title: The influence of mindfulness and moral disengagement on the psychological health and willingness to work of civil servants experiencing compassion fatigue

text: Both public administration scholars and practitioners believe that “good governance” relies on the involvement of compassionate officials. However, they overlook the fact that “compassion fatigue” often occurs when officials face the dual pressure arising from superiors’ orders and empathy for service receivers. This would inevitably not only affect their individual behaviors, but also influence the effectiveness of their service. A full-scale investigation of animal protection administrators in Taiwan was conducted so as to analyze compassion fatigue that civil servants would encounter and further establish a relationship between various variables and the hypotheses of this study by combining the studies of public administration and psychology. It should be noted that compassion fatigue may affect animal protection administrators’ mental health in spite of little influence on their willingness to work hard. However, both “mindfulness” and “moral disengagement” are coping strategies which were developed for helping tackle the dilemma of compassion fatigue. Although applying the strategy of mindfulness can generate more positive impacts on individuals and organizations than that of moral disengagement, animal protection administrators tended to adopt the latter. Accordingly, encouraging animal protection administrators to adopt mindfulness instead of moral disengagement as their coping strategy will be a priority of work for the authorities in the future.


title: Prediction of Potential Epitopes for Peptide Vaccine Formulation Against Teschovirus A Using Immunoinformatics

text: Teschovirus A belongs to the family Picornaviridae and is a causal agent of the disease Teschovirus encephalomyelitis and other infections that remain asymptomatic. The present study was performed to design epitope-based peptide vaccine against Teschovirus A by identifying the potential T cell and B-cell epitopes from capsid proteins (VP1, VP3 and VP2) of the virus using reverse vaccinology and immunoinformatics approaches. In the current study, hexapeptide T-cell and octapeptide B-cell epitopes were analyzed for immunogenicity, antigenicity and hydrophilicity scores of each epitope. Each potential epitope was further characterized using ExPASy-ProtParam and Antimicrobial Peptide Database (APD3) tools for determining various physical and chemical parameters of the epitope. One linear hexapeptide T-cell epitope, i.e., RPVNDE (epitope position 77–82) and one linear octapeptide B-cell epitope, i.e., AYSRSHPQ (236–243) were identified from the viral capsid protein as they possess the capability to raise effective immunogenic reaction in the host organism against the virus. Pharmaceutical industries could harness the results of this investigation to develop epitope-based peptide vaccines by loading the identified epitopes in combination with targeting signal peptides of T-cells and B-cells and then inserting the combination into virus like particle (vlp) or constructing subunit vaccines for further trial.


title: Design, synthesis, and screening of sulfonylurea-derived NLRP3 inflammasome inhibitors

text: Inflammasomes are multiprotein assemblies that produce robust inflammatory responses upon stimulation with pathogen- and/or danger-associated molecular patterns. Uncontrolled inflammasome activation has been linked to the pathophysiology of a wide array of disorders including life-threatening pathogenic infections, e.g., Francisella tularensis. There has been a great deal of interest in the development of small molecule inflammasome inhibitors. Using computational modeling based on chalcone derivatives, we have developed novel tertiary sulfonylurea compounds as inhibitors of the NLRP3 inflammasome. The polar enone functional alert of chalcone was replaced with a sulfonylurea scaffold while maintaining the relative positions of the two aromatic rings. These compounds were evaluated for their ability to inhibit NLRP3 and AIM2 inflammasome activation triggered by Francisella tularensis infection.


docid: pndmsytz

title: Vaccine hesitancy: Report of a student study group

text: In summer 2019 an extracurricular activity was started at the Medical University of Vienna (MUW) with the title: “Esoterism in Medicine”, where different chapters were evaluated by students. Here we present the subheading “Vaccine Hesitancy”. Three students formulated arguments from sceptic, hesitant or anti-vaccine groups and discussed the scientific literature to rebut it. Frequent objections were partly taken from the homepage of the German Robert-Koch-Institute, the home of the “Ständige Impfkommission”. Other objections were taken from blogs and social media. The students’ rebuttal was based on current scientific literature (preferentially pubmed), but also from other scientific sources like authorities.


title: Exploring oncology nurses’ perception of the consequences of clinical empathy in patients and nurses: a qualitative study

text: PURPOSE: Clinical empathy is the ability to understand the patient's situation, perspective, feelings, and actions, based on the patient’s perception, in a helping or therapeutic way. This study was conducted with the aim of exploring oncology nurses’ perception of the consequences of clinical empathy in patients and nurses and the factors influencing it. METHODS: A qualitative study was conducted by semi-structured face-to-face interviews. The participants were 6 male and 9 female oncology nurses who were selected by purposive sampling. Data were analyzed using conventional content analysis. RESULTS: The theme of “empathy as a double-sided mirror” was created, based on oncology nurses’ perception of the effects of clinical empathy in patients and nurses. Two themes of “organizational factors” and “contextual factors” were generated in response to influencing factors on clinical empathy. CONCLUSIONS: By awareness of the effects of clinical empathy, controlling the barriers and strengthening the facilitators, there is a possibility to design interventional programs to develop empathy as a clinical competency in oncology nurses.


title: Transcending the Professional–Client Divide: Supporting Young People with Complex Support Needs Through Transitions

text: Young people with complex support needs frequently experience multiple intersecting forms of disadvantage including experiences of violence, abuse and neglect, housing instability and homelessness, problematic substance use, exclusion from education, and contact with the criminal justice system. Many of these young people have mental health, cognitive disability and/or other health issues that also impact on their lives. These young people need to navigate multiple, diverse, and often difficult transitions between services, adding to the existing chaos in their lives. This article explores the experiences of young people with complex support needs in transition, specifically young people’s viewpoints and experiences of supports they receive from paid professionals. This qualitative study used body mapping research methods and in-depth interviews with 38 young people aged 16 to 26 years in three Australian states. Helpful and trusting paid relationships could serve as an anchor to young people during complex transitions and other highly turbulent life periods. These relationships were contingent on a deep and non-judgmental knowing of the young person, contributed constructive outcomes and stability in young people’s lives, and for some young people, had ‘life-saving’ effects. These findings present opportunities and challenges for policymakers and practitioners to balance the tensions between authentic relationship-based work with young people and risk-averse, economically-driven imperatives in contemporary youth service provision.


title: Synthesis and Photocatalytic Sterilization Performance of SA/TiO(2)

text: The photocatalyst sorbic acid (SA)/titanium dioxide (TiO(2)) was successfully synthesized by sol–gel method and characterized. The composite exhibited regularly spherical particles with the size of 50 nm and the specific surface area of 90.3 m(2) g(−1), furthermore, it showed mesoporous structure and significantly improved dispersion. SA was grafted on TiO(2) surface by –COOTi and TiO(2) existed as pure anatase phase in the composite. The addition of SA made the band gap of TiO(2) increased from 3.03 to 3.35 eV, which indicting that the composite exhibited a strong response to the ultraviolet light. The optimum preparation parameters of the catalyst were as follows: n(Ti):n(SA) = 1:0.05, ethanol 60 mL, glacial acetic acid 40 mL, hydrothermal temperature 180 °C, hydrothermal time 12 h. The composite could reach the 4.31 log reduction of E. coli, with the optimum catalyst dosage of 0.7 g L(−1), irradiated by UV light for 60 min. SA/TiO(2) was an environmentally friendly, non-toxic and safe sterilized nanocomposite material appropriate for future bactericidal applications, providing a new way to effectively increase the dispersion of TiO(2) particles to achieve superior photocatalytic sterilization efficiency.


title: HIV Prevalence and Factors Related to HIV Infection Among Transgender Women in Vietnam: A Respondent Driven Sampling Approach

text: Transgender women are at higher risk of HIV infection, however, there is a lack of information about HIV infection and related factors among transgender women in Vietnam. From February 2018 to June 2018, 456 transgender women were recruited in the study using Respondent-Driven Sampling technique. Participants completed the computer-based questionnaire and were tested for HIV serostatus. Multivariable logistic regression was used to identify factors related to HIV infection. The prevalence of HIV infection was 77 (16.5%), of which 19 (24.7%) were not aware of their HIV-positive status prior to the study. Factors associated with HIV infection included popper use (aOR 2.01, p = 0.044) and having regular male partner(s) (aOR 0.42, p = 0.006). More efforts are needed to reduce the high prevalence of HIV infection, such as expanding the reach of HIV screening and prevention programs to the transgender women population, particularly for substance users. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10461-020-02867-5) contains supplementary material, which is available to authorized users.


title: Oestrogen Receptor β Activation Protects Against Myocardial Infarction via Notch1 Signalling

text: PURPOSE: Oestrogen receptor β is believed to exert a cardioprotective effect against ischaemic injury. Nonetheless, the mechanism underlying its protective action remains to be fully elucidated. Recently, increased attention has been focused on Notch1 signalling for ameliorating cardiac ischaemic injury. Here, we hypothesised that oestrogen receptor β activation attenuates myocardial infarction (MI)-induced cardiac damage by modulating the Notch1 signalling pathway. METHODS: Male C57BL/6 mice were used to establish an MI model through the ligation of the anterior descending branch of the left coronary artery. Two chemical drugs, 2,3-Bis(4-hydroxyphenyl)-propionitrile (DPN) and N-[N-(3,5-difluorophenacetyl)-l-alanyl]-s-phenylglycine t-butyl ester (DAPT), a specific inhibitor of Notch1 signalling) were administered via intraperitoneal injection to change oestrogen receptor β and Notch1 activities. Immunohistochemistry, western blot analysis, enzyme-linked immunosorbent assay (Elisa) assessment and echocardiography were used in this study to analyse cardiac oxidative stress, apoptosis, infraction volume, fibrosis and cardiac function. RESULTS: DPN-mediated oestrogen receptor β activation effectively protected cardiomyocytes from MI-induced oxidative damage and apoptosis. Furthermore, oestrogen receptor β activation reduced the infarct size and lowered the levels of myocardial enzymes in the serum, thereby leading to greater overall cardiac function improvement. Ischaemic injury–induced myocardial fibrosis was attenuated by oestrogen receptor β activation. Nevertheless, all of these cardioprotective effects of oestrogen receptor β activation were almost abrogated by DAPT administration, i.e. DAPT attenuated the anti-oxidative and anti-apoptotic effects and the decrease in infarct and fibrotic areas and reversed cardiac functional recovery. The levels of phospho-phosphatidylinositol-3-kinase (PI3K) and phospho-protein kinase B (Akt) were increased after DPN administration, and this change was reversed after DAPT was administered. CONCLUSIONS: All of these new findings indicate that oestrogen receptor β activation is effective in ameliorating MI-induced cardiac dysfunction by enhancing Notch1 signalling and that PI3K/Akt signalling is the downstream mediator. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10557-020-06949-3) contains supplementary material, which is available to authorized users.


