title: Distinct functions of AKT isoforms in breast cancer: a comprehensive review.

text: BACKGROUND AKT, also known as protein kinase B, is a key element of the PI3K/AKT signaling pathway. Moreover, AKT regulates the hallmarks of cancer, e.g. tumor growth, survival and invasiveness of tumor cells. After AKT was discovered in the early 1990s, further studies revealed that there are three different AKT isoforms, namely AKT1, AKT2 and AKT3. Despite their high similarity of 80%, the distinct AKT isoforms exert non-redundant, partly even opposing effects under physiological and pathological conditions. Breast cancer as the most common cancer entity in women, frequently shows alterations of the PI3K/AKT signaling. MAIN CONTENT A plethora of studies addressed the impact of AKT isoforms on tumor growth, metastasis and angiogenesis of breast cancer as well as on therapy response and overall survival in patients. Therefore, this review aimed to give a comprehensive overview about the isoform-specific effects of AKT in breast cancer and to summarize known downstream and upstream mechanisms. Taking account of conflicting findings among the studies, the majority of the studies reported a tumor initiating role of AKT1, whereas AKT2 is mainly responsible for tumor progression and metastasis. In detail, AKT1 increases cell proliferation through cell cycle proteins like p21, p27 and cyclin D1 and impairs apoptosis e.g. via p53. On the downside AKT1 decreases migration of breast cancer cells, for instance by regulating TSC2, palladin and EMT-proteins. However, AKT2 promotes migration and invasion most notably through regulation of β-integrins, EMT-proteins and F-actin. Whilst AKT3 is associated with a negative ER-status, findings about the role of AKT3 in regulation of the key properties of breast cancer are sparse. Accordingly, AKT1 is mutated and AKT2 is amplified in some cases of breast cancer and AKT isoforms are associated with overall survival and therapy response in an isoform-specific manner. CONCLUSIONS Although there are several discussed hypotheses how isoform specificity is achieved, the mechanisms behind the isoform-specific effects remain mostly unrevealed. As a consequence, further effort is necessary to achieve deeper insights into an isoform-specific AKT signaling in breast cancer and the mechanism behind it.


Cost implications of duplicative influenza polymerase chain reaction testing during the 2013-2014 influenza season: the price of certainty.


title: Mechanical thrombectomy in children and adolescents: report of five cases and literature review.

text: Background Paediatric arterial ischaemic stroke is an important cause of morbidity and mortality among children. Currently, there are no recommendations regarding mechanical thrombectomy in children despite overwhelming evidence of improved outcomes in adults. Therefore, the need for individual case reports and case series is important to highlight potential advantages and disadvantages in this approach. Case descriptions We retrospectively searched our prospectively maintained database of patients undergoing mechanical thrombectomy for ischaemic stroke. We describe five children, aged between 7 and 17, who underwent mechanical thrombectomy for acute ischaemic stroke. We provide an account of their clinical presentations, operative treatment and postoperative outcome. Discussion Mechanical thrombectomy in children, especially older children, can be performed safely and with existing devices. Although a randomised controlled trial would provide compelling evidence of the potential advantages to this technique, the lack of this should not prevent the use of this procedure by trained neurointerventionists.


title: Clinical Characteristics and Outcomes of COVID-19 in Solid Organ Transplant Recipients: A Case-Control Study.

text: Solid organ transplant recipients (SOTr) with COVID-19 are expected to have poorer outcomes compared to non-transplant patients due to immunosuppression and comorbidities. The clinical characteristics of 47 SOTr (38 kidneys and 9 non-kidney organs) were compared to 100 consecutive hospitalized non-transplant controls. 12/47 SOTr managed as outpatients were subsequently excluded from the outcome analyses to avoid potential selection bias. Chronic kidney disease (89% vs. 57% p=0.0007), diabetes (66% vs. 33% p=0.0007), and hypertension (94% vs. 72% p=0.006) were more common in the 35 hospitalized SOTr compared to controls. Diarrhea (54% vs. 17%, p<0.0001) was more frequent in SOTr. Primary composite outcome (escalation to ICU, mechanical ventilation, or in-hospital all-cause mortality) was comparable between SOTr and controls (40% vs. 48%, OR 0.72 CI [0.33-1.58] p=0.42), despite more comorbidities in SOTr. Acute kidney injury (AKI) requiring renal replacement therapy occurred in 20% of SOTr compared to 4% of controls (OR 6 CI [1.64-22] p=0.007). Multivariate analysis demonstrated that increasing age and clinical severity was associated with mortality. Transplant status itself was not associated with mortality.


