bluuebunny/crossref_metadata_2025 huggingface dataset:
Refractory Chronic Urticaria in Adults: Clinical Characterization and Predictors of Severity
Authors: Coutinho Iolanda Alen , Regateiro Frederico Soares , Fernandes Rosa Anita , Pita Joana Sofia , Gomes Raquel , Coelho Constança , Todo-Bom Ana
Published: October 2020

Background: Chronic urticaria (CU) is defined as recurrent urticaria lasting for more than 6 weeks. Objectives: We aimed to characterize the phenotypes of patients with CU refractory to standard dose anti-H1 antihistamine treatment and search for clinical predictors of poor disease control.Methods: Retrospective collection of data regarding clinical characteristics, comorbidities, treatment, and disease control of all adult refractory CU patients presenting to the Allergy and Immunology Department during one year.Results: Sixty-one adult patients were included, 74% females, average age 44.5 years (18 to 84 years old). Most patients (78.7%) had initiated CU less than 1 year before enrolment. Chronic spontaneous urticaria (CSU) accounted for 55.7% of the patients, CSU associated with chronic inducible urticaria (CIndU) as a comorbidity for 44.3%, and angioedema was present in 55.7%. Medically-confirmed psychiatric disorders were present in 78.7%. Complementary diagnostic tests were performed in cases with more severe presentation (UAS7 ≥28 and/or UCT <12) or with longer evolution (>1 year), corresponding to 42 tested patient. Evidence for autoimmunity (positive anti-thyroid peroxidase antibodies, anti-nuclear antibodies or autologous serum test) was found in 45.2% (n=19/42), and high C-reactive protein was present in 14.3% (n=6/42), half of these also had positive antinuclear antibodies. Forty-six patients (75.4%) had at least one significant exacerbation, requiring medical appointment, emergency room, hospitalization or job absenteeism. The number of exacerbations correlated with the presence of angioedema (p=0.022), with a recent diagnosis (<1 year), and with higher UAS7 severity (p=0.006). Although ClndU was associated with poor symptom control (p=0.022), it was also associated with less exacerbations requiring medical observation or hospitalization (p=0.015). All patients were using antihistamines and 21.3% (n = 13) of them were also under treatment with omalizumab, ciclosporine or montelukast for disease control.Conclusions: Autoimmunity can affect about half of the patients with severe or long-term CU. UAS7 and angioedema are associated with disease exacerbations. UAS7 and UCT presented unequal accuracy, with UAS7 better associating with the occurrence of exacerbations and treatment doses. Patients with refractory CU frequently present psychiatric disorders. Accurate diagnostic tests, namely autoimmune parameters and inflammatory markers, should be recommended in some individual cases.
Just Say “No”: Can Dentists Refuse Care on the Basis of Finances? A Survey Using an Ethical Vignette in an Iranian Dental School
Authors: Kazemian Ali , Fayyazi Mahsa , Shafiee Shahrzad
Published: October 2020

Objective: The aim of this study was to evaluate how dental students and tutors think about their position for, or against fee reduction at dental offices. Method: It was a questionnaire-based survey, which examined the ethical attitudes of students and tutors of an Iranian Dental School. The questionnaire included a vignette about an ethical dilemma at a dental office. Different ethical approaches, i.e. duty-based, virtue-oriented and consequentialist arguments, for or against fee reduction at dental office were suggested. Respondents were asked to rank those ethical options. Data was entered and analyzed in SPSS 16.0. Result: 121 dental students and thirty-six faculty members (dental specialists) participated in this study. It revealed that a majority of dental students and tutors (68%) are in favor of charging patients less, when facing an imagined request at dental office, using either virtue-oriented (54%) or consequentialist (14%) argument for fee reduction. The difference between rankings of four options was statistically significant, while no statistically significant difference exists neither between male and female respondents, nor students and tutors. Conclusion: This case study provides a basis for fruitful discussions in ethics courses for dental students. Our study suggests that financial issues should be considered as a part of ethical training within the dental student's curriculum.
Active learning of medical students in Taiwan: A realist evaluation
Authors: Huang Chien-Da , Tseng Hsu-Min , Jenq Chang-Chyi , Ou Liang-Shiou
Published: October 2020

Background: Active learning is defined as any instructional method that engages students in the learning process. Cultural differences in learning patterns can play an important role in engagement with active learning. We aimed to examine process models of active learning to understand what works, for whom and why.
Methods: Forty-eight sixth- and seventh-year medical students with experience of active learning methods were purposively selected to participate in ten group interviews. Interactions around active learning were analysed using a realist evaluation framework to unpack the ‘context-mechanism-outcome’ (CMO) configurations.
Results: Three core CMO configurations, including cultural, training and individual domains, were identified. In the cultural context of a strong hierarchical culture, the mechanisms of fear prompted students to be silent (outcome) and dare not give their opinions. In the training context of teacher-student familiarity alongside teachers’ guidance, the mechanisms of learning motivation, self-regulation and enthusiasm were triggered, prompting positive learning outcomes and competencies (outcome). In the individual context of learning how to learn actively at an early stage within the medical learning environment, the mechanisms of internalisation, professional identity and stress resulted in recognising active learning and advanced preparation (outcomes).
Conclusions: We identified three CMO configurations of Taiwanese medical students’ active learning. The connections among hierarchical culture, fear, teachers’ guidance, motivation, the medical environment and professional identity have been shown to affect the complex interactions of learning outcomes. Fear derived from a hierarchical culture is a concern as it is a significant and specific contextual factor, often sparking fear with negative outcomes.
The effect of solution-focused counseling on violence rate and quality of life of pregnant women at risk of domestic violence: A randomized controlled trial
Authors: Mohammadi Sepideh Din , Dadashi Mohsen , Ahmadnia Elahe , Janani leila , Kharaghani Roghieh
Published: October 2020