title: Aberrant B cell repertoire selection associated with HIV neutralizing antibody breadth

text: A goal of HIV vaccine development is to elicit antibodies with neutralizing breadth. Broadly neutralizing antibodies (bNAbs) to HIV often have unusual sequences with long heavy-chain complementarity-determining region loops, high somatic mutation rates and polyreactivity. A subset of HIV-infected individuals develops such antibodies, but it is unclear whether this reflects systematic differences in their antibody repertoires or is a consequence of rare stochastic events involving individual clones. We sequenced antibody heavy-chain repertoires in a large cohort of HIV-infected individuals with bNAb responses or no neutralization breadth and uninfected controls, identifying consistent features of bNAb repertoires, encompassing thousands of B cell clones per individual, with correlated T cell phenotypes. These repertoire features were not observed during chronic cytomegalovirus infection in an independent cohort. Our data indicate that the development of numerous B cell lineages with antibody features associated with autoreactivity may be a key aspect in the development of HIV neutralizing antibody breadth.


title: Prediction of Postoperative Mortality in Patients with Organ Failure After Gastric Cancer Surgery

text: BACKGROUND: Scarce data are available on the characteristics of postoperative organ failure (POF) and mortality after gastrectomy. We aimed to describe the causes of organ failure and mortality related to gastrectomy for gastric cancer and to identify patients with POF who are at a risk of failure to rescue (FTR). METHODS: The study examined patients with POF or in-hospital mortality in Seoul National University Hospital between 2005 and 2014. We identified patients at a high risk of FTR by analyzing laboratory findings, complication data, intensive care unit records, and risk scoring including Acute Physiology and Chronic Health Evaluation (APACHE) IV, Sequential Organ Failure Assessment (SOFA) score, and Simplified Acute Physiology Score (SAPS) 3 at ICU admission. RESULTS: Among the 7304 patients who underwent gastrectomy, 80 (1.1%) were identified with Clavien–Dindo classification (CDC) grade ≥ IVa. The numbers of patients with CDC grade IVa, IVb, and V were 48 (0.66%), 11 (0.15%), and 21 (0.29%), respectively. Pulmonary failure (43.8%), surgical site complication (27.5%), and cardiac failure (13.8%) were the most common causes of POF and mortality. Cancer progression (100%) and cardiac events (45.5%) showed high FTR rates. In univariate analysis, acidosis, hypoalbuminemia, SOFA, APACHE IV, and SAPS 3 were identified as risk factors for FTR (P < 0.05). Finally, SAPS 3 was identified as an independent predictive factor for FTR. CONCLUSIONS: Cancer progression and acute cardiac failure were the most lethal causes of FTR. SAPS 3 is an independent predictor of FTR among POF patients after gastrectomy.


title: Effect of Early Tracheostomy on Mortality of Mechanically Ventilated Patients with Guillain–Barré Syndrome: A Nationwide Observational Study

text: BACKGROUND: Patients with Guillain–Barré syndrome (GBS) who require mechanical ventilation (MV) are regarded as candidates for early tracheostomy because of the high risk of prolonged MV; however, the association between early tracheostomy and favorable outcomes in patients with GBS remains unclear. In this study, we evaluated the association between early tracheostomy and outcomes in mechanically ventilated patients with GBS. METHODS: This retrospective observational study included adult patients with GBS identified in the Japanese Diagnosis Procedure Combination national inpatient database from July 1, 2010, to March 31, 2018, who initiated MV within the first week of admission and who received MV for more than 1 week. Early tracheostomy was defined as tracheostomy performed within 7 days of MV. The primary outcome was in-hospital mortality, and the secondary outcomes were 28-day mortality, nosocomial pneumonia, length of hospital stay, length of intensive care unit (ICU) stay, duration of MV, duration of sedation, duration of analgesia, duration of delirium, and total hospitalization costs. Propensity scores for early tracheostomy were calculated using a logistic regression model on the following variables: age; sex; body mass index; Japan Coma Scale status at admission; Charlson comorbidity index score; comorbidity of chronic pulmonary disease; complication of pneumonia at admission; complication of hyponatremia at admission; neurological presentation at admission; ambulance use; referral from other hospitals; treatment year; days from hospital admission to MV initiation; ICU admission until the day of MV initiation; and treatments until the day of MV initiation. Stabilized inverse probability of treatment weighting analyses was performed to compare the outcomes between patients with and without early tracheostomy. RESULTS: Among 919 eligible patients, 654 patients (71%) underwent tracheostomy, with 136 patients (15%) receiving early tracheostomy. Overall, the median time from initiation of MV to tracheostomy was 12 days (interquartile range 8–15 days). After stabilized inverse probability of treatment weighting, early tracheostomy was not associated with lower in-hospital mortality (risk difference 0.4%; 95% confidence interval − 5.6 to 6.7%) compared with patients without early tracheostomy. There were no significant differences in 28-day mortality (risk difference − 1.3%; 95% confidence interval − 3.5 to 0.9%) and incidence of nosocomial pneumonia (risk difference − 2.6%; 95% confidence interval − 9.1 to 4.2%) between the two groups. None of the other secondary outcomes differed significantly between the groups. CONCLUSIONS: Early tracheostomy was not significantly associated with decreased mortality or morbidity in patients with GBS requiring MV for more than 1 week.


Lung–kidney cross-talk in the critically ill: insights from the Lung Safe study


title: Self-Injury in Japanese Manga: A Content Analysis

text: This study explored representations of self-injury in Japanese manga (graphic novels). A content analysis of fifteen slice-of-life manga published between 2000-2017 was conducted, focusing on forty scenes that depict eighteen characters engaging in self-injury. Most depictions of self-injury reflect a stereotypical perception of “self-injurer,” a young girl cutting herself to cope with negative emotion. Characters receive informal support from friends and partners, while parents are portrayed as unsupportive and even triggering. An emergent trend was observed among manga targeting male readers to label self-injuring women as “menhera” - mentally vulnerable damsels in distress - inviting a fetishistic gaze on the self-injuring female bodies.


Trials on oxygen supplementation in sepsis: better late than never


title: Quality assessment and response to less invasive surfactant administration (LISA) without sedation

text: BACKGROUND: Although sedative premedication for endotracheal intubation is considered standard of care, less invasive surfactant administration (LISA) is often performed without sedative premedication. The aim of this study was to assess success rates, technical quality and vital parameters in LISA without sedative premedication. METHODS: Prospective observational study in 86 neonates <32 weeks’ gestation. LISA was performed according to a standardized protocol without use of sedative premedication. Outcome measures were success rates of LISA attempts, reasons for failure and quality of technical conditions. In 37 neonates, heart rate and oxygen saturation levels from 20 min before until 30 min after start of LISA were collected. RESULTS: In 48% of LISAs the first attempt failed and in 34% quality of technical conditions was inadequate. The success rate was significantly correlated with quality of technical conditions and experience of the performer. Desaturations <80% occurred in 54% of patients while bradycardia <80/min did not occur. CONCLUSION: This study shows a relatively low success rate of the first attempt of LISA, frequent inadequacy of technical quality and frequent oxygen desaturations. These effects may be improved by the use of sedative premedication.


title: Minds, brains, and hearts: an empirical study on pluralism concerning death determination

text: Several authors in bioethics literature have expressed the view that a whole brain conception of death is philosophically indefensible. If they are right, what are the alternatives? Some authors have suggested that we should go back to the old cardiopulmonary criterion of death and abandon the so-called Dead Donor Rule. Others argue for a pluralist solution. For example, Robert Veatch has defended a view that competent persons should be free to decide which criterion of death should be used to determine their death. However, there is very little data on people’s preferences about death determination criteria. We conducted online vignette-based survey with Latvian participants (N = 1416). The data suggest that the pluralist solution fits best with the way our study participants think about death determination—widely differing preferences concerning death determination criteria were observed. Namely, most participants choose one of the three criteria discussed in the literature: whole brain, higher brain, and cardiopulmonary. Interestingly, our data also indicate that study participants tend to prefer less restrictive criteria for determination of their own deaths than for determination of deaths of their closest relatives. Finally, the preferences observed in our sample are largely in accord with the Dead Donor Rule for organ procurement for transplantation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40592-020-00114-0) contains supplementary material, which is available to authorized users.


title: Tracheoesophageal fistula in the developing world: are we ready for thoracoscopic repair?

text: PURPOSE: Tracheoesophageal fistula (TEF) is a bellwether for a country’s ability to care for sick newborns. We aim to review the existing literature from low- and middle-income countries in regard to management of those newborns and the possible approaches to improve their outcomes. METHODS: A review of the existing English literature was conducted with the aim of assessing challenges faced by providers in LMIC in terms of diagnostic, preoperative, operative and post-operative care for TEF patients. We also review the limited literature for performing thoracoscopic repair in the developing world context and suggest methods for introduction of advanced thoracoscopic procedures including techniques for providing anesthesia to these challenging babies. RESULTS: While outcomes related to technique from LMIC are comparable to the developed world, rates of secondary complications like sepsis and pneumonia are higher. In many areas, repairs are conducted in a staged fashion with minimal utilization of thoracoscopic approach. The paucity of resources creates strain on intraoperative and post-operative management. CONCLUSION: Clearly, not all developing world contexts are ready to attempt thoracoscopic repair but we outline suggestions for assessing the existing capabilities and a stepwise gradual implementation of advanced thoracoscopy when appropriate.


