title: Intravenous paracetamol for fever control in acute brain injury patients: cerebral and hemodynamic effects.

text: BACKGROUND Fever occurs frequently in acute brain injury patients, and its occurrence is associated with poorer outcomes. Paracetamol, an antipyretic frequently employed in patients with cerebral damage, may cause hypotension. We evaluated the cerebral and hemodynamic effects of intravenous (IV) paracetamol for the control of fever in Neuro-Intensive Care Unit (NICU) patients. METHODS This is a prospective observational study in which we enrolled 32 NICU patients: Subarachnoid Hemorrhage (SAH, n = 18), Traumatic Brain Injury (TBI, n = 10), Intracerebral Hemorrhage (ICH, n = 2) and Acute Ischemic Stroke (AIS, n = 2). RESULTS The administration of paracetamol resulted in a decrease of core body temperature (Tc) (p = 0,0001), mean arterial pressure (MAP) (p = 0,0006), cerebral perfusion pressure (CPP) (p = 0,0033), and jugular venous oxygen saturation (SjVO2) (p = 0.0193), and in an increase of arteriojugular venous differences of oxygen (AVDO2) (p = 0.0012). The proportion of patients who had an infusion of norepinephrine increased from 47 % to 75 % (p = 0.0039 McNemar Test). When intracranial pressure (ICP) at the start of paracetamol infusion (t-0) was compared with the measurement of ICP after 2 h, a significant correlation was observed (r = 0.669, p = 0.0002). This marked and significant correlation can be explained by the fact that for the higher levels of ICP assessed at t-0 (greater than 15 mmHg), we observed a marked reduction of ICP concomitant with the decrease of Tc. No problems related to norepinephrine administration and/or increase in dosage were observed. CONCLUSION Paracetamol administration is effective but exposes patients to hypotensive episodes that must be recognized and treated expeditiously to prevent further damage to the injured brain.


title: Sevoflurane-induced changes in infants' quantifiable electroencephalogram parameters.

text: BACKGROUND Electroencephalogram (EEG) based depth of anesthesia algorithms developed in the adult population have not demonstrated the same reliability when applied to infants. This may be due to frequency changes occurring in the EEG during development. Amplitude-integrated EEG (aEEG) is based primarily in the time domain and hence may have greater utility in infants. OBJECTIVE To investigate the relationship between age adjusted Minimal Alveolar Concentration (MAC) multiples and aEEG in children under 2 years of age. METHODS The aEEG, Spectral Edge Frequency 90% (SEF90) and Bispectral Index™ (BIS) were investigated in a prospective study of children <2 years of age. After anesthetic induction, and caudal block administration, EEG data were collected simultaneously with BrainZ BRM2™ and BIS™ monitors. Using a randomized crossover design, children received up to three age adjusted concentrations of sevoflurane: 0.75, 1 and 1.25 MAC. After 15 min of stable anesthetic delivery EEG readings were obtained. Prediction Probability (Pk ) and correlation coefficients were calculated for each EEG parameter. RESULTS From 51 children 102 stable anesthetics concentrations were obtained. For all age groups Pk of aEEG to multiple of age adjusted MAC was <0.72 indicating a poor predictive power for aEEG. In contrast for the SEF90 and BIS there was evidence for better predictive properties in children aged between 6 months and 2 years, with a Pk >0.81. CONCLUSION The aEEG is unlikely to be a useful measure of anesthesia depth in young children.


title: ASGE guideline on the role of endoscopy for bleeding from chronic radiation proctopathy.

text: Chronic radiation proctopathy is a common sequela of radiation therapy for malignancies in the pelvic region. A variety of medical and endoscopic therapies have been used for the management of bleeding from chronic radiation proctopathy. In this guideline, we reviewed the results of a systematic search of the literature from 1946 to 2017 to formulate clinical questions and recommendations on the role of endoscopy for bleeding from chronic radiation proctopathy. The following endoscopic modalities are discussed in our document: argon plasma coagulation, bipolar electrocoagulation, heater probe, radiofrequency ablation, and cryoablation. Most studies were small observational studies, and the evidence for effectiveness of endoscopic therapy for chronic radiation proctopathy was limited because of a lack of controlled trials and comparative studies. Despite this limitation, our systematic review found that argon plasma coagulation, bipolar electrocoagulation, heater probe, and radiofrequency ablation were effective in the treatment of rectal bleeding from chronic radiation proctopathy.


title: Using 3 TLR ligands as a combination adjuvant induces qualitative changes in T cell responses needed for antiviral protection in mice.

text: TLR ligands are promising candidates for the development of novel vaccine adjuvants that can elicit protective immunity against emerging infectious diseases. Adjuvants have been used most frequently to increase the quantity of an immune response. However, the quality of a T cell response can be more important than its quantity. Stimulating certain pairs of TLRs induces a synergistic response in terms of activating dendritic cells and eliciting/enhancing T cell responses through clonal expansion, which increases the number of responding T cells. Here, we have found that utilizing ligands for 3 TLRs (TLR2/6, TLR3, and TLR9) greatly increased the protective efficacy of vaccination with an HIV envelope peptide in mice when compared with using ligands for only any 2 of these TLRs; surprisingly, increased protection was induced without a marked increase in the number of peptide-specific T cells. Rather, the combination of these 3 TLR ligands augmented the quality of the T cell responses primarily by amplifying their functional avidity for the antigen, which was necessary for clearance of virus. The triple combination increased production of DC IL-15 along with its receptor, IL-15Ralpha, which contributed to high avidity, and decreased expression of programmed death-ligand 1 and induction of Tregs. Therefore, selective TLR ligand combinations can increase protective efficacy by increasing the quality rather than the quantity of T cell responses.


title: Development of RT-qPCR assays for the specific identification of two major genotypes of avian infectious bronchitis virus.

text: Infectious bronchitis virus (Gammacoronavirus, Coronaviridae) is a genetically variable RNA virus (27.6kb) that causes one of the most persistent respiratory disease in poultry. The virus is classified in genotypes with different epidemiological relevance and clinical implications. The present study reports the development and validation of specific RT-qPCR assays for the detection of two major IBV genotypes: South America I (SAI) and Asia/South America II (A/SAII). The SAI genotype is an exclusive and widespread South American lineage while the A/SAII genotype is distributed in Asia, Europe and South America. Both identification assays employ TaqMan probes that hybridize with unique sequences in the spike glycoprotein gene. The assays successfully detected all the assessed strains belonging to both genotypes, showing high specificity and absence of cross-reactivity. Using serial dilutions of in vitro-transcribed RNA we obtained acceptable determination coefficients, PCR efficiencies and relatively small intra- and inter-assay variability. The assays demonstrated a wide dynamic range between 10(1)-10(7) and 10(2)-10(7) RNA copies/reaction for SAI and A/SAII strains, respectively. The possibility to characterize a large number of samples in a rapid, sensitive and reproducible way makes these techniques suitable tools for routine testing, IBV control, and epidemiological research in poultry.


title: Health-related quality of life scores changes significantly within the first three months after hernia mesh repair.

text: BACKGROUND Patient-related outcome measures (PROM) such as quality of life (QoL) after hernia repair are important to monitor, since QoL is an important indication of a hernia repair. Carolinas Comfort Scale (CCS) is a hernia-specific questionnaire regarding health-related QoL after a mesh hernia repair. The primary objective of this study was to monitor changes in health-related QoL over time after different mesh hernia repair procedures using the CCS. METHODS We performed a prospective study with an exploratory, intraobserver design enrolling consecutive patients who were to undergo elective mesh hernia repair. Four different hernia repair techniques were included and analyzed specifically for each surgical group. Patients scored themselves using CCS preoperatively and at several fixed times postoperatively. Since no gold standard exists for either hernia-specific QoL questionnaires or change of scores on PROMs as a function of time after hernia repair, we compared the CCS scores with the visual analog scale (VAS) scores reflecting the subdomains of the CCS. RESULTS A total of 166 patients completed the study. CCS scores for QoL, pain, sensation of mesh, and activity limitations changed significantly with time during the 90-day study period. Furthermore, CCS and VAS showed significant agreement and correlation (ρ = 0.52-0.82, P < 0.001). CONCLUSIONS The present study is the first to demonstrate significant changes over time in health-related QoL using the CCS after four different types of hernia repair with mesh.


title: Community gardening, community farming and other local community-based gardening interventions to prevent overweight and obesity in high-income and middle-income countries: protocol for a systematic review.

text: INTRODUCTION The worldwide prevalence of overweight/obesity has continued to rise over the last decades. To reverse this trend, public health authorities are exploring cost-effective interventions, especially in high-income and middle-income countries. Community gardening offers a unique opportunity for individuals to enhance physical activity levels and improve their diet. However, synthesised evidence on the short-term or long-term effectiveness and on the costs of community gardening interventions to prevent overweight/obesity remains limited. Therefore, this review will investigate: (1) the effectiveness of voluntary participation in community gardening compared with no or a control intervention on overweight/obesity and associated health outcomes, (2) effects on different subgroups of populations and (3) the costs of community gardening interventions. METHODS AND ANALYSIS We will conduct a systematic review, limited to evaluations of community gardening interventions with controlled quantitative and interrupted time series designs. To identify relevant articles, we will systematically search 12 academic and 5 grey literature databases, as well as 2 trial registers and 6 websites. Articles will then be assessed for eligibility based on a predefined set of criteria. At least two independent reviewers will assess each article for relevance, before evaluating the methodological quality and potential bias of the studies. Data relevant to the objectives of this review will be extracted and cross-validated. Any disagreements will be mediated by a third reviewer. If feasible, meta-analyses of primary outcomes (overweight/obesity, physical activity, food intake, energy intake) will be conducted. We will use the Grading of Recommendations Assessment, Development and Evaluation method to assess the overall quality of evidence. ETHICS AND DISSEMINATION For this review, no ethical approval is required as we will only extract and analyse secondary data. We aim to submit the final review manuscript to an open access journal for publication and disseminate results via conferences and social media. TRIAL REGISTRATION NUMBER International Prospective Register of Systematic Reviews (PROSPERO)(CRD42017043696).