Background: Domestic violence is considered as one of the most common social problems, which can affect the quality of life of women. The problem of preventing and controlling this problem, especially during pregnancy, is one of the basic challenges of health systems. The aim of this study was to determine the effect of counseling based on conflict solution on the rate of violence and quality of life of pregnant women at risk of domestic violence. Methods: This study was a randomized controlled trial on 90 pregnant women, who were selected from maternity wards in health center number three in Zanjan city. Women who had inclusion criteria based on the domestic violence conflict tactics scale (CTS-2) selected using convenience sampling and randomly divided into two groups of intervention (45 people) and control (45 people) with a blocked randomization method. The intervention group received six counseling sessions with a solution-focused approach and the control group received no intervention. Study tool included demographic and reproductive questionnaires CTS- 2 and short form health survey (SF-36); which completed at baseline and six weeks follow-up in both groups. The results were analyzed by nonparametric ANCOVA using SPSS and R soft wares.Results: The results showed that there was a significant difference in the physical violence (P=0.001), psychological violence (P=0.001), and sexual violence (P=0.001) in the intervention group compared to the control group at six weeks follow- up. There were significant improvements in negotiation scores in the intervention group (P˂0.001). Moreover, there were significant differences in the quality of life scores (P=0.001), vitality (p=0.003), psychological health (p=0.004), bodily pain (p=0.014), physical functioning (p=0.023), and social functioning (p=0.019) between the two groups at the follow- up period.Conclusion: According to the result, individual counseling based on a solution-based approach reduces the amount of domestic violence and increases the quality of life of pregnant women at risk of violence.Trial registration: Iranian Registry of Clinical Trials IRCT2017040628352N4. Date of registration: August 20th 2017.
Presumed Sympathetic Ophthalmia after Scleral Buckling Surgery: Case Report
Authors: Hosseini Seyedeh Maryam , Shoeibi Nasser , Zadeh Mahdieh Azimi , Ghasemi Mahdi , Abrishami Mojtaba
Published: October 2020

Background: Scleral buckling (SB) is usually considered an extraocular operation, and it is presumed to have low risk of sympathetic ophthalmia (SO). We aimed to report a rare case of presumed SO in a young female patient following SB. Case Presentation: A nineteen year-old female patient was referred for visual loss in her left eye because of macula off inferior longstanding rhegmatogenous retinal detachment (RD). Best corrected visual acuity (BCVA) was 20/400 in the left eye. SB with 360 degrees encircling band and inferior segmental tire, with one spot cryoretinopexy at the break site and subretinal fluid drainage was performed. One week after operation, BCVA was improved to 20/80 and retina was totally attached. Six weeks later, patient came with severe visual loss in both eyes as counting finger 1 meter. Bilateral multifocal serous RD and vitreous cells was found. The patient was diagnosed as sympathetic Ophthalmia, and treated with intravenous corticosteroid pulse therapy and mycophenolate mofetil. The inflammation was controlled and serous RD resolved after five days intravenous treatment and was not relapsed after six months. BCVA became 20/20 in right eye and 20/50 in the left eye after six months. Systemic workup was negative for any extraocular disease or systemic involvement.Conclusion: As SB usually considered as a procedure without manipulating intraocular tissues, it is considered to have low risk for SO. In this report, we presented SO occurance after successful SB. Inciting the choroid and retinal pigment epithelium with cryoretinopexy or perforating for drainage may induce SO.
Utilization of Integrated Angiography-CT Interventional Radiology Suites at a Tertiary Cancer Center
Authors: Erinjeri Joseph P. , Doustaly Raphael , Avignon Grégoire , Bendet Achiude , Petre Elena , Ziv Etay , Yarmohammadi Hooman , Solomon Stephen B.
Published: October 2020

