bluuebunny/crossref_metadata_2025 huggingface dataset:
Student migration from Nepal to Japan: Factors behind the steep rise
Authors: Kharel Dipesh
Published: March 2022

Nepali student migration to Japan is a relatively new phenomenon, but one that has accelerated in recent years. The number of Nepali students increased from fewer than 1,000 in 2008 to over 29,000 in 2019, making them the third largest foreign student community in Japan. They migrate despite the exorbitant cost, with each student migrant usually paying 1.4 million Nepali rupees (USD 14,000) to a Japanese language institute (JLI) in Japan through an international educational consultancy (IEC) in Nepal to enter Japan on a student visa. Based on my ethnographic fieldwork in Japan and Nepal conducted from 2013 to 2019, this article examines the role of JLIs in Japan and IECs in Nepal in channeling students from Nepal to Japan. The paper shows the relationship among JLIs, IECs, student migrants and both states, and displays how push and pull factors operate between Japan and Nepal. The article shows the interconnection between the JLIs’ and IECs’ migration businesses and Japan’s side door policy for bringing in unskilled labor. The different actors do not compete with one another but are mutual beneficiaries, a reality that challenges the existing literature on the relationship between the states and the migration industry in both countries.
Successful removal of metallic foreign body in the neck-mediastinum via the parapharyngeal space approach
Authors: Ma Zuxia
Published: March 2022

Neck-mediastinum foreign body (FB) is a common emergency in otorhinolaryngology head and neck surgery departments, and it can be lethal. We present a case of an uncommon foreign body in the neck-mediastinum. The FB was metallic and about 12 cm long. A 74-year-old male accidentally swallowed a metallic FB that lodged in his throat for > 3 days. The intake of the object was associated with smoking a peace pipe, and was an indication for surgery. Aerodermectasia was observed in the neck upon physical examination, and a high-density foreign body was found in the neck-mediastinum through cervicothoracic computed-tomography (CT) scan. Electronic laryngoscopy showed a white pseudo-membrane adhering to the surface of the bilateral piriform fossa in the right laryngeal vestibule, and the root of the tongue, and mucosa were swollen. Cervicothoracic CT revealed dense shadows in the neck-mediastinum. However, electronic laryngoscopy showed no FB in the larynx or piriform fossa. The metal FB was removed by surgery via the parapharyngeal space approach instead of endoscopy. After preoperative assessment and preparation, we successfully removed the metal FB from the neck-mediastinum via the parapharyngeal space approach. The patient was doing well at one-month follow-up. Neck-mediastinum FB is an emergency but rare case necessitating otorhinolaryngology head and neck surgery. It can easily lead to mediastinal and lung infection; given its location in the body, it may lead to aortic arch rupture if not handled promptly.
Economic Burden Associated With Nasal Polyposis Recurrence Among Commercially Insured Patients in the United States
Authors: Zhdanava Maryia , Ndife Briana , Pilon Dominic , Rossi Carmine , Vermette-Laforme Maude , Lefebvre Patrick , Suh Jeffrey D.
Published: March 2022

Objective

To compare health care resource utilization (HRU) and costs among commercially insured patients with nasal polyposis (NP) with and without recurrence after endoscopic sinus surgery (ESS).

Study Design

Retrospective matched cohort study.

Setting

Adults with initial ESS or an NP excision after a new NP diagnosis were identified in Optum’s Clinformatics Data Mart Database (October 1, 2014–December 31, 2019).

Methods

The index date was the date of NP recurrence, identified with a claims‐based algorithm for the recurrent cohort, or a random date for the nonrecurrent cohort. Patients in both cohorts were matched 1:1 on baseline characteristics (12 months preindex) via propensity scores and exact matching factors. Annual HRU and costs (2019 US$) were compared between the matched cohorts at 12 months postindex.

Results

NP recurrence was identified among 3343 of 16,693 patients with initial ESS; after matching, each cohort comprised 1574 patients (median age, 54 years; 40% female) with similar baseline health care costs (recurrent, $34,420; nonrecurrent, $33,737). At 12 months postindex, the recurrent cohort had higher HRU, including 36% and 51% more outpatient and emergency department visits, respectively (all P < .01). Mean health care costs were $9676 higher in the recurrent cohort ($24,039) relative to the nonrecurrent cohort ($14,363, P < .01). The mean cost difference between cohorts was driven by $8211 in additional outpatient costs, as well as $6062 in additional NP‐related outpatient costs, in the recurrent cohort (all P < .01).

