survived and were discharged. Less than 25% of cats and male dogs required supplemental anesthesia. Fifty seven percent of female dogs required supplemental anesthesia. More than 89% of patients (in any group) required atipamezole administration. One cat recovered with agitation and hyperthermia (41.1C/ 106F). Some dogs required ventilatory assistance to remain normoxemic while anesthetized.

Conclusion

Total injectable anesthesia can be accomplished for remote location sterilization clinics with minimal morbidity.
Upregulated 5-HT1A receptor-mediated currents in the prefrontal cortex layer 5 neurons in the 15q11–13 duplication mouse model of autism
Authors: Saitow Fumihito , Takumi Toru , Suzuki Hidenori
Published: August 2020

Serotonin (5-HT) is a well-known modulator of behavioral, physiological, and emotional functions of the forebrain region. We recently discovered alterations of serotonergic synaptic modulations in both, the prefrontal cortex (PFC) and the somatosensory cortex, in the 15q dup mouse model of autism spectrum disorder (ASD). To further understand the roles of the 5-HT system implicated in developmental disorders such as ASD, comparison with model animals exhibiting different phenotypes may be useful. In this study, we investigated the relationship between sociability and the magnitude of 5-HT1A receptor (5-HT1AR) activation-induced outward currents from layer 5 pyramidal neurons in the PFC, because a mouse model of Williams-Beuren syndrome (WBS; another developmental disorder exhibiting low innate anxiety and high sociability) reportedly showed larger 5-HT-induced currents. To investigate whether the 5-HT1AR activation-induced outward currents are involved in the endophenotype determination of social behavior, we examined 15q dup mice with a phenotype opposite to WBS. We found 5-HT elicited significantly larger outward currents in 15q dup mice than in WT controls, regardless of sociability. In contrast, baclofen-induced GABAB receptor-mediated outward currents were not significantly different between genotypes, although GABAB receptor was coupled to Gi/o as well as 5-HT1A. Further, we found the larger 5-HT1AR-mediated currents in 15q dup mice did not affect the magnitude of inhibitory action of NMDA receptor functions. Taken together, our results provide a potential physiological hallmark for developmental disorders that may involve the imbalance of the neuronal circuity in the PFC.
History of global burden of disease assessment at the World Health Organization
Authors: Mathers Colin D.
Published: August 2020

Background

The World Health Organization collaborated in the first Global Burden of Disease Study (GBD), published in the 1993 World Development Report. This paper summarizes the substantial methodological improvements and expanding scope of GBD work carried out by WHO over the next 25 years.

Methods

This review is based on a review of WHO and UN interagency work relating to Global Burden of Disease over the last 20 years, supplemented by a literature review of published papers and commentaries on global burden of disease activities and the production of global health statistics.

Results

WHO development of global burden of disease work in the Millenium Development Goal era resulted in regular publication of time series estimates of deaths by cause, age and sex at country level, consistent with UN population and life table estimates, and with cause-specific statistics produced across UN agencies and interagency collaborations. This positioned WHO as the lead agency to monitor many of the 43 health-related indicators for the UN Sustainable Development Goals.

In 2007, the Institute of Health Metrics and Evaluation (IHME) was established to conduct new global burden of disease and related work, funded by the Bill and Melinda Gates Foundation (BMGF). WHO was a core collaborator in its first GBD2010 study, but withdrew prior to publication as it was unable to obtain full access input data and methods. The publication of global health statistics by IHME resulted in user confusion and in debate over differences and the reasons for them. The new WHO administration of Director General Dr. Tedros Ghebreyesus has sought to make greater use of IHME outputs for its global health statistics and SDG monitoring.

Conclusions

WHO work on global burden of disease has positioned it to be the lead agency for monitoring many of the UN Sustainable Development Goals. Current moves to use IHME analyses raises a number of issues for WHO and for Member States in relation to WHO’s constitutional mandate, its accountability to Member States, the consistency of WHO and UN demographic and health statistics, and the ability of Member States to engage with the results of the complex and computer-intensive modelling procedures used by IHME. As new global health actors and funders have arisen in recent decades, and funding to carry out WHO’s expanding mandate has declined, it is unclear whether WHO has the ability or desire to continue as the lead agency for global health statistics.
Comparison of correction factor for both dynamic total thermal insulation and evaporative resistance between ISO 7933 and ISO 9920
Authors: Ueno Satoru
Published: August 2020