Background: Integrated Angiography-Computed Tomography (ACT) suites were initially designed in the 1990’s to perform complex procedures requiring high-resolution cross-sectional imaging and fluoroscopy. Since then, there have been technology developments and changes in patient management. The purpose of this study was to review the current usage patterns of a single center’s integrated ACT suites. Methods: All procedures performed in 2017 in 3 ACT suites (InterACT Discovery RT, GE Healthcare) at a tertiary cancer center were reviewed retrospectively. Usage was classified as: Standard, in which the patient underwent a single procedure using either fluoroscopy, CT, or ultrasound (US); Combined, in which the patient underwent a single procedure utilizing both fluoroscopy and CT; or Staged, in which the patient underwent 2 separate but successive procedures using fluoroscopy and CT individually. The most frequently performed Combined and Staged procedures were further reviewed to determine how the different modalities were used. The duration of the most common Staged procedures was compared to analogous procedures’ durations in single modality rooms over the period Jan 2016 to Sep 2019.Results: A total of 3591 procedures were performed on 2678 patients in the 3 ACT Suites. 80% of patients underwent a Standard procedure using fluoroscopy (38%), CT (32%) or US (10%) and accounted for 70% of the room occupation time. 14% and 3% of the patients underwent Combined or Staged procedures, occupying 19% and 5% of the room time, respectively. The remaining procedures were classified as both Combined and Staged, representing 3% of the patients and 6% of the room occupation time. The most common Combined procedures were drainages, hepatic arterial embolizations or radioembolizations, arterial, and biliary interventions. The most common Staged procedures were multiple drainages and hepatic arterial embolizations followed by biopsies or ablations. The room occupation time for liver tumor embolization and ablation was significantly shorter (p<0.01) when performed in a Staged fashion versus the analogous procedures in single modality room.Conclusion: An integrated ACT system provides the capability to perform complex Combined or Staged procedures as well as scheduling flexibility by allowing any type of case to be performed in the IR suite.
MCCMF: Collaborative matrix factorization based on matrix completion for predicting miRNA-disease associations
Authors: Wu Tian-Ru , Yin Meng-Meng , Jiao Cui-Na , Gao Ying-Lian , Kong Xiang-Zhen , Liu Jin-Xing
Published: October 2020

Background: microRNAs (miRNAs) are non-coding RNAs with regulatory functions. Many studies have shown that miRNAs are closely associated with human diseases. Among the methods to explore the relationship between the miRNA and the disease, traditional methods are time-consuming and the accuracy needs to be improved. In view of the shortcoming of previous models, a method, collaborative matrix factorization based on matrix completion (MCCMF) is proposed to predict the unknown miRNA-disease associations.Results: The complete matrix of the miRNA and the disease is obtained by matrix completion. Moreover, Gaussian Interaction Profile (GIP) kernel is added to the miRNA functional similarity matrix and the disease semantic similarity matrix. Then the Weight K Nearest Known Neighbors (WKNKN) method is used to pretreat the association matrix, so the model is close to the reality. Finally, collaborative matrix factorization (CMF) method is applied to obtain the prediction results. Therefore, the MCCMF obtains a satisfactory result in the five-fold cross-validation, with an AUC of 0.9569(0.0005).Conclusions: The AUC value of MCCMF is higher than other advanced methods in the 5-fold cross validation experiment. In order to comprehensively evaluate the performance of MCCMF, accuracy, precision, recall and f-measure are also added. The final experimental results demonstrate that MCCMF outperforms other methods in predicting miRNA-disease associations. In the end, the effectiveness and practicability of MCCMF are further verified by researching three specific diseases.
MHC class I evolution; from Northern pike to salmonids
Authors: Grimholt Unni , Lukacs Morten
Published: October 2020

BackgroundSalmonids are of major importance both as farmed and wild animals. With the changing environment comes changes in pathogenic pressures so understanding the immune system of all salmonid species is of essence. Major histocompatibility complex (MHC) genes are key players in the adaptive immune system signalling infection to responding T-cells populations. Classical MHC class I (MHCI) genes, defined by high polymorphism, broad expression patterns and peptide binding ability, have a key role in inducing immunity. In salmonids, the fourth whole genome duplication that occurred 94 million years ago has provided salmonids with duplicate MHCI regions, while Northern Pike, a basal sister clade to salmonids, represent a species which has not experienced this whole genome duplication. ResultsComparing the gene organization and evolution of MHC class I gene sequences in Northern pike versus salmonids displays a complex picture of how many of these genes evolved. Regional salmonid Ia and Ib Z lineage gene duplicates are not orthologs to the Northern pike Z lineage sequences. Instead, salmonids have experienced unique gene duplications in both duplicate regions as well as in the Salmo and Oncorhynchus branch. Species-specific gene duplications are even more pronounced for some L lineage genes. ConclusionsAlthough both Northern pike as well as salmonids have expanded their U and Z lineage genes, these gene duplications occurred separately in pike and in salmonids. However, the similarity between these duplications suggest the transposable machinery was present in a common ancestor. The salmonid MHCIa and MHCIb regions were formed during the 94 MYA since the split from pike and before the Oncorhynchus and Salmo branch separated. As seen in tetrapods, the non-classical U lineage genes are diversified duplicates of their classical counterpart. One MHCI lineage, the L lineage, experienced massive species-specific gene duplications after Oncorhynchus and Salmo split approximately 25 MYA. Based on what we currently know about L lineage genes, this large variation in number of L lineage genes also signals a large functional diversity in salmonids.
Evaluating survey designs for targeting preventive chemotherapy against Schistosoma haematobium and Schistosoma mansoni across Sub-Saharan Africa: a geostatistical analysis and modelling study
Authors: Fornace Kimberly , Fronterrè Claudio , Fleming Fiona M , Simpson Hope , Zoure Honorat , Rebollo Maria , Mwinzi Pauline , Vounatsou Penelope , Pullan Rachel L
Published: October 2020

