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In this study, a new non-invasive near-infrared fluorescence imaging strategy based on glucose-conjugated quantum dots (QDs-Glu) labeling to target and track EVs in a sciatic nerve injury rat model in real-time was introduced.

Simin Yang,1,&ast; Lihua He,2,&ast; Ke Li,3,&ast; Xiaoyu Yu,1 Lijun Ni,1 Liang Hu,1 Jian Guo,1 Ewelina Biskup,4,5 Lunxian Tang,3 Wenjuan Wu1 1Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Hospital Infection Management, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Department of Emergency Intensive Care Unit, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Department of Basic and Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 5Department of Internal Medicine, University Hospital of Basel, Basel, Switzerland&ast;These authors contributed equally to this workCorrespondence: Lunxian Tang; Wenjuan Wu, Tel +86-15921155750 ; +86-13386057159, Email 456tlx@163.com; wwj1210@126.comPurpose: To investigate whether rapid active molecular screening and infection prevention and control (IPC) interventions can reduce colonization or infection with carbapenem-resistant Enterobacterales (CRE) in a general emergency intensive care unit (EICU) without enough single-room isolation.Methods: The study was designed as a before-and-after quasi-experiment. Before the experimental period, the ward was rescheduled and the staff were trained. From May 2018 to April 2021, active screening was performed by seminested real-time fluorescent polymerase chain reaction (PCR) detection with rectal swabs from all patients on admission to the EICU, and the results were reported in 1 hour. Other IPC interventions including hand hygiene, contact precautions, patient isolation, environmental disinfection, environment surveillance, monitoring, auditing and feedback were conducted under strict supervision. The patients’ clinical characteristics were collected simultaneously.Results: In this 3-year study, 630 patients were enrolled and 19.84% of the patients were initially colonized or infected with CRE as shown by active molecular screening. The average drug resistance ratio to carbapenem shown by clinical culture detection of Klebsiella pneumoniae (KPN) before the study was performed was 71.43% in EICU. The drug resistance ratio decreased significantly from 75%, 66.67% to 46.67% in the next 3 years (p< 0.05) during which active screening and IPC interventions were strictly executed. While the ratio gaps between EICU and the whole hospital were narrowed from 22.81%, 21.11% to 4.64%. Patients with invasive devices, skin barrier damage, and the recent use of antibiotics on admission were found to have a higher risk of being colonized or infected with CRE (p< 0.05).Conclusion: Active rapid molecular screening and other IPC interventions may significantly reduce CRE nosocomial infections even in wards without enough single-room isolation. The key to reduce the spread of CRE in the EICU is the strict execution of IPC interventions by all medical staff and healthcare workers.Keywords: carbapenem-resistant, Enterobacterales, active screening, infection prevention and control intervention, emergency intensive care unit, nosocomial infection

Breast cancer is the most common cancer in the world. There are several implications of bone health in early and late breast cancer cases. In early breast cancer, the therapy might cause reduction of bone mineral density due to early menopause induction or as a side effect of therapy options, such as aromatase inhibitors. In late-stage breast cancer, most common site of metastasis is in the skeletal bone. Early management of bone metastasis needs special focus because of skeletal-related complications such as fractures, pain, hypercalcemia, and surgery. This chapter will focus on most common diagnostic and therapeutic measures of osseous metastasis, in early and advanced breast cancer.

Approximately one in four myocardial infarctions occur in older patients. The majority of therapeutic advances are either not appropriate or not tested in elderly patients. The main reasons for deviating from the guidelines are justified concerns regarding the effectiveness of the recommended forms of therapy, fear of adverse drug reactions and ethical concerns. Targeting interleukin 6 (IL-6) for ventricular remodeling after cardiovascular damage is a feasible alternative to standard polypharmaceutics, but the underlying molecular mechanisms are not well understood. Continuous activation of the IL-6-associated cytokine receptor gp130 leads to cardiomyopathic hypertrophy. TGFβ1 is involved in forming fibrosis in various organs, and its overexpression can cause myocardial hypertrophy and fibrosis. Il-6 has been hypothesized to be indirectly involved in cardiac remodeling via the TGFβ1/Smad signaling transduction pathway. In the present study, a rat model of acute myocardial ischemia, IL-6 and IL-6 receptor blockers were injected directly into the necrotic myocardium. Changes in cardiac function, myocardial infarction area, myocardial collagen, necrotic myocardial fibrosis and levels of TGFβ1, IL-6 and MMP2/9 were quantified in myocardial tissue fibrosis by ELISA. The present study demonstrated that IL-6 stimulated myocardial fibrosis through the TGFβ1-Smad-MM2/9 signaling transduction pathway. Overall, this provided a solid foundation for understanding the relationship between IL-6 and ventricular remodeling.