Conclusion

NP recurrence is associated with a substantial economic burden, which appears to be driven by outpatient services.
From a Slave to a Surgeon: David Kearney McDonogh, the First Black Otolaryngologist
Authors: Gudis David A. , McKinney Kibwei A. , Lustig Lawrence R.
Published: March 2022

David McDonogh, born into chattel slavery in Louisiana in the early 1800s, accomplished the unfathomable by becoming the first Black otolaryngologist in the United States of America. With tireless determination and profound intellect, Dr McDonogh surmounted immeasurable adversity along his improbable journey to freedom and success as an eye, ear, nose, and throat doctor in New York. His doctorate in medicine was posthumously awarded to his great‐great‐granddaughter in 2018 by the Columbia University Vagelos College of Physicians and Surgeons. In this History of Otolaryngology piece, we share his extraordinary story.
“A day-to-day struggle”: A comparative qualitative study on experiences of women with endometriosis and chronic pelvic pain
Authors: Hawkey Alexandra , Chalmers K. Jane , Micheal Sowbhagya , Diezel Helene , Armour Mike
Published: March 2022

Chronic pelvic pain (CPP) in women is a term that encompasses a range of conditions, including endometriosis, vulvodynia, painful bladder syndrome and adenomyosis. Given the impact on penetrative sex, fertility and potentially motherhood, CPP may also impact on women's identities as a wife or partner, a mother, and a woman. The aim of this study was to explore similarities and differences in experiences of women with endometriosis and non-endometriosis related CPP. A total of 17 participants aged between 21 and 48 years old participated in three focus groups. Using reflexive thematic analysis three main themes were found: the struggling woman, the unheard woman and the self-silenced woman. Women, regardless of the cause of their CPP, reported significant impacts on their intimate relationships, fertility, and parenting but those with non-endometriosis CPP often reported greater trouble communicating about pelvic pain in the workplace due to the “taboo” nature of discussing their vulval pain. Many participants described how a societal normalisation of pelvic pain resulted in women silencing their experiences, rendering their pain invisible. While women wanted to resist such silencing through information and support seeking, women with non-endometriosis CPP described fewer avenues to accessing credible informational resources or networks for support.
Early detect left ventricular subclinical myocardial dysfunction in patients with systemic lupus erythematosus by a left ventricular pressure-strain loop
Authors: Zhong Xiao-Fang , Chen Li-Xin , Liu Li-Xiong , Peng Gui-Juan , Luo Shu-Yu , Liu Dong-Sheng , Xu Jin-Feng , Liu Ying-Ying
Published: March 2022

Objective

Noninvasive myocardial work (MW) is a new technology which is based on strain after considering the load influence on myocardial deformation. We aimed to investigate the feasibility of quantitatively assessing left ventricular myocardial work (LVMW) in patients with systemic lupus erythematosus (SLE) using a left ventricular pressure-strain loop (LVPSL).

Methods

76 patients with SLE were included in the study (A), further divided into two subgroups according to the presence of lupus nephritis (LN). Global longitudinal strain (GLS), peak strain dispersion (PSD), global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were obtained.

Results

1: Patients with SLE demonstrated a significantly reduced GWE and GLS compared with control group, GWW and PSD were increased, above changes were more pronounced in patients with LN. There was no significant difference in GWI and GCW. 2: Receiver operating characteristic (ROC) analysis demonstrated that GWE was the most powerful tool for detecting myocardial insufficiency early in SLE patients, and the area under the curve (AUC) was 0.804, and was superior to GLS (AUC = 0.707). GWE remains the best indicator of subclinical myocardial injury in patients with LN. The AUC was 0.910, and the best cutoff point was 96.5% (sensitivity 83.3%, specificity 73.3%).

Conclusions

LVPSL can be used to noninvasively assess changes in MW in patients with SLE. Noninvasive GWE is a more sensitive index than GLS to detect subclinical myocardial injury early in SLE patients. This is a potential valuable clinical tool to assist in the early-find myocardial damage.
17 Months of the Pandemic: A Study of the Stress Spillover Among the BRICS Countries During COVID-19
Authors: Kumar Mohit , Gupta Arushi
Published: March 2022

This study examines the stress spillover of the stock market, bond market and exchange market among the BRICS countries during the COVID-19 pandemic. Following the principal component analysis approach, a composite stress index is developed for each country to measure the stress level in BRICS. We use the dynamic conditional correlation-generalized autoregressive conditional heteroskedasticity (DCC-GARCH) approach to investigate the dynamic connectedness among the countries. While the stress in the stock market and exchange market is measured by their respective volatility, the bond market fluctuation is examined by using the yield spreads between the 10-year government bonds yield of BRICS countries and 10-year government bond yield of the United States. The study finds that among all the BRICS countries, India and China have been major transmitters as well as receivers of the stress spillover. The findings of our study contribute to the literature by highlighting the importance of understanding the behaviour and interconnectedness of the economies in a group. The study also provides valuable insights to policymakers who need to be more vigilant about the financial crisis and spillover among the countries.
Gender Disparities Among Craniofacial Surgeons
Authors: Lala Brittany M , Salvador Trina M , Wang Fei , Shah Jinesh , Ricci Joseph A
Published: March 2022

To delineate career differences between genders of practicing plastic surgeons who have completed craniofacial fellowship given the known disparities in surgeons’ professional and personal lives and an already lengthy residency training, there is concern that less women may commit to further fellowship training.

Craniofacial fellowship programs were contacted to identify graduates and an internet search was attempted where information was not available. Surgeon profiles and literature databases were used to obtain practice demographics and publications.

Accredited fellowships were identified through the American Society of Craniofacial Surgeons directory.

Program responses along with internet searches identified 201 graduates from 26 programs, of which 132 (66%) were men and 69 (34%) were women. On average, male graduates had 7.1 years in practice versus 6.6 years for females graduates ( P = .176). There were significant differences between average number of publications (24.7 publications for males vs 14.1 for females, P = .009) and academic practice (46% males vs 64% females, P = .018). A similar percentage of males and females held leadership positions (13% males vs 16%, P = .552).

