bluuebunny/crossref_metadata_2025 huggingface dataset:
Recovery from hypoxemia and Hypercapnia following noninvasive pressure support ventilation in a patient with statin-associated necrotizing myopathy: a case report
Authors: Yamamura Yuriko , Matsumoto Yoshinori , Tadokoro Koh , Ohta Yasuyuki , Sato Kota , Yamashita Toru , Yamamura Masahiro , Sada Ken-Ei , Abe Koji , Wada Jun
Published: June 2020

Background

Statin-associated necrotizing myopathy (SANM) is a rare autoimmune disorder caused by administration of statins. SANM is characterized by weakness due to necrosis and regeneration of myofibers. Here we report the first case of SANM with acute respiratory failure treated with noninvasive pressure support ventilation in addition to immunosuppressants.

Case presentation

A 59-year-old woman who had been treated with 2.5 mg/day of rosuvastatin calcium for 5 years stopped taking the drug 4 months before admission to our hospital due to elevation of creatine kinase (CK). Withdrawal of rosuvastatin for 1 month did not decrease the level of CK, and she was admitted to our hospital due to the development of muscle weakness of her neck and bilateral upper extremities. Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies were positive. Magnetic resonance imaging showed myositis, and muscle biopsy from the right biceps brachii muscle showed muscle fiber necrosis and regeneration without inflammatory cell infiltration, suggesting SANM. After the diagnosis, she received methylprednisolone pulse therapy (mPSL, 1 g/day × 3 days, twice) and subsequent oral prednisolone therapy (PSL, 30 mg/day for 1 month, 25 mg/day for 1 month and 22.5 mg/day for 1 month), leading to improvement of her muscle weakness. One month after the PSL tapering to 20 mg/day, her muscle weakness deteriorated with oxygen desaturation (SpO2: 93% at room air) due to hypoventilation caused by weakness of respiratory muscles. BIPAP was used for the management of acute respiratory failure in combination with IVIG (20 g/day × 5 days) followed by mPSL pulse therapy (1 g/day × 3 days), oral PSL (30 mg/day × 3 weeks, then tapered to 25 mg/day) and tacrolimus (3 mg/day). Twenty-seven days after the start of BIPAP, she was weaned from BIPAP with improvement of muscle weakness, hypoxemia and hypercapnia. After she achieved remission with improvement of muscle weakness and reduction of serum CK level to a normal level, the dose of oral prednisolone was gradually tapered to 12.5 mg/day without relapse for 3 months.

Conclusions

Our report provides new insights into the role of immunosuppressants and biphasic positive airway pressure for induction of remission in patients with SANM.
Treatment of superimposed preeclampsia on chronic hypertension in a twin pregnancy with automatic continuous positive airway pressure: a case report
Authors: Kim Mi Sun , Moon Myoung Jin , Lee Yoon Hee , Chae Kyu Young , Ahn Eun Hee
Published: June 2020

Background

Obstructive sleep apnoea (OSA) is related with adverse pregnancy outcomes, including preeclampsia. However, there are small studies about treatment of OSA with automatic continuous positive airway pressure (CPAP) in adverse obstetric outcomes.

Case presentation

We introduce a case of 34 year old twin pregnant woman diagnosed with superimposed preeclampsia on chronic hypertension at 28 + 1/7 weeks of gestation. A level III polysomnography showed obstructive sleep apnoea, and automatic CPAP was applied. After the CPAP treatment concomitant with an antihypertensive drugs, both blood pressure and urinary protein concentration were reduced. The pregnancy safely continued for 49 days (to 35 + 1/7 weeks), with stable blood pressure, allowing prolongation of gestation of the foetuses.

Conclusion

This is the first case to report OSA with preeclampsia in a twin pregnancy. Our results suggest that automatic CPAP as an adjunct treatment to antihypertensive drugs may be beneficial in controlling blood pressure in early-onset preeclampsia associated with OSA.
Prevalence and incidence of low back pain among runners: a systematic review
Authors: Maselli Filippo , Storari Lorenzo , Barbari Valerio , Colombi Andrea , Turolla Andrea , Gianola Silvia , Rossettini Giacomo , Testa Marco
Published: June 2020

Background

Running is one of the most popular sports worldwide. Despite low back pain (LBP) represents the most common musculoskeletal disorder in population and in sports, there is currently sparse evidence about prevalence, incidence and risk factors for LBP among runners. The aims of this systematic review were to investigate among runners: prevalence and incidence of LBP and specific risk factors for the onset of LBP.

Methods

A systematic review has been conducted according to the guidelines of the PRISMA statement. The research was conducted in the following databases from their inception to 31st of July 2019: PubMed; CINAHL; Google Scholar; Ovid; PsycINFO; PSYNDEX; Embase; SPORTDiscus; Scientific Electronic Library Online; Cochrane Library and Web of Science. The checklists of The Joanna Briggs Institute Critical Appraisal tools were used to investigate the risk of bias of the included studies.

Results

Nineteen studies were included and the interrater agreement for full-text selection was good (K = 0.78; 0.61–0.80 IC 95%). Overall, low values of prevalence (0.7–20.2%) and incidence (0.3–22%) of LBP among runners were reported. Most reported risk factors were: running for more than 6 years; body mass index > 24; higher physical height; not performing traditional aerobics activity weekly; restricted range of motion of hip flexion; difference between leg-length; poor hamstrings and back flexibility.