Background Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that lack of effective therapeutic drugs. K-001 is an oral antitumor drug made from active ingredients of marine microorganisms. The current study aimed to evaluate safety and antitumor activity of K-001 in patients with advanced PDAC. Methods In this phase I, open-label trial, patients with advanced PDAC were recruited to a dose-escalation study in a standard 3 + 3 design. K-001 was administered twice daily in four-week cycles, and dose escalation from 1350 mg to 2160 mg was evaluated twice daily. Physical examination and laboratory tests were done at screening and then weekly. The safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of K-001 were assessed while tumor response was estimated by Response Evaluation Criteria in Solid Tumor (RECIST). Results Eighteen patients with advanced PDAC were screened, and twelve eligible patients were analyzed in the study. No DLT was observed. Totally, 47 adverse events (AEs) presented, and 14 drug-related AEs were reported in 7 patients, including 8 grade 1 events (57.1%) and 6 grade 2 events (42.9%). There was no grade 3 or 4 drug-related AE. In these 14 drug-related AEs, the most frequent ones were dyspepsia (21.4%), followed by flatulence, constipation, and hemorrhoid bleeding (above 10% of each). Among all 12 patients, 10 patients (83.3%) maintained stable disease (SD), and 2 patients (16.7%) had progressive disease (PD). The objective response rate (ORR) was 0% and the disease control rate (DCR) was 83.3%. Conclusions K-001 manifests satisfactory safety and tolerability, as well as meaningful antitumor activity in advanced PDAC patients. Further evaluation of K-001 in phase II/III appears warranted. Trial registration NCT02720666. Registered 28 Match 2016 - Retrospectively registered.

The treatment of hypertrophic scar (HS) has thus far been a clinical challenge. We evaluated the therapeutic effect of CO2 fractional laser combined with 5-fluorouracil ethosomal gel (5-FU EG) in rabbit HS model. HS model was established as standardized scars on the ventral surface of rabbit ears, divided into four groups: control (no intervention), EG treatment, laser treatment, and combined treatment group (laser plus 5-FU EG). Clinical macroscopic and H&E-stained microscopic observations were conducted to assess HS improvement. The mRNA levels of types I and III collagen, transforming growth factor-β1 (TGF-β1), and interleukin-6 (IL-6) were detected by real-time PCR. After 14 days, H&E staining shows that the thickness of HS in treatment groups was significantly lower compared with the control group, and the thickness in laser treatment group and combined treatment group was significantly lower compared with the EG treatment group. The mRNA levels of types I and III collagen, TGF-β1 were significantly low in all treatment groups, whereas IL-6 was highest in the laser treatment group at day 14. The macro- and microscopic effects of the combined and CO2 fractional laser treatment were better compared with 5-FU EG only. Inhibition of types I and III collagen, TGF-β1 are the possible underlying mechanism of action, whereas the function of IL-6 remains to be further studied. Our study suggests that the effect of combined 5-FU EG and laser, as well as laser-only treatment are superior to 5-FU EG monotreatment. The mechanism of HS improvement is related to reduction of collagen I/III and the inhibition of TGF-β1 expression.

An academic pioneer makes many trials to find relations and results that were unknown before. The verified relations and repeatable results the pioneer finds guide followers to create a new subject area. We investigated how a pioneer opened up a research stream for a translational research area by systemic mapping and clustering of all available publications on Her-2 and of this pioneer’s work. Characteristics of clusters in both maps were largely similar, but we also identified differences, indicating that the pioneer opened a dominant research stream for the whole area. We show how different clusters representing TR stages took shape. Strong links and the terms connected by these strong links made it possible to deduce the roles of these clusters in the translational process. The strong links between clusters build a broad and solid bridge between the clusters in the pioneer’s term map, realizing the translational process. We discuss and then conclude that verified relations and repeatable results strengthen links between terms that reflect main relations found by the pioneer. Further investigations of the relations between linkage strength and the translational process might lead to interesting information about the process of translational research.