Despite similar years in practice, men had significantly higher publications while women were significantly more likely to practice in an academic setting. Females are increasing their representation in academia and leadership within the craniofacial community. However, efforts must still be directed at increasing exposure to craniofacial surgery and supporting research and leadership pursuits earlier on during their careers.
The Current Landscape of Oral Squamous Cell Carcinoma: A Comprehensive Analysis from ClinicalTrials.gov
Authors: Zou Zhaolei , Li Bin , Wen Shuqiong , Lin Dongjia , Hu Qiannan , Wang Zhi , Fang Juan
Published: March 2022

Objective

A better understanding of the current characteristics of clinical trials in oral squamous cell carcinoma (OSCC) is important to improve trial design and identify neglected areas of research. The objective is to summarize the current characteristics and publication status of OSCC trials registered on ClinicalTrials.gov.

Methods

The ClinicalTrials.gov database was searched on November 9, 2020, for trials containing the term “oral squamous cell carcinoma”. We assessed the characteristics of the included trials and searched the publication status of the primary completed trials by using PubMed and Google Scholar.

Results

Our search identified 325 studies for analysis, including 279 interventional (85.8%) and 46 observational (14.2%) studies. Interventional studies were mostly single-group (50.9%), single-center (57.0%), non-randomized (59.1%), open-label (81.4%), and early-phase (70.6%) trials. The vast majority of the studies (82.8%) focused on the treatment of OSCC. Chemotherapy (36.8%) was the most common treatment, followed by targeted therapy (15.2%) and immunotherapy (15.2%). Furthermore, 58.9% of the primary completed interventional studies were published by January 8, 2021, and the median time to publication was 48.0 months. Studies registered before this study began (HR = 1.69, 95% CI = 1.02–2.80, P = .040) and in phases 1/2 or 2 (HR = 2.10, 95% CI = 1.09–4.06, P = .026) were associated with an improved likelihood of publication.

Conclusions

OSCC clinical trials usually have small sample size and are open-label and non-randomized studies. Advanced OSCC and immunotherapy-oriented therapy are becoming the focus of current trials. Researchers should perform standardized registration and publish their results in a timely manner.
Health professionals’ practice to care cytotoxic drug handling and associated factors: The case of university of gondar specialized hospital
Authors: Simegn Wudneh , Dagnew Baye , Dagne Henok
Published: March 2022

Background

Health care professionals are potential to be in contact with cytotoxic drugs during their daily work activ­ities. The study aimed to assess the practice of health professionals to care for cytotoxic drugs and associated factors in the University of Gondar Specialized Hospital.

Methods

Cross-sectional study design was employed. EPI Info 7 was used for data entry and then exported into SPSS 20 for statistical analysis. Frequencies and mean with standard deviation were computed. Logistic regression had been performed to find out associated factors. Crude’ and adjusted Odds’ ratio with 95% uncertainty interval was done. Variables with a p < 0.05 were declared as significant factors for practice of cytotoxic drug handling.

Results

The study used four-hundred and twelve health professionals took part in the study with 97.4% response rate. The mean age of study participants was 29.9 years ranging from 20–60 years and twenty (53.4%) participants were males. One hundred and fifty-five (37.6%) health professionals had good cytotoxic drug handling practice. Attending an average of 4–9 patients per day (AOR = 2.12, 95% CI: 1.05, 4.22), Medium work stress (AOR = 2.01, 95% CI: 1.04, 3.90), availability of cytotoxic drug handling manual (AOR = 2.51: 95% CI: 1.22, 5.12), and good knowledge (AOR = 4.09, 95% CI: 2.35, 7.11) were significantly associated with cytotoxic drug handling practice.

Conclusion

The practice of cytotoxic drug handling care was low. It demands the engagement of the health sector to avert such inadequate practice and has to focus on delivering knowledge and logistics for the practice of cytotoxic drug handling.
Non-arteritic anterior ischemic optic neuropathy after uneventful delivery in a healthy woman
Authors: Montolío-Marzo Santiago , Gallego-Pinazo Roberto , Dolz-Marco Rosa , Lanzagorta-Aresti Aitor , Pérez-López Marta
Published: March 2022

Introduction

Non-arteritic anterior ischemic optic neuropathy (NAION) is the most common cause of optic nerve swelling and optic neuropathy in adults over 50 years of age. It has been rarely reported during pregnancy, mostly related to systemic and ocular predisposing conditions.

Case Report

We report the case of a 44 years-old healthy female with no previous remarkable clinical history. She had in vitro fertilisation treatment to get pregnant. 18 days after uneventful cesarean section she referred sudden painless vision loss in her right eye (RE), denser inferiorly, with concurrent optic disc edema and relative afferent pupillary defect. Steroid intravenous treatment during the acute episode showed no improvement. Our patient showed normal magnetic resonance imaging (MRI), blood test, autoimmune disease biomarkers, infectious serology and inflammatory markers. She was diagnosed of RE NAION. After one year follow-up visual field defect remains stable.