Conclusions: Prevalence and incidence of LBP among runners are low compared to the others running related injuries and to general, or specific population of athletes. View the low level of incidence and prevalence of LBP, running could be interpreted as a protective factor against the onset of LBP.

Systematic review registration

PROSPERO CRD42018102001.
Sex differences in postsurgical skeletal muscle depletion after donation of living-donor liver transplantation, although minimal, should not be ignored
Authors: Nagata Rihito , Akamatsu Nobuhisa , Nakazawa Akiko , Kaneko Junichi , Ishizawa Takeaki , Arita Junichi , Hasegawa Kiyoshi
Published: June 2020

Background

Donor safety is the top priority in living-donor liver transplantation. Splenic hypertrophy and platelet count decrease after donor surgery are reported to correlate with the extent of hepatectomy, but other aftereffects of donor surgeries are unclear. In this study, we evaluated the surgical effects of donor hepatectomy on skeletal muscle depletion and their potential sex differences.

Methods

Among a total of 450 consecutive donor hepatectomies performed from April 2001 through March 2017, 277 donors who completed both preoperative and postoperative (60–119 days postsurgery) evaluation by computed tomography were the subjects of this study. Donors aged 45 years or older were considered elderly donors. Postoperative skeletal muscle depletion was assessed on the basis of the cross-sectional area of the psoas major muscle. Postoperative changes in the spleen volume and platelet count ratios were also analysed to evaluate the effects of major hepatectomy.

Results

The decrease in the postoperative skeletal muscle mass in the overall donor population was slight (99.4 ± 6.3%). Of the 277 donors, 59 (21.3%) exhibited skeletal muscle depletion (i.e., < 95% of the preoperative value). Multivariate analysis revealed that elderly donor (OR:2.30, 95% C.I.: 1.27–4.24) and female donor (OR: 1.94, 95% C.I. 1.04–3.59) were independent risk factors for postoperative skeletal muscle depletion. Stratification of the subjects into four groups by age and sex revealed that the elderly female donor group had significantly less skeletal muscle mass postoperatively compared with the preoperative values (95.6 ± 6.8%), while the other three groups showed no significant decrease. Due to their smaller physical characteristics, right liver donation was significantly more prevalent in the female groups than in the male groups (112/144, 77.8% vs 65/133, 48.9%; p < 0.001). The estimated liver resection rate correlated significantly with the splenic hypertrophy ratio (r = 0.528, p < 0.001) and the extent of the platelet count decrease (r = − 0.314, p < 0.001), but donor age and sex did not affect these parameters.

Conclusion

Elderly female donors have a higher risk of postoperative skeletal muscle depletion. Additionally, female donors are more likely to donate a right liver graft, whose potential subclinical risks include postoperative splenic enlargement and a platelet count decrease.
Traditional medicine use in Timor-Leste
Authors: Grace Robert , Vaz Jacinto , Da Costa Julianti
Published: June 2020

Background

Traditional medicine use is common amongst peoples in developing nations. Timor-Leste is no exception. However little is known about the prevalence, pattern, satisfaction with, cost or type of traditional medicine used in Timor-Leste. This study aims to describe the prevalence, nature and basic demographic factors associated with contemporary traditional medicine use in Timor-Leste.

Methods

A structured interview questionnaire was administered in Tetun to 50 surgical patients, 50 internal medicine patients, 50 hospital staff and 50 hospital visitors at Hospital Nacional Guido Valadares, Timor-Leste’s major referral hospital.

Results

60% of respondents reported having used traditional medicine; 32% within the last year. The greatest use was amongst surgical patients, the least amongst hospital staff. The frequency of traditional medicine use was comparable amongst all groups regardless of size of community, residence or level of education. Traditional medicine use in Timor-Leste is sufficiently common to represent part of the cultural norm. Factors described as promoting traditional medicine use included cost, limited access to other medical services and a belief that traditional medicine was free of side effects. Approximately half the patients reported using traditional medicine for their current illness and many for chronic illness in conjunction with conventional medicine. Conclusion: Traditional medicine use is common in Timor-Leste. Medical practitioners need to be cognizant of the common and potentially concomitant use of traditional medicine alongside conventional medicine when treating patients in Timor-Leste.
Soyasaponins reduce inflammation by downregulating MyD88 expression and suppressing the recruitments of TLR4 and MyD88 into lipid rafts
Authors: Chen Junbin , Ullah Hidayat , Zheng Zhongdaixi , Gu Xiangfu , Su Chuhong , Xiao Lingyu , Wu Xinglong , Xiong Fei , Li Qing , Zha Longying
Published: June 2020

Background

Previous studies indicate that soyasaponins may reduce inflammation via modulating toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling. However, its underlying mechanisms are still not fully understood.

