bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of complement C1s in patients with cold agglutinin disease: lessons learned from a named patient program
Authors: Gelbenegger Georg , Schoergenhofer Christian , Derhaschnig Ulla , Buchtele Nina , Sillaber Christian , Fillitz Michael , Schenk Thomas M. , D’Sa Shirley , Cartwright Ronwyn , Gilbert James C. , Jilma Bernd , Jaeger Ulrich 
Published: March 2020

AbstractCold agglutinin disease (CAD) causes predominantly extravascular hemolysis and anemia via complement activation. Sutimlimab is a novel humanized monoclonal antibody directed against classical pathway complement factor C1s. We aimed to evaluate the safety and efficacy of long-term maintenance treatment with sutimlimab in patients with CAD. Seven CAD patients treated with sutimlimab as part of a phase 1B study were transitioned to a named patient program. After a loading dose, patients received biweekly (once every 2 weeks) infusions of sutimlimab at various doses. When a patient’s laboratory data showed signs of breakthrough hemolysis, the dose of sutimlimab was increased. Three patients started with a dose of 45 mg/kg, another 3 with 60 mg/kg, and 1 with a fixed dose of 5.5 g every other week. All CAD patients responded to re-treatment, and sutimlimab increased hemoglobin from a median initial level of 7.7 g/dL to a median peak of 12.5 g/dL (P = .016). Patients maintained near normal hemoglobin levels except for a few breakthrough events that were related to underdosing and which resolved after the appropriate dose increase. Four of the patients included were eventually treated with a biweekly 5.5 g fixed-dose regimen of sutimlimab. None of them had any breakthrough hemolysis. All patients remained transfusion free while receiving sutimlimab. There were no treatment-related serious adverse events. Overlapping treatment with erythropoietin, rituximab, or ibrutinib in individual patients was safe and did not cause untoward drug interactions. Long-term maintenance treatment with sutimlimab was safe, effectively inhibited hemolysis, and significantly increased hemoglobin levels in re-exposed, previously transfusion-dependent CAD patients.
Relationship between pneumonitis induced by immune checkpoint inhibitors and the underlying parenchymal status: a retrospective study
Authors: Pozzessere Chiara , Bouchaab Hasna , Jumeau Raphael , Letovanec Igor , Daccord Cécile , Bourhis Jean , Prior John O. , Peters Solange , Lazor Romain , Beigelman-Aubry Catherine 
Published: March 2020

In patients with primary or secondary lung tumour treated with immune checkpoint inhibitors, immune-related pneumonitis is a rare adverse event but may evolve to respiratory failure. Prompt management is required and usually consists of treatment interruption and immunosuppressive drug administration. The aim of this study was to evaluate relationships between immune-related pneumonitis and pre-existing parenchymal status, especially tumour location and history of chest radiotherapy.Computed tomography (CT) scans of patients with immune-related pneumonitis were retrospectively reviewed. Pattern, distribution and extent of pneumonitis were assessed in six lung regions. In patients who received radiotherapy, the extent of pneumonitis was evaluated according to the radiation field.Among 253 patients treated with immunotherapy, 15 cases of immune-related pneumonitis were identified. 10 had previous or concomitant chest radiotherapy in addition to immunotherapy. At CT scan, 29 (33%) out of 88 regions encompassed the primary tumour (n=4), a lung metastasis (n=4) and/or radiation fields (n=21). A significantly higher prevalence of parenchymal involvement by immune-related pneumonitis occurred within areas of primary or metastatic malignancy and/or radiation field (97%) as compared to other areas (3%, p=0.009). Lung regions affected by the primary tumour, metastasis or radiotherapy had a higher probability of immune-related pneumonitis than others (OR 10.8, p=0.024). An organising pneumonia (OP) pattern was more frequent after radiotherapy (70%versus0%, p=0.024), whereas nonspecific interstitial pneumonia features were more commonly seen in radiotherapy-naive patients (100%versus10%, p=0.002).In patients with primary or secondary lung tumour treated with immune checkpoint inhibitors, immune-related pneumonitis is preferentially located within lung areas involved by tumour and/or radiation fields.
Improving lung cancer diagnosis by combining exhaled-breath data and clinical parameters
Authors: Kort Sharina , Brusse-Keizer Marjolein , Gerritsen Jan Willem , Schouwink Hugo , Citgez Emanuel , de Jongh Frans , van der Maten Jan , Samii Suzy , van den Bogart Marco , van der Palen Job 
Published: March 2020

Introduction
Exhaled-breath analysis of volatile organic compounds could detect lung cancer earlier, possibly leading to improved outcomes. Combining exhaled-breath data with clinical parameters may improve lung cancer diagnosis.