Ghrelin Reduces A-Type Potassium Currents in Dopaminergic Nigral Neurons via the PLC/PKCδ Pathway.


title: Can we predict the severity of COVID-19 with a routine blood test?

text: INTRODUCTION The ongoing worldwide pandemic of Coronavirus Disease 2019 (COVID-19) has posed a huge threat to global public health. However, whether routine blood test could be used to monitor and predict the severity and prognosis of COVID-19 has never been comprehensively investigated. OBJECTIVES To provide an overview of the association of markers in routine blood test with the severity of COVID-19. METHODS PubMed, Embase, Cochrane Library, Wanfang and CNKI database were searched to identify studies reporting the markers in the routine blood test with the severity of COVID-19 until March 20, 2020. STATA software was used for the meta- analysis. RESULTS A total of 15 studies with 3090 COVID-19 patients were included in this analysis. Patients in non-severe group had fewer white blood cells (WBC) (WMD = -0.85 [109/L], 95% CI = [-1.54, -0.16], P = 0.02) and neutrophils (WMD = -1.57 [109/L], 95% CI = [-2.60, -0.54], P = 0.003), more lymphocytes (WMD = 0.29 [109/L], 95% CI = [0.22, 0.36], P < 0.001) and platelets (WMD = 19.05 [109/L], 95% CI = [3.04, 35.06], P = 0.02), and lower neutrophil-to-lymphocyte ratio (NLR) level (WMD = -2.48, 95% CI = [-3.81, -1.15], P < 0.001), compared with those in severe group. There was no statistical difference in monocytes (WMD = 0.01 [109/L], 95% CI = [-0.01, 0.03], P = 0.029) between these two groups. Sensitivity analysis and meta-analysis based on standard mean difference (SMD) did not change the conclusions about neutrophils, lymphocytes and NLR while the results were inconsistent in WBC and platelets. CONCLUSIONS Severe patients had more neutrophils, higher NLR level, and fewer lymphocytes than non-severe patients with COVID-19. Measurement of these markers might assist clinicians to monitor and predict the severity and prognosis of COVID-19.


title: Economic evaluation of endoscopic radiofrequency ablation for the treatment of dysplastic Barrett's esophagus in Spain.

text: BACKGROUND AND STUDY AIMS To assess the cost-effectiveness of introducing endoscopic treatment based on radiofrequency ablation plus endoscopic mucosal resection in selected patients into the standard of care of Barrett's esophagus patients with high-grade dysplasia or low-grade dysplasia in Spain. METHODS The disease evolution was modeled via a semi-Markov model. The treatment strategies compared included endoscopic treatment based on radiofrequency ablation plus endoscopic mucosal resection and the Standard of Care (esophagectomy or palliative chemoradiotherapy according to disease status for high-grade dysplasia and endoscopic surveillance for low-grade dysplasia). Efficacy rates, transition probabilities and utility values were obtained from the literature. Clinical management patterns and resource use were modeled according to Spanish clinical expert opinion. Costs were expressed in euros (€) from 2016 reflecting the Spanish National Health System perspective. Sensitivity analyses were performed to assess the robustness of the model. RESULTS With respect to the Spanish Standard of Care, endoscopic treatment based on radiofrequency ablation plus endoscopic mucosal resection was a dominant strategy for high-grade dysplasia patients. When a willingness-to-pay threshold of €30,000 per quality-adjusted life-years gained was considered, this was cost-effective for low-grade dysplasia patients (€12,865 per quality-adjusted life-years gained). The sensitivity analyses supported the base case analysis results and pointed towards the main drivers of uncertainty in the model. CONCLUSIONS From a health care decision-maker, endoscopic treatment based on radiofrequency ablation plus endoscopic mucosal resection is the intervention of choice for dysplasic Barrett's esophagus patients in Spain.


title: Evaluation of a feline-specific multiplex, bead-based assay for detection of cytokines, chemokines, growth factors, and other immunologically active proteins in serum and plasma samples from cats.

text: OBJECTIVE To evaluate a feline-specific multiplex, bead-based assay system for detection of recombinant and native proteins in serum samples and in EDTA-treated and heparinized plasma samples. SAMPLE Serum samples and EDTA-treated and heparinized plasma samples from 30 sick cats and 9 healthy client-owned cats and heparinized whole blood samples from 5 healthy purpose-bred cats. PROCEDURES Ability of the assay system to detect 19 recombinant and native immunologically active proteins in plasma and serum samples from healthy and purpose-bred cats was evaluated via spike-and-recovery tests, assessments of inter- and intra-assay variation, linearity results, and leukocyte stimulation. Effects of various concentrations of heparin and serum matrix solution on percentages of analytes recovered were also evaluated. Analyte concentrations in samples from healthy and sick cats were measured and compared between groups. RESULTS Percentages of analytes recovered were unsatisfactory for most assays. Serum and heparinized plasma samples yielded better recovery results than did EDTA-treated plasma samples. Use of serum matrix solution did not improve results. Use of heparin concentrations greater than the recommended range affected the results. Linearity of results was difficult to assess because of the poor recovery. For the analytes that were recovered sufficiently for assessment, linearity appeared to be reasonable despite the limited detection. CONCLUSIONS AND CLINICAL RELEVANCE Poor percentages of analytes recovered and adverse effects of sample protein matrix limited the usefulness of the multiplex, bead-based assay system for measurement of immunologically active proteins in solutions with high protein content; however, recovery results were fairly linear, potentially allowing evaluation of feline plasma or serum samples with high analyte concentrations.


Covid-19: Deprived areas have the highest death rates in England and Wales.


title: Delayed prefrontal hemodynamic response associated with suicide risk in autism spectrum disorder.

text: Adults diagnosed with Autism spectrum disorder (ASD) are at high risk of experiencing suicidality compared with other clinical groups. Recently, near-infrared spectroscopy (NIRS) studies have investigated the association between frontotemporal functional abnormalities and suicidality in patients with mood disorders. However, whether these prefrontal hemodynamic responses are associated with suicide vulnerability in individuals with ASD remains unclear. Here, we used 24-channel NIRS to examine the characteristics of prefrontal hemodynamic responses during a verbal fluency task in 20 adults with ASD and in age-, sex-, and intelligence quotient-matched healthy controls. In addition, we used Spearman's correlation analysis to identify the relationship between the time-course of prefrontal hemodynamic activation and the current suicide risk in patients with ASD. We found no significant differences between the verbal fluency task-induced prefrontal hemodynamic responses in the ASD vs. control group. However, we found a significant positive correlation between the current suicide risk score and the time-course of prefrontal hemodynamic activation in the ASD group. Thus, the 24-channel NIRS system appears to be useful in assessing suicide risk in individuals with ASD.


title: Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence.

text: Tocotrienol (T3) is a subfamily of vitamin E known for its wide array of medicinal properties. This review aimed to summarize the health benefits of T3, particularly in prevention or treatment of non-communicable diseases (NCDs), including cardiovascular, musculoskeletal, metabolic, gastric, and skin disorders, as well as cancers. Studies showed that T3 could prevent various NCDs, by suppressing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the mevalonate pathway, inflammatory response, oxidative stress, and alternating hormones. The efficacy of T3 in preventing/treating these NCDs is similar or greater compared to tocopherol (TF). TF may lower the efficacy of T3 because the efficacy of the combination of TF and T3 was lower than T3 alone in some studies. Data investigating the effects of T3 on osteoporosis, arthritis, and peptic ulcers in human are limited. The positive outcomes of T3 treatment obtained from the preclinical studies warrant further validation from clinical trials.


title: Flexible Laryngoscopy and COVID-19.

text: Flexible laryngoscopy, the gold-standard evaluation of the larynx and the pharynx, is one of the most commonly performed procedures in otolaryngology. During the coronavirus disease 2019 (COVID-19) pandemic, flexible laryngoscopy represents a risk for patients and an occupational hazard for otolaryngologists and any clinic staff involved with the procedure or endoscope reprocessing. Here we present a set of recommendations on flexible laryngoscopy performance during the pandemic, including patient selection, personal protective equipment, and endoscope disinfection, based on a consensus reached during a virtual webinar on March 24, 2020, attended by approximately 300 participants from the American laryngology community.


Telehealth visits in a tertiary cardiovascular centre as a response of the healthcare system to the pandemic of SARS-CoV-2 in Poland.


Covid-19: ibuprofen can be used for symptoms, says UK agency, but reasons for change in advice are unclear.


title: Telemedicine in Otolaryngology: A Systematic Review of Image Quality, Diagnostic Concordance, and Patient and Provider Satisfaction.

text: OBJECTIVES Telemedicine allows for the remote delivery of patient care and has been found to have a wide range of uses in otolaryngology. In order to achieve best practices in telemedicine, a platform must be effective and both patients and providers must be satisfied with the use of technology. As telemedicine becomes more widely used in otolaryngology clinics, particularly in the face of the current COVID-19 pandemic, it is important to assess its applicability in this field. The goal of this study was to evaluate existing literature on telemedicine and assess overall image quality, diagnostic concordance, and patient and provider satisfaction with telemedicine technologies. METHODS A systematic review was conducted on PubMed and MEDLINE according to the PRISMA 2009 guidelines for articles from 1982 to 2019 relating to telemedicine in otolaryngology. English language studies with primary or secondary endpoints pertaining to image quality, diagnostic concordance, or patient or provider satisfaction were included. Descriptive studies, editorials, and literature reviews were excluded. RESULTS A total of 32 studies were included in our review. Studies assessing imaging quality and diagnostic concordance reported adequate results but with some heterogeneity. Patient and provider satisfaction were consistently high. CONCLUSIONS The literature supports telemedicine delivery of otorhinolaryngologic care as having achieved high rates of patient and provider satisfaction with adequate image quality and heterogeneity in diagnostic concordance. Variability in diagnostic accuracy was reported, but appears improved given proper clinical context. More standardized studies are needed specific to telemedicine in the field of otolaryngology.


title: A randomized clinical trial of three options for N95 respirators and medical masks in health workers.

text: RATIONALE We compared three policy options for the use of medical masks and N95 respirators in healthcare workers (HCWs). OBJECTIVES A cluster randomized clinical trial of 1,669 hospital-based HCWs in Beijing, China in the winter of 2009-2010. METHODS Participants were randomized to medical masks, N95 respirators, or targeted use of N95 respirators while doing high-risk procedures or barrier nursing. Outcomes included clinical respiratory illness (CRI) and laboratory-confirmed respiratory pathogens in symptomatic subjects. MEASUREMENTS AND MAIN RESULTS The rate of CRI was highest in the medical mask arm (98 of 572; 17%), followed by the targeted N95 arm (61 of 516; 11.8%), and the N95 arm (42 of 581; 7.2%) (P < 0.05). Bacterial respiratory tract colonization in subjects with CRI was highest in the medical mask arm (14.7%; 84 of 572), followed by the targeted N95 arm (10.1%; 52 of 516), and lowest in the N95 arm (6.2%; 36 of 581) (P = 0.02). After adjusting for confounders, only continuous use of N95 remained significant against CRI and bacterial colonization, and for just CRI compared with targeted N95 use. Targeted N95 use was not superior to medical masks. CONCLUSIONS Continuous use of N95 respirators was more efficacious against CRI than intermittent use of N95 or medical masks. Most policies for HCWs recommend use of medical masks alone or targeted N95 respirator use. Continuous use of N95s resulted in significantly lower rates of bacterial colonization, a novel finding that points to more research on the clinical significance of bacterial infection in symptomatic HCWs. This study provides further data to inform occupational policy options for HCWs. Clinical trial registered with Australian New Zealand Clinical Trials Registry http://www.anzctr.org.au (ACTRN 12609000778280).