Background

Thermal insulation and evaporative resistance of clothing are the physical parameters to quantify heat transfer and evaporative dissipation from the human body to the environment, respectively. Wind and body movement decrease thermal insulation and evaporative resistance of clothing, which is represented as correction factors for dynamic total thermal insulation (CFi) and evaporative resistance (CFe), respectively. Then, CFi and CFe are parts of the key parameters to predict heat strain of workers by computer simulation. The objective of this study was to elucidate the difference of CFi and CFe between ISO 7933 and ISO 9920 and compare the difference of predicted rectal temperature, water loss, and exposure time limit calculated by using each correction factor.

Methods

CFi of ISO 7933 (CFi7933) and ISO 9920 (CFi9920), and CFe of ISO 7933 (CFe7933) and two kinds of CFe of ISO 9920 (CFe9920a, CFe9920b) were compared in terms of relative air velocity, walking speed for three kinds of thermal insulation of clothing. Next, two modified predicted heat strain (PHS) models were developed: modified PHS integrated with CFi9920 and CFe9920a (PHSmA) and modified PHS integrated with CFi9920 and CFe9920b (PHSmB). We calculated the rectal temperature, water loss, and exposure time limit by PHS, PHSmA, and PHSmB and compared the results.

Results

CFi7933 and CFi9920 were almost similar in terms of Var and walking speed, while CFe9920a and CFe9920b were larger than CFe7933 when Var was more than 1.0 m·s−1. Intrinsic clothing insulation (Icl) diminished the effects of Var on CFi7933, CFi9920, CFe7933, and CFe9920b. However, CFe9920a was not influenced by Icl. The predicted rectal temperature and water loss difference were larger between PHS and PHSmA as CFe difference got larger. The duration time when limit of rectal temperature of 38 °C was reached (DlimTre38) calculated by PHS was significantly longer than PHSmA, PHSmB at higher Var.

Conclusions

Precise correction factors for evaporative resistance are required to predict rectal temperature, water loss, and work-time limits.
An unusual presentation of an extragastrointestinal stromal tumour: a case report
Authors: Oliveira Santos Pedro , Cunha Teresa Margarida , Lemos Maria Manuel
Published: August 2020

Background

Gastrointestinal stromal tumours (GISTs) account for most mesenchymal gastrointestinal tumours, which in turn represent 1% of all gastrointestinal cancers. They mainly affect older adults, with a slight male preponderance. These lesions can be found along the digestive tract and most frequently in the stomach. Extragastrointestinal stromal tumours (EGISTs) are even rarer lesions, with few cases or series reported.

Case presentation

A 51-year-old woman was referred to our hospital due to progressive abdominal volume increase. Evaluation by multidetector computed tomography (MDCT) revealed a large intraperitoneal mixed tumour with few solid components, measuring up to 30 cm and compressing the surrounding structures, thought to be an ovarian tumour. Diagnostic laparotomy showed that the lesion was adherent to the greater gastric curvature and the vesical peritoneum. The lesion was removed without complications.

Conclusions

Imaging plays an essential role in the diagnosis of large intraperitoneal tumours. MDCT is the preferred technique to stage and to follow-up EGISTs.
Clinical features of adolescents diagnosed with eating disorders and at risk for psychosis
Authors: Mensi Martina Maria , Rogantini Chiara , Nacinovich Renata , Riva Anna , Provenzi Livio , Chiappedi Matteo , Balottin Umberto , Borgatti Renato
Published: August 2020

Background.

The presence of subthreshold psychotic symptoms in adolescents with eating disorders is poorly described. This study provides a detailed characterization of adolescents affected by eating disorders in the absence or presence of subthreshold psychotic symptoms, taking into account a wide set of sociodemographic, psychological, and clinical variables.

Methods.

Ninety-four adolescents diagnosed with eating disorders were interviewed, focusing on clinical anamnesis and sociodemographic data collection. The Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to assess the presence (HR+) or absence (HR−) of subthreshold psychosis. The clinicians completed a questionnaire on eating disorders severity, whereas patients provided self-report measures of global social functioning and psychological symptoms associated with eating disorders.

Results.