Alzheimer's disease (AD) is characterized by high heterogeneity in disease manifestation, progression and risk factors. High phenotypic variability is currently regarded as one of the largest hurdles in early diagnosis and in the design of clinical trials; there is therefore great interest in identifying factors driving variability that can be used for patient stratification. In addition to genetic and lifestyle factors, the individual's sex and gender are emerging as crucial drivers of phenotypic variability. Evidence exists on sex and gender differences in the rate of cognitive deterioration and brain atrophy, and in the effect of risk factors as well as in the patterns of diagnostic biomarkers. Such evidence might be of high relevance and requires attention in clinical practice and clinical trials. However, sex and gender differences are currently seldom appreciated; importantly, consideration of sex and gender differences is not currently a focus in the design and analysis of clinical trials for AD. The objective of this position paper is (i) to provide an overview of known sex and gender differences that might have implications for clinical practice, (ii) to identify the most important knowledge gaps in the field (with a special regard to clinical trials) and (iii) to provide conclusions for future studies. This scientific statement is endorsed by the European Academy of Neurology.

Whether multiple laser irradiations affect skin sensitivity is still elusive. We aimed to investigate if repeated ablative erbium:yttrium-aluminum-garnet (Er:YAG) laser therapy could cause or increase skin sensitivity in the treatment areas. Nineteen healthy females received three sessions of a randomized, split-face, Er:YAG laser treatment in a scanning ablative mode (MicroLaserPeel™), with a 6-mm spot size, 8-μm ablative depths, and 30% of pulse overlap first. The next round was conducted in the fractional mode (ProFractional™) at depths ranging from 100 to 150 μm, with one pass by at coverage of 11% in the coagulation mode. Objective biophysical parameters, including transepidermal water loss (TEWL), skin glossiness, epidermal and dermal thickness and density, sensory nerve current perception threshold (CPT), and local blood flow, were measured before and after treatment. Quantitative evaluation of the Er:YAG laser treatment's effect on skin sensitivity is presented. Seventeen volunteers completed a follow-up of 12 months. On days 1 and 3, skin TEWL and epidermal thickness increased, while glossiness decreased. On day 7, there was no significant difference in the skin barrier function between the treated and the control side. Similarly, there was no significant difference in CPT values or local microvascular blood flow between sides at any time point before or after treatment, except that the local microvascular blood flow on the treated side was higher on the first day post-treatment. Er:YAG laser treatment does not influence skin sensitivity in healthy subjects in a long-term follow-up.

Background: While the incidence of cancer continues to rise worldwide, mortality rates have decreased due to advancements in treatment regimens. Many pre-adolescent and reproductive age cancer survivors experience chronic health conditions, including premature ovarian insufficiency (POI) and failure (POF) and greater than 75% of reproductive age cancer survivors report the desire to parent in the future. Fertility preservation counseling and initiation of fertility preservation treatments are an important part of the management of these patients, but its utilization in the Chinese medical system is unclear. Objectives: This study aimed to investigate attitudes and gaps of knowledge regarding fertility preservation among medical and surgical oncology healthcare professionals (HCPs) and breast cancer patients in Chinese academic settings. Materials and Methods: An online questionnaire assessing participants’ demographics, attitudes knowledge, and utilization regarding oncofertility services was designed and distributed to HCPs and breast cancer patients in an academic teaching setting in Shanghai. Results: Surveys were sent to all breast cancer patients of 6 collaborative hospitals and medical and surgical oncology HCPs in the Shanghai district via Wechar-based questionnaire program. To date, 61 HCPs and 52 patients responded to the survey. Sixty-nine percent (42) of HCPs compared to 19.2% (10) of patients were familiar with the term “oncofertility”. Overall, 80.3% (49) of HCPs reported positive attitudes about oncofertility and discussing fertility-sparing options compared to 80.3% (48), 75.4% (41), and 55.7% (34) of their reproductive, adolescent, and pre-adolescent age patients. 40 out of 43 HCPs (93%) stated that they have initiated a discussion about oncofertility options, while only 30.8% of patients (4/13, p Conclusion: Preliminary results suggest that while the majority of academic oncologic Chinese HCPs are aware of oncofertility, their knowledge of eligibility and costs of fertility preservation services is limited. Furthermore, a significant knowledge gap exists between HCPs and breast cancer patients. This may represent ineffective communication or lack of patient comprehension, resulting in severe under-utilization of oncofertility services. Continued education and raised awareness are urgently needed to optimize care. Citation Format: Ewelina Maria Biskup, Xin Zhaochen, Leslie C Appiah, Yun Sun, Yan Lu, Hangwei Zhang, Steven R. Lindheim. Oncofertility awareness and attitudes among health care providers and patients in a Chinese academic setting: Preliminary results [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-05.