docid: uiabpbxd

title: An appraisal of oriental theileriosis and the Theileria orientalis complex, with an emphasis on diagnosis and genetic characterisation

text: Oriental theileriosis, a tick-borne disease of bovids caused by members of the Theileria orientalis complex, has a worldwide distribution. Globally, at least 11 distinct genotypes of T. orientalis complex, including type 1 (chitose), type 2 (ikeda), type 3 (buffeli), types 4 to 8, and N1–N3, have been described based on the sequence of the major piroplasm surface protein (MPSP) gene. Of these 11 genotypes, mainly ikeda and chitose are known to be pathogenic and cause considerable morbidity (including high fever, anaemia, jaundice and abortion), production losses and/or mortality in cattle. Mixed infections with two or more genotypes of T. orientalis is common, but do not always lead to a clinical disease, posing challenges in the diagnosis of asymptomatic or subclinical forms of oriental theileriosis. The diagnosis of oriental theileriosis is usually based on clinical signs, the detection of piroplasms of T. orientalis in blood smears, and/or the use of serological or molecular techniques. This paper reviews current methods used for the diagnosis of T. orientalis infections and the genetic characterisation of members of the T. orientalis complex, and proposes that advanced genomic tools should be established for investigations of these and related haemoparasites.


title: Measuring endotracheal tube intracuff pressure: no room for complacency

text: Tracheal intubation constitutes a routine part in the care of critically ill and anaesthetised patients. Prolonged use of endotracheal with inflated cuff is one of the major multifactorial causes of complications. Both under-inflation and over-inflation of cuff are associated with complications. Despite known problems, regular measurement of cuff pressure is not routine, and it is performed on an ad hoc basis.


title: Towards new TB vaccines

text: Mycobacterium tuberculosis remains the leading cause of death attributed to a single infectious organism. Bacillus Calmette-Guerin (BCG), the standard vaccine against M. tuberculosis, is thought to prevent only 5% of all vaccine-preventable deaths due to tuberculosis, thus an alternative vaccine is required. One of the principal barriers to vaccine development against M. tuberculosis is the complexity of the immune response to infection, with uncertainty as to what constitutes an immunological correlate of protection. In this paper, we seek to give an overview of the immunology of M. tuberculosis infection, and by doing so, investigate possible targets of vaccine development. This encompasses the innate, adaptive, mucosal and humoral immune systems. Though MVA85A did not improve protection compared with BCG alone in a large-scale clinical trial, the correlates of protection this has revealed, in addition to promising results from candidate such as VPM1002, M72/ASO1E and H56:IC31 point to a brighter future in the field of TB vaccine development.


title: Incidence of coagulase-negative staphylococcal bacteremia among ICU patients: decontamination studies as a natural experiment

text: The epidemiology of coagulase-negative staphylococcal (CNS) bacteremia among adult ICU patients remains unclear. Decontamination studies among ICU patients provide a unique opportunity to study the impacts of different diagnostic criteria, exposure to various decontamination interventions, and various other factors, on its incidence over three decades. Decontamination studies among ICU patients reporting CNS bacteremia incidence data were obtained mostly from recent systematic reviews. The CNS bacteremia incidence within component (control and intervention) groups of decontamination studies was benchmarked versus studies without intervention (observational groups). The impacts of antibiotic versus chlorhexidine decontamination interventions, control group concurrency, publication year, and diagnostic criteria were examined in meta-regression models. Among non-intervention (observational) studies which did versus did not specify stringent (≥ 2 positive blood cultures) diagnostic criteria, the mean CNS bacteremia incidence per 100 patients (and 95% CI; n) is 1.3 (0.9–2.0; n = 23) versus 3.6 (1.8–6.9; n = 8), respectively, giving an overall benchmark of 1.8 (1.2–2.4; n = 31). Versus the benchmark incidence, the mean incidence is high among concurrent control (5.7; 3.6–9.1%) and intervention (5.2; 3.6–6.9%), but not non-concurrent control (1.0; 0.4–3.9%) groups of 21 antibiotic studies, nor among eleven component groups of chlorhexidine studies. This high incidence remained apparent (p < 0.01) in meta-regression models adjusting for group wide factors such as diagnostic criteria and publication year. The incidence of CNS bacteremia within both intervention and concurrent (but not non-concurrent) control groups of antibiotic-based decontamination studies are unusually high even accounting for variable diagnostic criteria and other factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-019-03763-0) contains supplementary material, which is available to authorized users.


title: Evaluation of respiratory syncytial virus IgG antibody dynamics in mother-infant pairs cohort

text: RSV is one of the most important agents of lower respiratory infections in childhood. In this study, anti-RSV antibody levels in mother-infant pairs and factors related to antibody transfer ratio were investigated. One hundred and twenty-seven women that had term babies and their babies and 84 mother-infant pairs of them who continued the study after 6 months were enrolled. Anti-RSV IgG antibodies of the mothers and infants were positive in 46.5% and 61.5%, respectively. At the sixth month, anti-RSV antibodies were negative in all infants. Median of the anti-RSV antibody levels of the mothers and infants at birth were 12.08 IU/ml (1.21–119.27) and 13.78 IU/ml (3.99–108.6), respectively. There was a significant correlation between anti-RSV antibody levels of mothers and infants at birth (p: 0.0001, r: 0.667) and anti-RSV antibody levels of infants at birth and at 6th month (p: 0.0001, r: 0.343). Median ratio of infant and mother antibody levels was 1.22 (0.14–6.05). Median ratio that was detected in appropriate for gestational age infants was significantly higher than in small for gestational age or large for gestational age infants. In this study, the significant positive correlation between maternal antibody levels and infants’ antibody levels at birth suggests that maternal vaccination strategies may be logical. We showed that antibody transfer rate was highest in appropriate for gestational age infants. It should be kept in mind that maternal vaccination strategies may be less effective in small for gestational age and large for gestational age infants.


Distinction between good palliative care and intending death


title: Intracranial pressure monitoring associated with increased mortality in pediatric brain injuries

text: BACKGROUND: Utilization of ICP monitors for pediatric patients is low and varies between centers. We hypothesized that in more severely injured patients (GCS 3–4), there would be a decreased mortality associated with invasive monitoring devices. METHODS: The pediatric Trauma Quality Improvement Program (TQIP) was queried for patients aged ≤ 16 years meeting criteria for invasive monitors. Our primary outcome was mortality. Patients with ICP monitoring were compared to those without. A logistic regression was used to examine the risk of mortality. RESULTS: Of 3,808 patients, 685 (18.0%) underwent ICP monitoring. ICP monitors were associated with increased risk of mortality (OR 1.82, CI 1.36–2.44, p < 0.001). A secondary analysis including type of invasive ICP monitor and dividing GCS into 3 categories revealed both intraventricular drain (OR 1.89, CI 1.3–2.7, p = 0.001) and intraparenchymal pressure monitor (OR 1.86, CI 1.32–2.6, p < 0.001) to be independently associated with an increased likelihood of mortality regardless of GCS, while intraparenchymal oxygen monitoring was not (OR 0.47, CI 0.11–2.05, p = 0.316). The strongest effect was seen in those patients with a GCS of 5–6. CONCLUSION: ICP monitors are an independent risk factor for mortality, particularly with intraventricular drains and intraparenchymal monitors in patients with a GCS 5–6.


docid: gqjcvxln

title: Structural proteomics, electron cryo-microscopy and structural modeling approaches in bacteria–human protein interactions

text: A central challenge in infection medicine is to determine the structure and function of host–pathogen protein–protein interactions to understand how these interactions facilitate bacterial adhesion, dissemination and survival. In this review, we focus on proteomics, electron cryo-microscopy and structural modeling to showcase instances where affinity-purification (AP) and cross-linking (XL) mass spectrometry (MS) has advanced our understanding of host–pathogen interactions. We highlight cases where XL-MS in combination with structural modeling has provided insight into the quaternary structure of interspecies protein complexes. We further exemplify how electron cryo-tomography has been used to visualize bacterial–human interactions during attachment and infection. Lastly, we discuss how AP-MS, XL-MS and electron cryo-microscopy and -tomography together with structural modeling approaches can be used in future studies to broaden our knowledge regarding the function, dynamics and evolution of such interactions. This knowledge will be of relevance for future drug and vaccine development programs.


docid: unwovoke

title: The role of vacuum-assisted closure (VAC) therapy in the management of FOURNIER’S gangrene: a retrospective multi-institutional cohort study

text: PURPOSE: To explore the role of vacuum assisted closure (VAC) therapy versus conventional dressings in the Fournier’s gangrene wound therapy. PATIENTS AND METHODS: This is a retrospective multi-institutional cohort study. Data of 92 patients from nine centers between 2007 and 2018 were retrospectively analyzed. After surgery, patient having a local or a disseminated FG were managed with VAC therapy or with conventional dressings. The 10-weeks wound closure cumulative rate and OS were analyzed. RESULTS: Of the 92 patients, 62 (67.4%) showed local and 30 (32.6%) a disseminated FG. After surgery, 19 patients (20.7%) with local and 14 (15.2%) with disseminated FG underwent to VAC therapy; 43 (46.7%) with local and 16 (17.4%) with disseminated FG were treated using conventional dressings. The multivariable logistic regression analysis demonstrated that the VAC in patients with disseminated FG led to a higher cumulative rate of wound closure than patients treated with no-VAC (OR = 6.5; 95% CI 1.1–37.4, p = 0.036). The Kaplan–Meier survival curves for the OS showed a significant difference between no-VAC patients with local and disseminated FG (OS rate at 90 days 0.90, 95% CI 0.71–0.97 vs 0.55, 95% CI 0.24–0.78, respectively; p = 0.039). Cox regression confirmed that no-VAC patients with disseminated FG showed the lowest OS (hazard ratio adjusted for sex and age HR = 3.4, 95% CI 1.1–10.4; p = 0.033). CONCLUSIONS: In this large cohort study, VAC therapy in patients with disseminated FG may offer an advantage in terms of 10-weeks wound closure cumulative rate and OS at 90 days after initial surgery.