Conclusion

As far as we know this is the first report of NAION after in vitro fertilisation, uneventful pregnancy and cesarean section showing no systemic or ocular risk factors other than a small cup to disc ratio. Hemodynamic and hormonal changes during late pregnancy and uneventful cesarean section can trigger an episode of NAION in a healthy young woman.
Study of vitamin D penetration in the human aqueous after topical administration
Authors: Lorusso Massimo , Micelli Ferrari Luisa , Cicinelli Maria Vittoria , Ciani Saba , Ceci Edmondo
Published: March 2022

Purpose

this study was designed to measure the concentration of Vitamin D in the aqueous and to investigate if its topical application can increase quantities in aqueous humor.

Methods

29 patients scheduled for cataract surgery were divided into two groups. Group 1 was used as a control group, in group 2 patients were instructed to instill one drop of vitamin D eye drops three times daily 10 days before surgery .Aqueous humor was collected with a 30-gauge needle immediately before surgery. Vitamin D concentrations were analyzed by liquid chromatography tandem mass spectrometry.

Results

Aqueous humor (AH) samples in both groups had small but detectable vitamin D levels. In the AH concentrations of vitamin D were, respectively, 2.1ng/mL 土0.4 in group 1 and 2.1ng/mL土0.3 in group 2(P = 0.9).

Conclusion

Our study confirmed the presence of vitamin D in AH. No significant difference of vitamin D concentration in AH was observed between the treatment and control group.
Preservice music teachers in New South Wales: How prepared do they feel for secondary music teaching in a changing world?
Authors: Carter Jennifer
Published: March 2022

The ideas and philosophies of preservice secondary music teachers (PSMTs) are formalized in their tertiary education years. In these years, PSMTs must reconcile the expectations, beliefs, and values espoused by their lecturers, tutors, and other significant people from their past. PSMTs have accumulated various musical experiences through prior interactions with their primary and secondary school teachers and private tutors, which nurture and shape the kind of teachers they anticipate becoming. This research focuses on a group of six PSMTs who face a very different future, teaching in the COVID-19 world of digital delivery amid a time of curriculum change in New South Wales (NSW), Australia. Thirty-minute Zoom interviews with the six participants took place over the two semesters of 2020, beginning before the COVID-19 outbreak in Australia and investigating how prepared PSMTs felt they were for classroom teaching. Their most positive responses regarding online learning provided evidence that their music lecturers had built PSMTs’ understanding of the curriculum, which increased their confidence in their musical ability during practicum. The findings in this article provide an informed NSW perspective about PSMTs’ tertiary education, adding to research about classroom music pedagogy. Finally, the opinions of PSMTs on their current learning and future careers are of importance and interest for both tertiary education institutions and curriculum designers.
Last chance to travel or safety first? The influence of exposure to natural hazards and coping capacities on tourism consumption
Authors: Nguyen Canh P
Published: March 2022

The literature shows that natural disasters adversely affect international (arrivals) tourism. However, there seems to have been a lack of consideration of the dynamics of domestic and outbound (departure) tourism consumption in respect of natural hazards. To address this gap, this study uses a unique dataset of exposure to natural hazards and coping capacities for a global sample of 145 economies from 2011 to 2019 to examine the influence on domestic, outbound and total tourism spending. Exposure appears to have inverted U-shaped relationships with domestic and total tourism spending, and a U-shaped relationship with outbound spending. Coping capacities, in contrast, have U-shaped relationships with domestic and total tourism spending, with an inverted U-shaped relationship with outbound spending. Lastly, the analyses for four income groups and seven regions show some heteroscedasticity. The findings suggest that governments should build coping capacities for the recovery of tourism after disaster events.

JEL codes: Z32, Z38, Q01, Q54
Consumer preference structure of online privacy concerns in an IoT environment
Authors: Kim Woojae , Park Yuri , Shin Jungwoo , Jo Manseok
Published: March 2022

Due to the development of the Internet of Things (IoT) and IoT environments, various concerns have been raised regarding personal information infringement and leakage. To establish a policy for addressing this issue, it is essential to estimate the damage caused by personal information infringement and leakage and decide upon an appropriate policy direction that reflects consumer’s value of their personal information. Therefore, we first estimated how much consumers value each type of personal information using contingent valuation method and assigning a monetary value to each information type. Second, we analyzed consumers’ preference for conditions in which they will provide personal information. A conjoint analysis was used to discover consumer preference concerning the various attributes of the conditions and a mixed logit model was used for the empirical analysis. The results of the analysis show that consumers valued personal information related to private life the most, at approximately USD 110 on average. We also found that demographic variables such as gender and income level affect personal information values. The results of the attributes required to provide personal information analysis found that opt-in was preferred to opt-out and that consumers preferred having optimal authority to control their personal information, rather than whole authority. These results show that consumers are willing to provide their personal information when an adequate reward is given. Therefore, formulating policy direction to establish a confidential market for trading personal information rather than unconditional personal information protection is required.
Use of Network Pharmacology and Molecular Docking Methods to Elucidate the Curative Effect of Epimedium–Anemarrhen on Osteoporosis
Authors: Xu Bo , Zhou Yu , Wang Qing , Liu Yujiang , Zhang Long , Wang Songlin , Zhang Xianda , Li Wenchao , Shen Xiaofeng , Li Yuwei
Published: March 2022