Methods
Based on data from a previous multi-centre study, this article reports additional analyses. 138 subjects with non-small cell lung cancer (NSCLC) and 143 controls without NSCLC breathed into the Aeonose. The diagnostic accuracy, presented as area under the receiver operating characteristic curve (AUC-ROC), of the Aeonose itself was compared with 1) performing a multivariate logistic regression analysis of the distinct clinical parameters obtained, and 2) using this clinical information beforehand in the training process of the artificial neural network (ANN) for the breath analysis.

Results
NSCLC patients (mean�
sd
age 67.1�9.1 years, 58% male) were compared with controls (62.1�7.0 years, 40.6% male). The AUC-ROC of the classification value of the Aeonose itself was 0.75 (95% CI 0.69�0.81). Adding age, number of pack-years and presence of COPD to this value in a multivariate regression analysis resulted in an improved performance with an AUC-ROC of 0.86 (95% CI 0.81�0.90). Adding these clinical variables beforehand to the ANN for classifying the breath print also led to an improved performance with an AUC-ROC of 0.84 (95% CI 0.79�0.89).

Conclusions
Adding readily available clinical information to the classification value of exhaled-breath analysis with the Aeonose, either
post hoc
in a multivariate regression analysis or
a priori
to the ANN, significantly improves the diagnostic accuracy to detect the presence or absence of lung cancer.
How consistently do physicians diagnose and manage drug-induced interstitial lung disease? Two surveys of European ILD specialist physicians
Authors: Eaden James A. , Skeoch Sarah , Waterton John C. , Chaudhuri Nazia , Bianchi Stephen M. 
Published: March 2020

IntroductionCurrently there are no general guidelines for diagnosis or management of suspected drug-induced (DI) interstitial lung disease (ILD). The objective was to survey a sample of current European practice in the diagnosis and management of DI-ILD, in the context of the prescribing information approved by regulatory authorities for 28 licenced drugs with a recognised risk of DI-ILD.MethodsConsultant physicians working in specialist ILD centres across Europe were emailed two surveysviaa website link. Initially, opinion was sought regarding various diagnostic and management options based on seven clinical ILD case vignettes and five general questions regarding DI-ILD. The second survey involved 29 statements regarding the diagnosis and management of DI-ILD, derived from the results of the first survey. Consensus agreement was defined as 75% or greater.ResultsWhen making a diagnosis of DI-ILD, the favoured investigations used (other than computed tomography) included pulmonary function tests, bronchoscopy and blood tests. The preferred method used to decide when to stop treatment was a pulmonary function test. In the second survey, the majority of the statements were accepted by the 33 respondents, with only four of 29 statements not achieving consensus when the responses “agree” and “strongly agree” were combined as one answer.ConclusionThe two surveys provide guidance for clinicians regarding an approach to the diagnosis and management of DI-ILD in which the current evidence base is severely lacking, as demonstrated by the limited information provided by the manufacturers of the drugs associated with a high risk of DI-ILD that we reviewed.
Protection of healthcare workers against transmission ofMycobacterium tuberculosisin hospitals: a review of the evidence
Authors: Diel Roland , Nienhaus Albert , Witte Peter , Ziegler Renate 
Published: March 2020