Authors’ Response to Drs. Ece Salihoglu and Ziya Salihoglu’s Letter to the Editor


title: Evidence supporting recommendations from international guidelines on treatment, diagnosis, and prevention of HAP and VAP in adults

text: Clinical practice guidelines (CPGs) are intended to support clinical decisions and should be based on high-quality evidence. The objective of the study was to evaluate the quality of evidence supporting the recommendations issued in CPGs for therapy, diagnosis, and prevention of hospital-acquired and ventilator-associated pneumonia (HAP/VAP). CPGs released by international scientific societies after year 2000, using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, were analyzed. Number and strength of recommendations and quality of evidence (high, moderate, low, and very low) were extracted and indexed in the aforementioned sections. High-quality evidence was based on randomized control trials (RCT) without important limitations and exceptionally on rigorous observational studies. Eighty recommendations were assessed, with 7 (8.7%), 24 (30.0%), 29 (36.3%), and 20 (25.0%) being supported by high, moderate, low, and very low-quality evidence, respectively. Highest evidence degree was reported for 26 prevention recommendations, with 7 (26.9%) supported by high-quality evidence and no recommendation based on very low-quality evidence. In contrast, among 9 recommendations for diagnosis and 45 for therapy, none was supported by high-quality evidence, in spite of being recommended as strong in 33.3% and 46.7%, respectively. Among HAP/VAP diagnosis recommendations, the majority of evidence was rated as low or very low-quality (55.6% and 22.2%, respectively) whereas among HAP/VAP therapy recommendations, 4/5 were rated as low and very low-quality (40% each). In conclusion, among HAP/VAP international guidelines, most recommendations, particularly in therapy, remain supported by observational studies, case reports, and expert opinion. Well-designed RCTs are urgently needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-019-03748-z) contains supplementary material, which is available to authorized users.


title: Influence of different PEEP levels on electrical impedance tomography findings in patients under general anesthesia ventilated in the lateral decubitus position

text: To determine the effect of various PEEP levels on electrical impedance tomography (EIT) measured differences in regional ventilation, hemodynamics, lung mechanics and parameters of alveolar gas exchange. Thirty three patients scheduled for elective urologic surgery in general anesthesia in lateral decubitus position were randomized into three groups—PEEP 0, 5 and 10 mbar. EIT recording, arterial blood gas analysis and hemodynamic parameters were captured at three timepoints—before induction (T0), 5 min after lateral positioning (T1) and 90 min after positioning (T2). Dynamic compliance (Cdyn) was measured at T1 and T2. Offline EIT data analysis was performed to calculate EIT derived parameters of ventilation distribution. Patients ventilated with PEEP of 10 mbar had a significantly lower A-a (alveolo arterial) gradient over measurements and symmetrical distribution of ventilation measured by EIT. There was no significant difference in Cdyn, center of ventilation indices and inhomogeneity index between groups. There was no difference of mean arterial pressure, cardiac index and heart rate between groups. Patients with 5 mbar of PEEP had higher stroke volume index compared to 0 and 10 mbar at baseline and over measurements. Nondependent/dependent TV ratio as well as global inhomogeneity index were correlated with A-a gradient. Dynamic compliance showed no correlation to A-a gradient. In our study, a PEEP level of 10 mbar improved alveolar gas exchange without compromising hemodynamic stability in patients mechanically ventilated in the lateral decubitus position. EIT measured parameters may be used to determine optimal ventilation parameters in these patients with inhomogeneous lung mechanics. Further studies are needed in patients with various lung pathologies.


title: Oropharyngeal colostrum therapy reduces the incidence of ventilator-associated pneumonia in very low birth weight infants: a systematic review and meta-analysis

text: BACKGROUND: Oropharyngeal colostrum (OC) is a novel feeding strategy to prevent complications of prematurity. A meta-analysis was conducted to investigate whether very low birth weight infants (VLBWs) can benefit from OC. METHODS: Randomized controlled trials (RCTs) were searched from Embase, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials from the date of inception until May 2019. RCTs were eligible if they used OC therapy on VLBW infants. The primary outcomes included ventilator-associated pneumonia (VAP), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), late-onset sepsis, and death. The secondary outcomes included the time of full enteral feeding and the length of stay. RESULTS: Eight RCTs involving 682 patients (OC group: 332; non-OC group: 350) were included in the meta-analysis. The results suggested that OC was associated with a significantly reduced incidence of VAP [odds ratio (OR) = 0.39, 95% confidence interval (CI): 0.17–0.88, P = 0.02] and full enteral feeding days (mean difference = −2.66, 95% CI: −4.51 to −0.80, P = 0.005), a potential significance of NEC (OR = 0.51, 95% CI: 0.26–0.99, P = 0.05), a trend toward downregulating mortality (OR = 0.60, 95% CI: 0.34–1.08, P = 0.09) and proven sepsis (OR = 0.64, 95% CI: 0.40–1.01, P = 0.06). CONCLUSIONS: OC could significantly reduce the occurrence of VAP, and consequently, its routine use should be considered for VLBWs to prevent infectious diseases. IMPACT: OC significantly reduces the occurrence of VAP and NEC in VLBW infants. OC may reduce the incidence of VAP and NEC by increasing IgA levels. Early OC therapy for mechanical ventilation of low-weight infants may prevent the occurrence of VAP.


title: Dynamic data in the ED predict requirement for ICU transfer following acute care admission

text: Misidentification of illness severity may lead to patients being admitted to a ward bed then unexpectedly transferring to an ICU as their condition deteriorates. Our objective was to develop a predictive analytic tool to identify emergency department (ED) patients that required upgrade to an intensive or intermediate care unit (ICU or IMU) within 24 h after being admitted to an acute care floor. We conducted a single-center retrospective cohort study to identify ED patients that were admitted to an acute care unit and identified cases where the patient was upgraded to ICU or IMU within 24 h. We used data available at the time of admission to build a logistic regression model that predicts early ICU transfer. We found 42,332 patients admitted between January 2012 and December 2016. There were 496 cases (1.2%) of early ICU transfer. Case patients had 18.0-fold higher mortality (11.1% vs. 0.6%, p < 0.001) and 3.4 days longer hospital stays (5.9 vs. 2.5, p < 0.001) than those without an early transfer. Our predictive analytic model had a cross-validated area under the receiver operating characteristic of 0.70 (95% CI 0.67–0.72) and identified 10% of early ICU transfers with an alert rate of 1.6 per week (162.2 acute care admits per week, 1.9 early ICU transfers). Predictive analytic monitoring based on data available in the emergency department can identify patients that will require upgrade to ICU or IMU if admitted to acute care. Incorporating this tool into ED practice may draw attention to high-risk patients before acute care admit and allow early intervention.


title: Melanocortin 4 receptor (MC4R) gene variants in children and adolescents having familial early-onset obesity: genetic and clinical characteristics

text: Melanocortin 4 receptor gene plays an important role in food intake, energy balance, and weight control. The autosomal dominantly inherited MC4R variants cause obesity by causing hyperphagia and decreased sense of satiety. Homozygous variants are rarely reported, and they cause earlier/severe obesity. Our objective is to determine the MC4R gene variant frequency in children and adolescents with familial early-onset obesity. One hundred thirty-nine children and adolescents (57 girls/82 boys) whose weight increase started before the age of 5 years and who had early-onset obesity in at least one of their first-degree relatives were included in the study. Obesity is defined as body mass index (BMI) of ≥ 95th percentile, and as extreme obesity is defined if the BMI ≥ 120% of the 95th percentile or ≥ 35 kg/m(2). Children having genetic syndromes associated with obesity and mental retardation or taking drugs that promote changes in eating behavior or weight were excluded from the study. Coding region of the MC4R gene was sequenced by using the Illumina MiSeq Next Generation Sequencing System. The mean age of the patients was 7.3 ± 3.7 years, and the mean BMI SDS was 3.7 ± 0.7. While 118 patients (85%) were prepubertal, 21 patients (15%) were pubertal. Seven different variants were identified in 12 patients by giving a variant detection rate of 8.6%, of these five were previously identified missense variants p.N274S, p.S136F, p.V166I, p.R165W, and p.I291SfsX10. One homozygous variant p.I291SfsX10 (c.870delG) was detected in a severely obese 2-year-old boy, and other variants were heterozygous. Two novel variants were found: p.M200del and p.S188L. By using the in silico analysis software, these novel variants were predicted to be disease causing. Conclusion: MC4R gene variants are quite common in childhood obesity in Turkish population. Screening the variants in MC4R gene is necessary in patients with severe childhood-onset obesity. In such patients, comorbidities of obesity can be seen from early years.


title: Correct Antemortem Diagnosis of Pneumonia in Children With Fatal Illnesses

text: This retrospective study analyzed the level of concordance between clinical and autopsy diagnosis of pneumonia over a 3-year period. Utilizing the Goldman classification, the concordance rate was found to be 37.5%. Major discrepancies (Class I and II) were found in 25% cases, and minor discrepancies (Class III and IV) in 37.5% cases.


title: Refeeding Syndrome with Hypoglycemia in a Severely Malnourished Infant

text: A 5-mo-old severely malnourished 3.5 kg boy was brought to the emergency department with hypoglycemia, bradycardia, bradypnea, and hypothermia. His findings were likely due to severe malnutrition secondary to parental neglect. Resuscitation with dextrose containing intravenous fluids was promptly started. On day 2 of admission, refeeding was initiated. From that time, he had multiple hypoglycemic episodes along with hypophosphatemia, hypomagnesemia, and hypokalemia. Hypoglycemia was associated with the initiation of enteral feeding and an increase in calories and amounts of enteral feeding. Hypoglycemia associated with refeeding syndrome in infant has not been previously reported.


title: Review of Cystic Echinococcosis in Nigeria: A Story of Neglect

text: PURPOSE: Cystic echinococcosis (CE) caused by Echinococcus granulosus sensu lato is a widespread zoonotic disease of global concern. In Nigeria, the exact picture/status of CE is unclear, as most of the states are largely uninvestigated. Yet, as with every parasitic zoonosis, the first step towards planning a comprehensive management and control programme involves assessment of available national/regional prevalence data, host range, and risk factors at play in the transmission dynamics. METHODS: Published articles on echinococcosis were searched on PubMed and Africa Journal Online (AJOL) databases. Inclusion criteria were based on studies reporting prevalence of echinococcosis in animals and humans (including case reports) from 1970 to 2018. RESULTS: In this study, we evaluated and summarized cystic echinococcosis reports in Nigeria and found that post 1970–80s, studies on cystic echinococcosis have remained sparse regardless of the high prevalence recorded in the early years of CE investigation. In addition, information on the genetic population structure and the role of wildlife in CE transmission is still lacking. CONCLUSIONS: This study appraises the prevalence and distribution of CE in Nigeria and identified areas where surveillance and control efforts should be focused and intensified.


title: Non-Amyloid Approaches to Disease Modification for Alzheimer’s Disease: An EU/US CTAD Task Force Report

text: While amyloid-targeting therapies continue to predominate in the Alzheimer’s disease (AD) drug development pipeline, there is increasing recognition that to effectively treat the disease it may be necessary to target other mechanisms and pathways as well. In December 2019, The EU/US CTAD Task Force discussed these alternative approaches to disease modification in AD, focusing on tau-targeting therapies, neurotrophin receptor modulation, anti-microbial strategies, and the innate immune response; as well as vascular approaches, aging, and non-pharmacological approaches such as lifestyle intervention strategies, photobiomodulation and neurostimulation. The Task Force proposed a general strategy to accelerate the development of alternative treatment approaches, which would include increased partnerships and collaborations, improved trial designs, and further exploration of combination therapy strategies.