Objective: Using network pharmacology and molecular docking methods, this study aimed to elucidate the key targets and molecular mechanisms of the Epimedium–Anemarrhen (EA) combination as a therapeutic approach for osteoporosis (OP). Methods: The TCMSP database was used to identify effective active ingredients and information on targets of EA according to the ADME threshold. An OP target database was established using the GeneCards, OMIM, DrugBank, and DisGeNET databases. The intersection of drug targets and disease targets was used to identify common genes, and protein interaction network, GO function enrichment, and KEGG signal pathway enrichment analyses were performed. A molecular docking analysis of active pharmaceutical ingredients with core genes was also conducted. Results: The analysis identified 30 effective active ingredients in EA and 149 common genes. A total of 20 core genes were identified by constructing a protein–protein interaction network and calculating the network topology parameters. An enrichment analysis revealed that these targets were primarily involved in biological functions and processes such as cell proliferation, apoptosis, inflammation, oxidative stress, and immunity. The signaling pathways associated with OP include the AGE-RAGE signaling pathway in relation to diabetes complications, the IL-17 signaling pathway, and the TNF signaling pathway. Molecular docking showed stable affinity between the core genes and most of the key components. Conclusion: These data provide mechanistic insights into the pharmacological activity of EA in the treatment of OP and provide an essential theoretical basis for clinical practice.
Src-related thrombocytopenia: a fine line between a megakaryocyte dysfunction and an immune-mediated disease
Authors: Palma-Barqueros Verónica , Revilla Nuria , Zaninetti Carlo , Galera Ana María , Sánchez-Fuentes Ana , Zámora-Cánovas Ana , Bohdan Natalia , Padilla José , Marín-Quilez Ana , Rodriguez-Alen Agustín , Fuster José Luis , Greinacher Andreas , Vicente Vicente , Bastida José María , Rivera José , Lozano María Luisa
Published: March 2022

Src-related thrombocytopenia (SRC-RT) is a rare autosomal dominant, inherited platelet disorder resulting from the p.E527K heterozygous germline gain-of-function variant of Src. To date, genetic diagnosis of the disease has only been reported in 7 patients from 3 unrelated families. The clinical features ranged from isolated thrombocytopenia to complex syndromic manifestations characterized by thrombocytopenia, bleeding, myelofibrosis, splenomegaly, and bone disease. We report a new 3-generation kindred with the Src p.E527K variant. Patients presented with rather variable platelet counts (38-139 × 109/L), mildly impaired platelet function, >15% immature platelet fraction, and with a significant proportion of large-giant platelets. Four adults from the family were diagnosed with immune thrombocytopenia (ITP) and underwent splenectomy, achieving sustained platelet counts >75 × 109/L for several years; increases in platelet counts were also observed after corticosteroid therapy. Four of 7 Src p.E527K variant carriers showed immune defects and recurrent infections. In addition, a range of neurological symptoms, from specific language impairment to epilepsy, was seen in some family members. Patient platelets exhibited constitutive Src, Bruton tyrosine kinase, and phospholipase Cγ2 activation, and after stimulating CD19 cells by crosslinking surface immunoglobulin M, phosphorylated extracellular signal-regulated kinase (ERK) was significantly increased in B cells from individuals carrying the Src p.E527K substitution. In summary, in addition to causing impaired platelet production, SRC-RT may associate immune dysregulation and increased platelet consumption. In families in whom several members are responsive to ITP-directed therapies, an underlying Src p.E527K variant should be excluded.
Effect of additional cytogenetic abnormalities on survival in arsenic trioxide-treated acute promyelocytic leukemia
Authors: Epstein-Peterson Zachary D. , Derkach Andriy , Geyer Susan , Mrózek Krzysztof , Kohlschmidt Jessica , Park Jae H. , Rajeeve Sridevi , Stein Eytan M. , Zhang Yanming , Iland Harry , Campbell Lynda J. , Larson Richard A. , Poiré Xavier , Powell Bayard L. , Stock Wendy , Stone Richard M. , Tallman Martin S.
Published: March 2022

Frontline arsenic trioxide (ATO)–based treatment regimens achieve high rates of long-term relapse-free survival in treating acute promyelocytic leukemia (APL) and form the current standard of care. Refining prognostic estimates for newly diagnosed patients treated with ATO-containing regimens remains important in continuing to improve outcomes and identify patients who achieve suboptimal outcomes. We performed a pooled analysis of exclusively ATO-treated patients at a single academic institution and from the ALLG APML4 and Alliance C9710 studies to determine the prognostic importance of additional cytogenetic abnormalities and/or complex karyotype. We demonstrated inferior event-free survival for patients harboring complex karyotype (hazard ratio [HR], 3.74; 95% confidence interval [CI], 1.63-8.56; P = .002), but not for patients harboring additional cytogenetic abnormalities (HR, 2.13; 95% CI, 0.78-5.82; P = .142). These data support a role for full karyotypic analysis of all patients with APL and indicate a need for novel treatment strategies to overcome the adverse effect of APL harboring complex karyotype.
Developing a dynamic simulation model to support the nationwide implementation of whole genome sequencing in lung cancer
Authors: van de Ven Michiel , IJzerman Maarten , Retèl Valesca , van Harten Wim , Koffijberg Hendrik
Published: March 2022

Background

This study shows how dynamic simulation modeling can be applied in the context of the nationwide implementation of Whole Genome Sequencing (WGS) for non-small cell lung cancer (NSCLC) to inform organizational decisions regarding the use of complex and disruptive health technologies and how these decisions affect their potential value.