Background: Schistosomiasis control programmes primarily use school-based surveys to identify areas for mass drug administration of preventive chemotherapy. However, as the spatial distribution of schistosomiasis can be highly focal, transmission may not be detected by surveys implemented at districts or larger spatial units. Improved mapping strategies are required to accurately and cost-effectively target preventive chemotherapy to remaining foci across all possible spatial distributions of schistosomiasis. Methods: Here, we use geostatistical models to quantify the spatial heterogeneity of Schistosoma haematobium and S. mansoni across sub-Saharan Africa using the most comprehensive dataset available on school-based surveys. Applying this information to parameterise simulations, we assess the accuracy and cost of targeting alternative implementation unit sizes across the range of plausible schistosomiasis distributions. We evaluate the consequences of decisions based on survey designs implemented at district and subdistrict levels sampling different numbers of schools. Cost data were obtained from field surveys conducted across multiple countries and years, with cost effectiveness evaluated as the cost per correctly identified school. Results: Models identified marked differences in prevalence and spatial distributions between countries and species; however, results suggest implementing surveys at subdistrict level increase the accuracy of treatment classifications across most scenarios. While sampling intensively at the subdistrict level resulted in the highest classification accuracy, this sampling strategy resulted in the highest costs. Alternatively, sampling the same numbers of schools currently recommended at the district level but stratifying by subdistrict increased cost effectiveness.Conclusions: This study provides a new tool to evaluate schistosomiasis survey designs across a range of transmission settings. Results highlight the importance of considering spatial structure when designing sampling strategies, illustrating that a substantial proportion of children may be undertreated even when an implementation unit is correctly classified. Control programmes need to weigh the increased accuracy of more detailed mapping strategies against the survey costs and treatment priorities.
Ticagrelor Monotherapy in Patients with Concomitant Diabetes Mellitus and Chronic Kidney Disease: A post hoc analysis of the GLOBAL LEADERS Trial
Authors: Gao Chao , Tomaniak Mariusz , Takahashi Kuniaki , Kawashima Hideyuki , Wang Rutao , Hara Hironori , Ono Masafumi , Montalescot Gilles , Garg Scot , Haude Michael , Slagboom Ton , Vranckx Pascal , Valgimigli Marco , Windecker Stephan , Geuns Robert-Jan van , Hamm Christian , Steg Philippe Gabriel , Onuma Yoshinobu , Angiolillo Dominick , Serruys Patrick W.
Published: October 2020

Background Patients with both diabetes mellitus (DM) and chronic kidney disease (CKD) are a subpopulation characterized by ultrahigh ischemic and bleeding risk after percutaneous coronary intervention. There are limited data on the impact of ticagrelor monotherapy among these patients.Methods In this post hoc analysis of the GLOBAL-LEADERS trial, the treatment effects of the experimental (one-month dual-antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus the reference regimen (12-month DAPT followed by 12-month aspirin alone) were analyzed according to DM/CKD status. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at two-years. The patient-oriented composite endpoint (POCE) was defined as the composite of all-cause death, any stroke, site-reported MI and any revascularization, whereas net adverse clinical events (NACE) combined POCE with BARC type 3 or 5 bleeding events.Results At two years, the DM+/CKD+ patients had significantly higher incidences of the primary endpoint (9.5% versus 3.1%, adjusted HR 2.16; 95%CI [1.66-2.80], p<0.001), BARC type 3 or 5 bleeding events, stroke, site-reported myocardial infraction, all revascularization, POCE, and NACE, compared with the DM-/CKD- patients. Among the DM+/CKD+ patients, after adjustment, there were no significant differences in the primary endpoints between the experimental and reference regimen; however, the experimental regimen was associated with lower rates of POCE (20.6% versus 25.9%, HR 0.74; 95%CI [0.55-0.99], p=0.043, pinteraction=0.155) and NACE (22.7% versus 28.3%, HR 0.75; 95%CI [0.56-0.99], p=0.044, pinteraction=0.310), which was mainly driven by a lower rate of all revascularization, as compared with the reference regimen. The landmark analysis showed that while the experimental and reference regimen had similar rates of all the clinical endpoints during the first year, the experimental regimen was associated with significantly lower rates of POCE (5.8% versus 11.0%, HR 0.49; 95%CI [0.29-0.82], p=0.007, pinteraction=0.040) and NACE (5.8% versus 11.2%, HR 0.48; 95%CI [0.29-0.82], p=0.007, pinteraction=0.013) in the second year.Conclusion Among patients with both DM and CKD, ticagrelor monotherapy was not associated with lower rates of all-cause death or new Q-wave, or major bleeding complications; however, it was associated with lower rates of POCE and NACE. These findings should be interpreted as hypothesis-generating.Clinical Trial Registration: ClinicalTrials.gov (NCT01813435).
STRIATAL DOPAMINE TRANSPORTER SPECT QUANTIFICATION: HEAD-TO-HEAD COMPARISON BETWEEN TWO THREE-DIMENSIONAL AUTOMATIC TOOLS
Authors: Morbelli Silvia , Arnaldi Dario , Cella Eugenia , Raffa Stefano , Donegani Isabella , Capitanio Selene , Massa Federico , Miceli Alberto , Filippi Laura , Chincarini Andrea , Nobili Flavio
Published: October 2020