title: Worldwide utilization of topical remedies in treatment of psoriasis: a systematic review.

text: OBJECTIVE To review published literature describing the global use of topical antipsoriatics. MATERIALS AND METHODS Search for English-language articles in Embase, Pubmed, PsycINFO and Cochrane Library. RESULTS Fifty-four selected publications were found, describing psoriasis patients' use of topical antipsoriatics, using six different methods to collect data. The eight most frequently used topical treatments from the regions North/South America, North/Central/South Europe, Asia, Middle East and Australia were: corticosteroids used by 16-79%, complementary and alternative medicines used by 10-62%, phototherapies used by 0.4-75%, calcipotriol used by 4.2-73%, corticosteroid/calcipotriol combinations used by 3.3-71%, tar used by 0.8-66%, anthralin used by 15% and emollients used as monotherapy by 1-23%. Rates of patient-reported adherence to topical remedies ranged from 51% to 90% and rates of patient-reported satisfaction with topical as it pertains to symptom control ranged from 12% to 52%. CONCLUSION The identified use patterns are varying and reflect a lack of data from large parts of the world and noncomparable studies using heterogeneous study designs. However, this study emphasizes the importance of medical professionals involvement of the patient with respect to choosing prescribed topical treatment and the possibility of patients' use of alternative treatments. More drug utilization studies, both survey and register based, from different parts of the world are needed to provide more conclusive evidence about patients' use of topical antipsoriatics.


title: Clinical and economic strategies in outpatient medical care during the COVID-19 pandemic.

text: The COVID-19 pandemic has resulted in significant clinical and economic consequences for medical practices of all specialties across the nation. Although the clinical implications are of the utmost importance, the economic consequences have also been serious and resulted in substantial damage to the US healthcare system, including pain practices. Outpatient pain practices have had to significantly change their clinical care pathways, including the incorporation of telemedicine. Elective medical and interventional care has been postponed. For the most part, ambulatory surgical centers have had to cease operations. As patient volumes have decreased for non-emergent elective care, the financial indicators have deteriorated. This review article will provide insight into solutions to mitigate the clinical and economic challenges induced by COVID-19. Undoubtedly, the COVID-19 pandemic will have short-term and long-term implications for all medical practices and facilities. In order to survive, medical practices will need dynamic, operational, and creative strategic plans to mitigate the disruption in medical care and pathways for successful reintegration of clinical and surgical practice.


title: Interplay between the Poly(A) Tail, Poly(A)-Binding Protein, and Coronavirus Nucleocapsid Protein Regulates Gene Expression of Coronavirus and the Host Cell.

text: In the present study, we investigated the roles of interactions among the poly(A) tail, coronavirus nucleocapsid (N) protein, and poly(A)-binding protein (PABP) in the regulation of coronavirus gene expression. Through dissociation constant (Kd ) comparison, we found that the coronavirus N protein can bind to the poly(A) tail with high affinity, establishing N protein as a PABP. A subsequent analysis with UV cross-linking and immunoprecipitation revealed that the N protein is able to bind to the poly(A) tail in infected cells. Further examination demonstrated that poly(A) tail binding by the N protein negatively regulates translation of coronaviral RNA and host mRNA both in vitro and in cells. Although the N protein can interact with PABP and eukaryotic initiation factor 4G (eIF4G), the poor interaction efficiency between the poly(A)-bound N protein and eIF4E may explain the observed decreased translation efficiency. In addition to interaction with translation factor eIF4G, the N protein is able to interact with coronavirus nonstructural protein 9 (nsp9), a replicase protein required for replication. The study demonstrates interactions among the poly(A) tail, N protein, and PABP both in vitro and in infected cells. Of the interactions, binding of the poly(A) tail to N protein decreases the interaction efficiency between the poly(A) tail and eIF4E, leading to translation inhibition. The poly(A)-dependent translation inhibition by N protein has not been previously demonstrated and thus extends our understanding of coronavirus gene expression.IMPORTANCE Gene expression in coronavirus is a complicated and dynamic process. In this study, we demonstrated that coronavirus N protein is able to bind to the poly(A) tail with high affinity, establishing N protein as a PABP. We also show how the interplay between coronavirus 3' poly(A) tail, PABP, and N protein regulates gene expression of the coronavirus and host cell. Of the interactions, poly(A) tail binding by the N protein negatively regulates translation, and to our knowledge, this inhibition of translation by binding of the N protein to poly(A) tail has not been previously studied. Accordingly, the study provides fundamental molecular details regarding coronavirus infection and expands our knowledge of coronavirus gene expression.


title: Nursing Continuing Professional Development-A Paradigm Shift.

text: The COVID-19 pandemic has created the need for rapid development and implementation of nursing continuing professional development (NCPD) to scale up nurses and other health care providers to meet a surge in critically ill patients. Through retooling and upskilling nurses and other health care providers, professional development is more important now than ever before. A heightened need for flexible professional development activity planning that is fully integrated into the professional environment is integral to prepare nurses to meet the challenges posed by this pandemic. This article addresses strategies to facilitate delivery of quality NCPD educational activities in real time. [J Contin Educ Nurs. 2020;51(7):297-299.].


title: Porcine epidemic diarrhea virus (PEDV) ORF3 protein is transported through the exocytic pathway.

text: Accessory genes occurring between the S and E genes of coronaviruses have been studied quite intensively during the last decades. In porcine epidemic diarrhea virus (PEDV) the only gene at this location, ORF3, encodes a 224-residues membrane protein shown to exhibit ion channel activity and to enhance virus production. However, little is known about its intracellular trafficking nor about its function during PEDV infection. In this study, two recombinant PEDVs were rescued by targeted RNA recombination, one carrying the full-length ORF3 gene and one from which the gene had been deleted entirely. These viruses as well as a PEDV encoding a naturally truncated ORF3 protein were employed to study the ORF3 protein's subcellular trafficking. In addition, ORF3 expression vectors were constructed to study the protein's independent transport. Our results show that the ORF3 protein uses the exocytic pathway to move to and accumulate in the Golgi area of the cell, similarly in infected and transfected cells. Like the S protein, but unlike the other structural proteins M and N, the ORF3 protein was additionally observed at the surface of PEDV-infected cells. Also the C-terminally truncated ORF3 protein entered the exocytic pathway but it was unable to leave the endoplasmic reticulum (ER) and ER-to-Golgi intermediate compartment (ERGIC). Consistently, an YxxØ motif essential for ER exit was identified in the C-terminal domain. Finally, despite the use of sensitive antibodies and assays no ORF3 protein could be detected in highly purified PEDV particles, indicating that the protein is not a structural virion component.IMPORTANCE Coronaviruses typically express several accessory proteins. They vary in number and nature, and only one is conserved among most of the coronaviruses, pointing at an important biological function for this protein. PEDV is peculiar in that it expresses just this one accessory protein, termed the ORF3 protein. While its analogues in other coronaviruses have been studied to different extents - indicating they share an ion channel property - little is still known about the features and functions of the PEDV ORF3 protein except for its association with virulence. Here we studied the intracellular trafficking of the ORF3 protein both in infected cells and when expressed independently. In addition, we analyzed the effects of mutations in five sorting motifs in its C-terminal domain and investigated whether the protein, found to follow the same exocytic route by which the viral structural membrane proteins travel, is also incorporated into virions.


ERAS protocols in gynecologic oncology during covid-19 pandemic.


Covid-19: Hospitals can remove 15% cap on testing of NHS staff.


title: Impact of local vascular lesions assessed with optical coherence tomography and ablation points on blood pressure reduction after renal denervation.

text: UNLABELLED Local vascular injury is detectable with optical coherence tomography (OCT) after catheter-based renal denervation (RDN). However, it is unclear whether the number and type of vascular lesions or the number of ablation points could affect blood pressure (BP) reduction. The aim of the study was to assess the impact of vascular injury induced by RDN detected with OCT and the number of ablation points on BP response after 1, 3 and 6 months. METHODS RDN was either performed with a Simplicity catheter or an EnligHTNTM multielectrode basket followed by OCT. BP was recorded prospectively as office measurement and 24-hour ambulatory blood pressure monitoring (24-h ABPM) at each time point. Correlations between type and number of vascular lesions, as well as ablation points, on BP reduction were performed. RESULTS Out of 16 patients, two were lost to BP follow-up. We documented a BP reduction at 1, 3 and 6 months in both office and 24-h ABPM. The Δmean office systolic BP (SBP) reduction was -18.75 ± 24.55 mm Hg, -20.58 ± 16.92 mm Hg and -18.75 ± 29.39 mm Hg, respectively, and the Δmean 24h-ABPM SBP reduction was -6.50 ± 23.45 mm Hg, -16.88 ± 26.64 mm Hg and -13.89 ± 21.20 mm Hg, respectively. The number of vascular lesions did not correlate with office and 24h-SBP and diastolic BP reduction. However, there was a correlation between ablation points and office Δmean SBP reduction at 6 months (p <0.02). CONCLUSIONS Our study demonstrates for the first time that the number and type of vascular lesions as assessed with OCT did not predict the success of BP reduction after RDN. However, we observed a substantial decrease in office SBP in relation to the number of ablation points at 6 months.


title: Inhibiting the system xC-/glutathione axis selectively targets cancers with mutant-p53 accumulation.

text: TP53, a critical tumour suppressor gene, is mutated in over half of all cancers resulting in mutant-p53 protein accumulation and poor patient survival. Therapeutic strategies to target mutant-p53 cancers are urgently needed. We show that accumulated mutant-p53 protein suppresses the expression of SLC7A11, a component of the cystine/glutamate antiporter, system xC-, through binding to the master antioxidant transcription factor NRF2. This diminishes glutathione synthesis, rendering mutant-p53 tumours susceptible to oxidative damage. System xC- inhibitors specifically exploit this vulnerability to preferentially kill cancer cells with stabilized mutant-p53 protein. Moreover, we demonstrate that SLC7A11 expression is a novel and robust predictive biomarker for APR-246, a first-in-class mutant-p53 reactivator that also binds and depletes glutathione in tumours, triggering lipid peroxidative cell death. Importantly, system xC- antagonism strongly synergizes with APR-246 to induce apoptosis in mutant-p53 tumours. We propose a new paradigm for targeting cancers that accumulate mutant-p53 protein by inhibiting the SLC7A11-glutathione axis.