Background: Unlike female breast cancer (fBC), male breast cancer (mBC) holds clinicopathological, radiological, and genetic differences including histologic grade that is often not correlated with clinical outcomes and most being ER/PR positive and Her2 negative. Recently, PGC-1α (hypoxia-related protein, expressed preferentially in cancer cells to enhance oxidative phosphorylation, mitochondrial biogenesis and functional motility/metastasogenesis) has been identified as a prognostic marker for fBC, but its value and impact in mBC have not been studied. Our objective was to assess the utility of PGC-1α as a prognostic marker and an indicator for disease-free survival (DFS) in mBC. Materials & Methods: 7000 female and 23 male patients de novo diagnosed with breast cancer, at the Breast Center, Yangpu Hospital, Tongji University School of Medicine, as well as 30 males with lesions that were non-tumorous (non-mBC, controls) were included prospectively between September 2012 and August 2018. Propensity Score Matching was used to balance confounding factors. Results: Mean PGC-1α plasma levels were significantly higher in fBC compared to mBC cohorts (248.9 ng/dl (95% CI 242.9-254.8) vs 224.9 ng/dl (95% CI 202.9-246.9, P =0.040), though after propensity matching, no differences were noted (225.7 ng/dl (95% CI 202.5-248.7) vs 204.5 ng/dl (95% CI 194.3-214.8, P=0.07). In a total, 681 (658 females and 23 males) out of 723 patients for a median of 43 months (range of 3 to 82 months). By the end of follow-up period, 16.6% (109/658) female patients and 21.7% (5/23, p-NS) male patients had local recurrence and/ or metastasis, 5.6% (38) died, 48.5% (33) due to breast cancer (4.7% (31) females and 8.7% (2) males. In unmatched samples, there were no differences in DFS between fBC and mBC (P = 0.439, log-rank test). After dichotomous division of unmatched patient samples into two groups by median of PGC-1α plasma levels 246.8 ng/dl, all patients with high PGC- 1α plasma levels (>246.813 ng/dl) had a higher risk of recurrence than those with low PGC-1α plasma levels (P= 0.008). When calculated only for unmatched female patients, the results were similar: patients with high PGC- 1α plasma levels (>246.813 ng/dl) had a higher risk of recurrence than those with low PGC-1α plasma levels (P= 0.016). However, in matched samples, 6.4% (5/78) of females and 22.7% (5/22) males had recurrences and the male DFS was significantly poorer than in women (P < 0.033) despite similar baseline clinicopathologic characteristics. After the dichotomous division of matched patient samples into two groups by median of PGC-1α plasma levels of 211.5 ng/dl, 47.4% (37/78) female and 59.1% (13/22) male patients showed high PGC-1α plasma levels (P = 0.334). Despite comparable clinicopathological features, patients with lower PGC- 1α plasma levels ( Conclusion: PGC-1α appears to be an independent marker of poor prognosis and more aggressive cancer characteristics in mBC, with a stronger prognostic value than in fBC. It may represent a non-invasive, innovative option to identify high-risk mBC individuals, predict the outcome, monitor treatment and screen for disease recurrence. Therefore, the marker can assist to determine, tailor and alternate therapy course for the highly fatal disease of mBC, where guidelines are still missing and most therapeutic options are transferred from fBC. Furthermore, inhibition of PGC-1α pathways might be a promising antitumor management option. Citation Format: Ewelina Maria Biskup, Fengfeng Cai, Steven Lindheim. Clinicopathological and prognostic significance of preoperative PGC-1alpha plasma levels in male breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-17-09.