Purpose. Our aim was the head-to-head comparison between two automatic tools for semi-quantification of striatal dopamine transporter (DAT) specific-to-non displaceable (SBR) ratio brain SPECT values in a naturalistic cohort of patients. Procedures. We analyzed consecutive scans from one-hundred and fifty-one outpatients submitted to brain DAT SPECT for a suspected parkinsonism. Images were post-processed using a commercial (Datquant®) and a free (BasGanV2) software. Reading by expert was the gold-standard. A subset of patients with pathological or borderline scan was evaluated with the clinical Unified Parkinson’s disease rating scale, motor part (MDS-UPDRS-III). Results. SBR, putamen-to-caudate (P/C) ratio, and both P and C asymmetries were highly correlated between the two software with Pearson’s ‘r’ correlation coefficients ranging from .706 to .887. Correlation coefficients with the MDS-UPDRS III score were higher with caudate than with putamen SBR values with both software, and in general higher with BasGanV2 than with Datquant® . Datquant® correspondence with expert reading was 84.1% (94.0% by additionally considering the P/C ratio as a further index). BasGanV2 correspondence with expert reading was 80.8% (86.1% by additionally considering the P/C ratio). Conclusions. Both Datquant® and BasGanV2 work reasonably well and similarly one another in semi-quantification of DAT SPECT. Both tools have their own strength and pitfalls that must be known in detail by users in order to obtain the best help in visual reading and reporting of DAT SPECT.
Clinical characteristics and laboratory biomarkers changes in COVID-19 patients requiring or not intensive or sub-intensive care: a comparative study
Authors: Cattelan Anna Maria , Meco Eugenia Di , Trevenzoli Marco , Frater Alessia , Ferrari Anna , Villano Marco , Gomiero Federica , Carretta Giovanni , Sasset Lolita
Published: October 2020

Background Identifying risk factors for severe novel-coronavirus disease (COVID-19) is useful to ascertain which patients may benefit from advanced supportive care. The study aims to offer a comparative description of the COVID-19 patients, admitted to a general ward for a non-critical clinical picture, who required or not to be transferred to the intensive (ICU) and/or sub-intensive care (SICU) units. Methods This observational retrospective study included all COVID-19 patients admitted to the Infectious Diseases Unit. Clinical, laboratory, radiological and treatment data were collected. The primary outcome was a composite of need of transfer to the ICU and/or SICU during the hospitalization. Patients who did not require to be transferred are defined Group 1; patients who were transferred to the ICU and/or SICU are defined Group 2. Demographic and clinical characteristics were compared between the two groups. Results 303 patients were included. Median age was 62 years. 69 patients (22,8%) met the primary outcome and were defined Group 2. The overall mortality rate was 6.8%. Group 2 were more likely to be men, had a higher mortality (14,5% vs. 3,8%, p<0,01), had more hypertension (72,4% vs. 44%, p<0,01) and diabetes (31,9% vs. 21%, p=0,04) and were more likely to present dry cough (49,3% vs. 25,2%, p<0.01). Overall, chest X-ray at admission showed findings suggestive of pneumonia in 63,2%, and Group 2 were more likely to develop pathological findings during the hospitalization (72,7%vs. 17,2%, p<0,01). At admission, Group 2 presented significantly higher neutrophil count, aspartate-transaminase and C-reactive-protein. At the 3rd measurement, Group 2 presented persistently higher neutrophil count, liver function tests and C-reactive-protein. Group 1 presented a shorter duration from admission to negativization of follow-up swabs (20 vs. 35 days, p<0,01). Conclusions The presence of comorbidities and the persistent observation of abnormal laboratory findings should be regarded as predisposing factors for clinical worsening.
Advancing Pediatric Palliative Care In a Low-Middle Income Country: An Implementation Study, A challenging but not impossible task
Authors: Garcia-Quintero Ximena , Parra-Lara Luis Gabriel , Claros-Hulbert Angelica , Cuervo-Suarez Maria Isabel , Gomez-Garcia Wendy , Desbrandes Francois , Arias-Casais Natalia
Published: October 2020

Background: The abyss of access to pediatric palliative care and pain management in Latin America remains to be an unaddressed global health issue. Efforts to improve the development level of Palliative Care (PC) provision have traditionally targeted services for adults, leaving the pediatric population unaddressed. Examples of such services are scarce and should be portrayed in scientific literature to inform decision-makers and service providers on models of care available to tackle the burden of Pediatric Palliative Cares (PPC) in Low-and middle-income countries (LMIC). The purpose of this study is to describe the implementation of a pediatric palliative care program “Taking Care of You ” (TCY) , in a tertiary care university hospital in Cali, Colombia. Methods: A program’s database was built with children between 0 to 18 years old and their families, from year 2017 to 2019. Descriptive analysis to evaluate the impact of the program and service delivery was conducted. A theory-based method was directed to describe the PPC program, according to the implementation of self-designed taxonomy, mapping theoretical levels and domains. Clinical outcomes in patients were included in the analysis. Results: Since 2017 the program has provided PPC services to 1.965 children. Most of them had an oncologic diagnosis and were referred from hospitalization services (53%). The number of outpatients increased by 80% every trimester between 2017-2018. A 50% increase was reported in hospitalization, emergency, and intensive care units during the same time period. Conclusions: The program addressed a gap in the provision of PPC to children in Cali. It shows effective strategies used to implement a program, and how the referral times, coordination of care, communication with other hospital services were improved. Providing compassionate/holistic care to children with Life-limiting and threatening diseases, and in end-of-life. The implementation of this program has required the onset of specific strategies and arrangements to promote awareness and education proving it a hard task, yet not impossible.
Simultaneous targeting tumor cells and cancer-associated fibroblasts with a Paclitaxel-Hyaluronan bioconjugate: in vitro evaluation in non-melanoma skin cancer
Authors: Bellei Barbara , Caputo Silvia , Migliano Emilia , Lopez Gianluca , Marcaccini Valeria , Cota Carlo , Picardo Mauro
Published: October 2020