Methods

Lipopolysaccharide (LPS)-challenged inflamed male ICR mice were intervened by intragastrical administration with 10 and 20 μmol/kg·BW of soyasaponin A1, A2 or I for 8 weeks. The serum inflammatory markers were determined by commercial kits and the expression of molecules in TLR4/MyD88 signaling pathway in liver by real-time PCR and western blotting. The recruitments of TLR4 and MyD88 into lipid rafts of live tissue lysates were detected by sucrose gradient ultracentrifugation and western blotting. LPS-stimulated RAW264.7 macrophages were treated with 10, 20 and 40 μmol/L of soyasaponin A1, A2 or I for 2 h. MyD88-overexpressed HEK293T cells were treated with 20 and 40 μmol/L of soyasaponins (A1, A2 or I) or 20 μmol/L of ST2825 (a MyD88 inhibitor) for 6 h. The expression of molecules in TLR4/MyD88 signaling pathway were determined by western blotting. Data were analyzed by using one way analysis of variance or t-test by SPSS 20.0 statistical software.

Results

Soyasaponins A1, A2 or I significantly reduced the levels of tumor necrosis factor alpha (TNFα), interleukin (IL)-6 and nitric oxide (NO) in serum (p < 0.05), and decreased the mRNA levels of TNFα, IL-6, IL-1β, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) (p < 0.05), the protein levels of myeloid differentiation protein 2 (MD-2), TLR4, MyD88, toll-interleukin1 receptor domain containing adaptor protein (TIRAP), phosphorylated interleukin-1 receptor-associated kinase 4 (p-IRAK-4), phosphorylated interleukin-1 receptor-associated kinase 1 (p-IRAK-1) and TNF receptor associated factor 6 (TRAF6) (p < 0.05), and the recruitments of TLR4 and MyD88 into lipid rafts in liver (p < 0.05). In LPS-stimulated macrophages, soyasaponins A2 or I significantly decreased MyD88 (p < 0.05), soyasaponins A1, A2 or I reduced p-IRAK-4 and p-IRAK-1 (p < 0.05), and soyasaponin I decreased TRAF6 (p < 0.05). In MyD88-overexpressed HEK293T cells, soyasaponins (A1, A2 or I) and ST2825 significantly decreased MyD88 and TRAF6 (p < 0.05).

Conclusion

Soyasaponins can reduce inflammation by downregulating MyD88 expression and suppressing the recruitments of TLR4 and MyD88 into lipid rafts. This study provides novel understanding about the anti-inflammatory mechanism of soyasaponins.
Impact of take-home messages written into slide presentations delivered during lectures on the retention of messages and the residents’ knowledge: a randomized controlled study
Authors: Lautrette Alexandre , Boyer Alexandre , Gruson Didier , Argaud Laurent , Schwebel Carole , Tardy Bernard , Vignon Philippe , Megarbane Bruno , Schoeffler Pierre , Chabrot Pascal , Schmidt Jeannot , Boirie Yves , Guerin Claude , Darmon Michaël , Klouche Kada , Souweine Bertrand , Dellamonica Jean , Pereira Bruno ,   for the TREX group, Timsit Jean-François , Terzi Nicolas , Papazian Laurent , Gainnier Marc , Roch Antoine , Forel Jean-Marie , Hraiech Sami , Eisenmann Nathanaël , Bohe Julien , Richard Jean-Christophe , Cour Martin , Zeni Fabrice , Thiery Guillaume , Perinel Sophie , Bernardin Gilles , Jung Boris , Jonquet Olivier , Silva Stein
Published: June 2020

Background

Lectures with slide presentations are widely used to teach evidence-based medicine to large groups. Take-home messages (THMs) are poorly identified and recollected by students. We investigated whether an instruction to list THMs in written form on slides would improve the retention thereof by residents, and the residents’ level of knowledge, 1 month after lectures.

Methods

Prospective blinded randomized controlled study was conducted. Twelve lectures (6 control and 6 intervention lectures) were delivered to 73 residents. For the intervention lectures, the lecturers were instructed to incorporate clear written THMs into their slide presentations. The outcomes were ability of resident to recollect THMs delivered during a lecture (as assessed by accordance rate between the lecturers’ and residents’ THMs) and knowledge (as assessed by multiple choice questions (MCQs)).

Results

Data for 3738 residents’ THMs and 3410 MCQs were analyzed. The intervention did not significantly increase the number of THMs written on slides (77% (n = 20/26), 95% CI 56–91 vs 64% (n = 18/28), 95% CI 44–81, p = 0.31) nor THMs retention (13% (n = 238/1791), 95% CI 12–15 vs 17% (n = 326/1947), 95% 15–18, p = 0.40) nor knowledge (63.8 ± 26.2 vs 61.1 ± 31.4 /100 points, p = 0.75). In multivariable analyses performed with all THMs written on slides from the two groups, a superior knowledge was associated with notetaking during lectures (OR 1.88, 95% CI 1.41–2.51) and THMs retention (OR 2.17, 95% CI 1.54–3.04); and THMs retention was associated with written THMs (OR 2.94, 95% CI 2.20–3.93).

Conclusions

In lectures delivered to residents, a third of the THMs were not in written form. An intervention based on an explicit instruction to lecturers to provide THMs in written form in their slide presentations did not result in increased use of written THMs into the slide presentation or improvement of the THMs retention or level of knowledge. However, we showed that there was a strong positive association between writing THMs on a slide, retention of THMs and residents’ knowledge. Further researches are needed to assess interventions to increase written THMs in lectures by faculty.