title: The global preclinical antibacterial pipeline

text: Antibacterial resistance is a great concern and requires global action. A critical question is whether enough new antibacterial drugs are being discovered and developed. A review of the clinical antibacterial drug pipeline was recently published, but comprehensive information about the global preclinical pipeline is unavailable. This Review focuses on discovery and preclinical development projects and has found, as of 1 May 2019, 407 antibacterial projects from 314 institutions. The focus is on Gram-negative pathogens, particularly bacteria on the WHO priority bacteria list. The preclinical pipeline is characterized by high levels of diversity and interesting scientific concepts, with 135 projects on direct-acting small molecules that represent new classes, new targets or new mechanisms of action. There is also a strong trend towards non-traditional approaches, including diverse antivirulence approaches, microbiome-modifying strategies, and engineered phages and probiotics. The high number of pathogen-specific and adjunctive approaches is unprecedented in antibiotic history. Translational hurdles are not adequately addressed yet, especially development pathways to show clinical impact of non-traditional approaches. The innovative potential of the preclinical pipeline compared with the clinical pipeline is encouraging but fragile. Much more work, focus and funding are needed for the novel approaches to result in effective antibacterial therapies to sustainably combat antibacterial resistance.


title: How I Manage Natural Killer Cell Deficiency

text: Natural killer (NK) cell deficiency (NKD) is a subset of primary immunodeficiency disorders (PID) in which an abnormality of NK cells represents a major immunological defect resulting in the patient’s clinical immunodeficiency. This is distinct from a much larger group of PIDs that include an NK cell abnormality as a minor component of the immunodeficiency. Patients with NKD most frequently have atypical consequences of herpesviral infections. There are now 6 genes that have been ascribed to causing NKD, some exclusively and others that also cause other known immunodeficiencies. This list has grown in recent years and as such the mechanistic and molecular clarity around what defines an NKD is an emerging and important field of research. Continued increased clarity will allow for more rational approaches to the patients themselves from a therapeutic standpoint. Having evaluated numerous individuals for NKD, I share my perspective on approaching the diagnosis and managing these patients.


title: Prostaglandin E(2) in a TLR3- and 7/8-agonist-based DC maturation cocktail generates mature, cytokine-producing, migratory DCs but impairs antigen cross-presentation to CD8(+) T cells

text: Mature dendritic cells (DCs) represent cellular adjuvants for optimal antigen presentation in cancer vaccines. Recently, a combination of prostaglandin E(2) (PGE(2)) with Toll-like receptor agonists (TLR-P) was proposed as a new standard to generate superior cytokine-producing DCs with high migratory capacity. Here, we compare TLR-P DCs with conventional DCs matured only with the proinflammatory cytokines TNFα and IL-1ß (CDCs), focussing on the interaction of resulting DCs with CD8(+) T-cells. TLR-P matured DCs showed elevated expression of activation markers such as CD80 and CD83 compared to CDCs, together with a significantly higher migration capacity. Secretion of IL-6, IL-8, IL-10, and IL-12 was highest after 16 h in TLR-P DCs, and only TLR-P DCs secreted active IL-12p70. TLR-P DCs as well as CDCs successfully primed multifunctional CD8(+) T-cells from naïve precursors specific for the peptide antigens Melan-A, NLGN4X, and PTP with comparable priming efficacy and T-cell receptor avidity. CD8(+) T-cells primed by TLR-P DCs showed significantly elevated expression of the integrin VLA-4 and a trend for higher T-cell numbers after expansion. In contrast, TLR-P DCs displayed a substantially reduced capability to cross-present CMVpp65 protein antigen to pp65-specific T cells, an effect that was dose-dependent on PGE(2) during DC maturation and reproducible with several responder T-cell lines. In conclusion, TLR-P matured DCs might be optimal presenters of antigens not requiring processing such as short peptides. However, PGE(2) seems less favorable for maturation of DCs intended to process and cross-present more complex vaccine antigens such as lysates, proteins or long peptides. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-019-02470-1) contains supplementary material, which is available to authorized users.


title: Respiratory Virus Co-infection in Acute Respiratory Infections in Children

text: PURPOSE OF REVIEW: This investigation aims to understand the role and burden of viral co-infections for acute respiratory illnesses in children. Co-infection can be either viral-viral or viral-bacterial and with new technology there is more information on the role they play on the health of children. RECENT FINDINGS: With the proliferation of multiplex PCR for rapid diagnosis of multiple viruses as well as innovations on identification of bacterial infections, research has been attempting to discover how these co-infections affect each other and the host. Studies are aiming to discern if the epidemiology of viruses seen at a population level is related to the interaction between different viruses on a host level. Studies are also attempting to discover the burden of morbidity and mortality of these viral-viral co-infections on the pediatric population. It is also becoming important to understand the interplay of certain viruses with specific bacteria and understanding the impact of viral-bacterial co-infections. SUMMARY: RSV continues to contribute to a large burden of disease for pediatric patients with acute respiratory illnesses. However, recent literature suggests that viral-viral co-infections do not add to this burden and might, in some cases, be protective of severe disease. Viral-bacterial co-infections, on the other hand, are most likely adding to the burden of morbidity in pediatric patients because of the synergistic way they can infect the nasopharyngeal space. Future research needs to focus on confirming these conclusions as it could affect hospital cohorting, role of molecular testing, and therapeutic interventions.


title: Antibody-based therapeutic interventions: possible strategy to counter chikungunya viral infection

text: Chikungunya virus (CHIKV), a mosquito-transmitted disease that belongs to the genus Alphaviruses, has been emerged as an epidemic threat over the last two decades, and the recent co-emergence of this virus along with other circulating arboviruses and comorbidities has influenced atypical mortality rate up to 10%. Genetic variation in the virus has resulted in its adaptability towards the new vector Aedes albopictus other than Aedes aegypti, which has widen the horizon of distribution towards non-tropical and non-endemic areas. As of now, no licensed vaccines or therapies are available against CHIKV; the treatment regimens for CHIKV are mostly symptomatic, based on the clinical manifestations. Development of small molecule drugs and neutralizing antibodies are potential alternatives of worth investigating until an efficient or safe vaccine is approved. Neutralizing antibodies play an important role in antiviral immunity, and their presence is a hallmark of viral infection. In this review, we describe prospects for effective vaccines and highlight importance of neutralizing antibody-based therapeutic and prophylactic applications to combat CHIKV infections. We further discuss about the progress made towards CHIKV therapeutic interventions as well as challenges and limitation associated with the vaccine development. Furthermore this review describes the lesson learned from chikungunya natural infection, which could help in better understanding for future development of antibody-based therapeutic measures.


Positive end-expiratory pressure titration via esophageal balloon monitoring in a morbidly obese patient undergoing laparoscopic nephrectomy


title: Closer and closer? Maternal immunization: current promise, future horizons

text: This state-of-the art manuscript highlights our current understanding of maternal immunization—the practice of vaccinating pregnant women to confer protection on them as well as on their young infants, and thereby reduce vaccine-preventable morbidity and mortality. Advances in our understanding of the immunologic processes that undergird a normal pregnancy, studies from vaccines currently available and recommended for pregnant women, and vaccines for administration in special situations are beginning to build the case for safe scale-up of maternal immunization. In addition to well-known diseases, new diseases are emerging which pose threats. Several new vaccines are currently under development and increasingly include pregnant women. In this manuscript, targeted at clinicians, vaccinologists, scientists, public health practitioners, and policymakers, we also outline key considerations around maternal immunization introduction and delivery, discuss noninfectious horizons for maternal immunization, and provide a framework for the clinician faced with immunizing a pregnant woman.


Naloxone as an antidote for angiotensin converting enzyme inhibitor poisoning: a case report


title: Patterns of Inpatient Antibiotic Use Among Public Hospitals in Hong Kong from 2000 to 2015

text: BACKGROUND: Studies have demonstrated that higher rates of antibiotic resistance are found in countries with higher antibiotic consumption. The global increase in antibiotic consumption is a major public health concern. OBJECTIVES: The objective of this study was to describe the antibiotic dispensing patterns in public hospitals in Hong Kong from 2000 to 2015. METHODS: We acquired data on all hospital admissions with any antibiotics dispensed from 2000 to 2015 from the Hong Kong public hospitals. The annual proportion of hospital admissions with antibiotics dispensed was estimated and stratified by age group. An interrupted time series analysis was conducted to examine any potential change in tetracycline dispensing after the release of the new clinical practice guideline. RESULTS: A total of 35,535,506 antibiotic prescriptions were dispensed among 2,161,360 unique hospitalized patients from 2000 to 2015. Antibiotics were dispensed in 29.2% of all hospital admissions in the public hospitals, the annual proportions of hospital admissions with antibiotics dispensed increased over the study period from 27.87% in 2000 to 31.39% in 2015, ranging from 27.17 to 31.39%. However, a significant increase was only observed in age groups of 5–19, 20–44, and 85 years or above when stratifying by age. In the interrupted time series analysis, a change in trend was detected for tetracycline dispensing that coincided with the time of publication of the new clinical practice guideline. CONCLUSIONS: We found that the overall volume of antibiotic use increased between 2000 and 2015. The rise in the dispensing of carbapenems in our study is concerning. The significant change in tetracycline use after being recommended as one of the preferred regimens demonstrated that the change in the clinical practice guideline had an immediate effect on the antibiotic prescribing practice in Hong Kong public hospitals.