Background: Cancers are complex organs which encompass not only the tumor cells but also cells within the surrounding stroma. Such cells, mainly cancer associated fibroblasts (CAFs) and immune infiltrating cells, facilitate many aspects of cancer development providing a structural and supportive framework rich of bioactive compounds. So far, there are emerging studies proposing the combination of conventional anti-cancer therapy, directed against neoplastic cells, to molecules targeting tumor microenviroment.Methods: The study was designed to evaluated the pharmacological properties of the anti-tumor agent paclitaxel conjugated to hyaluronic acid (HA) on non-melanoma skin cancer (NMSC) and on the surronding dermal fibroblasts. This molecule, named Oncofid-P20 (Onco-P20), targets preferentially cells expressing high level of CD44, the natural ligand of HA.Results: Consistent with paclitaxel’s mechanism of action involving interferences with the normal breackdown of microtubules during cell division, highly sensible carcinoma cells underwent rapidly to apoptotic cell death. Interestingly, less sensible cells such as dermal fibroblasts resisted to the Onco-P20 treatment and experirenced a prologed growth arrest characterized by morphological change and significant modification of the gene espression profile that partially overlaps with that of senescent cells. Onco-P20-treated fibroblasts lowered growth factors production, down-modulate Wnt signal pathway and acquired a marked pro-inflammatory profile. Independently to the direct exposure to taxol, in presence of Onco-P20-treated fibroblasts or their conditioned medium, carcinoma cells reduced the proliferation rate. Similar to NHF, fibroblasts isolated from skin cancer tumor lesion or from tissue adjacent to the tumor acquired an anti-neoplastic activity under Oncofid-P20 treatment.Conclusion: Collectively, our data demonstrated that Onco-P20, exerting both a direct and a NHF-mediated indirect paracrine effect on carcinoma cells, is a good candidate for an innovative therapy alternative to surgery for treatment of NMSC.
The Effectiveness of Laid-back Position on Lactation Related Nipple problems and comfort: A meta-analysis
Authors: WANG Zhi , LIU Qiuyue , MIN Lihua , MAO Xiaorong
Published: October 2020

Background The importance of breastfeeding for maternal and child health has become an international consensus. However, it has been found that lactation-related nipple problems are common and there are some important factors affecting the breastfeeding. Multiple studies recommended the laid-back breastfeeding, but they are on various levels of quality and the results are inconclusive. Methods We systematically searched the following twelve databases: Cochrane Library, EMBASE, Medline, Ovid, PubMed, Web of Science, CINAHL, Scopus, SinoMed, Chinese National Knowledge Infrastructure (CNKI), WanFang, and VIP from inception to January 28,2020. All studies regarding the laid-back breastfeeding or biological nurturing were considered, regardless of whether they are randomized controlled trials or not. Two trained investigators independently evaluated the quality of the selected articles and screened the data. All the data were analyzed separately using Review Manager Version 5.3 and STATA/SE Version 15.1.Results A total of 12 studies involving 1,936 groups of postpartum women and their newborns were included. The results of meta-analysis showed that nipple pain (RR = 0.24; 95% CI 0.14,0.40; p < 0.00001), nipple trauma (RR = 0.47; 95% CI 0.29,0.75; p = 0.002), the correct position of latching (RR = 1.22; 95% CI 1.11,1.33; p < 0.00001) and position comfort (ES = 0.09; 95% CI -0.63,0.81; p = 0.000) of experimental groups were all better than that of the control groups, and the differences were statistically significant (p < 0.05), which indicate that the laid-back position has a positive effect on maternal breastfeeding.Conclusion Laid-back position has been proved to related with decreasing the incidence of nipple trauma and nipple pain compared with traditional breastfeeding positions, and it appears that laid-back position is conducive to the correct position of latching. However, current evidence does not show different breastfeeding outcomes in the two groups of position comfort. Laid-back position is helpful to solve lactation-related nipple problems and it can be used as a recommended position for breastfeeding.
Validation of Living with Chronic Illness Scale in a Type 2 Diabetes Mellitus population
Authors: Caro-Bautista Jorge , Rodriguez-Blazquez Carmen , Perez-Manchon David , Timonet Eva , Carvajal Gloria , Fuentes-Ramirez Alejandra , Corchon Silvia , Aranda Marta , Ambrosio Leire
Published: October 2020