Methods

Using the case of the nationwide implementation of WGS into clinical practice in lung cancer in the Dutch healthcare system, we developed a simulation model to show that including service delivery features across the diagnostic pathway can provide essential insight into the affordability and accessibility of care at the systems level. The model was implemented as a hybrid Agent-Based Model and Discrete-Event Simulation model in AnyLogic and included 78 hospital agents, 7 molecular tumor board agents, 1 WGS facility agent, and 5313 patient agents each year in simulation time.

Results

The model included patient and provider heterogeneity, including referral patterns, capacity constraints, and diagnostic workflows. Patient preference and adoption by healthcare professionals were also modeled. The model was used to analyze a scenario in which only academic hospitals have implemented WGS. To prevent delays in the diagnostic pathway, the capacity to sequence at least 1600 biopsies yearly should be present. There is a two-fold increase in mean diagnostic pathway duration between no patients referred or all patients referred for further diagnostics.

Conclusions

The systems model can complement conventional health economic evaluations to investigate how the organization of the workflow can influence the actual use and impact of WGS. Insufficient capacity to provide WGS and referral patterns can substantially impact the duration of the diagnostic pathway and thus should be considered in the implementation of WGS.
Clinical characteristics and risk factors of Aeromonas bloodstream infections in patients with hematological diseases
Authors: Xu Chunhui , Lin Qingsong , Zhao Yuanqi , Zhu Guoqing , Jiang Erlie , Li Shangzhu , Mi Yingchang , Zheng Yizhou , Zhang Fengkui , Zhu Xiaofan , Xiao Zhijian , Han Mingzhe , Wang Jianxiang , Feng Sizhou
Published: March 2022

Background

To analyze the clinical features, risk factors and outcomes of Aeromonas bloodstream infections (BSIs) in patients with hematological diseases to establish an effective optimal therapy against it.

Methods

A retrospective study was performed by reviewing medical records of patients admitted to a tertiary blood disease hospital in China. Patients with hematological diseases who suffered from Aeromonas bacteremia during January 2002 to December 2020 were enrolled in this study.

Results

A total of 63 patients who developed Aeromonas bacteremia were enrolled in the study, and 91.9% of patients were neutropenic at the onset of BSIs. The major complications were skin and soft tissue infection (SSTI) (22.2%), followed by gastroenteritis (19.0%) and pneumonia (14.3%). High carbapenem resistance rates (70.8% for imipenem, 71.4% for meropenem) were note among the cases. Furthermore, Aeromonas strains isolated from five individuals developed resistance to quinolone, β-lactams and tigecycline during the therapy. The 30-day mortality rate was 15.9%, while bacteremia with SSTI showed a much worse prognosis, with 50.0% (7/14) of the patients dying within 30 days of initiating the therapy. In the multivariate analysis, SSTI (OR = 28.72; 95% CI, 1.50–551.30; P = 0.026) and shock (OR = 47.58; 95% CI,1.06–2126.80; P = 0.046) were independent risk factors for mortality.

Conclusions

Aeromonas bacteremia usually occurred in patients with neutropenic status, and patients with SSTIs were more likely to show a worse prognosis. Carbapenems should be avoided in patients with Aeromonas BSIs and SSTIs given high resistance rate.
Disseminated cutaneous Actinomyces bovis infection in an immunocompromised host: case report and review of the literature
Authors: Cunha Flávia , Sousa David Lopes , Trindade Luís , Duque Vítor
Published: March 2022

Background

Actinomycosis is an uncommon endogenous bacterial infection caused by Actinomyces species, characterized by the development of abscesses, tissue fibrosis, and fistulisation. It remains a diagnostic challenge, due to its similarities with diverse aetiologies’ presentation, such as neoplasms, tuberculosis, or fungal infections. Actinomyces bovis is a microorganism rarely reported as a cause of human disease. Cutaneous involvement is sporadic. In this case, Actinomyces bovis was responsible for disseminated cutaneous disease in an immunosuppressed patient.

Case presentation

We report the case of a 69-year-old female with multiple skin masses, under immunosuppressive therapy due to ulcerative colitis. Imaging exams were compatible with multiple cutaneous abscesses in the cervicofacial region and limbs. Actinomyces bovis was isolated in culture after abscess drainage. Antimicrobial therapy with parenteral penicillin G and oral amoxicillin was administered for 6 months, with complete resolution of cutaneous lesions and no relapse of the infection.

Conclusions

Considering actinomycosis as a possible diagnosis in the presence of subacute/chronic recurrent mass-like cutaneous lesions, especially in the setting of immunosuppression, may reduce the burden associated with delayed diagnosis and incorrect treatment and provide better outcomes and improvement of patient’s quality of life.
Listeriosis during pregnancy: a retrospective cohort study
Authors: Ke Yefang , Ye Lina , Zhu Pan , Sun Ying , Zhu Zhe
Published: March 2022

Background

Pregnancy-associated listeriosis is a severe infectious disease and potentially leads to fetal/neonatal fatal, while limited information on pregnancy-associated listeriosis is available in China. This study aimed to reveal the clinical characteristics and outcomes of pregnancy-associated listeriosis cases and provide references for treating and managing this disease.