title: The Impact of Circular Stapler Size on the Incidence of Cervical Anastomotic Stricture After Esophagectomy.

text: BACKGROUND Cervical anastomotic stricture after esophagectomy is a serious complication that adversely affects postoperative recovery, nutritional status and quality of life. Cervical anastomosis by a circular stapler (CS) has been widely accepted as a simple and convenient method, but anastomotic strictures are likely to occur. The aim of this study was to investigate an association between CS size and the incidence of anastomotic stricture after cervical esophagogastric anastomosis performed by a CS. METHODS Between April 2011 and March 2016, 236 consecutive patients underwent cervical esophagogastric anastomosis by a CS via a retrosternal route after esophagectomy for esophageal cancer. These patients were divided into according to CS size for the procedure as follows: small-sized (25 mm) CS group (SG, n = 116) and large-sized (28 or 29 mm) CS group (LG, n = 120). The clinical data of patients were analyzed retrospectively to compare the two groups. RESULTS Overall, anastomotic strictures were observed in 90 patients (38%). The incidence of anastomotic stricture was significantly lower in the LG than the SG (23% vs. 53%, p < 0.001) (Table 3). Chronic obstructive pulmonary disease (COPD: FEV1.0% <70%) (OR 2.35, 95% CI = 1.09-5.14; p = 0.029), anastomotic leakage (OR 8.97, 95% CI = 2.69-41.30; p < 0.001), and a small-sized CS (OR 3.42, 95% CI = 1.82-6.62; p < 0.001) were independent risk factors for anastomotic stricture in the multivariate analysis. CONCLUSIONS If possible, a large-sized CS should be used to prevent cervical anastomotic strictures when performing cervical anastomoses by CS.


title: Surgical adjuncts to laparoscopic distal pancreatectomy.

text: Abstract Laparoscopic distal pancreatectomy (LDP) has emerged as an alternative approach to traditional open surgery for managing isolated pathology in the body and tail of the pancreas. Experience with this technique to date is limited with only small series reported in the literature. Common difficulties with this operation are related to dissection of the pancreas from the portal vein and management of the pancreatic stump. In this paper we describe our single centre experience to date and describe strategies we have developed which we believe facilitate safe and effective laparoscopic distal pancreatectomy.


title: Human mannose-binding lectin inhibits human cytomegalovirus infection in human embryonic pulmonary fibroblast.

text: A limited number of drugs have been used for treatment of human cytomegalovirus (HCMV), all sharing the similar antiviral mechanism of inhibiting virus replication. This study investigates the anti-HCMV activities of mannose-binding lectin (MBL) from blocking virus entry and inhibiting virus spread. Recombinant human MBL was produced in CHO cells and native human MBL was isolated from human serum. A HCMV neutralization test was performed by pre-treating HCMV with each diluted MBL solution. Then the treated HCMV was inoculated onto the human embryonic pulmonary fibroblasts (HELF), which was followed by HCMV-DNA detection, PP65 positivity examination and confocal imaging of the infected cells. To test the activity of MBL in inhibiting viral spreading after viral invasion, HCMV growth inhibition test was performed. The infected cells were incubated with each diluted MBL, every 24 h, the supernatant was tested for HCMV-DNA. After 72 h, cells were collected for HCMV-DNA and PP65 examination. Then the cytopathic effect was observed and cell viability was measured at the 5 days after infection. HCMV neutralization test revealed 10 μg/mL MBL significantly decreased the HCMV invasion in HELF and the anti-HCMV activity can be blocked by 20 mg/mL mannan. HCMV growth inhibition test indicated that at 48 h after HCMV invasion, the HCMV-DNA level in the culture supernatant with 10 μg/mL MBL was lower than the control. After 72 h, both the HCMV-DNA levels and PP65 positivity in cells incubated with MBL were reduced. This is the first to report on the anti-HCMV activities of MBL by in vitro studies.


title: 3T magnetic resonance imaging accurately depicts radiofrequency ablation zones in a blood-perfused bovine liver model.

text: PURPOSE To determine if noncontrast T1-weighted (T1W) images from 3T magnetic resonance (MR) imaging accurately depict radiofrequency (RF) ablation zones as determined macroscopically and microscopically in a blood-perfused bovine liver model. MATERIALS AND METHODS Three-dimensional (3D) gradient-recalled echo (GRE) T1W images were obtained on a 3T MR imaging scanner after RF ablations (n = 14) of in vitro blood-perfused bovine livers. The resulting central hypointense and peripheral hyperintense signal regions were measured and compared with the inner tan and outer red zones of the gross specimen. Corresponding ablated hepatic tissue samples were examined microscopically and stained with nicotinamide adenine dinucleotide phosphate (NADPH) to assess for the presence or absence of NADPH diaphorase activity. Bootstrap two-sample hypothesis tests were used to compare MR imaging, gross, and histopathologic measurements. RESULTS The MR imaging inner ablation zone had a mean radius of 0.80 cm (range 0.33-1.14 cm); the inner zone plus the outer ablation zone had a mean radius of 1.40 cm (range 1.01-1.74 cm). Comparison of the measurements of the inner ablation zone on MR imaging versus the gross specimen showed equivalence (95% confidence interval [CI] -0.122 cm, 0.223 cm). Comparison of the measurements of the outer ablation zone on MR imaging versus the gross and histologic specimens also showed equivalence (95% CI -0.095 cm, 0.244 cm, and -0.146 cm, 0.142 cm). CONCLUSIONS Noncontrast 3D GRE T1W 3T MR imaging accurately depicts the RF ablation zones in a blood-perfused bovine liver model and can be used as a noninvasive means to assess the 3D morphologic characteristics of RF ablation lesions in the model.


title: Short-term effect analysis of radiofrequency ablation combined chemotherapy on middle and late period non-small cell lung cancer.

text: In this study, we investigated the effect of radiofrequency ablation (RFA) combined chemotherapy on middle and late period non-small cell lung cancer (NSCLC). In total, 85 cases of middle and late period NSCLC patients were selected, and were randomly divided into the RFA combined chemotherapy group, RFA treatment group and chemotherapy group. After treatment, the three groups were followed up for computed tomography (CT) scan, and were analyzed for the effect of RFA combined chemotherapy on middle and late period NSCLC. It was found that CT value of RFA combined chemotherapy group decreased significantly compared to before surgery (P<0.05). The CT value of the RFA group decreased significantly compared to before surgery (P<0.05). The CT value of chemotherapy group was not significantly changed compared to before surgery (P>0.05). The postoperative CT value of the RFA combined chemotherapy group and RFA group was smaller compared to that of the chemotherapy group (P<0.05). Effective rate [complete response (CR) + partial response (PR)] of RFA combined chemotherapy group was significantly higher than that of the EFA and chemotherapy groups (P<0.05). Effective rate (CR+PR) of the RFA group was significantly higher than that of the chemotherapy group (P<0.05). By contrast, the progressive rate (P) of RFA combined chemotherapy group was significantly lower than that of the RFA and chemotherapy groups (P<0.05). In conclusion, RFA combined chemotherapy has obvious effect on middle and late period NSCLC, and is safe and feasible.


title: Prospective study on the treatment of lower-extremity chronic venous and mixed ulcers using tissue-engineered skin substitute made by the self-assembly approach.

text: BACKGROUND Despite present optimal standard treatment of lower-extremity ulceration, a high incidence of recurrence and treatment failure is observed. The objective of this project was to evaluate the effect of a self-assembled skin substitute (SASS) made by tissue engineering as a temporary cutaneous dressing in the treatment of hard-to-heal chronic ulcers. PATIENTS AND METHODS The prospective uncontrolled case study includes patients suffering from venous or mixed ulcers lasting more than 6 months and unresponsive to compression therapy, with an Ankle Brachial Index greater than 0.5. Compression therapy was combined with the weekly application of SASS, produced from the patient's own skin cells, until healing. A weekly follow-up recorded wound size, skin aspect, pain, drainage, and percentage of wound healing. Photographs were also taken to assess ulcer evolution. RESULTS Fourteen ulcers present on 5 patients were treated. A mean of 6.7 SASS depositions by ulcer was required for healing. Two ulcers developed a minor wound infection, which was treated with oral antibiotics; another 2 ulcers recurred, and 1 healed with a second course of treatment, whereas 1 ulcer had a small recurrence treated with local wound care. CONCLUSION The authors' study suggests that the SASS used as a biological dressing is a promising treatment for hard-to-heal chronic venous and mixed ulcers that are unresponsive to compression therapy.


title: Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19.

text: Background & objectives Healthcare workers (HCWs) are at an elevated risk of contracting COVID-19. While intense occupational exposure associated with aerosol-generating procedures underlines the necessity of using personal protective equipment (PPE) by HCWs, high-transmission efficiency of the causative agent [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] could also lead to infections beyond such settings. Hydroxychloroquine (HCQ), a repurposed antimalarial drug, was empirically recommended as prophylaxis by the National COVID-19 Task Force in India to cover such added risk. Against this background, the current investigation was carried out to identify the factors associated with SARS-CoV-2 infection among HCWs in the country. Methods A case-control design was adopted and participants were randomly drawn from the countrywide COVID-19 testing data portal maintained by the ICMR. The test results and contact details of HCWs, diagnosed as positive (cases) or negative (controls) for SARS-CoV-2 using real-time reverse transcription-polymerase chain reaction (qRT-PCR), were available from this database. A 20-item brief-questionnaire elicited information on place of work, procedures conducted and use of PPE. Results Compared to controls, cases were slightly older (34.7 vs. 33.5 yr) and had more males (58 vs. 50%). In multivariate analyses, HCWs performing endotracheal intubation had higher odds of being SARS-CoV-2 infected [adjusted odds ratio (AOR): 4.33, 95% confidence interval (CI): 1.16-16.07]. Consumption of four or more maintenance doses of HCQ was associated with a significant decline in the odds of getting infected (AOR: 0.44; 95% CI: 0.22-0.88); a dose-response relationship existed between frequency of exposure to HCQ and such reductions (χ[2] for trend=48.88; P <0.001). In addition, the use of PPE was independently associated with the reduction in odds of getting infected with SARS-CoV-2. Interpretations & conclusions Until results of clinical trials for HCQ prophylaxis become available, this study provides actionable information for policymakers to protect HCWs at the forefront of COVID-19 response. The public health message of sustained intake of HCQ prophylaxis as well as appropriate PPE use need to be considered in conjunction with risk homoeostasis operating at individual levels.


title: Cohesion in Distancing.

text: In isolation, we are physically apart; in solidarity, we are together. The COVID-19 pandemic emphasizes our social responsibility to maintain physical distance from one another. In doing so, we solidify our collective strength.


title: Emergency department syndromic surveillance providing early warning of seasonal respiratory activity in England.

text: Seasonal respiratory infections place an increased burden on health services annually. We used a sentinel emergency department syndromic surveillance system to understand the factors driving respiratory attendances at emergency departments (EDs) in England. Trends in different respiratory indicators were observed to peak at different points during winter, with further variation observed in the distribution of attendances by age. Multiple linear regression analysis revealed acute respiratory infection and bronchitis/bronchiolitis ED attendances in patients aged 1-4 years were particularly sensitive indicators for increasing respiratory syncytial virus activity. Using near real-time surveillance of respiratory ED attendances may provide early warning of increased winter pressures in EDs, particularly driven by seasonal pathogens. This surveillance may provide additional intelligence about different categories of attendance, highlighting pressures in particular age groups, thereby aiding planning and preparation to respond to acute changes in EDs, and thus the health service in general.