Trial registration

ClinicalTrials.gov NCT01795651 (Fev 21, 2013).
Medical students as health coaches: adding value for patients and students
Authors: Maini Arti , Fyfe Molly , Kumar Sonia
Published: June 2020

Background

Underlying the global burden of chronic disease are common and modifiable risk factors such as unhealthy diet, physical inactivity and tobacco use. Health coaching is being introduced into healthcare as an effective tool in facilitating behaviour change and addressing lifestyle risk factors in patients. Although some medical schools are training students in health coaching, there is little research on this emerging practice. This qualitative study explores the experience and application of health coaching approaches by third year medical students that have been trained in health coaching.

Methods

Six focus groups were conducted with medical students (n = 39) who had participated in an experiential health coaching training module and practiced their health coaching skills in primary care settings. Interactive facilitated discussions between students aimed to explore experiences of health coaching, how this related to their ongoing practice, and their perceived impacts of engagement with patients. Data was thematically analysed.

Results

Themes emerged around ‘mindset’, ‘skills’, ‘application of skills’, ‘perceived value’ and ‘context’. Training in health coaching prompted a shift towards a non-judgemental, solution-oriented mindset in which students increasingly accepted the ability of each person to define their needs and identify individually appropriate solutions. Mindset change supported skill development in person-centred communication, active listening, and self-refection. Mindset and skills related to changes in how students conducted patient consultations, their practice of self-refection, and their personal relationships. Perceived value of coaching approaches reinforced mindset. Students described facilitators to their coaching practice, and also tensions due to misalignment between their coaching mindset and ongoing practices in medical education and service delivery.

Conclusions

Training medical students in health coaching and supporting them to contribute meaningfully through empowering patients in real-world settings can help develop students’ professional identity and a non-judgemental, solution-oriented mindset and skills in self-reflection, person-centred care and facilitating health behaviour change.
Healthcare system inputs and patient-reported outcomes: a study in adults with congenital heart defect from 15 countries
Authors: Van Bulck Liesbet , Goossens Eva , Luyckx Koen , Apers Silke , Oechslin Erwin , Thomet Corina , Budts Werner , Enomoto Junko , Sluman Maayke A. , Lu Chun-Wei , Jackson Jamie L. , Khairy Paul , Cook Stephen C. , Chidambarathanu Shanthi , Alday Luis , Eriksen Katrine , Dellborg Mikael , Berghammer Malin , Johansson Bengt , Mackie Andrew S. , Menahem Samuel , Caruana Maryanne , Veldtman Gruschen , Soufi Alexandra , Fernandes Susan M. , White Kamila , Callus Edward , Kutty Shelby , Moons Philip ,   on behalf of the APPROACH-IS consortium and the International Society for Adult Congenital Heart Disease (ISACHD)
Published: June 2020

Background

The relationship between healthcare system inputs (e.g., human resources and infrastructure) and mortality has been extensively studied. However, the association between healthcare system inputs and patient-reported outcomes remains unclear. Hence, we explored the predictive value of human resources and infrastructures of the countries’ healthcare system on patient-reported outcomes in adults with congenital heart disease.

Methods

This cross-sectional study included 3588 patients with congenital heart disease (median age = 31y; IQR = 16.0; 52% women; 26% simple, 49% moderate, and 25% complex defects) from 15 countries. The following patient-reported outcomes were measured: perceived physical and mental health, psychological distress, health behaviors, and quality of life. The assessed inputs of the healthcare system were: (i) human resources (i.e., density of physicians and nurses, both per 1000 people) and (ii) infrastructure (i.e., density of hospital beds per 10,000 people). Univariable, multivariable, and sensitivity analyses using general linear mixed models were conducted, adjusting for patient-specific variables and unmeasured country differences.

Results

Sensitivity analyses showed that higher density of physicians was significantly associated with better self-reported physical and mental health, less psychological distress, and better quality of life. A greater number of nurses was significantly associated with better self-reported physical health, less psychological distress, and less risky health behavior. No associations between a higher density of hospital beds and patient-reported outcomes were observed.

Conclusions

This explorative study suggests that density of human resources for health, measured on country level, are associated with patient-reported outcomes in adults with congenital heart disease. More research needs to be conducted before firm conclusions about the relationships observed can be drawn.

Trial registration

ClinicalTrials.gov: NCT02150603. Registered 30 May 2014,
‘There is no such thing as getting sick justly or unjustly’ – a qualitative study of clinicians’ beliefs on the relevance of personal responsibility as a basis for health prioritisation
Authors: Traina Gloria , Feiring Eli
Published: June 2020

Background

Concerns have been raised regarding the reasonableness of using personal health responsibility as a principle or criterion for setting priorities in healthcare. While this debate continues, little is known about clinicians’ views on the role of patient responsibility in clinical contexts. This paper contributes to the knowledge on the empirical relevance of personal responsibility for priority setting at the clinical level.

Methods

A qualitative study of Norwegian clinicians (n = 15) was designed, using semi-structured interviews with vignettes to elicit beliefs on the relevance of personal responsibility as a basis for health prioritisation. Sampling was undertaken purposefully. The interviews were conducted in three hospital trusts in South-Eastern Norway between May 2018 and February 2019 and were analysed with conceptually driven thematic analysis.