The peripheral nervous system (PNS) is essential for performing and maintaining various motor and sensory functions. Abnormalities can lead to a series of peripheral neurological conditions, such as paraesthesia, pain, or spasms, which are debilitating and lowering the quality of life. The current guidelines for diagnosis rely predominantly on clinical symptoms resulting from PNS dysfunction, which occur already at an advanced stage. There are currently no effective methods that visually reflect the extent of peripheral neuropathy. In our study, we present a novel in vivo and in situ real-time imaging of peripheral nerves based on the second near-infrared window (NIR-II) fluorescence. In NIR-II system, PbS Qds with NIR-II fluorescence specifically bound to motor neuron-specific protein agrin, acting as image contrast. In mice model, peripheral nerves were visible as soon as after 2 h post injection. We provide evidence for the efficacy of this approach, which allows to directly demonstrate peripheral nerves, their structure, and potential damage sites and degree. Furthermore, our products were of good biocompatibility, while the neural fluorescence signal was solid, bright and stable for 4 h in vivo. Thus, overall, our results suggest that NIR-II is an effective new method for direct imaging of peripheral nerves in vivo, opening new horizons on early, improved and more precise, targeted diagnosis. A resulting more rapid installation of personalized therapy facilitates a better prognosis of clinical peripheral neuropathy.

Background: Several trials have been conducted in the last decades that challenged the management of patients with acute pulmonary embolism (PE) in terms of diagnosis and treatment. Updated international clinical practice guidelines (CPGs) endorsed the evidence from these trials. The aim of this document was to adapt recommendations from existing CPGs to assist physicians in decision making concerning specific and complex scenarios related to acute PE. Methods: The flow for the adaptation procedure was first the identification of unsolved clinical issues in patients with acute PE (PICOs), then critically appraise the existing CPGs and choose the recommendations, which are the most applicable to these specific and complex scenarios. Results: Five PICOs were identified and CPGs appraisal was performed. Concerning diagnosis of PE when computed tomographic pulmonary angiography is not available/contraindicated and D-dimer is less specific, perfusion lung scan is the preferred option in the majority of clinical scenarios. For the treatment of PE when relevant clinical conditions like pregnancy or severe renal failure are present heparin is to be used. Poor evidence and low-level recommendations exist on the best bleeding prediction rule in patients treated for PE. The duration of anticoagulation needs to be tailored concerning the presence of predisposing factors for index PE and the consequent risk for recurrence. Finally, recommendations on the opportunity to screen for cancer and thrombophilia patients without recognized thrombosis risk factors for PE are reported. Overall, 35 recommendations were endorsed and the rationale for the selection is reported in the main text. Conclusion: By the use of proper methodology for the adaptation process, this document offers a simple and updated guide for practicing clinicians dealing with complex patients.

Background: Trastuzumab and pertuzumab with taxane-based chemotherapy are considered the first-line standard therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC). Pertuzumab is also a later-line therapy for mBC in Switzerland, although limited safety and efficacy data are available. This study assesses the therapeutic regimens, toxicities, and clinical outcomes after second- or later-line pertuzumab therapy in patients with mBC who did not receive pertuzumab as a first-line therapy. Materials and Methods: Physicians from major Swiss oncology centers retrospectively completed a questionnaire for each pertuzumab-naive patient who was treated with pertuzumab as a second- or later-line therapy. Results: Of 35 patients with HER2-positive mBC (median age: 49 years; range: 35-87 years), 14 received pertuzumab as a second-line therapy, six as a third-line therapy, and 15 as a fourth- or later-line therapy. Twenty patients (57%) died during the study period. The median overall survival was 74.2 months (95% confidence interval: 47.6-139.8 months). Grade (G) 3/4 adverse events (AEs) were reported in 14% of patients, with only one patient discontinuing therapy due to pertuzumab-related toxicities. The most common AE was fatigue (overall: 46%; G3: 11%). Overall, congestive heart disease occurred in 14% of patients (G3: 6%), nausea in 14% (all G1), and myelosuppression in 12% (G3: 6%). Conclusion: The median overall survival of second- or later-line pertuzumab is similar to that reported for first-line pertuzumab, and the safety profile was acceptable. These data support using pertuzumab for second- or later-line therapy when it was not administered as first-line therapy.