Breaking Down Myasthenic Crisis


title: Translation of the Frailty Paradigm from Older Adults to Children with Cardiac Disease

text: Children and adolescents with cardiac disease (CCD) have significant morbidity and lower quality of life. However, there are no broadly applicable tools similar to the frailty score as described in the elderly, to define functional phenotype in terms of physical capability and psychosocial wellbeing in CCD. The purpose of this study is to investigate the domains of the frailty in CCD. We prospectively recruited CCD (8–17.5 years old, 70% single ventricle, 27% heart failure, 12% pulmonary hypertension; NYHA classes I, II and III) and age and gender matched healthy controls (total n = 56; CCD n = 34, controls n = 22; age 12.6 ± 2.6 years; 39.3% female). We measured the five domains of frailty: slowness, weakness, exhaustion, body composition and physical activity using developmentally appropriate methods. Age and gender-based population norms were used to obtain Z scores and percentiles for each measurement. Two-tailed t-tests were used to compare the two groups. The CCD group performed significantly worse in all five domains of frailty compared to healthy controls. Slowness: 6-min walk test with Z score −3.9 ± 1.3 vs −1.4 ± 1.3, p < 0.001; weakness: handgrip strength percentile 18.9 ± 20.9 vs 57.9 ± 26.0, p < 0.001; exhaustion: multidimensional fatigue scale percentile 63.7 ± 13.5 vs 83.3 ± 14.4, p < 0.001; body composition: height percentile 43.4 ± 29.5 vs 71.4 ± 25.2, p < 0.001, weight percentile 46.0 ± 36.0 vs 70.9 ± 24.3, p = 0.006, BMI percentile 48.4 ± 35.5 vs 66.9 ± 24.2, p = 0.04, triceps skinfold thickness 41.0 ± 24.0 vs 54.4 ± 22.1, p = 0.04; physical activity: pediatric activity questionnaire score 2 ± 0.6 vs 2.7 ± 0.6, p < 0.001. The domains of frailty can be quantified in children using developmentally appropriate methods. CCD differ significantly from controls in all five domains, supporting the concept of quantifying the domains of frailty. Larger longitudinal studies are needed to study frailty in CCD and examine if it predicts adverse health outcomes. Clinical Trial Registration: The ClinicalTrials.gov identification number is NCT02999438. https://clinicaltrials.gov/ct2/show/NCT02999438.


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title: Factors Predictive of Ventilator-associated Pneumonia in Critically Ill Trauma Patients

text: BACKGROUND: Ventilator-associated pneumonia (VAP) is a serious complication of mechanical ventilation. We sought to investigate factors associated with the development of VAP in critically ill trauma patients. METHODS: We conducted a retrospective review of trauma patients admitted to our trauma intensive care unit between 2016 and 2018. Patients with ventilator-associated pneumonia were identified from the trauma database. Data collected from the trauma database included demographics (age, gender and race), mechanism of injury (blunt, penetrating), injury severity (injury severity score “ISS”), the presence of VAP, transfused blood products and presenting vital signs. RESULTS: A total of 1403 patients were admitted to the trauma intensive care unit (TICU) during the study period; of these, 45 had ventilator-associated pneumonia. Patients with VAP were older (p = 0.030), and they had a higher incidence of massive transfusion (p = 0.015) and received more packed cells in the first 24 h of admission (p = 0.028). They had a higher incidence of face injury (p = 0.001), injury to sternum (p = 0.011) and injury to spine (p = 0.024). Patients with VAP also had a higher incidence of acute kidney injury (AKI) (p < 0.001) and had a longer ICU (p < 0.001) and hospital length of stay (p < 0.001). Multiple logistic regression models controlling for age and injury severity (ISS) showed massive transfusion (p = 0.017), AKI (p < 0.001), injury to face (p < 0.001), injury to sternum (p = 0.007), injury to spine (p = 0.047) and ICU length of stay (p < 0.001) to be independent predictors of VAP. CONCLUSIONS: Among critically ill trauma patients, acute kidney injury, injury to the spine, face or sternum, massive transfusion and intensive care unit length of stay were associated with VAP.


Remote Control and Monitoring of GE Aisys Anesthesia Machines Repurposed as Intensive Care Unit Ventilators


title: Transesophageal Echocardiography Probe Sheath to Decrease Provider and Environment Contamination

text: Supplemental Digital Content is available in the text.


title: Andronov–Hopf and Neimark–Sacker bifurcations in time-delay differential equations and difference equations with applications to models for diseases and animal populations

text: In many areas, researchers might think that a differential equation model is required, but one might be forced to use an approximate difference equation model if data is only available at discrete points in time. In this paper, a detailed comparison is given of the behavior of continuous and discrete models for two representative time-delay models, namely a model for HIV and an extended logistic growth model. For each model, there are seven different time-delay versions because there are seven different positions to include time delays. For the seven different time-delay versions of each model, proofs are given of necessary and sufficient conditions for the existence and stability of equilibrium points and for the existence of Andronov–Hopf bifurcations in the differential equations and Neimark–Sacker bifurcations in the difference equations. We show that only five of the seven time-delay versions have bifurcations and that all bifurcation versions have supercritical limit cycles with one having a repelling cycle and four having attracting cycles. Numerical simulations are used to illustrate the analytical results and to show that critical times for Neimark–Sacker bifurcations are less than critical times for Andronov–Hopf bifurcations but converge to them as the time step of the discretization tends to zero.


title: Full-genome sequences of GII.13[P21] recombinant norovirus strains from an outbreak in Changsha, China

text: On 31 March 2019, 68 school students suffered from vomiting, diarrhea, and abdominal pain after participating in a group activity at a commercial park. In this outbreak, multiple norovirus genotypes were observed, including GII.2[P16], GII.17[P17], and GII.13[P21]. Further, we determined the full-genome sequences of two strains of GII.13[P21] recombinant noroviruses, which were 7434 nt long. Phylogenetic analysis based on open reading frames (ORFs) 1 and 2 revealed that these recombinants were related to stains of different genotypes from different countries. The full genome nucleotide sequences of the two isolates were 97.0% and 98.0% identical to those of strains from London and Thailand, respectively. Simplot analysis revealed the presence of a break point at nt 5059 in the ORF1 region. The histo-blood group antigen binding sites were conserved in both recombinant viruses. Our findings not only provide valuable genetic information about a recombinant norovirus but also contribute to our general understanding of the evolution, genetic diversity, and distribution of noroviruses.


title: Antiviral Activities of Hibiscus sabdariffa L. Tea Extract Against Human Influenza A Virus Rely Largely on Acidic pH but Partially on a Low-pH-Independent Mechanism

text: Influenza A virus (IAV) infection is perennially one of the leading causes of death worldwide. Effective therapy and vaccination are needed to control viral expansion. However, current anti-IAV drugs risk inducing drug-resistant virus emergence. Although intranasal administration of whole inactivated virus vaccine can induce efficient protective immunity, formalin and β-propiolactone are the currently used and harmful inactivating agents. Here, we analyzed the antiviral activity of hibiscus (Hibiscus sabdariffa L.) tea extract against human IAV and evaluated its potential as a novel anti-IAV drug and a safe inactivating agent for whole inactivated vaccine. The in vitro study revealed that the pH of hibiscus tea extract is acidic, and its rapid and potent antiviral activity relied largely on the acidic pH. Furthermore, the mouse study showed that the acidic extract was not effective for either therapeutic or vaccination purposes. However, hibiscus tea extract and protocatechuic acid, one of the major components of the extract, showed not only potent acid-dependent antiviral activity but also weak low-pH-independent activity. The low-pH-independent activity did not affect the conformation of immunodominant hemagglutinin protein. Although this low-pH-independent activity is very limited, it may be suitable for the application to medication and vaccination because this activity is not affected by the neutral blood environment and does not lose antigenicity of hemagglutinin. Further study of the low-pH-independent antiviral mechanism and attempts to enhance the antiviral activity may establish a novel anti-IAV therapy and vaccination strategy.


title: Uniportal Thoracoscopic McKeown Esophagectomy

text: We performed the technique of uniportal thoracoscopic McKeown esophagectomy. The incision was located in the fourth intercostal space on the right axillary midline. The right recurrent laryngeal nerve lymph nodes were dissected. Four hemlocks were applied to clamp the proximal and distal ends of the aortic arch. The esophagus was suspended with purse-string at the level of the azygos vein arch to assist the dissection of the left recurrent laryngeal nerve lymph nodes. A silk thread was drawn out from the incision in order to remove the subcarinal lymph nodes. A thoracic drainage tube was placed at the back of the incision at the end.


title: Carbapenem-Resistant Enterobacterales: Considerations for Treatment in the Era of New Antimicrobials and Evolving Enzymology

text: PURPOSE OF REVIEW: Gram-negative resistance is a growing concern globally. Enterobacterales, formerly Enterobacteriaceae, have developed resistance mechanisms to carbapenems that leave very few antimicrobial options in the clinician’s armamentarium. RECENT FINDINGS: New antimicrobials like ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and plazomicin have the potential to overcome resistance mechanisms in Enterobacterales including different classes of carbapenemases. SUMMARY: Novel β-lactam/β-lactamase inhibitors, plazomicin, and cefiderocol give the clinician options that were once not available. Utilizing these options is of the utmost importance when treating carbapenem-resistant Enterobacterales.


title: Hypocapnia after traumatic brain injury: how does it affect the time constant of the cerebral circulation?

text: The time constant of the cerebral arterial bed (“tau”) estimates how fast the blood entering the brain fills the arterial vascular sector. Analogous to an electrical resistor–capacitor circuit, it is expressed as the product of arterial compliance (Ca) and cerebrovascular resistance (CVR). Hypocapnia increases the time constant in healthy volunteers and decreases arterial compliance in head trauma. How the combination of hyocapnia and trauma affects this parameter has yet to be studied. We hypothesized that in TBI patients the intense vasoconstrictive action of hypocapnia would dominate over the decrease in compliance seen after hyperventilation. The predominant vasoconstrictive response would maintain an incoming blood volume in the arterial circulation, thereby lengthening tau. We retrospectively analyzed recordings of intracranial pressure (ICP), arterial blood pressure (ABP), and blood flow velocity (FV) obtained from a cohort of 27 severe TBI patients [(39/30 years (median/IQR), 5 women; admission GCS 6/5 (median/IQR)] studied during a standard clinical CO(2) reactivity test. The reactivity test was performed by means of a 50-min increase in ventilation (20% increase in respiratory minute volume). CVR and Ca were estimated from these recordings, and their product calculated to find the time constant. CVR significantly increased [median CVR pre-hypocapnia/during hypocapnia: 1.05/1.35 mmHg/(cm(3)/s)]. Ca decreased (median Ca pre-hypocapnia/during hypocapnia: 0.130/0.124 arbitrary units) to statistical significance (p = 0.005). The product of these two parameters resulted in a significant prolongation of the time constant (median tau pre-hypocapnia/during hypocapnia: 0.136 s/0.152 s, p ˂ .001). Overall, the increase in CVR dominated over the decrease in compliance, hence tau was longer. We demonstrate a significant increase in the time constant of the cerebral circulation during hypocapnia after severe TBI, and attribute this to an increase in cerebrovascular resistance which outweighs the decrease in cerebral arterial bed compliance.