Results

The findings suggest that clinicians endorsed a general principle of personal health responsibility but were reluctant to introduce personal health responsibility as a formal priority setting criterion. Five main objections were cited, relating to avoidability, causality, harshness, intrusiveness, and inequity. Still, both retrospective and prospective attributions of personal responsibility were perceived as relevant in specific clinical settings. The most prominent argument in favour of personal health responsibility was grounded in the idea that holding patients responsible for their conduct would contribute to the efficient use of healthcare resources. Other arguments included fairness to others, desert and autonomy, but such standpoints were controversial and held only marginal relevance.

Conclusions

Our study provides important novel insights into the clinicians’ beliefs about personal health responsibility improving the empirical knowledge concerning its fairness and potential applications to healthcare prioritisation. These findings suggest that although personal health responsibility would be difficult to implement as a steering criterion within the main priority setting framework, there might be clinical contexts where it could figure in prioritisation practices. Additional research on personal health responsibility would benefit from considering the multiple clinical encounters that shape doctor-patient relationships and that create the information basis for eligibility and prioritisation for treatment.
Post-incident reviews—a gift to the Ward or just another procedure? Care providers’ experiences and considerations regarding post-incident reviews after restraint in mental health services. A qualitative study
Authors: Hammervold Unn Elisabeth , Norvoll Reidun , Vevatne Kari , Sagvaag Hildegunn
Published: June 2020

Public guidelines in many western countries recommend post-incident reviews (PIRs) with patients after restraint use in mental health care. PIRs are one of several elements of seclusion and restraint reduction in internationally used programmes. PIRs may improve restraint prevention, patients’ recovery processes and care providers’ ethical mindfulness. The knowledge base on PIRs is, however, vague. This qualitative study explores professional care providers’ experiences and considerations regarding PIRs that included patients after restraint use in a Norwegian context.

Methods

Within a phenomenological hermeneutical framework, 19 multidisciplinary care providers were interviewed about their experiences and views regarding PIRs that included patients after restraint events. The interviews were performed over the period 2015–2016. Data analysis followed a data-driven stepwise approach in line with thematic content analysis. A group of two patient consultants in mental health services, and one patient’s next of kin, contributed with input regarding the interview guide and analysis process.

Results

Care providers experienced PIRs as having the potential to improve the quality of care through a) knowledge of other perspectives and solutions; b) increased ethical and professional awareness; and c) emotional and relational processing. However, the care providers considered that PIRs’ potential could be further exploited as they struggled to get hold on the patients’ voices in the encounter. The care providers considered that issue to be attributable to the patients’ conditions, the care providers’ safety and skills and the characteristics of institutional and cultural conditions.

Conclusion

Human care philosophies and a framework of care ethics seem to be preconditions for promoting patients’ active participation in PIRs after restraints. Patients’ voices strengthen PIRs’ potential to improve care and may also contribute to restraint prevention. To minimise the power imbalance in PIRs, patients’ vulnerability, dependency and perceived dignity must be recognised. Patients’ individual needs and preferences should be assessed and mapped when planning PIRs, particularly regarding location, time and preferred participants. Care providers must receive training to strengthen their confidence in conducting PIRs in the best possible way. Patients’ experiences with PIRs should be explored, especially if participation by trusted family members, peers or advocates may support the patients in PIRs.
Infectious disease specialist consultations in a Japanese cancer center: a retrospective review of 776 cases
Authors: Itoh Naoya , Hadano Yoshiro , Yamamoto Yasumasa , Terada Norihiko , Kurai Hanako
Published: June 2020

Background

Little is known about the impact of infectious disease (ID) consultations on the management of patients with cancer. This study aimed to describe the consultation services provided by ID specialists to all departments in a comprehensive cancer center in Japan.

Methods

We conducted a retrospective review of ID consultations with adult patients at a comprehensive cancer center in Japan from April 2017 to March 2018.

Results

During the study period, 776 patients with cancer had an ID consultation. Of these, 414 (53.4%) were hospital inpatients. Reasons for the ID consultation comprised clinical management (n = 481, 62.0%), immunization (n = 272, 35.1%), and infection control (n = 23, 3.0%). Of the 474 ID consultations for diagnostic purposes, the most frequent condition was fever or elevated inflammatory markers of unknown origin (n = 125, 26.4%). The most frequent diagnoses after the diagnostic ID consultation were hepatobiliary infections (n = 97, 22.4%), respiratory infections (n = 89, 20.618.8%), and intra-abdominal infections (n = 71, 16.4%). The commonest reasons for immunization consultations were to prevent seasonal influenza (n = 193, 71.0%) and post-splenectomy vaccination (n = 58, 21.3%). The commonest reasons for infection control consultations were suspected tuberculosis or contact with tuberculosis (n = 11, 47.8%) and herpes zoster infection (shingles) (n = 7, 30.4%).

Conclusions

ID specialists play an important role in the clinical management of patients with cancer. ID physicians who work in cancer centers need to be specialized in treating IDs, diagnosing the causes of fevers of unknown origin, and controlling infection.
A tissue level atlas of the healthy human virome
Authors: Kumata Ryuichi , Ito Jumpei , Takahashi Kenta , Suzuki Tadaki , Sato Kei
Published: June 2020

Background

Human-resident microbes can influence both health and disease. Investigating the microbiome using next-generation sequencing technology has revealed examples of mutualism and conflict between microbes and humans. Comparing to bacteria, the viral component of the microbiome (i.e., the “virome”) is understudied. Somatic tissues of healthy individuals are usually inaccessible for the virome sampling; therefore, there is limited understanding of the presence and distribution of viruses in tissues in healthy individuals and how virus infection associates with human gene expression and perturbs immunological homeostasis.