Attenuated psychotic symptoms were highly frequent (84% of subjects). HR+ patients experienced more frequently purging behaviors and dysmorphophobia and received a greater amount of antipsychotic drugs. Compared to HR− counterparts, HR+ patients reported higher eating disorders severity and psychological symptoms (i.e., ineffectiveness, interpersonal and affective problems) associated with eating disorders. Finally, a significant correlation between global social functioning and eating disorders severity emerged only for HR− subjects.

Conclusions.

These descriptive data are warranted to identify a potential psychotic core in eating disorders, mainly concerning body image and weight as well as specific psychological features. The availability of reliable and valid markers of risk can further increase our capacity to detect the early emergence of psychosis in adolescents with eating disorders, whose outcome might be worsened by the presence of psychotic symptoms.
Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer
Authors: Tutt A. , Robson M. , Garber J. E. , Domchek S. , Audeh M. W. , Weitzel J. N. , Friedlander M. , Carmichael J.
Published: August 2020

CRA501

The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology.

[Table: see text]
Partial breast irradiation or whole breast radiotherapy for early breast cancer: A meta-analysis of randomized controlled trials
Authors: Valachis A. , Mauri D. , Polyzos N. P. , Mavroudis D. , Georgoulias V. , Casazza G.
Published: August 2020

CRA532

The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology.

No significant financial relationships to disclose.
HER-2/neu in tissue and serum at time of primary diagnosis of breast cancer
Authors: Dresse M. , Mayr D. , Heinemann V. , Kahlert S. , Bauerfeind I. , Nagel D. , Seidel D. , Stieber P.
Published: August 2020

e11500

Aim: HER2 in breast cancer tissue is a marker of high prognostic and predictive relevance. Soluble HER-2, the extracellular domain of the HER-2/neu receptor which is shed into the blood, has been suggested to be a helpful tumor marker. We investigated whether there exists a relationship between the concentration of HER-2/neu Shed Antigen in serum (s-HER-2/neu) and HER- 2/neu in breast cancer tissue and whether this relationship could be used for diagnostic purposes. Patients and Methods: s-HER- 2/neu was measured at time of primary diagnosis in the pretherapeutical (presurgical) sera of 525 breast cancer patients with known HER- 2/neu-status in breast cancer tissue. 33 of the patients (6,3%) revealed to have distant metastases (M1). The HER-2/neu- status in tumor tissue was determined by immunhistochemistry, followed by subsequent FISH analysis in case of score 2+. Dako-Score 3+ or 2+ and geneamplification in FISH analysis were regarded as HER-2/neu-positive. HER-2/neu shed antigen was analysed by Immunoassay. Results: For patients without distant metastases (M0) as well as patients with distant metastases (M1) we observed a correlation of s-HER-2/neu with HER-2/neu-status. The median s-HER-2/neu-concentrations were 11.7 ng/ml (13.2 ng/ml) for the HER-2/neu-negative resp. -positive patients in the M0 group (p<0,001) and 11.9 ng/ml (16,0 ng/ml) in the M1 group (p=0,01). In 492 M0-patients we performed a ROC-analysis in order to investigate the diagnostic capacity of s-HER-2/neu concerning its predictive value for the HER-2/neu-status: using a cut off value of 30 ng/ml the HER-2/neu-status was always positive, corresponding to a specificity of 100% and a sensitivity of 7.7 %. Conclusions: There is a correlation between high s-HER-2/neu-values and a positive HER-2/neu-status. Pretherapeutical s-HER- 2/neu-values ≥30 ng/ml were only observed in HER-2/neu-positive patients. HER-2/neu shed antigen in serum can add up to the HER-2/neu-status and might reveal false-negative tissue findings.

[Table: see text]
Pharmacogenomic prediction of breast cancer treatment outcome with adjuvant tamoxifen in postmenopausal women with estrogen receptor-positive breast cancer
Authors: Pribylova O. , Petruzelka L. B. , Argalaczova S. , Konopasek B. , Drazdakova J. , Slanar O. , Slanar O. , Zima T.
Published: August 2020

e11501

Background: The clinical outcome of tamoxifen-treated breast cancer patients may be influenced by the activity of cytochrome P450 enzymes that catalyze the formation of antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. Methods: The AmpliChip CYP450 Test was used to identify CYP2D6 genotypes which have an impaired ability to metabolize tamoxifen into the active metabolite, endoxifen. Results: Our aim is to determine the share of ultrarapid (UM), extensive (EM), intermediate (IM) and poor (PM) metabolizers in the group of postmenopausal women with estrogen receptor-positive breast cancer. We are presenting first 72 results as the part of long term study on 180 women. It is evident that EM and UM have significantly lower percentage of disease progression (22% respectively 0%) compare to IM (67%). No progression observed at PM needs further monitoring and investigation. Conclusions: The results tentatively support the hypothesis, that the genetic variants associated with activity of CYP2D6 could help to clinicians in determining the therapeutic strategy.