BackgroundEmployees in contact with infectious tuberculosis (TB) patients in healthcare facilities of low-incidence countries are still at considerable risk of acquiring TB infections. However, formal precautions recommended on the protection of healthcare workers may not only vary from country to country but also within a single country. The objective of this study was to compare current guidelines with respect to hospital infection control of TB, focusing on common shared priorities and discrepancies between sets of recommendations.MethodsFive types of procedures captured in guidelines of the World Health Organization, the United States of America, the United Kingdom and Germany are compared and the underlying evidence is discussed.ResultsUncontroversially, personal protection by respirators in the TB ward and during aerosol-generating procedures is key to reducingMycobacterium tuberculosisexposure. However, there is no consensus on the types of masks that should be worn in different situations. Closely connected to this, there is considerable uncertainty with respect to the optimal date of removing sputum smear-negative and multidrug-resistant TB patients from isolation. Indeed, the use of notable new tools for this purpose, such as the highly sensitive PCR tests recommended by the World Health Organization for detecting TB/multidrug-resistant TB, have yet to be sufficiently incorporated into TB guidelines. Perceptions differ, too, as to whether long-term control measures forM. tuberculosisinfections in healthcare workers by serial testing for latent TB infection should be established and, if so, how testing results should be interpreted.ConclusionsAlthough the current recommendations on protection of healthcare workers are otherwise homogeneous, there are considerable discrepancies that have important implications for daily practice.
The propionic acid and butyric acid in serum but not in feces are increased in patients with diarrhea-predominant irritable bowel syndrome
Authors: Tian Zhenyi , Zhuang Xiaojun , Luo Mei , Yin Wei , Xiong Lishou 
Published: March 2020

AbstractBackgroundShort-chain fatty acids (SCFAs) alteration have been reported in irritable bowel syndrome (IBS), but the results are conflicting. Our study aims to explore the alteration of SCFAs in patients with diarrhea-predominant IBS (IBS-D) and their potential role in the occurrence and development of IBS.MethodsWe recruited patients with IBS-D defined by Rome IV criteria and age-and-gender matched healthy controls (HCs). A headspace solid-phase microextraction gas chromatography–mass spectrometric (HS-SPME-GC-MS) method was developed for the analysis of acetic, propionic and butyric acid in feces and serum.ResultsCompared with HCs, the levels of the serum propionate (2.957 ± 0.157 vs 2.843 ± 0.098 mmol/L,P = 0.012) and butyrate (2.798 ± 0.126 vs 2.697 ± 0.077 mmol/L,P = 0.012) were significantly higher in IBS-D group. No significant differences were found among two groups with regard to the concentration of fecal acetate (4.953 ± 1.065 vs 4.774 ± 1.465 mg/g,P = 0.679), propionate (6.342 ± 1.005 vs 6.282 ± 1.077 mg/g,P = 0.868) and butyrate (2.984 ± 0.512 vs 3.071 ± 0.447 mg/g,P = 0.607).ConclusionsMetabolites of gut microbiota, the propionic and butyric acid, are increased in patients with IBS-D in serum but not in feces. It suggests that propionic and butyric acid might be associated with the occurrence and development of IBS.
HOXB4 promotes the malignant progression of ovarian cancer via DHDDS
Authors: Li Na , Gou Jin-hai , Xiong Jiao , You Juan-juan , Li Zheng-yu 
Published: March 2020

Abstract
Background
Homeobox B4 (HOXB4) is correlated with poor prognosis of various cancer types. However, how HOXB4 promotes ovarian cancer (OV) progression remains unclear.

Methods
The Cancer Genome Atlas (TCGA) database indicated that a high level of HOXB4 in OV was correlated with poor prognosis. The biological functions of HOXB4 were confirmed by colony formation, migration, and invasion assays. The effect of HOXB4 on the expression of EMT cell markers was determined. The transcriptional target of HOXB4 was DHDDS, which was detected by a ChIP assay. A xenograft tumor model was generated in nude mice to detect the role of HOXB4 in tumor proliferation and metastasis.

Results
The results showed that HOXB4 protein levels were higher in OV tissues than in normal tissues and correlated with poor prognosis of OV. HOXB4 reduction inhibited the proliferation and invasion ability of OV cells in vitro. Conversely, these effects were enhanced by the upregulation of HOXB4 in OV cells. The binding of HOXB4 to two DNA motifs regulated DHDDS expression and contributed to the malignant progression of OV. The role of HOXB4 in contributing to tumor development in vivo was verified in mice. Further results indicated that HOXB4 induced Snail and Zeb1 expression.

Conclusion
Overall, HOXB4 overexpression was remarkably correlated with poor prognosis of OV. Mechanistically, HOXB4 enhances the proliferation and invasion of tumor cells by activating DHDDS, thereby promoting the malignant progression of OV.
Low willingness to pay for pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in China
Authors: Cao Wangnan , Sun Shengzhi , Peng Liping , Gu Jing , Hao Chun , Li Jibin , Wei Dannuo , Gilmour Stuart , Li Jinghua 
Published: March 2020

Abstract
Background
Pre-exposure prophylaxis (PrEP) is recommended as an HIV prevention strategy for key populations, in particular men who have sex with men (MSM). However, the willingness to pay market rate for PrEP is largely unknown. This study aimed to investigate the willingness to pay for PrEP and its associated factors among MSM living in Mainland China.