Diffuse Myocardial Inflammation in COVID-19 Associated Myocarditis Detected by Multiparametric Cardiac Magnetic Resonance Imaging.


An Italian paediatric department at the time of Coronavirus: a resident's point of view.


title: Association of Computed Tomography Ischemic Lesion Location With Functional Outcome in Acute Large Vessel Occlusion Ischemic Stroke.

text: BACKGROUND AND PURPOSE Ischemic lesion volume (ILV) assessed by follow-up noncontrast computed tomography correlates only moderately with clinical end points, such as the modified Rankin Scale (mRS). We hypothesized that the association between follow-up noncontrast computed tomography ILV and outcome as assessed with mRS 3 months after stroke is strengthened when taking the mRS relevance of the infarct location into account. METHODS An anatomic atlas with 66 areas was registered to the follow-up noncontrast computed tomographic images of 254 patients from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). The anatomic brain areas were divided into brain areas of high, moderate, and low mRS relevance as reported in the literature. Based on this distinction, the ILV in brain areas of high, moderate, and low mRS relevance was assessed for each patient. Binary and ordinal logistic regression analyses with and without adjustment for known confounders were performed to assess the association between the ILVs of different mRS relevance and outcome. RESULTS The odds for a worse outcome (higher mRS) were markedly higher given an increase of ILV in brain areas of high mRS relevance (odds ratio, 1.42; 95% confidence interval, 1.31-1.55 per 10 mL) compared with an increase in total ILV (odds ratios, 1.16; 95% confidence interval, 1.12-1.19 per 10 mL). Regression models using ILV in brain areas of high mRS relevance instead of total ILV showed a higher quality. CONCLUSIONS The association between follow-up noncontrast computed tomography ILV and outcome as assessed with mRS 3 months after stroke is strengthened by accounting for the mRS relevance of the affected brain areas. Future prediction models should account for the ILV in brain areas of high mRS relevance.


title: Radiofrequency Ablation for Iatrogenic Thyroid Artery Pseudoaneurysm: Initial Experience.

text: Eight iatrogenic thyroid pseudoaneurysms (ITPAs) after thyroid biopsy are reported. The mean ITPA diameter was 7.2 mm (range 4 to 12 mm). Ultrasound (US)-guided compression was initially performed at the neck of the ITPA in all cases. Among them, 4 ITPAs persisted (50%) in which radiofrequency (RF) ablation was performed. Mean RF ablation time and power were 13.5 seconds (range 5 to 24 seconds) and 20 W (range 10 to 50 W), respectively. All 4 cases were treated with RF ablation without any complications.


title: Alternatives to Traditional Per-Oral Endoscopy for Screening.

text: Barrett's esophagus (BE) predisposes patients to esophageal adenocarcinoma. 3 to 6% of individuals with gastro-esophageal reflux disease are estimated to have BE but only 20 to 25% of BE patients are currently diagnosed. The current gold standard for diagnosis of BE is per-oral upper GI endoscopy. As this is not suitable for large-scale screening, a number of alternative methods are currently being investigated: transnasal and video capsule endoscopy, endomicroscopy, cell collection devices like the cytosponge and biomarkers. Some of these are promising, however, well powered studies carried out in relevant screening populations are needed.


title: Exploration of (hetero)aryl Derived Thienylchalcones for Antiviral and Anticancer Activities.

text: BACKGROUND Search for new antiviral and anticancer agents are essential because of the emergence of drug resistance in recent years. In continuation of our efforts in identifying the new small molecule antiviral and anticancer agents, we identified chalcones as potent antiviral and anticancer agents. OBJECTIVE With the aim of identifying the broad acting antiviral and anticancer agents, we discovered substituted aryl/heteroaryl derived thienyl chalcones as antiviral and anticancer agents. METHOD A focused set of thienyl chalcone derivaties II-VI was screened for selected viruses Hepatitis B virus (HBV), Herpes simplex virus 1 (HSV-1), Human cytomegalovirus (HCMV), Dengue virus 2 (DENV2), Influenza A (H1N1) virus, MERS coronavirus, Poliovirus 1 (PV 1), Rift Valley fever (RVF), Tacaribe virus (TCRV), Venezuelan equine encephalitis virus (VEE) and Zika virus (ZIKV) using the National Institute of Allergy and Infectious Diseases (NIAID)'s Division of Microbiology and Infectious Diseases (DMID) antiviral screening program. Additionally, a cyclopropylquinoline derivative IV has been screened for 60 human cancer cell lines using the Development Therapeutics Program (DTP) of NCI. RESULTS All thienyl chalcone derivatives II-VI displayed moderate to excellent antiviral activity towards several viruses tested. Compounds V and VI were turned out be active compounds towards human cytomegalovirus for both normal strain (AD169) as well as resistant isolate (GDGr K17). Particularly, cyano derivative V showed very high potency (EC50: <0.05 µM) towards AD169 strain of HCMV compared to standard drug Ganciclovir (EC50: 0.12 µM). Additionally, it showed moderate activity in the secondary assay (AD169; EC50: 2.30 µM). The cyclopropylquinoline derivative IV displayed high potency towards Rift Valley fever virus (RVFV) and Tacaribe virus (TCRV) towards Rift Valley fever virus (RVFV). The cyclopropylquinoline derivative IV is nearly 28 times more potent in our initial in vitro visual assay (EC50: 0.39 µg/ml) and nearly 17 times more potent in neutral red assay (EC50: 0.71 μg/ml) compared to the standard drug Ribavirin (EC50: 11 µg/ml; visual assay and EC50: 12 µg/ml; neutral red assay). It is nearly 12 times more potent in our initial in vitro visual assay (EC50: >1 µg/ml) and nearly 8 times more potent in neutral red assay (EC50: >1.3 µg/ml) compared to the standard drug Ribavirin (EC50: 12 µg/ml; visual assay and EC50: 9.9 µg/ml; neutral red assay) towards Tacaribe virus (TCRV). Additionally, cyclopropylquinoline derivative IV has shown strong growth inhibitory activity towards three major cancers (colon, breast, and leukemia) cell lines and moderate growth inhibition shown towards other cancer cell lines screened. CONCLUSION Compounds V and VI were demonstrated viral inhibition towards Human cytomegalovirus, whereas cyclopropylquinoline derivative IV towards Rift Valley fever virus and Tacaribe virus. Additionally, cyclopropylquinoline derivative IV has displayed very good cytotoxicity against colon, breast and leukemia cell lines in vitro.


title: Disproportionate burden of COVID-19 among racial minorities and those in congregate settings among a large cohort of people with HIV.

text: BACKGROUND Many people living with HIV (PLWH) have comorbidities which are risk factors for severe COVID-19 or have exposures that may lead to acquisition of SARS-CoV-2. There are few studies, however, on the demographics, comorbidities, clinical presentation or outcomes of COVID-19 in people with HIV. OBJECTIVE To evaluate risk factors, clinical manifestations and outcomes in a large cohort of PLWH with COVID-19. METHODS We systematically identified all PLWH who were diagnosed with COVID-19 at a large hospital from March 3 to April 26, 2020 during an outbreak in Massachusetts. We analyzed each of the cases to extract information including demographics, medical comorbidities, clinical presentation, and illness course after COVID-19 diagnosis. RESULTS We describe a cohort of 36 PLWH with confirmed COVID-19 and another 11 patients with probable COVID-19. Almost 85% of PLWH with confirmed COVID-19 had a comorbidity associated with severe disease, including obesity, cardiovascular disease, or hypertension. Approximately 77% of PLWH with COVID-19 were non-Hispanic Black or Latinx whereas only 40% of the PLWH in our clinic were Black or Latinx. Nearly half of PLWH with COVID-19 had exposure to congregate settings. In addition to people with confirmed COVID-19, we identified another 11 individuals with probable COVID-19, almost all of whom had negative PCR testing. CONCLUSION In the largest cohort to date of PLWH and confirmed COVID-19, almost all had a comorbidity associated with severe disease, highlighting the importance of non-HIV risk factors in this population. The racial disparities and frequent link to congregate settings in PLWH and COVID-19 need to be explored urgently.


title: Reprocessed bipolar energy for laparoscopic colectomy: Is it worth it?

text: BACKGROUND Reprocessed (re-sterilized) bipolar energy devices represent one effort to reduce operative costs. METHODS Between January 2014 to October 2015, 76 patients underwent laparoscopic colectomy using a reprocessed bipolar energy device and were case-matched to 76 patients from a prospectively-maintained database from November 2012 to December 2013 when an identical, new device was used. Outcomes included reprocessed device safety, efficiency and hospital costs. RESULTS There was no difference in patient demographics, operative times or failed pedicle ligation requiring intervention between groups (all P > 0.05). In 19.7% of reprocessed cases, the surgeon opened an additional new device after dissatisfaction with the reprocessed instrument. Operating room costs and total costs were less for the reprocessed device group (all P < 0.05). CONCLUSION Reprocessed bipolar energy devices were associated with savings in operative expenses, however, larger studies are warranted due to the high surgeon dissatisfaction regarding safety concerns with the reprocessed equipment.


title: Development of a primer-probe energy transfer real-time PCR assay for improved detection of classical swine fever virus.

text: Classical swine fever (CSF) is a contagious and devastating disease, causing serious losses in the pig industry worldwide. Vaccination of pigs with the conventional C-strain vaccine has been practised in different regions of the world in order to prevent the disease. In the control programmes of CSF, rapid detection and identification of the causing agent, classical swine fever virus (CSFV) is a crucial step. This study describes a novel real-time PCR assay based on primer-probe energy transfer (PriProET) technology for improved detection of CSFV. The assay is able to detect 20 copies of viral cDNA per reaction, showing a high sensitivity. The specificity has been evaluated by testing 57 pestiviruses, representing all species and unclassified pestiviruses. The assay has been found to be highly reproducible. Following PCR amplification, melting curve analysis allows confirmation of specific amplicons, and differentiation between wild-type CSFV and certain C-strain vaccines. This study provides a new tool for the diagnosis of CSF.