Ebola: DRC's 10th outbreak is declared over.


title: Esophageal reconstruction: posterior mediastinal or retrosternal route.

text: BACKGROUND Although posterior mediastinal (PM) route and retrosternal (RS) route have been used for reconstruction after minimally invasive esophagectomy (MIE), the optimal route remains controversial. This study reviewed our experiences with McKeown MIEs for esophageal cancer and aimed to investigate which route was better for esophageal reconstruction. MATERIALS AND METHODS From December 2011 to December 2013, 103 patients who underwent McKeown MIE and esophageal reconstruction by PM or RS routes were reviewed. The decision regarding which approach was appropriated mainly depended on the first surgeon's preference and experience. Baseline demographics, operative, and postoperative data of the patients were analyzed. RESULTS Fifty-six and forty-seven patients receiving PM and RS route reconstruction were reviewed, respectively. Shorter operation time (P = 0.001), less blood loss (P = 0.029), and longer route length (P < 0.001) were observed in PM route compared with RS route. No difference was observed in the resection type, harvested lymph node, intensive care unit and hospital stay, postoperative complications, and in-hospital mortality between the two routes (all P > 0.05). CONCLUSIONS Both RS route and PM route were safe and effective. PM route was associated with shorter operation time, less blood loss, but longer route length compared with RS route.


title: Phenylephrine versus ephedrine on cerebral perfusion during carotid endarterectomy (PEPPER): study protocol for a randomized controlled trial.

text: BACKGROUND Intraoperative arterial hypotension can lead to severe complications in patients undergoing carotid endarterectomy, in particular if cerebral auto-regulation is impaired. Short-acting agents, such as phenylephrine or ephedrine, commonly used to correct intra-operative hypotension, have different hemodynamic effects. Recently, it was reported that, in healthy anesthetized subjects with intact cerebral auto-regulation, frontal lobe cerebral tissue oxygenation declined after phenylephrine bolus administration, while it was preserved after ephedrine use (Br J Anaesth 107:209-217, 2011; Neurocrit Care 12:17-23, 2010). However, the effect of both agents in patients undergoing carotid endarterectomy is unknown. The aim of this study is to assess the effect of two routinely used vasopressors (phenylephrine and ephedrine) on the cerebral hemodynamics during carotid endarterectomy. METHODS/DESIGN Patients undergoing carotid endarterectomy will be prospectively included and randomized for correction of intraoperative hypotension with either phenylephrine (50 to 100 μg) or ephedrine (5 to 10 mg). If hypotension persists for more than five minutes after treatment, the patient will be classified as a non-responder and escape medication as preferred by the anesthesiologist will be administered. Changes in cerebral hemodynamics will be quantified by changes in transcranial Doppler-derived middle cerebral artery blood velocity and near infra-red spectroscopy-derived frontal lobe cerebral tissue oxygenation, when intra-operative hypotension is treated with phenylephrine or ephedrine in patients who undergo carotid endarterectomy with or without an adequate functioning cerebral auto-regulation.To quantify whether the intra-operative cerebral auto-regulation is impaired or not, a decrease in breathing frequency from the normal 12 breaths per minute to 6 breaths per minute for an episode of three minutes will be performed. DISCUSSION Phenylephrine and ephedrine are two of the most commonly used short-acting agents to increase blood pressure in clinical anesthesiologic practice. Monitoring of middle cerebral artery blood velocity with transcranial Doppler and frontal lobe cerebral tissue oxygenation with near infra-red spectroscopy are part of the standard of care. Furthermore, there are no reports that the three-minute modification in breathing frequency described in the "intervention"-section is harmful. Therefore, the risks for participating patients are negligible and the burden minimal. TRIAL REGISTRATION Clinical trials.gov: NCT01451294.