Results

To characterize the human virome in a tissue-specific manner, here we performed meta-transcriptomic analysis using the RNA-sequencing dataset from the Genotype-Tissue Expression (GTEx) Project. We analyzed the 8991 RNA-sequencing data obtained from 51 somatic tissues from 547 individuals and successfully detected 39 viral species in at least one tissue. We then investigated associations between virus infection and human gene expression and human disease onset. We detected some expected relationships; for instance, hepatitis C virus infection in the liver was strongly associated with interferon-stimulated gene upregulation and pathological findings of chronic hepatitis. The presence of herpes simplex virus type 1 in one subject’s brain strongly associated with immune gene expression. While torque teno virus was detected in a broad range of human tissues, it was not associated with interferon responses. Being notable in light of its association with lymphoproliferative disorders, Epstein-Barr virus infection in the spleen and blood was associated with an increase in plasma cells in healthy subjects. Human herpesvirus 7 was often detected in the stomach; intriguingly, it associated with the proportion of human leukocytes in the stomach as well as digestive gene expression. Moreover, virus infections in the local tissues associated with systemic immune responses in circulating blood.

Conclusions

To our knowledge, this study is the first comprehensive investigation of the human virome in a variety of tissues in healthy individuals through meta-transcriptomic analysis. Further investigation of the associations described here, and application of this analytical pipeline to additional datasets, will be useful to reveal the impact of viral infections on human health.
Correction to: Activation of TGR5 protects blood brain barrier via the BRCA1/Sirt1 pathway after middle cerebral artery occlusion in rats
Authors: Liang Hui , Matei Nathanael , McBride Devin W. , Xu Yang , Tang Jiping , Luo Benyan , Zhang John H.
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Short-term effects of Lumacaftor/Ivacaftor (Orkambi™) on exertional symptoms, exercise performance, and ventilatory responses in adults with cystic fibrosis
Authors: Quon Bradley S. , Ramsook Andrew H. , Dhillon Satvir S. , Mitchell Reid A. , Boyle Kyle G. , Wilcox Pearce G. , Guenette Jordan A.
Published: June 2020

Rationale

Lumacaftor/ivacaftor (LUM/IVA) modestly improves lung function following 1 month of treatment but it is unknown if this translates into improvements in exercise endurance and exertional symptoms.

Methods

Adult CF participants completed a symptom-limited constant load cycling test with simultaneous assessments of dyspnea and leg discomfort ratings pre- and 1 month post-initiation of LUM/IVA.

Results

Endurance time, exertional dyspnea and leg discomfort ratings at submaximal exercise did not change significantly. There was a significant inverse correlation between changes in leg discomfort and endurance time (r = − 0.88; p = 0.009) following 1-month of LUM/IVA.

Conclusions

Overall, 1-month of LUM/IVA did not increase endurance time or modify exertional dyspnea or leg discomfort ratings. However, individuals who experienced a reduction in leg discomfort following LUM/IVA had an improvement in endurance time. Future studies with a larger sample size are needed to verify these findings and to assess the long-term effects of LUM/IVA on exercise outcomes.

Trial registration

ClinicalTrials.gov Identifier: NCT02821130. Registered July 1, 2016.
Obtaining a series of native gradient promoter-5′-UTR sequences in Corynebacterium glutamicum ATCC 13032
Authors: Li Ning , Zeng Weizhu , Xu Sha , Zhou Jingwen
Published: June 2020

Background

Corynebacterium glutamicum is an important industrial microorganism used for the production of many valuable compounds, especially amino acids and their derivatives. For fine-tuning of metabolic pathways, synthetic biological tools are largely based on the rational application of promoters. However, the limited number of promoters make it difficult.

Results

In this study, according to the analysis of RNA-Seq data, 90 DNA fragments with lengths of 200-500 bp that may contain promoter-5′-UTR (PUTR) sequences were amplified and linked to a fluorescent protein gene. When compared with the common strong PUTR PsodUTR, 17 strong PUTRs were obtained, which maintained stable expression strengths from the early to post stationary phase. Among them, PNCgl1676UTR was the strongest and its fluorescent protein expression level was more than five times higher than that of PsodUTR. Furthermore, nine typical chemicals related to the biosynthesis of sulfur-containing amino acids (such as l-methionine, l-cysteine) were selected as stress substances to preliminarily explore the stress on these PUTRs. The results showed that the expression of PbrnFUTR was activated by l-methionine, while that of PNCgl1202UTR was severely inhibited by l-lysine.

Conclusions

These findings demonstrated that the selected PUTRs can stably express different genes, such as the red fluorescence protein gene, and can be useful for fine-tuning regulation of metabolic networks in C. glutamicum or for establishing high-throughput screening strategies through biosensor for the production of useful compounds.
A robust twelve-gene signature for prognosis prediction of hepatocellular carcinoma
Authors: Ouyang Guoqing , Yi Bin , Pan Guangdong , Chen Xiang
Published: June 2020

Background

The prognosis of hepatocellular carcinoma (HCC) patients remains poor. Identifying prognostic markers to stratify HCC patients might help to improve their outcomes.