Methods

We performed a retrospective study on maternal and neonatal patients with pregnancy-associated listeriosis. The clinical characteristics of pregnancy-associated listeriosis were studied, and the outcome determinants of neonatal listeriosis were explored.

Results

14 cases of pregnancy-associated listeriosis were identified. The incidence of pregnancy-associated listeriosis in our hospital was 16.69/100,000 births. All of the 14 maternal patients eventually recovered after delivery shortly with no sequelae. None of the 12 mothers who delivered in this hospital received antepartum first-line empirical treatment. Among the 14 neonatal cases, 1 was late-onset listeriosis and 13 were early-onset cases; 11 survived and 3 died. Fatality rates were significantly higher in outborn neonates (P = 0.005). Besides, higher mortality rates were observed in neonates with lower birth weight (P = 0.038), gestational age < 28 weeks (P = 0.056), and Apgar score (5th min) < 5 (P = 0.056), with marginally significant differences.

Conclusions

Pregnancy-associated listeriosis would bring disastrous effects to the neonatal cases, especially to the outborn, low birth weight, and low gestational age of neonates. Timely detection and treatment should be taken seriously for the key neonates. How to early detect L. monocytogenes infected cases, especially in the prenatal stage, remains a serious challenge.
Suppressive effect of α-mangostin for cancer stem cells in colorectal cancer via the Notch pathway
Authors: Jo Min Kyoung , Moon Chang Mo , Kim Eun Ju , Kwon Ji-Hee , Fei Xiang , Kim Seong-Eun , Jung Sung-Ae , Kim Minsuk , Mun Yeung-Chul , Ahn Young-Ho , Seo Seung-Yong , Kim Tae Il
Published: March 2022

Background

Since colon cancer stem cells (CSCs) play an important role in chemoresistance and in tumor recurrence and metastasis, targeting of CSCs has emerged as a sophisticated strategy for cancer therapy. α-mangostin (αM) has been confirmed to have antiproliferative and apoptotic effects on cancer cells. This study aimed to evaluate the selective inhibition of αM on CSCs in colorectal cancer (CRC) and the suppressive effect on 5-fluorouracil (5-FU)-induced CSCs.

Methods

The cell viability assay was performed to determine the optimal concentration of αM. A sphere forming assay and flow cytometry with CSC markers were carried out to evaluate the αM-mediated inhibition of CSCs. Western blot analysis and quantitative real-time PCR were performed to investigate the effects of αM on the Notch signaling pathway and colon CSCs. The in vivo anticancer efficacy of αM in combination with 5-FU was investigated using a xenograft mouse model.

Results

αM inhibited the cell viability and reduced the number of spheres in HT29 and SW620 cells. αM treatment decreased CSCs and suppressed the 5-FU-induced an increase in CSCs on flow cytometry. αM markedly suppressed Notch1, NICD1, and Hes1 in the Notch signaling pathway in a time- and dose-dependent manner. Moreover, αM attenuated CSC markers CD44 and CD133, in a manner similar to that upon DAPT treatment, in HT29 cells. In xenograft mice, the tumor and CSC makers were suppressed in the αM group and in the αM group with 5-FU treatment.

Conclusion

This study shows that low-dose αM inhibits CSCs in CRC and suppresses 5-FU–induced augmentation of CSCs via the Notch signaling pathway.
Late combination of transarterial chemoembolization with apatinib and camrelizumab for unresectable hepatocellular carcinoma is superior to early combination
Authors: Ju Shuguang , Zhou Chen , Hu Junwen , Wang Yingliang , Wang Chaoyang , Liu Jiacheng , Yang Chongtu , Huang Songjiang , Li Tongqiang , Chen Yang , Bai Yaowei , Yao Wei , Xiong Bin
Published: March 2022

Objective

The purpose of this study was to explore the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab (TACE + AC) for unresectable hepatocellular carcinoma (HCC), and the impact of the timing of the combination on it.

Methods

In this single-arm retrospective study, consecutive data of patients with unresectable HCC treated to our hospital from March 2017 to September 2021 were collected. These patients were treated with TACE and started on camrelizumab and apatinib within one week of TACE. Camrelizumab 200 mg intravenously once every three weeks and apatinib 250 mg orally once daily. Repeat TACE treatment was available on an on-demand basis. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. The univariate and multivariate Cox regression analyses were used to assess the effect of early and late combination on OS and PFS.

Results

A total of 80 patients were enrolled in this study. The median OS was 22.1 months (95% confidence interval [CI]: 13.8–30.5 months) and the median PFS was 15.7 months (95% CI: 14.7–16.6 months). The ORR was 58.8% (95% CI: 47.2–69.6) and DCR reached 81.2% (95% CI: 71.0–89.1). Multivariable Cox proportional hazard regression analyses showed that TACE late combined with apatinib and camrelizumab provided better OS than early combination (HR = 0.175, 95% CI:0.060–0.509, P = 0.001), as did PFS (HR = 0.422, 95% CI:0.184–0.967, P = 0.041). All treatment-related adverse events were tolerable, and no serious adverse events were observed.