title: The molecular virology of Coronaviruses.

text: Few human pathogens have been the focus of as much concentrated worldwide attention as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), the cause of COVID-19. Its emergence into the human population and ensuing pandemic came on the heels of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), two other highly pathogenic coronavirus spillovers, which collectively have reshaped our view of a virus family previously associated primarily with the common cold. It has placed intense pressure on the collective scientific community to develop therapeutics and vaccines, whose engineering relies on a detailed understanding of coronavirus biology. Here, we present the molecular virology of coronavirus infection, including its entry into cells, its remarkably sophisticated gene expression and replication mechanisms, its extensive remodeling of the intracellular environment and its multi-faceted immune evasion strategies. We highlight aspects of the viral lifecycle that may be amenable to antiviral targeting as well as key features of its biology that await discovery.


Re: Chiriac et al. Experience of using the bioresorbable copolyester poly(DL-lactide-ε-caprolactone) nerve conduit guide Neurolac™ for nerve repair in peripheral nerve defects: report on a series of 28 lesions. J Hand Surg Eur. 2011, 37: 342-9.


title: Cannula malposition during antegrade cerebral perfusion for aortic surgery: role of cerebral oximetry.

text: PURPOSE To describe the use of cerebral oximetry to detect a lack of right cerebral perfusion resulting from a malpositioned catheter used for antegrade cerebral perfusion during deep hypothermic circulatory arrest (DHCA). The simple corrective surgical adjustment that followed averted a potentially serious complication. CLINICAL FEATURES A 57-yr-old male with a type-A aortic dissection undergoing DHCA required antegrade cerebral perfusion for cerebral protection. Catheters were placed accordingly in the left common carotid and brachiocephalic arteries. Whereas frontal cerebral oximetry immediately improved on the left, it did not improve on the right. It was immediately suspected that the tip of the brachiocephalic cannula had advanced into the right subclavian artery, thus depriving the right common carotid artery of blood flow. The problem resolved upon slight withdrawal of the cannula. CONCLUSION Vigilance in anesthesia should not stop during DHCA or cardiopulmonary bypass. Cerebral oximetry may provide important information leading to actions that improve brain protection. Vigilances proved important in this case where the cannula tip used for antegrade cerebral perfusion was advanced too far into the right subclavian artery.


title: Preparing Hospitals for Coronavirus (COVID-19).

text: The COVID-19 virus has generated worldwide attention due to its recent discovery and rapid spread. There are currently almost 2 million confirmed cases of COVID-19 worldwide of which about 117,000 patients have died (WHO). March has seen fast rises in the number of cases in Italy, Spain and the US, which has focused the need for countries medical systems to contain the virus and prevent its spread. Currently the US has over 500,000 cases, the largest number of any country in the world.This has resulted in hospitals around the world producing action plans to isolate and treat suspected COVID-19 patients. In this exclusive interview for Hospital Practice Dr. Edward Jasper of Jefferson Hospitals discusses how his hospital has dealt with outbreaks in the past as well as how it is now preparing for COVID-19.Interview with Edward Jasper by Mike Gregg, Editor.


title: Psychometric properties of the Turkish version of the Bullying and Cyber Bullying Scale for Adolescents (BCS-A).

text: This study aimed to examine the psychometric properties of Bullying and Cyber-bullying Scale for Adolescents (BCS-A). The sample of the study was consisted of 600 adolescents, aged between 12 and 18 years. The data were collected with the Adolescent Identifier Form and Bullying and Cyber Bullying Scale for Adolescents (BCS-A). BCS-A was suitable for Turkish language, Content Validity Ratio (CVR) values were above 0.733. In the victimization subscale, all factor loads were above 0.630 and in the bullying subscale, all factor loads were above 0.679. The Cronbach's Alpha values for the victimization subscale ranged between 0.606 and 0.806, and the perpetration subscale ranged between 0.616 and 0.815. There was no difference between the pre- and post-test values and Intraclass Correlation Coefficients (ICC) values were 0.559 and above. BCS-A was found to be a valid and reliable instrument for determining bullying and cyber bullying among adolescents aged between 12 and 18 years. In conclusion, the scale may be suggested to be used as an assessment tool in new studies to determine bullying and cyber bullying among adolescents aged between 12 and 18 years.