Methods

Six gene expression profiles (GSE121248, GSE84402, GSE65372, GSE51401, GSE45267 and GSE14520) were obtained for differentially expressed genes (DEGs) analysis between HCC tissues and non-tumor tissues. To identify the prognostic genes and establish risk score model, univariable Cox regression survival analysis and Lasso-penalized Cox regression analysis were performed based on the integrated DEGs by robust rank aggregation method. Then Kaplan–Meier and time-dependent receiver operating characteristic (ROC) curves were generated to validate the prognostic performance of risk score in training datasets and validation datasets. Multivariable Cox regression analysis was used to identify independent prognostic factors in liver cancer. A prognostic nomogram was constructed based on The Cancer Genome Atlas (TCGA) dataset. Finally, the correlation between DNA methylation and prognosis-related genes was analyzed.

Results

A twelve-gene signature including SPP1, KIF20A, HMMR, TPX2, LAPTM4B, TTK, MAGEA6, ANX10, LECT2, CYP2C9, RDH16 and LCAT was identified, and risk score was calculated by corresponding coefficients. The risk score model showed a strong diagnosis performance to distinguish HCC from normal samples. The HCC patients were stratified into high-risk and low-risk group based on the cutoff value of risk score. The Kaplan–Meier survival curves revealed significantly favorable overall survival in groups with lower risk score (P < 0.0001). Time-dependent ROC analysis showed well prognostic performance of the twelve-gene signature, which was comparable or superior to AJCC stage at predicting 1-, 3-, and 5-year overall survival. In addition, the twelve-gene signature was independent with other clinical factors and performed better in predicting overall survival after combining with age and AJCC stage by nomogram. Moreover, most of the prognostic twelve genes were negatively correlated with DNA methylation in HCC tissues, which SPP1 and LCAT were identified as the DNA methylation-driven genes.

Conclusions

We identified a twelve-gene signature as a robust marker with great potential for clinical application in risk stratification and overall survival prediction in HCC patients.
Construction of a metastasis-associated ceRNA network reveals a prognostic signature in lung cancer
Authors: Cao Qing , Dong Zewen , Liu Shuzhen , An Guoyan , Yan Bianbian , Lei Lei
Published: June 2020

Background

Lung cancer is the most common cancer worldwide, and metastasis is the leading cause of lung cancer related death. However, the molecular network involved in lung cancer metastasis remains incompletely described. Here, we aimed to construct a metastasis-associated ceRNA network and identify a lncRNA prognostic signature in lung cancer.

Methods

RNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and gene set enrichment analysis (GSEA) were performed to investigate the function of these genes. Using Cox regression analysis, we found that a 6 lncRNA signature may serve as a candidate prognostic factor in lung cancer. Finally, we used Transwell assays with lung cancer cell lines to verify that LINC01010 acts as a tumor suppressor.

Results

We identified 1249 differentially expressed (DE) mRNAs, 440 DE lncRNAs and 26 DE miRNAs between nonmetastatic and metastatic lung cancer tissues. GO and KEGG analyses confirmed that the identified DE mRNAs are involved in lung cancer metastasis. Using bioinformatics tools, we constructed a metastasis-associated ceRNA network for lung cancer that includes 117 mRNAs, 23 lncRNAs and 22 miRNAs. We then identified a 6 lncRNA signature (LINC01287, SNAP25-AS1, LINC00470, AC104809.2, LINC00645 and LINC01010) that had the greatest prognostic value for lung cancer. Furthermore, we found that suppression of LINC01010 promoted lung cancer cell migration and invasion.

Conclusions

This study might provide insight into the identification of potential lncRNA biomarkers for diagnosis and prognosis in lung cancer.
Adverse reaction to Ficus Carica: reported case of a possible cross-reactivity with Der p1
Authors: Urbani S. , Aruanno A. , Nucera E.
Published: June 2020

Background

Ficus carica is an edible fruit, belonging to the Moraceae family, rarely described as cause of food allergy. We describe the first case of fig allergy that occurred as a cross-reactivity between fig and Derp 1.

Case presentation

We present a case of a 10-years-old-girl, with a history of no-seasonal mild intermittent rhinitis, who experienced an immediate reaction after ingestion of a fresh fig. Skin prick tests (SPT) with commercial extracts of food, airborne allergens, latex and panallergens (profilin, PR-10 and lipid transfer protein) were performed. SPT revealed a sensitization only for dermatophagoides farina and dermatophagoides pteronyssinus which was then confirmed with by specific IgE assay (UniCAP, Phadia, Uppsala, Sweden). We also carried out a positive SPT with a commercial fig allergen (Lofarma, Milan, Italy) and prick-by-prick (PBP) both with skin and pulp of green raw and cooked fig. Fig specific serum IgE levels were 1.08 U/ml and specific IgE for rDer p1 was 16.20 U/ml (total serum IgE = 377 U/ml). In contrast specific IgE levels for latex, LTP, profilin, PR-10 and pollen allergens were negative.