Background: Worldwide, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases and one of those producing greatest impact on patients’ day-to-day quality of life. Our study aim is to validate the “Living with Chronic Illness Scale” for a Spanish-speaking T2DM population.Methods: In this observational, international, cross-sectional study, 582 persons with T2DM were recruited in primary care and outpatient hospital consultations, in Spain and Colombia, during the period from May 2018 to June 2019. The properties analysed were feasibility/acceptability, internal consistency, reliability, precision and (structural) content-construct validity including confirmatory factor analysis (CFA). The COSMIN checklist was used to assess the methodological/psychometric quality of the instrument.Results: The scale had an adequate internal consistency and test retest reliability (Cronbach’s alpha = 0.90; intraclass correlation coefficient = 0.96, respectively). In addition, the instrument is precise (standard error of measurement = 3.34, with values <½SD = 8.52) and correlates positively with social support (DUFSS) (rs = 0.56), quality of life (WHOQOL) (rs = 0.51-0.30) and satisfaction (SLS-6) (rs = 0.50-0.38). The CFA supported the 5-domains structure, but a 23-item version showed better fit: CMIN/df= 3.11; goodness of fit index= 0.91; comparative fit index= 0.91 and root mean square error of approximation = 0.06 (90% confidence interval, 0.06-0.07). The COSMIN checklist is favourable for all the properties analysed, although weaknesses are detected for content validity.Conclusions: “Living with T2DM” (LW-T2DM) is a valid, reliable and accurate instrument for use in clinical practice to determine how a person’s life is affected by the presence of diabetes. This instrument correlates well with the associated constructs of social support, quality of life and satisfaction. Additional research is needed to determine how well the questionnaire structure performs when robust factor analysis methods are applied.
An Infrared 3D Scanning Device as a Novel Limb Volume Measurement Tool in Breast Cancer Patients
Authors: White Bernadette N , Lu Iris M , Kao LeslieAnn S , Dixon Brandon J , Weiler Michael J , Frank Nathan D , Binkley Jill , Subhedar Preeti , Okoli Joel , Buhariwalla Karen , Suarez-Ligon Adriana , Gabram Sheryl G
Published: October 2020

Background Lymphedema is a common complication of breast cancer treatment that affects one in five breast cancer survivors yet there is no reliable method to detect lymphedema in the subclinical range. The objective of this study was to determine the feasibility and reliability of using an infrared 3D scanning device (ISD) as a peri-operative limb volume measurement tool.Methods Fifteen patients were analyzed based on inclusion criteria. Peri-operative measurements were obtained using tape measure and an ISD. Volumes were calculated using a standard algorithm for tape measure and a custom algorithm for ISD measurements. Linear regression models were used to assess ISD and tape measurement volume and circumference correlation. One-way ANOVA was used to compare change in percent difference at set time points post-operatively (2-3 weeks, 4-6 weeks, and 7-12 weeks) for both ISD and tape measure. T-Tests for unequal variances with the Bonferroni correction were performed among these groups.Results There is a positive linear correlation (R-squared = 0.8518) between absolute volume measurements by the ISD and tape measure. Analyses over 2-10 weeks post-operatively showed that the ISD was able to detect volume changes in both the unaffected and the affected arm. Furthermore, the affected arm tended to have a greater increase in volume in the majority of patients, indicating these patients could be at risk for lymphedema. Conclusions Technology utilizing infrared 3D scanners can reliably measure limb volume pre and post treatment similarly to tape measure in a small sample of patients. Further research using 3D scanning technology with a longer follow up is warranted.
Retinal involvement and ocular findings in COVID‐19 pneumonia patients 
Authors: Pirraglia Maria Pia , Ceccarelli Giancarlo , Cerini Alberto , Visioli Giacomo , d'Ettorre Gabriella , Mastroianni Claudio Maria , Pugliese Francesco , Lambiase Alessandro , Gharbiya Magda
Published: October 2020

Background: changes in immune and coagulation systems and possible viral spread through blood-brain barrier have been described in SARS-CoV-2 infection. In this study, we evaluate the possible retinal involvement and ocular findings in severe COVID-19 pneumonia patients. Methods: a cross sectional study was conducted on 46 patients affected by severe COVID-19 who were hospitalized in one Intensive Care Unit (ICU) and in two Infectious Diseases wards, including a bedside eye screening, corneal sensitivity assessment and retinography. Results: a total of 43 SARS-CoV-2 positive pneumonia patients affected with COVID-19 pneumonia were included, 25 males and 18 females, with a median age of 70 [IQR 59-78]. Except for one patient with unilateral posterior chorioretinitis of opportunistic origin, of whom aqueous tap was negative for SARS-CoV-2, no further retinal manifestation related to COVID-19 infection was found in our cohort. We found 3 patients (7%) with bilateral conjunctivitis in whom PCR analysis on conjunctival swab provided negative results for SARS-CoV-2. No alterations of corneal sensitivity were found.Conclusion: we demonstrated the absence of retinal involvement in SARS-CoV-2 pneumonia patients. Ophthalmologic evaluation in COVID-19, particularly in patients hospitalized in an ICU setting, may be useful to reveal systemic co-infections by opportunistic pathogens.
Ex vivo porcine model study on the treatment outcomes of scissor-type knife versus needle-type knife in endoscopic submucosal dissection performed by trainees
Authors: Ichijima Ryoji , Esaki Mitsuru , Yamakawa Shun , Minoda Yosuke , Suzuki Sho , Kusano Chika , Ikehara Hisatomo , Gotoda Takuji
Published: October 2020