Methods
A cross-sectional survey was conducted among 689 MSM who were recruited through a gay-friendly health consulting service center in Chengdu, China during 2018–2019. We collected information on participants’ willingness to pay for PrEP and its potential correlates (e.g., PrEP awareness and acceptability, perceived risk of HIV infection) using a structured questionnaire. Univariate and multivariate logistic regression were used for data analyses.

Results
Only 14.1% of respondents indicated they would not pay any money for PrEP, around half (49.3%) would like to pay $14–84 per month, and very few (6.8%) would like to pay ≥283 per month (market rate). We found that PrEP awareness (unadjusted odds ratio (ORu) = 1.41; 95% CI: 1.01–1.97), acceptability (ORu =1.20; 95% CI: 1.07–1.34), perceived PrEP adherence (ORu =1.23; 95% CI: 1.08–1.41), and perceived PrEP benefit in reducing condom use (ORu =1.29; 95% CI: 1.07–1.55) were all associated with participants’ willingness to pay the market rate for PrEP. Other facilitators of PrEP pay willingness included full disclosure of sexual orientation to health professionals, high HIV literacy, and a high degree of HIV disclosure with sex partners.

Conclusions
The overall willingness to pay for the market rate of PrEP was low among this urban sample of Chinese MSM. Programs aiming to promote PrEP pay willingness should provide enhanced counseling to improve PrEP-related cognition, deliver accurate HIV/PrEP information to increase health literacy, and decrease stigma towards sexual minorities to develop trust with health professionals.
Comparative analysis of retrograde intrarenal surgery and modified ultra-mini percutaneous nephrolithotomy in management of lower pole renal stones (1.5–3.5 cm)
Authors: Li Zhuohang , Lai Cong , Shah Arvind K. , Xie Weibin , Liu Cheng , Huang Li , Li Kuiqing , Yu Hao , Xu Kewei 
Published: March 2020

AbstractBackgroundTo compare the safety and efficacy of retrograde intrarenal surgery (RIRS) and modified Ultra-mini percutaneous nephrolithotomy (UMP) in semi-supine combined lithotomy position for the management of 1.5–3.5 cm lower pole renal stones (LPSs).MethodsA total of 63 patients with 1.5–3.5 cm LPSs who underwent RIRS (n = 33) or modified UMP (n = 30) in diameter between January 2017 and January 2019 were analyzed retrospectively. Modified UMP was performed in semi-supine combined lithotomy position and a 9.5/11.5 F ureteral access sheath (UAS) was inserted during the procedure in order to maintain low pelvic pressure and to facilitate the removal of stone fragments. Base-line parameters, stone characteristics, illness condition, operation time, postoperative hemoglobin (Hb) drop, postoperative creatinine (Cr) elevation, length of hospital stay, length of postoperative hospital stay, stone-free rate (SFR) and complications were compared between the two groups.ResultsThere were no significant differences between the two groups in base-line parameters, stone characteristics and illness condition. The mean operating time of RIRS group was longer than UMP group (95.61 ± 21.9 vs. 55.0 ± 16.1 min,p < 0.001). The mean postoperative Hb drop was less in RIRS group (7.42 ± 4.7 vs. 15.70 ± 9.8 g/L,p < 0.001). The length of hospital stay and postoperative hospital stay for RIRS were shorter than UMP (4.76 ± 1.1 vs. 5.83 ± 0.8 d,p < 0.001, 2.97 ± 0.9 vs. 4.07 ± 0.9 d,p < 0.001). The Early SFR was higher in UMP group (54.5 vs. 80.0%,p < 0.050) while SFR at 1-month and 3-months postoperatively was similar in both groups (p = 0.504,p = 0.675). There were no significant differences between the two groups in complications (p = 0.228).ConclusionFor patients with 1.5–3.5 cm LPSs, both modified UMP and RIRS are safe and viable. The modified UMP technique was used in this study, application semi-supine combined lithotomy position and the retention of UAS can improve the surgical efficiency and maintain low pressure perfusion in the kidney, which resulted in superior treatment efficacy. Therefore, we highly recommend this technique for LPSs with heavy stone burdens.
Baseline white blood cell count-to-apolipoprotein A1 ratio as a novel predictor of long-term adverse outcomes in patients who underwent percutaneous coronary intervention: a retrospective cohort study
Authors: Pan Ying , Zhang Jian , Wu Ting-Ting , Hou Xian-Geng , Yang Yi , Ma Xiang , Ma Yi-Tong , Zheng Ying-Ying , XIE Xiang 
Published: March 2020