Thoracic Computed Tomography Features of Coronavirus Disease 2019 Patients with Emphysema.


title: Anatomy Revisited: Hemodialysis Catheter Malposition into the Chest.

text: In most situations, central catheters are implanted in the right jugular vein as initial access for hemodialysis. However, after repeated punctures, the proximal vessels become stenosed and thrombosed and misplacement is likely to occur. Correct catheter position in the vein can be easily ascertained with X-ray or cross-sectional CT imaging. In this report, we describe the case of a 77-year-old patient on chronic hemodialysis via catheter due to arteriovenous fistula dysfunction. We placed a cuffed-tunneled hemodialysis catheter in the left internal jugular vein. Malpositioning of the catheter led to perforation of the great veins and migration of the catheter tip into the chest. It is important to be aware of the risk of potential incorrect positioning of dialysis catheters. Due to the stenosis and fragility of the vessel wall, perforation may occur. In cases of doubt, correct placement of large-bore catheters via the internal jugular vein should be verified by means of appropriate imaging before hemodialysis is performed.


title: Protocol of a scoping review assessing injury rates and their determinants among healthcare workers in western countries.

text: INTRODUCTION Healthcare workers (HCWs) are exposed to various risk factors and risky behaviours that may seriously affect their health and ability to work. The aim of this protocol is to detail the steps to follow in order to carry out a scoping review to assess the prevalence/incidence of injuries among HCWs. METHODS AND ANALYSIS The study will be carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Protocols guidelines. Studies will be selected according to the following criteria: P (HCWs), E (exposure to injuries), C (different types of exposure and different categories of HCWs) and O (prevalence/incidence and determinants of injuries). A time filter has been set (literature between 2000 and 2018) to enable updated, direct comparison between the findings and the epidemiological data available at national and local 'Istituto Nazionale per l'Assicurazione contro gli Infortuni sul Lavoro' (National Institute for Insurance Against Accidents at Work) centres in Italy. No language restriction will be applied. ETHICS AND DISSEMINATION Formal ethical approval is not required; primary data will not be collected, as they have already been published. The results will be disseminated through peer-reviewed publication(s), conference presentation(s) and the press.


title: Vibration-induced depression in spinal loop excitability revisited.

text: KEY POINTS While it has been well described that prolonged vibration locally applied to a muscle or its tendon (up to 1 h) decreases spinal loop excitability between homonymous Ia afferents and motoneurons, the involved mechanisms are not fully understood. By combining electrophysiological methods, this study aimed to provide new insights on the mechanisms involved in LV post-effect in SOL spinal excitability after prolonged LV. We reported that prolonged vibration induces a decrease in motoneuron excitability rather than an increase in presynaptic mechanisms (as commonly hypothesized in the current literature) The present results may help to design appropriate clinical intervention and could reinforce the interest of vibration as a treatment in spastic patients who are characterized by spinal hyper-excitability responsible for spasms and long-lasting reflexes. ABSTRACT The mechanisms that can explain the decreased spinal loop excitability in response to prolonged local vibration (LV), as assessed by the H-reflex, remain to be precisely determined. This study provides new insights on how prolonged Achilles tendon LV (30 min, 100 Hz) acutely interacts with the spinal circuitry. The roles of presynaptic inhibition exerted on Ia afferents (Experiment A, n = 15), neurotransmitter release at the synapse level (Experiment B, n = 11) and motoneuron excitability (Experiment C, n = 11) were investigated in soleus (SOL). Modulation of presynaptic inhibition was assessed by conditioning the SOL H-reflex (tibial nerve electrical stimulation) with fibular nerve (D1 inhibition) and femoral nerve (heteronymous facilitation, HF) electrical stimulations. Potential vibration-induced changes in neurotransmitter depletion at the Ia afferent terminals was assessed through paired stimulations applied over the tibial nerve (HD). Intrinsic motoneuron excitability was assessed with thoracic motor evoked potentials (TMEPs) in response to electrical stimulation over the thoracic spine. Non-conditioned H-reflex was depressed by ∼60% after LV (p < 0.001), while D1 and HF H-reflexes increased by ∼75% after LV (p = 0.03 and 0.06, respectively). In Experiment B, HD remained unchanged at POST (p = 0.80). In Experiment C, TMEPs were reduced by ∼13% at POST (p = 0.01). Overall, presynaptic mechanisms do not seem to be involved in the depression of spinal excitability after LV. It rather seems to rely, at least in part, on a decrease in intrinsic motoneuron excitability. These results may have implications in reducing spinal hyper-excitability in spastic patients. This article is protected by copyright. All rights reserved.


title: Influenza and COVID-19 Co-infection: Report of 6 cases and review of the Literature.

text: COVID-19 pandemic caused infection in a season when influenza is still prevalent. Both viruses have similar transmission characteristics and common clinical manifestations. Influenza has been described to cause respiratory infection with some other respiratory pathogens. However the information of COVID-19 and influenza co-infection is limited. In this study, we reported our co-infected cases and reviewed the literature. We included all COVID-19 diagnosed patients. All patients with a presumed diagnosis of COVID-19 were routinely screened for influenza. Their thorax radiology was reviewed for COVID-19 -influenza differentiation. During the study period, 1103 patients have been diagnosed COVID-19. Among them, 6 patients (0.54%) were diagnosed co-infected with influenza. There have been 28 more co-infected patients reported. Laboratory-based, screening studies reported more patients. Thorax radiology findings were compatible with COVID-19 in 5 and with influenza in 1 one of our patients. Our cases were mild-to-moderate in severity. The reported cases in the literature included patients died (n=2) and those living ventilator dependent or under mechanical ventilation. COVID-19 and influenza co-infection is rare. Screening studies report more cases, suggesting that unless screening COVID-19 patients, the co-infection remains undiagnosed and underestimated. Increasing experience in thoracic radiology may contribute to diagnose the responsible virus(es) from the clinical illness. Influenza vaccine for larger population groups can be recommended to simplify clinicians' work. This article is protected by copyright. All rights reserved.


title: Three-dimensional rotational angiography of the foot in critical limb ischemia: a new dimension in revascularization strategy.

text: PURPOSE To evaluate the additional value of three-dimensional rotational angiography (3DRA) of the foot compared with digital subtraction angiography (DSA) in patients with critical limb ischemia (CLI). TECHNIQUE For 3DRA, the C-arm was placed in the propeller position with the foot in an isocentric position. The patient's unaffected foot was positioned in a footrest outside the field of view. For correct timing of 3DRA, the delay from contrast injection in the popliteal artery at the level of knee joint to complete pedal arterial enhancement was assessed using DSA. With this delay, 3DRA was started after injection of 15 ml contrast. Imaging of the 3DRA could directly be reconstructed and visualized. MATERIALS AND METHODS Patients undergoing 3DRA of the foot were prospectively registered. DSA and 3DRA images were scored separately for arterial patency and presence of collaterals. Treatment strategies were proposed based on DSA with and without the availability of 3DRA. RESULTS Eleven patients underwent 3DRA of the foot. One 3DRA was not included because the acquisition was focused on the heel instead of the entire foot. Diagnostic quality of 3DRA was good in all ten patients. 3DRA compared with DSA showed additional patent arteries in six patients, patent plantar arch in three patients, and collaterals between the pedal arteries in five patients. Additional information from 3DRA resulted in a change of treatment strategy in six patients. CONCLUSION 3DRA of the foot contains valuable additional real-time information to better guide peripheral vascular interventions in patients with CLI and nonhealing tissue lesions.


title: Mapping the innate signaling cascade essential for cytokine storm during influenza virus infection.

text: During pathogenic influenza virus infection, robust cytokine production (cytokine storm), excessive inflammatory infiltrates, and virus-induced tissue destruction all contribute to morbidity and mortality. Earlier we reported that modulation of sphingosine-1-phosphate-1 receptor (S1P1R) signaling provided a chemically tractable approach for the effective blunting of cytokine storm, leading to the improvement of clinical and survival outcomes. Here, we show that S1P1R agonist treatment suppresses global cytokine amplification. Importantly, S1P1R agonist treatment was able to blunt cytokine/chemokine production and innate immune cell recruitment in the lung independently of endosomal and cytosolic innate sensing pathways. S1P1R signaling suppression of cytokine amplification was independent of multiple innate signaling adaptor pathways for myeloid differentiation primary response gene 88 (MyD88) and IFN-β promoter stimulator-1 signaling, indicating a common pathway inhibition of cytokine storm. We identify the MyD88 adaptor molecule as responsible for the majority of cytokine amplification observed following influenza virus challenge.


title: Quantitative analysis of the effect of institutional case volume on complications after surgical clipping of unruptured aneurysms.

text: OBJECTIVE The mechanism by which greater institutional case volume translates into improved outcomes after surgical clipping of unruptured intracranial aneurysms (UIAs) is not well established. The authors thus aimed to assess the effect of case volume on the rate of various types of complications after clipping of UIAs. METHODS Using information on the outcomes of inpatient admissions for surgical clipping of UIAs collected within a national database, the relationship of institutional case volume to the incidence of different types of complications after clipping was investigated. Complications were subdivided into different categories, which included all complications, ischemic stroke, intracerebral hemorrhage, medical complications, infectious complications, complications related to anesthesia, and wound complications. The relationship of case volume to different types of complications was assessed using linear regression analysis. The relationships between case volume and overall complication and stroke rates were fit with both linear and quadratic equations. The numerical cutoff for institutional case volume above and below which the authors found the greatest differences in mean overall complication and stroke rate was determined using classification and regression tree (CART) analysis. RESULTS Between October 2012 and September 2015, 125 health care institutions reported patient outcomes from a total of 6040 cases of clipping of UIAs. On linear regression analysis, increasing case volume was negatively correlated to both overall complications (r2 = 0.046, p = 0.0234) and stroke (r2 = 0.029, p = 0.0557) rate, although the relationship of case volume to the complication (r2 = 0.092) and stroke (r2 = 0.067) rate was better fit with a quadratic equation. On CART analysis, the cutoff for the case number that yielded the greatest difference in overall complications and stroke rate between higher- or lower-volume centers was 6 cases/year and 3 cases/year, respectively. CONCLUSIONS Although the authors confirm that increasing case volume is associated with reduced complications after clipping of UIAs, their results suggest that the relationship between case volume and complications is not necessarily linear. Moreover, these results indicate that the effect of case volume on outcome is most evident between very-low-volume centers relative to centers with a medium-to-high volume.