Sociocultural gender is a complex construct encompassing different aspects of individuals' life, whereas sex refers to biological factors. These terms are often misused, although they impact differently on individuals' health. Recognizing the role of sex and gender on health status is fundamental in the pursuit of a personalized medicine. Aim of the current study was to investigate the awareness in approaching clinical and research questions on the impact of sex and gender on health among European internists. Clinicians affiliated with the European Federation of Internal Medicine from 33 countries participated to the study on a voluntary basis between January 1st, 2018 and July 31st, 2019. Internists' awareness and knowledge on sex and gender issues in clinical medicine were measured by an online anonymized 7-item survey. A total of 1323 European internists responded to the survey of which 57% were women, mostly young or middle-aged (78%), and practicing in public general medicine services (74.5%). The majority (79%) recognized that sex and gender are not interchangeable terms, though a wide discrepancy exists on what clinicians think sex and gender concepts incorporate. Biological sex and sociocultural gender were recognized as determinants of health mainly in cardiovascular and autoimmune/rheumatic diseases. Up to 80% of respondents acknowledged the low participation of female individuals in trials and more than 60% the lack of sex-specific clinical guidelines. Internists also express the willingness of getting more knowledge on the impact of sex and gender in cerebrovascular/cognitive and inflammatory bowel diseases. Biological sex and sociocultural gender are factors influencing health and disease. Although awareness and knowledge remain suboptimal across European internists, most acknowledge the underrepresentation of female subjects in trials, the lack of sex-specific guidelines and the need of being more informed on sex and gender-based differences in diseases.

Psychiatry qualifications are automatically recognized among European Union (EU) countries despite differences in national training programs. A widening gap between the number of psychiatrists, their competencies and the growing burden of mental illnesses in Europe has renewed calls for international standardization of training. Comprehensive information about training programs is missing, which limits thorough comparisons and undermines development of an actionable strategy to improve and harmonize psychiatry training. This study describes and compares the existing postgraduate psychiatry programs in 42 countries in the European region. Representatives of national psychiatry associations completed a semi-structured, 58item questionnaire. Training structure and working conditions of each country were compared with population needs calculated by the World Health Organization to determine the European mean and contrasted among pre-2004 and post-2004 EU members and countries with unrecognized qualifications. Differences were tested with nonparametric (Wilcoxon) and parametric (Anova) tests. Median training duration was 60 months, significantly shorter in countries with unrecognized qualifications (48 months,. chi(2)16.5, p < 0.001). In 80% of the countries, placement in a non-psychiatric specialty such as neurology or internal medicine was mandatory. Only 17 countries (40%) stipulated a one-month rotation in substance abuse and 11 (26%) in old-age psychiatry. The overall deficit of training versus population need was 22% for substance abuse and 15% for old-age psychiatry. Salaries were significantly higher in pre-2004 EU members (. (2)22.9, p < 0.001) with the highest in Switzerland ((sic)5,000). Significant variations in curricula, training structure and salaries exist in Europe. Harmonization of training standards could offer significant benefits for improving mental healthcare. (c) 2021 Elsevier B.V. and ECNP. All rights reserved.

Our prospective comparative study of 60 patients aimed to compare the efficacy and feasibility of a single injection ranibizumab versus a single grid laser photocoagulation and versus a combined treatment in macular edema secondary to branch retinal vein occlusion in Asian population. Patients were randomized 1:1:1 (

Transcription intermediary factor 1γ (Tif1γ), a ubiquitous nuclear protein, is a regulator of transforming growth factor‑β (TGF‑β)/Smad signaling. Tif1γ can function as an oncogene and as a tumor suppressor. In the present study, Tif1γ levels were measured in the plasma of patients with breast cancer in order to investigate the association of Tif1γ with overall survival (OS). The results indicated that Tif1γ is an independent prognostic and predictive factor in breast cancer, and thus, a promising target protein for use in diagnostics and patient follow‑up. Plasma levels of Tif1γ were measured in samples obtained from 110 patients with operable breast cancer and in 110 healthy volunteers at the Breast Cancer Department of Yangpu Hospital between 2008 and 2016. The association between Tif1γ levels and clinicopathologic parameters, and the OS in a follow‑up period of 98 months was evaluated. The prognostic significance was assessed using the Kaplan‑Meier method. The levels of Tif1γ were significantly lower in patients with breast cancer compared with healthy controls. The average concentration of 18.40 ng/ml was used to discriminate between Tif1γ‑positive (52) and Tif1γ‑negative patients (58). Tif1γ‑positive patients had a significantly improved OS compared with Tif1γ‑negative patients. In the multivariate analysis, Tif1γ was an independent predictor of a favorable OS in a prospective follow‑up setting; thus, Tif1γ plasma levels are an independent prognostic factor for patients with breast cancer. These findings support the potential of using measurements of Tif1γ plasma levels to guide breast cancer therapy and monitoring. Further studies are required to validate Tif1γ as an easily detectable, non‑invasive prognostic biomarker for breast cancer.