title: Poly-phosphate increases SMC differentiation of mesenchymal stem cells on PLGA–polyurethane nanofibrous scaffold

text: The use of bioactive scaffolds in tissue engineering has a significant effect on the damaged tissue healing by an increase in speed and quality of the process. Herein, electrospinning was applied to fabricate composite nanofibrous scaffolds by Poly lactic-co-glycolic acid (PLGA) and Polyurethane (PU) with and without poly-phosphate (poly-P). Scaffolds were characterized morphologically by scanning electron microscope (SEM), and their biocompatibility was also investigated by SEM, protein adsorption, cell attachment and survival assays. The applicability of the scaffolds for bladder tissue engineering was also evaluated by culturing mesenchymal stem cells (MSCs) on the scaffolds and their differentiation into smooth muscle cell (SMC) was studied at the gene and protein levels. The results demonstrated that scaffold biocompatibility was increased significantly by loading poly-P. SMC related gene and protein expression level in MSCs cultured on poly-P-loaded scaffold was also increased significantly compared to those cells cultured on empty scaffold. It can be concluded that poly-P hasn’t also increased scaffold biocompatibility, but also SMC differentiation potential of MSCs was also increased while cultured on the poly-P containing scaffold compared to the empty scaffold. Taken together, our study showed that PLGA–PU–poly-P alone and in combination with MSCs has a promising potential for support urinary bladder smooth muscle tissue engineering.


docid: iahfqmgh

title: Evaluation of specific quality metrics to assess the performance of a specialised newborn transport programme

text: There is a lack of consensus on quality indicators suitable for neonatal transport. The aim of this study is to make a proposal for specific quality indicators for newborn transport. A retrospective descriptive study was performed (2009 to 2015) where twenty-four indicators were selected, evaluated and classified according to the 6 dimensions of quality of the Institute of Medicine. Among the 24 evaluated quality metrics, there were 3 of them which needed a correction when evaluating neonatal transport performance, because they were significantly correlated with gestational age. They were (a) stabilisation time, (b) prevalence of newborn arterial hypotension (defined by gestational age) and (c) unnoticed hypothermia at referral hospital. Conclusion: Quality evaluation through the definition of specific metrics in newborn transport is feasible. These indicators should be defined or adjusted for newborn population to measure the actual performance of the transport service.


title: Antioxidant molecular mechanism of adenosyl homocysteinase from cyanobacteria and its wound healing process in fibroblast cells

text: An antioxidant molecule namely, adenosyl homocysteinase (AHc) was identified from the earlier constructed transcriptome database of Spirulina, where it was cultured in a sulphur deprived condition. From the AHc protein, a small peptide NL13 was identified using bioinformatics tools and was predicted to have antioxidant property. Further, the peptide was synthesised and its antioxidant mechanism was addressed at molecular level. NL13 was subjected to various antioxidant assays including DPPH assay, HARS assay, SARS Assay, NO assay and ABTS assay, where NL13 exhibited significant (P < 0.05) potential antioxidant activity compared to its antioxidant control, Trolox. Cytotoxicity was performed on Human whole blood and the cell viability was performed on VERO fibroblast cells. In both assays, it was found that NL13 did not exhibit any cytotoxic effect towards the cells. Further, the intracellular ROS was performed on Multimode reader followed by imaging on fluorescence microscope which showed scavenging activity even at lower concentration of NL13 (31.2 µM). An effective wound healing property of NL13 on VERO cells was confirmed by analysing the cell migration rate at two different time intervals (24 and 48 h). Overall, the study shows that NL13 peptide scavenges the intracellular oxidative stress. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11033-020-05276-y) contains supplementary material, which is available to authorized users.


title: A seven-gene-deleted African swine fever virus is safe and effective as a live attenuated vaccine in pigs

text: African swine fever (ASF) is a devastating infectious disease in swine that is severely threatening the global pig industry. An efficacious vaccine is urgently required. Here, we used the Chinese ASFV HLJ/18 as a backbone and generated a series of gene-deleted viruses. The virulence, immunogenicity, safety, and protective efficacy evaluation in specific-pathogen-free pigs, commercial pigs, and pregnant sows indicated that one virus, namely HLJ/18-7GD, which has seven genes deleted, is fully attenuated in pigs, cannot convert to the virulent strain, and provides complete protection of pigs against lethal ASFV challenge. Our study shows that HLJ/-18-7GD is a safe and effective vaccine against ASFV, and as such is expected to play an important role in controlling the spread of ASFV. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1657-9 and is accessible for authorized users.


title: A Component Analysis of the Mindfulness-Based Positive Behavior Support (MBPBS) Program for Mindful Parenting by Mothers of Children with Autism Spectrum Disorder

text: OBJECTIVES: Mindfulness-Based Positive Behavior Support (MBPBS) has been shown to be effective in reducing stress and burnout in parents and professional caregivers of children and adolescents with intellectual and developmental disabilities (IDD) and autism spectrum disorder (ASD). The aim of this study was to assess the comparative effects of the mindfulness (MB) and positive behavior support (PBS) components against the MBPBS program for mindful parenting. METHODS: The study utilized a three-arm randomized controlled trial design, with a 10-week pre-treatment control condition, 30 weeks of intervention, and 3 years of post-intervention follow-up. Mothers of children with ASD were randomly assigned to the MB, PBS, and MBPBS conditions and provided 3 days of training specific to each condition. The effects of these programs were assessed on the mothers (i.e., training attendance, meditation time, perceived psychological stress) and spillover effects were assessed on their children with ASD (i.e., aggression, disruptive behavior, compliance with mothers’ requests). RESULTS: Mothers in the MBPBS condition reported greater reductions in perceived psychological stress, followed by those in the MB condition, and with no significant changes reported by those in the PBS condition. Reduction in the children’s aggression and disruptive behavior followed a similar pattern, with most to least significant reductions being in MBPBS, MB, and PBS condition, respectively. Significant increases in compliance (i.e., responsiveness to mothers’ requests) were largest in the MBPBS condition, followed by MB, and then PBS. Changes across all variables for both mothers and their children were maintained for 3 years post-intervention. After time and training type were controlled for, meditation time was a significant predictor in reducing aggressive and disruptive behaviors, and in enhancing compliance of the children with mothers’ requests. CONCLUSIONS: Positive outcomes for mothers and their children with ASD were significantly greater in the MBPBS condition, followed by the MB condition, and least in the PBS condition. MBPBS appears to be an effective mindful parenting program on the assessed variables.


title: Sense of coherence and burnout among school psychologists: The moderating role of loneliness

text: School psychologist have been considered at a high risk for developing work burnout due to their multiple responsibilities, overload and engagement in caring for children, families and professionals. In line with the salutogenic approach, the aim of the current research was to investigate protective and risk factors to burnout. Research has indicated that sense of coherence (SOC) may act as a protective factor. Studies reported that loneliness has been found a risk factor that may advance burnout. The current study hypothesized that loneliness may moderate the link between SOC and burnout. In a sample of 104 Israeli school psychologists, demographic aspects such as the gender, years of experience, or type of school in which they work did not predict the burnout, focusing on the importance of emotional aspects. The analysis demonstrated that the SOC was negatively associated with burnout among low or mean levels of loneliness, but not among psychologists with high levels of loneliness. The current study provides a new insight into the burnout risk, through the focus on personal resources and social perceptions. Implications for theoretical and practices are further discussed.


title: Perioperative Outcomes of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy in Patients with Diabetes Mellitus: an Analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Database

text: BACKGROUND: The safety and efficacy of laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) to treat obesity and associated comorbidities, including diabetes mellitus, is well established. As diabetes may add risk to the perioperative period, we sought to characterize perioperative outcomes of these surgical procedures in diabetic patients. METHODS: Using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database, we identified patients who underwent LSG and LRYGB between 2015 and 2017, grouping by non-diabetics (NDM), non-insulin-dependent diabetics (NIDDM), and insulin-dependent diabetics (IDDM). Primary outcomes included serious adverse events, 30-day readmission, 30-day reoperation, and 30-day mortality. Univariate and multivariable analyses were used to evaluate the outcome in each diabetic cohort. RESULTS: Multivariable analysis of patients who underwent LSG (with NDM patients as reference) showed higher 30-day mortality (NIDDM AOR = 1.52, p = 0.043; IDDM AOR = 1.91, p = 0.007) and risk of serious adverse events (NIDDM AOR = 1.15, p < 0.001; IDDM AOR = 1.58, p < 0.001) in the diabetic versus NDM groups. Multivariable analysis of patients who underwent LRYGB (with NDM patients as reference) showed higher risk of serious adverse events (NIDDM AOR = 1.09, p = 0.014; IDDM AOR = 1.43, p < 0.001) in the diabetic versus NDM groups. CONCLUSIONS: Diabetics who underwent LSG and LRYGB had higher rates of several perioperative complications compared with non-diabetics. IDDM had a stronger association with several perioperative complications compared with NIDDM. This increase in morbidity and mortality is modest and should be weighed against the real benefits of bariatric surgery in patient with obesity and diabetes mellitus.


title: Heart Retransplantation: Candidacy, Outcomes, and Management

text: PURPOSE OF REVIEW: To describe the incidence and epidemiology of heart retransplantation in adults and children and to review the risk factors associated with adverse outcome following retransplantation to help guide recipient selection. RECENT FINDINGS: Heart retransplantation is associated with inferior short-term and long-term survival when compared with primary heart transplantation and its use remains controversial although less so in the pediatric heart transplant population. SUMMARY: In the most recent era of heart transplantation, patients retransplanted for CAV, greater than 1 year from their primary transplant, and who are not in critical condition have improved survival compared with other retransplant recipients. Survival with retransplantation can approach that of primary transplantation when patients are appropriately selected. More research is needed regarding the optimal timing for retransplantation and the optimal management for patients after retransplantation.