Abstract
Background
Previous studies suggested that baseline white blood cell count and apolipoprotein A1 levels were associated with clinical outcomes in patients with coronary heart disease (CAD) who underwent percutaneous coronary intervention (PCI). However, the ratio of baseline white blood cell count-to-apolipoprotein A1 level (WAR) and CAD after PCI have not been investigated. The present study investigated the effects of baseline WAR on long-term outcomes after PCI in patients with CAD.

Methods
A total of 6050 patients with CAD who underwent PCI were included in the study. Of these, 372 patients were excluded because no baseline white blood cell counts or apolipoprotein A1 (ApoA1) data was available or because of malignancies or other diseases. Finally, 5678 patients were enrolled in the present study and were divided into 3 groups according to WAR value: lower group - WAR< 5.25 (n = 1889); median group - 5.25 ≤ WAR≤7.15 (n = 1892); and higher group - WAR≥7.15 (n = 1897). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM), after PCI. The average follow-up time was 35.9 ± 22.6 months.

Results
A total of 293 patients developed ACM, including 85 (4.5%) patients in the lower group, 90 (4.8%) patients in the median group, and 118 (6.2%) patients in the higher group. The risk of ACM, cardiac mortality (CM), major adverse cardiovascular and cerebrovascular events (MACCEs), and major adverse cardiovascular events (MACEs) increased 62.6% (hazard risk [HR] =1.626, 95%CI: 1.214–2.179, P = 0.001), 45.5% (HR = 1.455, 95%CI: 1.051–2.014, P = 0.024), 21.2% (HR = 1.212, 95%CI: 1.011–1.454, P = 0.038), and 23.8% (HR = 1.238, 95%CI: 1.025–1.495, P = 0.027), respectively, as determined by multivariate Cox regression analyses comparing the patients in the higher group to patients in the lower group. Patients with a WAR≥4.635 had 92.3, 81.3, 58.1 and 58.2% increased risks of ACM, CM, MACCEs and MACEs, respectively, compared to the patients with WAR< 4.635. Every 1 unit increase in WAR was associated with 3.4, 3.2, 2.0 and 2.2% increased risks of ACM, CM, MACCEs and MACEs, respectively, at the 10-year follow-up.

Conclusion
The present study indicated that baseline WAR is a novel and an independent predictor of adverse long-term outcomes in CAD patients who underwent PCI.
CTLA-4 polymorphisms and predisposition to digestive system malignancies: a meta-analysis of 31 published studies
Authors: Li Jien , Wang Wenping , Sun Yanyan , Zhu Yeduo 
Published: March 2020

Abstract
Background
The results of genetic association studies regarding cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) polymorphisms and digestive system malignancies were controversial. The authors designed this meta-analysis to more precisely estimate relationships between CTLA-4 polymorphisms and digestive system malignancies by pooling the results of related studies.

Methods
The authors searched PubMed, Embase, Web of Science, and CNKI for eligible studies. Thirty-one eligible studies were pooled analyzed in this meta-analysis.

Results
The pooled meta-analysis results showed that genetic distributions of rs231775, rs4553808, and rs733618 polymorphisms among patients with digestive system malignancies and controls differed significantly. Moreover, genotypic distribution differences were also observed for rs231775 polymorphism among patients with colorectal cancer/pancreatic cancer and controls, for rs4553808 and rs5742909 polymorphisms among patients with gastric cancer and controls, for rs3087243 polymorphism among patients with liver cancer and controls, and for rs733618 polymorphism among patients with colorectal cancer and controls in pooled meta-analyses.

Conclusions
This meta-analysis suggested that rs231775 polymorphism was associated with predisposition to colorectal cancer and pancreatic cancer, rs4553808 and rs5742909 polymorphisms were associated with predisposition to gastric cancer, rs3087243 polymorphism was associated with predisposition to liver cancer, and rs733618 polymorphism was associated with predisposition to colorectal cancer.