BackgroundEndoscopic submucosal dissection (ESD) for gastrointestinal neoplasms can be technically difficult for trainee endoscopists. Presently, there is no consensus for trainees to select the endo-knife type in ESD. Therefore, we conducted a comparison study of treatment outcomes between scissors-type and needle-type knives in ESD performed by trainees in an ex vivo porcine model. MethodsThis study was conducted on trainee endoscopists who participated in ESD hands-on seminars held in August 2018 and September 2019. A total of 22 trainees from 13 institutions were divided into two groups according to their endoscopic experience. Under expert supervision, each trainee performed two ESDs in porcine models, namely, scissor-type knife (ESD-S) and needle-type knife (ESD-N). The efficacy and safety, including the procedure time and rates of self-completion, en bloc resection, and complications, were compared between ESD-S and ESD-N. In subgroup analysis, we also investigated the predictors associated with the difficulty of ESD for trainees using multivariate logistic regression analysis.ResultsEight trainees had an experience of over 1,000 endoscopies (senior trainee: S-Trainee), whereas the others had an experience of less than 1,000 endoscopies (junior trainee: J-Trainee). Among the S-Trainees, no significant differences were observed in any treatment outcome between ESD-S and ESD-N. Among the J-Trainees, the total procedure and mucosal incision times were significantly shorter in ESD-S than in ESD-N [total procedure time: 16.5 min (range: 10.0–31.0) vs. 22.3 min (range: 10.0–38.0), P = 0.018; circumferential incision time: 10.0 min (range: 6-16) vs. 17.0 min (range: 5.0–31.5); P = 0.019]. Regarding complications, muscular injury occurred in two patients during ESD-N performed by J-Trainees; however, no muscular injury occurred during ESD-S. In subgroup analysis, ESD-N was an independent predictive factor of difficult ESD (odds ratio 5.28, 95% confidence interval 1.25–22.30; p = 0.024).ConclusionsThis study revealed that trainees, particularly those who have experienced less than 1,000 endoscopies, should opt for the scissor-type knife to perform ESD.
The dual HDAC-PI3K inhibitor CUDC-907 displays single-agent activity and synergizes with PARP inhibitor olaparib in small cell lung cancer
Authors: Ma Liying , Bian Xing , Lin Wenchu
Published: October 2020

Background: Small cell lung cancer (SCLC) is a deadly neuroendocrine tumor with limited therapeutic options. Recent data suggest that histone deacetylases (HDACs) and the phosphatidylinositol 3-kinase (PI3K) pathway play essential roles in SCLC cell proliferation and survival.Methods: The inhibition of the PI3K signaling and HDAC activity by CUDC-907 was analysized by western bloting. The effect of CUDC-907 on olaprib-induced DNA damage response was assessed by western blotting and Immunofluorescence staining. The cytotoxcity of CUDC-907 alone or in combination with olaparib in a panel of SCLC cell lines were evaluated by the CellTiter-Glo Luminescent Cell Viability Assay and flow cytometry. The in vivo effects of CUDC-907 and olaparib alone or in combination were examined using a patient-derived xenografts (PDX) model of SCLC.Results: CUDC-907 treatment downregulated MYC paralogs and FoxM1, induced G1 cell-cycle arrest, and impaired DNA double-strand break (DSB) repair capacity in SCLC cells, which produced a potent antiproliferative effect. Furthermore, we showed that CUDC-907 treatment enhanced the therapeutic efficacy of PARP inhibitor olaparib in SCLC cellular models and a PDX model. Mechanistic investigations demonstrated that CUDC-907 synergized with olaparib through the blockade of DSB repair pathways and downregulation of MYC paralogs and FoxM1.Conclusions: Our study uncovers that dual PI3K and HDAC inhibition by CUDC-907 exerts significant single-agent activity and strong synergistic effects with PARP inhibitor olaparib in SCLC, which thus provides a rational combination treatment strategy for SCLC clinical investigation.
Efficacy of EUS-guided FNB using a Franseen needle for tissue acquisition and microsatellite instability evaluation in unresectable pancreatic lesions
Authors: Sugimoto Mitsuru , Irie Hiroki , Takagi Tadayuki , Suzuki Rei , Konno Naoki , Asama Hiroyuki , Sato Yuki , Nakamura Jun , Takasumi Mika , Hashimoto Minami , Kato Tsunetaka , Kobashi Ryoichiro , Kobayashi Yasuyuki , Hashimoto Yuko , Hikichi Takuto , Ohira Hiromasa
Published: October 2020

Background: The efficacy of immune checkpoint blockade in the treatment of microsatellite instability (MSI)-high tumors was recently reported. Therefore, the acquisition of histological specimens is desired in cases of unresectable solid pancreatic lesions (UR SPLs). This study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for UR SPL tissue acquisition and MSI evaluation.Methods: A total of 195 SPL patients who underwent EUS-guided fine-needle aspiration (EUS-FNA) or EUS-FNB (EUS-FNAB) between January 2017 and March 2020 were enrolled in this study. Among them, 89 SPL patients (FNB: 28, FNA: 61) underwent EUS-FNAB using a 22-G needle (UR SPLs: 58, FNB: 22, FNA: 36) (UR SPLs after starting MSI evaluation: 23, FNB: 9, FNA: 14).Results: The puncture number was significantly lower with FNB than with FNA (median (range): 3 (2-5) vs 4 (1-8), P < 0.01, UR SPLs: 3 (2-5) vs 4 (1-8), P = 0.036). Histological specimen acquisition was more commonly achieved with FNB than with FNA (92.9% (26/28) vs 68.9% (42/61), P = 0.015, UR SPLs: 100% (22/22) vs 72.2% (26/36), P < 0.01). The histological specimen required for MSI evaluation was acquired more often with FNB than with FNA (88.9% (8/9) vs 35.7% (5/14), P = 0.03).Conclusions: EUS-FNB using a Franseen needle is efficient for histological specimen acquisition and sampling the required amount of specimen for MSI evaluation in UR SPL patients.