[Table: see text]

No significant financial relationships to disclose.
Non-sentinel lymph node status and prognosis of the breast cancer patients with micrometastatic sentinel lymph nodes
Authors: Jinno H. , Onishi T. , Takahashi M. , Sakata M. , Kitagawa Y. , Kitamura N. , Nakahara T. , Mukai M.
Published: August 2020

e11504

Background: Sentinel lymph node biopsy (SLNB) has become a standard therapy for clinically node-negative breast cancer patients and improvements of histopathological and molecular analysis of sentinel lymph node (SLN) have increased the rate of micrometastases identified. However it remains controversial whether to perform axillary lymph node dissection (ALND) for patients with micrometastases in SLNs and their prognostic significance is also a matter of debate. The purpose of this study is to determine the non- sentinel lymph node (NSLN) status and prognosis of the patients with micrometastatic SLNs. Methods: A prospective database of 666 breast cancer patients with the tumor size less than 3cm and clinical negative node, who underwent SLNB from January 2002 to July 2007 at Keio University Hospital was analyzed. SLNs were detected using a combined method of isosulfun blue dye and small-sized technetium-99m-labeled tin colloid. SLNs were diagnosed with standard hematoxylin and eosin (HE) staining and immunohistochemical (IHC) analysis. Results: Micrometastases in SLNs were found in 50 (7.5%) of 666 patients. Twenty nine (58.0%) of 50 patients with micrometastatic SLNs underwent ALND and revealed no NSLN metastasis. Among 21 (42.0%) patients with micrometastatic SLNs who skipped ALND, no axillary lymph node recurrence has been observed in the median follow-up time of 43 months, although 20 patients (95.2%) in 21 patients received adjuvant systemic therapy. There is no significant difference in recurrence free survival between the patients with micrometastatic and negative SLNs (98.0% vs. 95.7%, respectively). Conclusions: These date suggested that it may not be necessary to perform ALND for the patients with micrometastases in SLNs and the presence of micrometastases in SLNs may not be associated with prognosis.

No significant financial relationships to disclose.
Prognostic value of serum level of HER-2 extracellular domain (ECD) at diagnosis of HER-2 overexpressed primary breast cancer (BC)
Authors: Thureau S. , Clatot F. , Pillé J. , Laberge-Le-Couteulx S. , Rigal O. , Veyret C. , Basuyau J. , Blot E.
Published: August 2020

e11508

Background: Serum level of HER2 ECD is an adverse prognostic factor in HER2 over-expressed metastatic BC. We analyzed the prognostic value of serum level of HER2 ECD at the diagnostic of HER2 over-expressed primary BC. Methods: Patients with HER2 over-expressed primary BC treated with adjuvant trastuzumab in 2005 and 2006 were retrospectively analyzed. Serum level of HER2 ECD was assessed on frozen sera collected for CA15–3 measurement before initial treatment. Serum level of HER2 ECD was measured with an Elisa commercial kit (Oncogene Science, Cambridge, MA). The cut-off was 15μg/l as recommended. Results: Pre-treatment serum was available for 65 patients treated for non metastatic HER2 over-expressed BC. Seven patients (11%) had initially an elevated serum level of HER2 ECD (mean 25μg/l, range 15.1–38.9). After an average follow-up of 30 months, 4 patients (57%) out of the 7 with initially elevated serum level of HER2 ECD had a metastatic relapse of BC. In contrast, only 3 patients (5%) out of 58 with initially low serum level of HER2 ECD experienced relapse (p=0.004). Median of serum level of HER2 ECD was 17μg/l in patients who experienced relapse during follow-up whereas it was 8.4μg/l in patients who remained relapse-free (p=0.03). Univariate analysis showed that only elevated serum level of HER2 ECD and absence of hormone receptors expression were linked with metastatic relapse (p=0.0004 and p=0.02, respectively). Multivariate analysis showed that elevated serum level of HER2 ECD and absence of hormone receptors expression were linked with metastatic relapse (p=0.02 and p=0.04, respectively). Survival curves showed also that elevated serum level of HER2 ECD was related with a worse disease-free survival (p=0.0004). Conclusions: In this small series, elevated serum level of HER2 ECD was an adverse prognostic factor for HER2 over- expressed non metastatic primary BC. It was also a predictive factor for early failure of adjuvant treatment with trastuzumab.