title: What is the long term impact of voucher scheme on primary care? Findings from a repeated cross sectional study using propensity score matching.

text: BACKGROUND Vouchers are increasingly used as a demand-side subsidy to reduce financial hardship and improve quality of services. Elderly Healthcare Voucher Scheme has been introduced by the Hong Kong Government since 2009 to provide subsidy to elderly aged 65 and above to visit ten different types of private primary care providers for curative, preventive and chronic disease management. Several enhancements have been made over the past few years. This paper (as part of an evaluation study of this unique healthcare voucher scheme) aims to assess the long term impact of the voucher scheme in encouraging the use of primary care services. METHODS Two rounds of cross-sectional survey among elderly in Hong Kong were conducted in 2010 and 2016. Propensity score matching and analysis were used to compare changes in perception and usage of vouchers over time. RESULTS 61.5% of respondents in 2016 agreed "the scheme encourages me to use more private primary care services", a significant increase from 36.2% in 2010. Among those who agreed in 2016, the majority thought the voucher scheme would encourage them to use acute services (90.3%) in the private sector, rather than preventive care (40.3%) and chronic disease management (12.2%). Respondents also reported that their current usual choice of care was visiting "both public and private doctors" (61.9%), representing a significant increase (up from 48.4%) prior to their use of voucher. CONCLUSIONS The voucher scheme has encouraged the use of more private care services, particularly acute services rather than disease prevention or management of chronic disease. However, there needs to be caution that the untargeted and open-ended nature of voucher scheme could result in supply-induced demand which would affect long term financial sustainability. The dual utilization of health services in both the public and private sector may also compromise continuity and quality of care. The design of the voucher needs to be more specific, targeting prevention and chronic disease management rather than unspecified care which is mainly acute and episodic in order to maximize service delivery capacity as a whole for equitable access in universal health coverage and to contribute to a sustainable financing system.


title: Impact of imitation processes on the effectiveness of ring vaccination.

text: Ring vaccination can be a highly effective control strategy for an emerging disease or in the final phase of disease eradication, as witnessed in the eradication of smallpox. However, the impact of behavioural dynamics on the effectiveness of ring vaccination has not been explored in mathematical models. Here, we analyze a series of stochastic models of voluntary ring vaccination. Contacts of an index case base vaccinating decisions on their own individual payoffs to vaccinate or not vaccinate, and they can also imitate the behaviour of other contacts of the index case. We find that including imitation changes the probability of containment through ring vaccination considerably. Imitation can cause a strong majority of contacts to choose vaccination in some cases, or to choose non-vaccination in other cases-even when the equivalent solution under perfectly rational (non-imitative) behaviour yields mixed choices. Moreover, imitation processes can result in very different outcomes in different stochastic realizations sampled from the same parameter distributions, by magnifying moderate tendencies toward one behaviour or the other: in some realizations, imitation causes a strong majority of contacts not to vaccinate, while in others, imitation promotes vaccination and reduces the number of secondary infections. Hence, the effectiveness of ring vaccination can depend significantly and unpredictably on imitation processes. Therefore, our results suggest that risk communication efforts should be initiated early in an outbreak when ring vaccination is to be applied, especially among subpopulations that are heavily influenced by peer opinions.


title: Totally laparoscopic versus laparoscopic-assisted total gastrectomy for upper and middle gastric cancer: a single-unit experience of 253 cases with meta-analysis.