Conclusion

The ficin, the major fig allergen, belongs to cysteine protease family like Der p 1. The symptoms presented by our patient could be related to a cross reactivity between these two proteins which present a structural homology.
Serum metabolites may be useful markers to assess vascular invasion and identify normal alpha-fetoprotein in hepatocellular carcinoma undergoing liver resection: a pilot study
Authors: Lee Chao-Wei , Yu Ming-Chin , Lin Gigin , Chiu Jo-Chu , Chiang Meng-Han , Sung Chang-Mu , Hsieh Yi-Chung , Kuo Tony , Lin Cheng-Yu , Tsai Hsin-I
Published: June 2020

Purpose

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with a dismal prognosis. Vascular invasion, among others, is the most robust indicator of postoperative recurrence and overall survival after liver resection for HCC. Few studies to date have attempted to search for effective markers to predict vascular invasion before the operation. The current study would examine the plasma metabolic profiling via 1H-NMR of HCC patients undergoing liver resection and aim to search for potential biomarkers in the early detection of HCC with normal alpha-fetoprotein (AFP) and the diagnosis of vascular invasion preoperatively.

Materials and methods

HCC patients scheduled to receive liver resections for their HCC were recruited and divided into two separate groups, investigation cohort and validation cohort. Their preoperative blood samples were collected and subjected to a comprehensive metabolomic profiling using 1H-nuclear magnetic resonance spectroscopy (NMR).

Results

There were 35 HCC patients in the investigation group and 22 patients in the validation group. Chronic hepatitis B remained the most common etiology of HCC, followed by chronic HCV infection. The two study cohorts were essentially comparable in terms of major clinicopathological variables. After 1H-nuclear NMR analysis, we found in the investigation cohort that HCC with normal alpha-fetoprotein (AFP < 15 ng/mL) had significantly higher serum level of O-acetylcarnitine than those with higher AFP (AFP ≥ 15 ng/mL, P = 0.025). In addition, HCC with microscopic vascular invasion (VI) had significantly higher preoperative serum level of formate than HCC without microscopic VI (P = 0.023). These findings were similar in the validation cohort.

Conclusion

A comprehensive metabolomic profiling of HCC demonstrated that serum metabolites may be utilized to assist the early diagnosis of AFP-negative HCC patients and recognition of microvascular invasion in order to facilitate preoperative surgical planning and postoperative follow-up. Further, larger scale prospective studies are warranted to consolidate our findings.
Implementing performance-based financing in peripheral health centres in Mali: what can we learn from it?
Authors: Coulibaly Abdourahmane , Gautier Lara , Zitti Tony , Ridde Valéry
Published: June 2020

Introduction

Numerous sub-Saharan African countries have experimented with performance-based financing (PBF) with the goal of improving health system performance. To date, few articles have examined the implementation of this type of complex intervention in Francophone West Africa. This qualitative research aims to understand the process of implementing a PBF pilot project in Mali's Koulikoro region.

Method

We conducted a contrasted multiple case study of performance in 12 community health centres in three districts. We collected 161 semi-structured interviews, 69 informal interviews and 96 non-participant observation sessions. Data collection and analysis were guided by the Consolidated Framework for Implementation Research adapted to the research topic and local context.

Results

Our analysis revealed that the internal context of the PBF implementation played a key role in the process. High-performing centres exercised leadership and commitment more strongly than low-performing ones. These two characteristics were associated with taking initiatives to promote PBF implementation and strengthening team spirit. Information regarding the intervention was best appropriated by qualified health professionals. However, the limited duration of the implementation did not allow for the emergence of networks or champions. The enthusiasm initially generated by PBF quickly dissipated, mainly due to delays in the implementation schedule and the payment modalities.

Conclusion

PBF is a complex intervention in which many actors intervene in diverse contexts. The initial level of performance and the internal and external contexts of primary healthcare facilities influence the implementation of PBF. Future work in this area would benefit from an interdisciplinary approach combining public health and anthropology to better understand such an intervention. The deductive–inductive approach must be the stepping-stone of such a methodological approach.
The urgency of utilizing COVID-19 biospecimens for research in the heart of the global pandemic
Authors: Osman Iman , Cotzia Paolo , Moran Una , Donnelly Douglas , Arguelles-Grande Carolina , Mendoza Sandra , Moreira Andre
Published: June 2020

The outbreak of the novel coronavirus disease 2019 (COVID-19) and consequent social distancing practices have disrupted essential clinical research functions worldwide. Ironically, this coincides with an immediate need for research to comprehend the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the pathology of COVID-19. As the global crisis has already led to over 15,000 deaths out of 175,000 confirmed cases in New York City and Nassau County, NY alone, it is increasingly urgent to collect patient biospecimens linked to active clinical follow up. However, building a COVID-19 biorepository amidst the active pandemic is a complex and delicate task. To help facilitate rapid, robust, and regulated research on this novel virus, we report on the successful model implemented by New York University Langone Health (NYULH) within days of outbreak in the most challenging hot spot of infection globally. Using an amended institutional biobanking protocol, these efforts led to accrual of 11,120 patients presenting for SARS-CoV-2 testing, 4267 (38.4%) of whom tested positive for COVID-19. The recently reported genomic characterization of SARS-CoV-2 in the New York City Region, which is a crucial development in tracing sources of infection and asymptomatic spread of the novel virus, is the first outcome of this effort. While this growing resource actively supports studies of the New York outbreak in real time, a worldwide effort is necessary to build a collective arsenal of research tools to deal with the global crisis now, and to exploit the virus’s biology for translational innovation that outlasts humanity’s current dilemma.