title: Familial aggregation in inflammatory bowel disease: is it genes or environment?

text: Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.


title: Hydrogen Flush After Cold Storage as a New End-Ischemic Ex Vivo Treatment for Liver Grafts Against Ischemia/Reperfusion Injury.

text: Cold storage (CS) remains the gold standard for organ preservation worldwide, although it is inevitably associated with ischemia/reperfusion injury (IRI). Molecular hydrogen (H2 ) is well known to have antioxidative properties. However, its unfavorable features, ie, inflammability, low solubility, and high tissue/substance permeability, have hampered its clinical application. To overcome such obstacles, we developed a novel reconditioning method for donor organs named hydrogen flush after cold storage (HyFACS), which is just an end-ischemic H2 flush directly to donor organs ex vivo, and, herein, we report its therapeutic impact against hepatic IRI. Whole liver grafts were retrieved from Wistar rats. After 24-hour CS in UW solution, livers were cold-flushed with H2 solution (1.0 ppm) via the portal vein (PV), the hepatic artery (HA), or both (PV + HA). Functional integrity and morphological damages were then evaluated by 2-hour oxygenated reperfusion at 37°C. HyFACS significantly lowered portal venous pressure, transaminase, and high mobility group box protein 1 release compared with vehicle-treated controls (P < 0.01). Hyaluronic acid clearance was significantly higher in the HyFACS-PV and -PV + HA groups when compared with the others (P < 0.01), demonstrating the efficacy of the PV route to maintain the sinusoidal endothelia. In contrast, bile production and lactate dehydrogenase leakage therein were both significantly improved in HyFACS-HA and -PV + HA (P < 0.01), representing the superiority of the arterial route to attenuate biliary damage. Electron microscopy consistently revealed that sinusoidal ultrastructures were well maintained by portal HyFACS, while microvilli in bile canaliculi were well preserved by arterial flush. As an underlying mechanism, HyFACS significantly lowered oxidative damages, thus improving the glutathione/glutathione disulfide ratio in liver tissue. In conclusion, HyFACS significantly protected liver grafts from IRI by ameliorating oxidative damage upon reperfusion in the characteristic manner with its route of administration. Given its safety, simplicity, and cost-effectiveness, end-ischemic HyFACS may be a novel pretransplant conditioning for cold-stored donor organs.


Management of Critically Ill Adults With COVID-19.


title: [Regulation of vasomotor tone].

text: This article provides a synthesis of physiology and pathophysiology of the cardiovascular system and briefly presents the principles of regulation at the level of the whole organism and regional circulations. Decision algorithms, based on knowledge of physiology and pathophysiology are proposed. Their goal is to contribute to the improvement of cardiopulmonary bypass practice.


title: Resting-state networks show dynamic functional connectivity in awake humans and anesthetized macaques.

text: Characterization of large-scale brain networks using blood-oxygenation-level-dependent functional magnetic resonance imaging is typically based on the assumption of network stationarity across the duration of scan. Recent studies in humans have questioned this assumption by showing that within-network functional connectivity fluctuates on the order of seconds to minutes. Time-varying profiles of resting-state networks (RSNs) may relate to spontaneously shifting, electrophysiological network states and are thus mechanistically of particular importance. However, because these studies acquired data from awake subjects, the fluctuating connectivity could reflect various forms of conscious brain processing such as passive mind wandering, active monitoring, memory formation, or changes in attention and arousal during image acquisition. Here, we characterize RSN dynamics of anesthetized macaques that control for these accounts, and compare them to awake human subjects. We find that functional connectivity among nodes comprising the "oculomotor (OCM) network" strongly fluctuated over time during awake as well as anaesthetized states. For time dependent analysis with short windows (<60 s), periods of positive functional correlations alternated with prominent anticorrelations that were missed when assessed with longer time windows. Similarly, the analysis identified network nodes that transiently link to the OCM network and did not emerge in average RSN analysis. Furthermore, time-dependent analysis reliably revealed transient states of large-scale synchronization that spanned all seeds. The results illustrate that resting-state functional connectivity is not static and that RSNs can exhibit nonstationary, spontaneous relationships irrespective of conscious, cognitive processing. The findings imply that mechanistically important network information can be missed when using average functional connectivity as the single network measure.


title: The relationship between pain with walking and self-rated health 12 months following total knee arthroplasty: a longitudinal study.

text: BACKGROUND A subgroup of patients continue to report pain with walking 12 months after total knee arthroplasty (TKA). The association between walking pain and self-rated health (SRH) after TKA is not known. This prospective longitudinal study aimed to investigate the association between a comprehensive list of preoperative factors, postoperative pain with walking, and SRH 12 months after TKA. METHODS Patients (N = 156) scheduled for TKA completed questionnaires that evaluated demographic and clinical characteristics, symptoms, psychological factors, and SRH. SRH was re-assessed 12 months after TKA. Clinical variables were retrieved from medical records. Pain with walking was assessed before surgery, at 6 weeks, 3, and 12 months after TKA. Subgroups with distinct trajectories of pain with walking over time were identified using growth mixture modeling. Multiple linear regression was used to investigate the relationships between pain with walking and other factors on SRH. RESULTS Higher body mass index, a higher number of painful sites at 12 months, recurrent pain with walking group membership, ketamine use, higher depression scores, and poorer preoperative self-rated health were associated with poorer SRH 12 months after TKA. The final model was statistically significant (p = 0.005) and explained 56.1% of the variance in SRH 12 months after surgery. SRH improved significantly over time. Higher C-reactive protein levels, higher number of painful sites before surgery, higher fatigue severity, and more illness concern was associated with poorer preoperative SRH. CONCLUSIONS In patients whose walking ability decreases over time, clinicians need to assess for unreleaved pain and decreases in SRH. Additional research is needed on interventions to improve walking ability and SRH.


title: Comparison of bag-valve-mask hand-sealing techniques in a simulated model.

text: STUDY OBJECTIVE Bag-valve-mask ventilation remains an essential component of airway management. Rescuers continue to use both traditional 1- or 2-handed mask-face sealing techniques, as well as a newer modified 2-handed technique. We compare the efficacy of 1-handed, 2-handed, and modified 2-handed bag-valve-mask technique. METHODS In this prospective, crossover study, health care providers performed 1-handed, 2-handed, and modified 2-handed bag-valve-mask ventilation on a standardized ventilation model. Subjects performed each technique for 5 minutes, with 3 minutes' rest between techniques. The primary outcome was expired tidal volume, defined as percentage of total possible expired tidal volume during a 5-minute bout. A specialized inline monitor measured expired tidal volume. We compared 2-handed versus modified 2-handed and 2-handed versus 1-handed techniques. RESULTS We enrolled 52 subjects: 28 (54%) men, 32 (62%) with greater than or equal to 5 actual emergency bag-valve-mask situations. Median expired tidal volume percentage for 1-handed technique was 31% (95% confidence interval [CI] 17% to 51%); for 2-handed technique, 85% (95% CI 78% to 91%); and for modified 2-handed technique, 85% (95% CI 82% to 90%). Both 2-handed (median difference 47%; 95% CI 34% to 62%) and modified 2-handed technique (median difference 56%; 95% CI 29% to 65%) resulted in significantly higher median expired tidal volume percentages compared with 1-handed technique. The median expired tidal volume percentages between 2-handed and modified 2-handed techniques did not significantly differ from each other (median difference 0; 95% CI -2% to 2%). CONCLUSION In a simulated model, both 2-handed mask-face sealing techniques resulted in higher ventilatory tidal volumes than 1-handed technique. Tidal volumes from 2-handed and modified 2-handed techniques did not differ. Rescuers should perform bag-valve-mask ventilation with 2-handed techniques.


title: Live bird markets characterization and trading network analysis in Mali: Implications for the surveillance and control of avian influenza and Newcastle disease.

text: Live bird markets (LBMs) play an important role in the transmission of avian influenza (AI) and Newcastle disease (ND) viruses in poultry. Our study had two objectives: (1) characterizing LBMs in Mali with a focus on practices influencing the risk of transmission of AI and ND, and (2) identifying which LBMs should be targeted for surveillance and control based on properties of the live poultry trade network. Two surveys were conducted in 2009-2010: a descriptive study in all 96 LBMs of an area encompassing approximately 98% of the Malian poultry population and a network analysis study in Sikasso county, the main poultry supplying county for the capital city Bamako. Regarding LBMs' characteristics, risk factors for the presence of AI and ND viruses (being open every day, more than 2 days before a bird is sold, absence of zoning to segregate poultry-related work flow areas, waste removal or cleaning and disinfecting less frequently than on a daily basis, trash disposal of dead birds and absence of manure processing) were present in 80-100% of the LBMs. Furthermore, LBMs tended to have wide catchment areas because of consumers' preference for village poultry meat, thereby involving a large number of villages in their supply chain. In the poultry trade network from/to Sikasso county, 182 traders were involved and 685 links were recorded among 159 locations. The network had a heterogeneous degree distribution and four hubs were identified based on measures of in-degrees, out-degrees and betweenness: the markets of Medine and Wayerma and the fairs of Farakala and Niena. These results can be used to design biosecurity-improvement interventions and to optimize the prevention, surveillance and control of transmissible poultry diseases in Malian LBMs. Further studies should investigate potential drivers (seasonality, prices) of the poultry trade network and the acceptability of biosecurity and behavior-change recommendations in the Malian socio-cultural context.


title: Successful Mechanical Thrombectomy of a Middle Cerebral Artery Occlusion 14 Hours after Stroke Onset.

text: A 54-year-old patient presented with mild right-sided weakness of hand and face with a National Institutes of Health Stroke Scale (NIHSS) of 2 and occlusion of the left middle cerebral artery (MCA) in the M1 segment with a large perfusion deficit on computed tomography (CT). Due to mild neurological deficits no IVT was performed. Nine hours after symptom onset the patient gradually deteriorated with a NIHSS fluctuating between 9 and 15. MRI showed a persistent occlusion of the MCA with a large diffusion-perfusion mismatch. Immediate endovascular thrombectomy was performed 14 hours after symptom onset with complete recanalization and complete clinical recovery. Although mechanical thrombectomy is generally considered an effective alternative strategy up to 8 hours after stroke onset, selected patients with a large diffusion/perfusion mismatch and small infarct cores may benefit from an expanded therapeutic window.