No significant financial relationships to disclose.
A phase II trial of a neoadjuvant platinum-containing regimen for locally advanced breast cancer: Pathologic response, long-term follow-up, and correlation with biomarkers
Authors: Shenkier T. N. , Hayes M. , Gelmon K. A. , Chia S. , Bajdik C. , Norris B. , Caroline S. , Hassell P. , O’Reilly S. E. , Allan S. , Yerushalmi R.
Published: August 2020

e11510

Background: To determine the response, tolerability, and long-term outcome of a neoadjuvant platinum-containing regimen for locally advanced breast cancer (LABC). To search for correlation between pathologic complete response (pCR) and predefined biomarkers in this cohort. Patients and Methods: Patients with LABC received eight cycles of either sequence A or B. Sequence A was doxorubicin 60 mg/m2 and paclitaxel 175 mg/m2 (AT) q3w X 4 followed by cisplatin (C) 60 mg/m2 and paclitaxel 90 mg/m2 (CT) q2w X 4. Sequence B was CT x 4 followed by AT x 4. In addition to estrogen receptor and HER2, immunohistochemistry (IHC) for MDR-1, MRP-1, topoisomerase IIα(topoIIα) and p53 was performed. Results: 88 patients were evaluable for response and toxicity. Median follow-up was 97 months. The overall pCR rate was 21.5%. For subgroups ER+/HER2-, HER2 +, and double negative (ER-/ HER2-) disease the pCR was 5.9%,23.3% and 35% respectively, p=0.006. Five year(y) overall survival for the entire cohort was 71.1%. Five y overall survival was 88.1% (CI 77.1%, 99.1%) for the ER positive HER2 negative group compared to 68.5% (CI 51.3%, 85.7%) and 49.5 (CI 27.4%, 71.6%) in the HER2 positive and “double negative” group respectively (p=0.0077). Over-expression of topo IIα was correlated with pCR (p<0.001). There were no toxic deaths. Conclusions: A platinum-containing neoadjuvant regimen was well tolerated and achieved a pCR rate which compares favorably to other recent studies of multi-agent chemotherapy. Further studies tailored for specific breast cancer subtypes are required.

No significant financial relationships to disclose.
Measurement of quality of life in women with breast cancer before and after adjuvant chemotherapy: A structural equation modelling
Authors: Choudhury J. B. , Beadle G. , Mengersen K.
Published: August 2020

e11513

Background: This study examines breast cancer patients’ individual changes in health related quality of life (HRQOL) measures over time and the relationships between these measures within the framework of Structural equation modeling (SEM). Methods: One hundred and fifty five Australian women with breast cancer were asked to complete the Functional Assessment of Cancer Therapy Breast, Version 4 (FACT-B) pre- and post-chemotherapy as measures of HRQOL. In SEM, growth curve modelling was required for the estimation of individual differences in developmental changes of HRQOL scales over time. A growth mixture model was also used for identifying the cross-group differences in the pattern of changes in a given population over time. Results: Reliability and validity of the FACT-G including the fatigue subscale and breast cancer subscale for evaluating Australian breast cancer patients was determined to be sufficient for research purposes. After adjustment for covariates, two subgroups of women were identified with respect of patterns of response, representing largely increasing and decreasing trends in HRQOL respectively. In the former group, on average 85% of breast cancer women reported changes over time with respect to individual HRQOL measures and 78% reported such changes with respect to combined HRQOL Scores. A small group of women reported changes with respect to HRQOL measures in the decreasing group. The greatest contribution to variation in HRQOL measures was in the breast cancer subscale for both individual and combined scores. Subsequent factor analysis of the breast cancer subscale revealed that with one exception, all items loaded onto three separate factors described as self-esteem, physical and psychological. The latter two improved over time, but self- esteem was largely unchanged. Conclusions: The study presents a technique that allows us to identify potential subgroups of study subjects that experience different trajectories of responses. The results of this study provide greater insight into HRQOL changes over time and can help to plan interventions in a better way, ultimately contributing to improvement in HRQOL of women with breast cancer.