Conclusion

TACE combined with apatinib plus camrelizumab for patients with unresectable HCC has promising antitumor activity and a manageable safety profile. For unresectable HCC with large tumor burden, late combination provides better OS and PFS compared to early combination.
Association between endoscopic cyclophotocoagulation and vitreous prolapse in trabeculectomy: a case report
Authors: Ng Vikki W. K. , Chan Jeffrey C. W. , Li Kenneth K. W.
Published: March 2022

Background

To propose that possible alteration or damage to the ciliary zonules during uncomplicated endoscopic cyclophotocoagulation (ECP) can cause complications in subsequent filtration surgery.

Case presentation

We present two cases with uncomplicated primary combined phacoemulsification and ECP that underwent subsequent trabeculectomy. Both cases were complicated with vitreous prolapse during the trabeculectomy procedure. We review the anatomy of the ciliary zonules and their spatial relationship with the ciliary processes targeted during ECP and propose an association between ECP, zonular damage and complications in subsequent trabeculectomy such as vitreous prolapse.

Conclusions

Damage to ciliary zonules during ECP may not manifest until subsequent glaucoma filtration surgery. In patients who received prior ECP, we may consider taking preventative measures to avoid associated complications such as vitreous prolapse. Patients with known risk factors for weak zonules may consider choosing alternative intraocular pressure-lowering means.
Change of risk behaviour in young people – the effectiveness of the trauma prevention programme P.A.R.T.Y. considering the effect of fear appeals and cognitive processes
Authors: Koehler Michael , Brockamp Thomas , Bamberg Sebastian , Gehlert Tina
Published: March 2022

Background

The purpose of the present study was to examine the effectiveness of the injury awareness and prevention programme P.A.R.T.Y. (Prevent Alcohol and Risk-Related Trauma in Youth) in Germany. On a designated P.A R.T.Y. day, school classes spend a day in a trauma hospital experiencing the various wards through which a seriously injured person goes. A further goal of the study was to reveal indications of the programme’s mechanism of action by testing theory-based impact models of fear appeals and cognitive beliefs.

Methods

In a quasi-experimental longitudinal study with three measurement times the participants of 19 P.A.R.T.Y. days (n = 330), as well as pupils who did not attend the programme (n = 244), were interviewed with a standardised questionnaire. They reported risk behaviour, feelings of threat and cognitive beliefs about road traffic. The data were analysed using a meta-analytical approach to estimate an average effect size across the different P.A.R.T.Y. days. Path models were used to identify possible mechanisms of action.

Results

For most of the parameters, small positive effects could be proven immediately after the P.A.R.T.Y. intervention. However, after four to 5 months only one statistically significant effect was found. Using path analytical models, important predictors for behavioural changes (e.g. self-efficacy) could be identified. But for these predictors no or only short-term effects were observed in the meta-analysis.

Conclusions

Fear appeals as used primarily in the P.A.R.T.Y. programme appear to cause behavioural changes only to a limited extent and only in the short-term, especially if the strengthening of psychosocial resources is not given sufficient consideration. The participants must also cognitively process the experiences in the hospital. Accordingly, consideration should be given to how the P.A.R.T.Y. program could be adapted to complement the fear appeal with cognitive components.
Prediction of future risk of any and higher-grade prostate cancer based on the PLCO and SELECT trials
Authors: Gelfond Jonathan A. , Hernandez Brian , Goros Martin , Ibrahim Joseph G. , Chen Ming-Hui , Sun Wei , Leach Robin J. , Kattan Michael W. , Thompson Ian M. , Ankerst Donna Pauler , Liss Michael
Published: March 2022

Background

A model was built that characterized effects of individual factors on five-year prostate cancer (PCa) risk in the Prostate, Lung, Colon, and Ovarian Cancer Screening Trial (PLCO) and the Selenium and Vitamin E Cancer Prevention Trial (SELECT). This model was validated in a third San Antonio Biomarkers of Risk (SABOR) screening cohort.

Methods

A prediction model for 1- to 5-year risk of developing PCa and Gleason > 7 PCa (HG PCa) was built on PLCO and SELECT using the Cox proportional hazards model adjusting for patient baseline characteristics. Random forests and neural networks were compared to Cox proportional hazard survival models, using the trial datasets for model building and the SABOR cohort for model evaluation. The most accurate prediction model is included in an online calculator.

Results

The respective rates of PCa were 8.9%, 7.2%, and 11.1% in PLCO (n = 31,495), SELECT (n = 35,507), and SABOR (n = 1790) over median follow-up of 11.7, 8.1 and 9.0 years. The Cox model showed higher prostate-specific antigen (PSA), BMI and age, and African American race to be associated with PCa and HGPCa. Five-year risk predictions from the combined SELECT and PLCO model effectively discriminated risk in the SABOR cohort with C-index 0.76 (95% CI [0.72, 0.79]) for PCa, and 0.74 (95% CI [0.65,0.83]) for HGPCa.

Conclusions

A 1- to 5-year PCa risk prediction model developed from PLCO and SELECT was validated with SABOR and implemented online. This model can individualize and inform shared screening decisions.