title: Starting the fight in the tumor: expert recommendations for the development of human intratumoral immunotherapy (HIT-IT).

text: A European Society for Medical Oncology (ESMO)-sponsored expert meeting was held in Paris on 8 March 2018 which comprised 11 experts from academia, 11 experts from the pharmaceutical industry and 2 clinicians who were representatives of ESMO. The focus of the meeting was exclusively on the intratumoral injection/delivery of immunostimulatory agents with the aim of harmonizing the standard terms and methodologies used in the reporting of human intratumoral immunotherapy (HIT-IT) clinical trials to ensure quality assurance and avoid a blurring of the data reported from different studies. The goal was to provide a reference document, endorsed by the panel members that could provide guidance to clinical investigators, pharmaceutical companies, ethics committees, independent review boards, patient advocates and the regulatory authorities and promote an increase in the number and quality of HIT-IT clinical trials in the future. Particular emphasis was placed not only on the development of precise definitions to facilitate a better understanding between investigators but also on the importance of systematic serial biopsies as a driver for translational research and the need for the recording and reporting of data, to facilitate a better understanding of the key processes involved.


title: Cerebral Perfusion Pressure is Maintained in Acute Intracerebral Hemorrhage: A CT Perfusion Study.

text: BACKGROUND AND PURPOSE Although blood pressure reduction has been postulated to result in a fall in cerebral perfusion pressure in patients with intracerebral hemorrhage, the latter is rarely measured. We assessed regional cerebral perfusion pressure in patients with intracerebral hemorrhage by using CT perfusion source data. MATERIALS AND METHODS Patients with acute primary intracerebral hemorrhage were randomized to target systolic blood pressures of <150 mm Hg (n = 37) or <180 mm Hg (n = 36). Regional maps of cerebral blood flow, cerebral perfusion pressure, and cerebrovascular resistance were generated by using CT perfusion source data, obtained 2 hours after randomization. RESULTS Perihematoma cerebral blood flow (38.7 ± 11.9 mL/100 g/min) was reduced relative to contralateral regions (44.1 ± 11.1 mL/100 g/min, P = .001), but cerebral perfusion pressure was not (14.4 ± 4.6 minutes(-1) versus 14.3 ± 4.8 minutes(-1), P = .93). Perihematoma cerebrovascular resistance (0.34 ± 0.11 g/mL) was higher than that in the contralateral region (0.30 ± 0.10 g/mL, P < .001). Ipsilateral and contralateral cerebral perfusion pressure in the external (15.0 ± 4.6 versus 15.6 ± 5.3 minutes(-1), P = .15) and internal (15.0 ± 4.8 versus 15.0 ± 4.8 minutes(-1), P = .90) borderzone regions were all similar. Borderzone cerebral perfusion pressure was similar to mean global cerebral perfusion pressure (14.7 ± 4.7 minutes(-1), P ≥ .29). Perihematoma cerebral perfusion pressure did not differ between blood pressure treatment groups (13.9 ± 5.5 minutes(-1) versus 14.8 ± 3.4 minutes(-1), P = .38) or vary with mean arterial pressure (r = -0.08, [-0.10, 0.05]). CONCLUSIONS Perihematoma cerebral perfusion pressure is maintained despite increased cerebrovascular resistance and reduced cerebral blood flow. Aggressive antihypertensive therapy does not affect perihematoma or borderzone cerebral perfusion pressure. Maintenance of cerebral perfusion pressure provides physiologic support for the safety of blood pressure reduction in intracerebral hemorrhage.


Un nouveau coronavirus venu du Moyen-Orient.


title: Laparoscopic spleen-preserving distal pancreatectomy: the technique must suit the lesion.

text: Splenic preservation is currently recommended during minimally invasive surgery for benign tumors of the distal pancreas. The aim of this study was to evaluate the outcomes of patients undergoing laparoscopic spleen-preserving distal pancreatectomy, with particular attention paid to the technique used for spleen preservation (splenic vessel ligation vs preservation). A review of consecutive patients who underwent laparoscopic distal pancreatectomy with the intention of splenic preservation was conducted. Patient demographics, operative data, and outcomes were collected and analyzed. Fifty-five consecutive patients underwent laparoscopic distal pancreatectomy with the intention of splenic preservation; 5 required splenectomy (9 %). Of the remaining 50 patients, 31 (62 %) had splenic vessel ligation, and 19 (38 %) had vessel preservation. Patient demographics and tumor size were similar. The vessel ligation group had significantly more pancreas removed (95 vs 52 mm, P < 0.001) and longer operative times (256 vs 201 min, P = 0.008). Postoperative outcomes, complication rates, and splenic viability were similar between groups. Laparoscopic spleen-preserving distal pancreatectomy is a safe operation with a high rate of success (91 %). Vessel ligation was the chosen technical strategy for lesions that required resection of a greater length of pancreas. We found no advantage to either technique with respect to outcomes and splenic preservation. Operative approach should reflect technical considerations including location in the pancreas.


title: Transvaginal specimen extraction in a laparoscopic anterior resection of a sigmoid colon neoplasia with en bloc right salpingo-oophorectomy.

text: Laparoscopic colorectal surgery has well-known benefits. However, an abdominal incision, albeit much smaller than conventional surgery, is still needed. A transvaginal extraction of a sigmoid colon neoplasia with en bloc salpingo-oophorectomy and colorectal mechanical anastomosis is described. The technique is feasible and safe. The excellent recovery of the 86-year-old patient shows the potential future of the natural orifices endoscopic surgery.


title: Robotic-assisted treatment of celiac artery compression syndrome: report of a case and review of the literature.

text: BACKGROUND The surgical management of celiac artery compression syndrome (CACS) is controversial. Controversies include the appropriate surgical technique, the surgical approach, and the utility of postoperative stents. The literature is reviewed, and a case of CACS is presented in which a robotic-assisted division of the median arcuate ligament (MAL) was performed. METHODS Robotic-assisted treatment of celiac artery syndrome was carried out using six (five 1 cm and one 2 cm) abdominal incisions. The robotic device was used to expose the aorta and celiac artery and divide the median arcuate ligament. RESULTS Postoperatively, the patient's postprandial abdominal pain subsided. On 16 month follow-up, the patient was doing well, tolerated an unrestricted diet without symptoms, and exhibited weight gain. CONCLUSION This case is the second reported in the literature and demonstrates that the robotic approach to division of the MAL is feasible, safe, and efficacious.


title: Changes in cardiac function and cerebral blood flow in relation to peri/intraventricular hemorrhage in extremely preterm infants.

text: OBJECTIVE To investigate whether changes in cardiac function and cerebral blood flow (CBF) precede the occurrence of peri/intraventricular hemorrhage (P/IVH) in extremely preterm infants. STUDY DESIGN In this prospective observational study, 22 preterm infants (gestational age 25.9 ± 1.2 weeks; range 23-27 weeks) were monitored between 4 and 76 hours after birth. Cardiac function and changes in CBF and P/IVH were assessed by ultrasound every 12 hours. Changes in CBF were also followed by continuous monitoring of cerebral regional oxygen saturation (rSO2) and by calculating cerebral fractional oxygen extraction. RESULTS Five patients developed P/IVH (1 patient grade II and 4 patients grade IV). Whereas measures of cardiac function and CBF remained unchanged in neonates without P/IVH, patients with P/IVH tended to have lower left ventricular output and had lower left ventricle stroke volume and cerebral rSO2 and higher cerebral fractional oxygen extraction during the first 12 hours of the study. By 28 hours, these variables were similar in the 2 groups and myocardial performance index was lower and middle cerebral artery mean flow velocity higher in the P/IVH group. P/IVH was detected after these changes occurred. CONCLUSIONS Cardiac function and CBF remain stable in very preterm neonates who do not develop P/IVH during the first 3 postnatal days. In very preterm neonates developing P/IVH during this period, lower systemic perfusion and CBF followed by an increase in these variables precede the development of P/IVH. Monitoring cardiac function and cerebral rSO2 may identify infants at higher risk for developing P/IVH before the bleeding occurs.


title: Adaptation of Coronavirus (COVID-19) protocols to a Parisian maternity unit during the 2020 pandemic: a managerial perspective.

text: The COVID-19 pandemic overwhelmed health services in France during March 2020 and to cope service delivery was reduced in most disciplines. However as this was impossible for Obstetrics, COVID-19 infection had to be added to existing clinical care pathways in Necker Children's Hospital. This was further complicated by increasing number pregnancies affected by infection in addition to scientific uncertainty about the virus. Procedures based on scientific recommendations from French and international authorities were adapted to maternity care and regularly updated as the situation progressed. Weekly medical manager team meetings discussed the evolving clinical situation and initial evaluation found our procedures worked well. However, it was necessary to adapt the policy as the epidemic progressed rapidly. Shortly after the 16th March, traffic control bundling was implemented in anticipation of a dramatic increase in pregnant women affected by infection and to better protect staff. By the 18th April, with the peak of the COVID-19 epidemic receding, protocols were again readjusted to meet new service delivery requirements. Although a full debrief is yet to occur, from an operational level perspective, staff response was more than satisfactory. While preventing another epidemic maybe impossible, this experience will improve our resilience in the future.


title: Use of flow diverters in the treatment of unruptured saccular aneurysms of the anterior cerebral artery.

text: BACKGROUND Few publications have dealt exclusively with the use of flow diverter stents for the treatment of aneurysms of the anterior cerebral artery (ACA). OBJECTIVE To determine the efficacy of flow-diverting stents in the treatment of small, unruptured aneurysms of the ACA. METHODS We retrospectively reviewed our database of prospectively collected information for all patients treated with flow diversion for an unruptured saccular aneurysm of the ACA between September 2009 and July 2016. The aneurysm fundus size, neck size, number and type of flow-diverting stent (FDS), complications, and follow-up data were recorded. RESULTS In total 26 patients, with 27 aneurysms were identified that matched our inclusion criteria (11 male and 15 female). The average age of the patients was 59.3 years (range 27-77 years). All patients, except one, had a single aneurysm affecting the ACA. Fourteen aneurysms were located on the left (51.9%). The average aneurysm fundus size was 2.9 mm (range 2-6 mm). Twenty patients had follow-up angiographic studies. In total, 16 aneurysms were completely excluded, 1 aneurysm showed a very small remnant, and no follow-up angiographic data are available for the remaining patients. One patient had a treatment-related complication. CONCLUSIONS Treatment of aneurysms arising from the ACA with flow diverters is technically feasible and carries a high degree of success with low complication rate.


COVID-19 in gastroenterology and hepatology: Living with the realities of a historic 21st century pandemic.