No significant financial relationships to disclose.
Racial differences in acute toxicities of FEC 100 chemotherapy in patients with breast cancer
Authors: Han H. S. , Reis I. , Kuroi K. , Toi M. , Suzuki E. , Syme R. , Chow L. , Yip A. , Zhao W. , Nimmagadda R. , Gluck S.
Published: August 2020

e11515

Background: Racial disparities in breast cancer outcomes are attributed to differences in baseline tumor characteristics, stage, and socioeconomic factors. However, little is known about racial differences in treatment-related toxicities. We hypothesized that racial and ethnic differences result in differential tolerance to chemotherapy and possibly compromise to the dose intensity of adjuvant/neoadjuvant chemotherapy. Methods: Data was collected from 4 international collaborating centers (University of Miami, JBCRG (Japan Breast Cancer Research Group), University of Hong Kong, and Tom Baker Cancer Center) at which patients of different ethnic background have been treated for non metastatic breast cancer with same adjuvant or neoadjuvant chemotherapy of FEC 100: fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 100 mg/m2). Racial/ethnic differences in toxicities were assessed by first episode of grade 2 or higher toxicity. Analysis of data was performed at the University of Miami. Results: Treatment-related toxicities are compared according to four race/ethnicity groups (120 Caucasian from USA and Canada (C), 16 African American (AA) from USA and Canada, 141 Japanese Asian (JA), and 23 Asian from Hong Kong (HKA)) (Table). JA and HKA had a significant higher rate of grade 3 or higher toxicity compared with C or AA women; 65%, 61%, 28%, and 31% respectively. However, there were no significant differences in chemotherapy dose intensity or density across the 4 race/ethnicity groups. Conclusions: This unique study noted racial differences in acute toxicity in women with breast cancer who were treated with FEC 100 chemotherapy. However, there are several limitations including the retrospective nature of our study, differences in practice across four countries, and different number of patients available for comparison. This study is ongoing and further statistical analyses are planned when a larger sample size is reached.

[Table: see text]

No significant financial relationships to disclose.
Response to neoadjuvant chemotherapy and outcome based on breast cancer subtype
Authors: Guerrero-Zotano A. , Gavila J. , Climent M. A. , Juan M. J. , Guillem V. , Ruiz A.
Published: August 2020

e11516

Background: Gene expression profiling identifies several breast cancer subtypes with different chemosensitivity and outcome. We used immunohistochemistry surrogate markers to classify tumors according to known breast cancer subtypes and examined the relationship between neoadjuvant chemotherapy (NAC) response and long-term end points, including distant disease-free survival (DDFS) and overall survival (OS). Methods: Review of clinical and pathological data from 271 breast cancer patients treated in our institution with NAC between 1991–2008. Breast cancer subtypes were defined as follows: Luminal A: Estrogen receptor positive (ER+) and/or progesterone peceptor positive (PR+), human epidermal growth factor receptor 2-positive (Her-2+); Luminal B: ER+ and/or PR+,Her-2+; Basal: ER-,PR-,Her-2-;HER2: ER-,PR-,Her-2 +. ER and PR positive scored as positive if tumor cell nuclear staining was at least 2+. Her-2 scored as positive if test DAKO scored 3+ or FISH ratio Her-2/CEP-17>2.2. Results: 121 (45.8%) patients were classifed as Luminal A; 22 (8.1%) as Luminal B; 75 (27.7%) as Basal, and 50 (18.5%) as HER2. Most patients (63%) received NAC based on anthracyclines and taxanes. 36% Her-2+ patients were treated with NAC based on trastuzumab, and 43% received trastuzumab as adjuvant treatment. Response and outcome results are shown below (Table). Independently from subtype, only four patients out of 58 with pCR relapsed. Among patients who didn´t achieved pathologic complete response (pCR), basal and HER2 subtypes have the worst outcome (4 years SG 80% and 72% respectevely) compared with Luminal A (4 years SG: 94.7%), (log-rank p=0.009). Conclusions: Basal and HER2 tumor despite high chemosensitivity have worst long term outcome, particularly if pCR is not achieved after NAC.

[Table: see text]

No significant financial relationships to disclose.