docid: tfivtleu

title: Nasal continuous positive airway pressure versus noninvasive NAVA in preterm neonates with apnea of prematurity: a pilot study with a novel approach

text: BACKGROUND: Neonates with apnea of prematurity often fail CPAP because it does not provide adequate support during apnea. NAVA provides proportional ventilator support based on electrical activity of the diaphragm. When the NAVA level is 0 cmH(2)0/mcV, the patient receives minimal support above PEEP when breathing and backup ventilation when apneic. This study compares number of clinically significant events on CPAP versus noninvasive NAVA level 0. METHODS: Retrospective study of preterm neonates having apnea of prematurity on nasal CPAP. Patients were then placed on NAVA level 0. The number of events on each mode was collected. Statistics were paired t-test. RESULTS: Seventeen subjects with gestational age 26.1 ± 1.7 weeks, study age 19.5 ± 12.5 days. Events decreased from 17.9 ± 7.8 on CPAP to 10.2 ± 8.1 events on NAVA level 0 (p = 0.00047). CONCLUSIONS: NAVA level 0 reduced the number of clinically significant events compared with CPAP in premature neonates with apnea of prematurity.


title: Spine neurosurgeons facing the judicialization of their profession: disenchantment and alteration of daily practice—a qualitative study

text: BACKGROUND: The judicialization of medicine can lead to professional disenchantment and defensive attitudes among surgeons. Some quantitative studies have investigated this topic in spine surgery, but none has provided direct thematic feedback from physicians. This qualitative study aimed to identify the impact of this phenomenon in the practice of spine neurosurgeons. METHODS: We proposed a qualitative study using grounded theory approach. Twenty-three purposively selected private neurosurgeons participated. Inclusion took place until data saturation was reached. Data were collected through individual interviews and analyzed thematically and independently by three researchers (an anthropologist, a psychiatrist, and a neurosurgeon). RESULTS: Data analysis identified five superordinate themes that were based on items that recurred in interviews: (1) private practice of spinal surgery (high-risk surgery based on frequent functional symptoms, in an unfavorable medicolegal context); (2) societal transformation of the doctor-patient relationship (new societal demands, impact of the internet and social network); (3) judicialization of spine surgery (surgeons’ feelings about the frequency and motivation of the complaints they receive, and their own management of them); (4) coping strategies (identification and solutions for “at risk” situations and patients); and (5) professional disenchantment (impact of these events on surgeons’ daily practice and career planning). Selected quotes of interviews were reported to support these findings. CONCLUSIONS: Our study highlights several elements that can alter the quality of care in a context of societal change and the judicialization of medicine. The alteration of the doctor-patient relationship and the permanent pressure of a possible complaint encourage surgeons to adopt defensive attitudes in order to minimize the risks of litigation and increased insurance premiums. These phenomena can affect the quality of care and the privacy of physicians to the extent that they may consider changing or interrupting their careers earlier. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00701-020-04302-z) contains supplementary material, which is available to authorized users.


title: Severe fever with thrombocytopenia syndrome (SFTS) treated with a novel antiviral medication, favipiravir (T-705)

text: BACKGROUND: Severe fever and thrombocytopenia syndrome (SFTS) is an acute illness with a high mortality (16.2–29.1%). Unfortunately, there is no specific cure or vaccine for SFTS. METHODS: In this open-label study, two patients with SFTS were treated with favipiravir, a new antiviral drug. RESULTS: Patients had a sustainable virologic, immunologic and symptomatic recovery. CONCLUSIONS: Favipiravir may be a prosiming drug for the treatment of SFTS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s15010-019-01364-9) contains supplementary material, which is available to authorized users.


docid: duzordud

title: The Role of Healthcare Robotics in Providing Support to Older Adults: a Socio-ecological Perspective

text: PURPOSE OF REVIEW: In this review, we provide an overview of how healthcare robotics can facilitate healthy aging, with an emphasis on physical, cognitive, and social supports. We next provide a synthesis of future challenges and considerations in the development and application of healthcare robots. We organize these considerations using a socio-ecological perspective and discuss considerations at the individual, care partner, community healthcare, and healthcare policy levels. RECENT FINDINGS: Older adults are the fastest growing segment of the US population. Age-related changes and challenges can present difficulties, for older adults want to age healthily and maintain independence. Technology, specifically healthcare robots, has potential to provide health supports to older adults. These supports span widely across the physical, cognitive, and social aspects of healthy aging. SUMMARY: Our review suggests that while healthcare robotics has potential to revolutionize the way in which older adults manage their health, there are many challenges such as clinical effectiveness, technology acceptance, health informatics, and healthcare policy and ethics. Addressing these challenges at all levels of the healthcare system will help ensure that healthcare robotics promote healthy aging and are applied safely, effectively, and reliably.


title: Non-invasive estimation of cerebral perfusion pressure using transcranial Doppler ultrasonography in children with severe traumatic brain injury

text: OBJECTIVE: To identify if cerebral perfusion pressure (CPP) can be non-invasively estimated by either of two methods calculated using transcranial Doppler ultrasound (TCD) parameters. DESIGN: Retrospective review of previously prospectively gathered data. SETTING: Pediatric intensive care unit in a tertiary care referral hospital. PATIENTS: Twenty-three children with severe traumatic brain injury (TBI) and invasive intracranial pressure (ICP) monitoring in place. INTERVENTIONS: TCD evaluation of the middle cerebral arteries was performed daily. CPP at the time of the TCD examination was recorded. For method 1, estimated cerebral perfusion pressure (CPPe) was calculated as: CPPe = MAP × (diastolic flow (Vd)/mean flow (Vm)) + 14. For method 2, critical closing pressure (CrCP) was identified as the intercept point on the x-axis of the linear regression line of blood pressure and flow velocity parameters. CrCP/CPPe was then calculated as MAP-CrCP. MEASUREMENTS AND MAIN RESULTS: One hundred eight paired measurements were available. Using patient averaged data, correlation between CPP and CPPe was significant (r = 0.78, p = < 0.001). However, on Bland-Altman plots, bias was 3.7 mmHg with 95% limits of agreement of − 17 to + 25 for CPPe. Using patient averaged data, correlation between CPP and CrCP/CPPe was significant (r = 0.59, p = < 0.001), but again bias was high at 11 mmHg with wide 95% limits of agreement of − 15 to + 38 mmHg. CONCLUSIONS: CPPe and CrCP/CPPe do not have clinical value to estimate the absolute CPP in pediatric patients with TBI.


title: Risk of Readmission and Mortality Following Hospitalization with Hypercapnic Respiratory Failure

text: PURPOSE: Hypercapnic respiratory failure (HRF) is a frequent cause of hospitalization and a common comorbidity in hospitalized patients. There are few studies addressing what factors might predict poor outcomes in this patient population. The purpose of the current study was to investigate characteristics and outcomes of patients hospitalized with HRF. METHODS: A study of patients ≥ 18 years admitted with HRF in a 1-year period. Patients with limited life expectancy related to other conditions, and those with a non-respiratory cause of HRF, were excluded. RESULTS: 202 subjects met eligibility criteria: 24% had a diagnosis of obstructive sleep apnea, 6% obesity hypoventilation, 46% chronic obstructive pulmonary disease, and 10% asthma. Fifteen (7%) died during the index admission. Forty-one patients (23%) were readmitted within 30 days: peripheral vascular disease [adjusted odds ratio (aOR) 4.78, CI 1.45–15.74] and tachycardia (aOR 2.97, CI 1.22–7.26) were associated with an increased risk of readmission. Sixty-six patients (36%) died after discharge. Risk of death was increased in older patients (aOR 1.32, CI 1.13–1.54 per 5 years), those with peripheral vascular disease (aOR 12.56, CI 2.35–67.21), higher Charlson co-morbidity index (aOR 1.39, CI 1.09–1.76), use of home oxygen (aOR 4.03, CI 1.89–8.57), and those who had been readmitted (aOR 3.07, CI 1.46–6.43). CONCLUSIONS: Hospitalization for HRF is associated with a high morbidity and mortality. Our observation that home oxygen use was associated with increased mortality suggests that oxygen use could be a risk factor for death in patients with HRF.


title: Inhaled nitric oxide as an adjunct to neonatal resuscitation in premature infants: a pilot, double blind, randomized controlled trial

text: BACKGROUND: Nitric oxide (NO) plays an important role in normal postnatal transition. Our aims were to determine whether adding inhaled NO (iNO) decreases supplemental oxygen exposure in preterm infants requiring positive pressure ventilation (PPV) during resuscitation and to study iNO effects on heart rate (HR), oxygen saturation (SpO(2)), and need for intubation during the first 20 min of life. METHODS: This was a pilot, double-blind, randomized, placebo-controlled trial. Infants 25 0/7–31 6/7 weeks’ gestational age requiring PPV with supplemental oxygen during resuscitation were enrolled. PPV was initiated with either oxygen (FiO(2)–0.30) + iNO at 20 ppm (iNO group) or oxygen (FiO(2)–0.30) + nitrogen (placebo group). Oxygen was titrated targeting defined SpO(2) per current guidelines. After 10 min, iNO/nitrogen was weaned stepwise per protocol and terminated at 17 min. RESULTS: Twenty-eight infants were studied (14 per group). The mean gestational age in both groups was similar. Cumulative FiO(2) and rate of exposure to high FiO(2) (>0.60) were significantly lower in the iNO group. There were no differences in HR, SpO(2), and need for intubation. CONCLUSIONS: Administration of iNO as an adjunct during neonatal resuscitation is feasible without side effects. It diminishes exposure to high levels of supplemental oxygen.


title: Plasmodium asexual growth and sexual development in the haematopoietic niche of the host

text: Plasmodium spp. parasites are the causative agents of malaria in humans and animals, and they are exceptionally diverse in their morphology and life cycles. They grow and develop in a wide range of host environments, both within blood-feeding mosquitoes, their definitive hosts, and in vertebrates, which are intermediate hosts. This diversity is testament to their exceptional adaptability and poses a major challenge for developing effective strategies to reduce the disease burden and transmission. Following one asexual amplification cycle in the liver, parasites reach high burdens by rounds of asexual replication within red blood cells. A few of these blood-stage parasites make a developmental switch into the sexual stage (or gametocyte), which is essential for transmission. The bone marrow, in particular the haematopoietic niche (in rodents, also the spleen), is a major site of parasite growth and sexual development. This Review focuses on our current understanding of blood-stage parasite development and vascular and tissue sequestration, which is responsible for disease symptoms and complications, and when involving the bone marrow, provides a niche for asexual replication and gametocyte development. Understanding these processes provides an opportunity for novel therapies and interventions.