Background The outbreak of coronavirus disease-2019(COVID-19)cause significant difficulties to the treatment of oncological patients, including colorectal cancer(CRC) patients. Establishing new manage strategies and emergency triage system is urgent. Methods We collected the outpatients, inpatients and surgeries number and COVID-19 nucleic acid test results of Shanghai East Hospital from December 2019 to January 2020, and the changes during this period were analyzed. Result The number of outpatients, inpatients and surgeries all decreased significantly. Not a single case of COVID-19 infection occurred in Shanghai East Hospital in this period. The triage system and management strategy are shared here. Conclusion Our triage strategy can help reduce the infection rate of COVID-19 in hospital, and the management strategies of CRC can be used as a reference for clinicians.

In this chapter we focus on sex- and gender-related aspects of psychiatric disorders as risk factors for dementia and outline major depression as a potentially modifiable risk factor of dementia. We pinpoint the twofold higher prevalence of depression in females over the entire adult life span and the current evidence of a different psychopathology in depressive disorders in males and females. A major concern in Alzheimer’s disease is behavioral and psychological symptoms of dementia (BPSD) that hamper the patient’s and caregiver’s wellbeing and often require hospitalization. The clinical presentation of BPSD seems to be sex- and gender-related, with males showing predominantly agitated and aggressive behaviors and with females suffering more from affective and psychotic symptoms. Nonpharmacologic management is the first-line recommendation to treat BPSD, although patients of both sexes often receive harmful polypharmacy. Antipsychotics need to be carefully prescribed with respect to their beneficial and detrimental effects, as they increase the mortality of patients with dementia and may result in a variety of harmful adverse side effects. Irrespective of disease status, females receive antipsychotics more frequently than males and, therefore, are at greater risk of pharmaceutical harm. Hence, prescribing antipsychotics in females needs our special focus to help improving the personalized treatment of psychiatric disorders. In addition, there is a need to reduce the stigma of mental disorders to help with diagnosing and treating major depression early on, thereby slowing down conversion to Alzheimer’s disease or dementia progression.

Sleep disorders and dementia have a bidirectional relationship, albeit not fully understood yet. Thus, diagnosing and treating sleep disorders might help to protect patients’ brains from cognitive decline evolving into dementia. In this chapter, we pinpoint the connection between sleep disorders and cognitive impairment advancing to Alzheimer’s disease, including sex- and gender-related aspects. We highlight sleep disorders and their implications for Alzheimer’s disease. Moreover, we focus on insomnia, obstructive sleep apnea syndrome (OSAS), and rapid eye movement (REM) sleep behavior disorder (RBD) as relevant and modifiable risk factors of dementia. Current evidence on sex- and gender-related differences in patients experiencing sleep disorders and suffering from mild cognitive impairment (MCI) or Alzheimer’s disease is sparse. Therefore, we provide current knowledge and future perspectives to enhance awareness of relevant differences between male and female patients experiencing sleep disorders to accelerate early diagnosis, treatment, and prevention of sleep-related cognitive impairment evolving into Alzheimer’s disease.

Sex and gender are increasingly recognized as major influencing factors in disorders across all medical specialties. Even though there is ample evidence of sex and gender differences in neuropsychiatric disorders, a sex and gender-differentiated approach has not yet been sufficiently applied to diagnostics and management. Therefore, there is an urgent need to establish general recommendations and guidelines toward precision and sex/gender medicine, with regard to dosage, tolerability, interactions and side effects, sensitivity of diagnostic tests, and distinct treatment strategies. This chapter illustrates the current knowledge about sex and gender aspects in neuropsychiatric disorders, providing a base not only to assist the clinician in the handling of specific pathologic entities, but also to sensitize medical practitioners to consider sex and gender in clinical decision-making. As such, the chapter is a call to action to physicians and researchers to produce more sex- and gender-stratified evidence, leading to an acceleration of guideline development. Such novel guidelines will provide a base for medical education, of both medical students and specialists, as well as a reference point for practitioners, toward precision medicine.

Background: Although psychoactive substance use disorders (PSUDs) are a domain of mental health, addiction psychiatry is only formally recognized as a subspecialty in a few European countries, and there is no standardized training curriculum.Methods: A 76-item questionnaire was developed and disseminated through an online anonymous data-collecting system and hand-to-hand amongst psychiatric trainees from the 47 European countries of the Council of Europe plus Israel and Belarus.Results: 1,049/1,118 psychiatric trainees from 30 European countries completed the questionnaire. Fifty-nine-point nine percent of trainees stated to have training in addictions. Amongst the trainees who described having training in addictions, 43% documented a not well-structured training and 37% an unsatisfactory training, mainly due to poor acquired knowledge. Overall, 97% of trainees stated that addiction represents a core curriculum for their training. Overall, general adult psychiatric trainees reported a better knowledge in addictions, compared to trainees in child and adolescent psychiatry.Conclusion: Despite a growing spread of PSUDs in European countries, addiction psychiatry is a relatively poorly trained field within psychiatry training programs. Further research should investigate reasons for poor training and timings of the educational activities to optimize experiential education training in addiction psychiatry.

The treatment of hypertrophic scar (HS) has thus far been a clinical challenge. We evaluated the therapeutic effect of CO

[Doctors ’Made in China’ – Locally Trained, Globally Excellent.]

A physician and researcher in China for the Covid-19 pandemic, Ewelina Biskup, MD, MPH, discusses that experience, and calls for a big data collection and analysis effort to address the many unanswered questions about the virus., Summary China’s strict and interrelated clinical and social protocols played a key role in its dealing with the first phase of the Covid-19 pandemic. While many now are looking to colleagues for lessons as the novel coronavirus spreads globally, unanswered questions remain regarding long-term side effects, prospects for organ or tissue damage, identification of prognostic biomarkers, and development of therapeutics. Ewelina Biskup, MD, MPH, calls for robust data recording and the creation of a big data set to support analysis to improve care for the next waves.

Depressive disorders are a curable, global health problem. However, most patients remain untreated, and more and more patients use internet-based interventions, but it is unclear whether it is beneficial for ongoing face-to-face psychotherapy. Thus, we compared the outcome of internet cognitive behavioral therapy (ICBT) with (ICBT+) or without (ICBT) additional face-to-face outpatient psychotherapy in adult patients with moderate to severe depressive disorder. For this longitudinal interventional clinical trial (NCT02112266), 168 of 252 online recruited adults with depressive symptoms received ICBT+ (n = 96) or ICBT (n = 72). Demographics (sex, age, age at first depressive episode, years of education, duration of depressive symptoms) were assessed and compared between groups. All patients underwent ICBT for 12 weeks. Quality of life (QoL) and severity of depressive symptoms were assessed within each group at three time points [baseline (T0), postinterventional after ICBT at 12 weeks (T1), and for follow-up at 6 months (T2)] using the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) global score to assess QoL as primary and the Beck Depression Inventory (BDI-II) to assess self-rated depressive symptoms as secondary outcome variables, respectively. Differences were assessed between groups using t test and over time using repeated-measures analysis of variance. Data of intention-to-treat analysis are given as mean ± SD. Group differences were assumed at p < 0.05. Partial η2 is given as effect size. Demographic data, QoL, and depressive symptoms did not differ between groups (ICBT+/ICBT) at baseline (T0). Patients of both groups suffered from moderate to severe depressive disorders and gained improved QoL scores (WHOQOL-BREF-global: p < 0.001, η2 = 0.16), as well as experienced decreased depressive symptoms (BDI-II: p < 0.001, η2 = 0.2) after 12 weeks of ICBT compared to baseline. Patients without additional face-to-face outpatient psychotherapy lost QoL-albeit not significant-and had increased depressive symptoms (BDI: p = 0.02, η2 = 0.04) at 6 months' follow-up. Thus, ICBT is suitable for psychiatric treatment, although additional face-to-face outpatient psychotherapy helps stabilizing long-term outcome.