text: BACKGROUND Laparoscopic-assisted total gastrectomy (LATG) is the most commonly used methods of laparoscopic gastrectomy for upper and middle gastric cancer. However, totally laparoscopic total gastrectomy (TLTG) is unpopular because reconstruction is difficult, especially for the intracorporeal esophagojejunostomy. We adopted TLTG with various types of intracorporeal esophagojejunostomy. In this study, we compared LATG and TLTG to evaluate their outcomes. METHODS From March 2006 to September 2015, 253 patients with upper and middle gastric cancer underwent laparoscopic total gastrectomy (LTG), 145 patients underwent LATG, and 108 patients underwent TLTG. The clinicopathological characteristics and postoperative outcomes were retrospectively compared between the two groups. Furthermore, a systematic review and meta-analysis were conducted. RESULTS The operation time and estimated blood loss were similar between the groups. There were no significant differences in first flatus, diet initiation, and postoperative hospital stay. The surgical complication rates were 17.2% (25/145) and 13.9% (15/108) in the LATG and TLTG groups, respectively. The meta-analysis also revealed no significant differences in the operation time, estimated blood loss, time to first flatus, length of hospital stay, overall, and anastomosis-related complications among the groups. CONCLUSIONS TLTG is a feasible choice for gastric cancer patients, with comparable results to the LATG approach.


title: Validation and verification of the Abbott RealTime SARS-CoV-2 assay analytical and clinical performance.

text: BACKGROUND High-throughput assays for the SARS-CoV-2 virus are critical to increasing test capacity and slowing the spread of COVID-19. Abbott Molecular developed and received emergency use authorization (EUA) to deploy the new RealTime SARS-CoV-2 assay, run on the automated m2000sp/rt system. OBJECTIVE To evaluate analytical and clinical performance of the RealTime SARS-CoV-2 assay compared to the SARS-CoV-2 CDC-based laboratory developed test (LDT) in clinical use by the University of Washington Clinical Virology Laboratory (UW Virology). METHODS RealTime SARS-CoV-2 assay limit of detection (LOD) was evaluated by testing two dilution panels of 60 replicates each. Cross-reactivity was evaluated by testing 24 clinical samples positive for various non‒SARS-CoV-2 respiratory viruses. Clinical performance was evaluated using 30 positive and 30 negative SARS-CoV-2 clinical samples previously tested using the UW Virology SARS-CoV-2 LDT. RESULTS Exceeding the 100 copies/mL LOD reported in the RealTime SARS-CoV-2 assay EUA product insert, 19 of 20 replicates were detected at 50 copies/mL and 16 of 20 replicates were detected at 25 copies/mL. All clinical samples positive for 24 non‒SARS-CoV-2 respiratory viruses were SARS-CoV-2 negative on the RealTime SARS-CoV-2 assay. The assay had high sensitivity (93%) and specificity (100%) for detecting SARS-CoV-2 in clinical samples. Two positive samples that tested negative with the RealTime SARS-CoV-2 assay had cycle numbers of 35.94 or greater and required dilution prior to testing. One of these samples was also inconclusive on the SARS-CoV-2 LDT. CONCLUSION The RealTime SARS-CoV-2 assay is acceptable for clinical use. With the high-throughput, fully automated m2000 system, this assay will accelerate the pace of SARS-CoV-2 testing.


title: Near-Infrared Transcranial Radiation for Major Depressive Disorder: Proof of Concept Study.

text: Transcranial near-infrared radiation (NIR) is an innovative treatment for major depressive disorder (MDD), but clinical evidence for its efficacy is limited. Our objective was to investigate the tolerability and efficacy of NIR in patients with MDD. We conducted a proof of concept, prospective, double-blind, randomized study of 6 sessions of NIR versus sham treatment for patients with MDD, using a crossover design. Four patients with MDD with mean age 47 ± 14 (SD) years (1 woman and 3 men) were exposed to irradiance of 700 mW/cm(2) and a fluence of 84 J/cm(2) for a total NIR energy of 2.40 kJ delivered per session for 6 sessions. Baseline mean HAM-D17 scores decreased from 19.8 ± 4.4 (SD) to 13 ± 5.35 (SD) after treatment (t = 7.905; df = 3; P = 0.004). Patients tolerated the treatment well without any serious adverse events. These findings confirm and extend the preliminary data on NIR as a novel intervention for patients with MDD, but further clinical trials are needed to better understand the efficacy of this new treatment. This trial is registered with ClinicalTrials.gov NCT01538199.


title: Evaluation of the pharmacokinetics, food effect, pharmacodynamics, and tolerability of DA-1229, a dipeptidyl peptidase IV inhibitor, in healthy volunteers: first-in-human study.

text: BACKGROUND Inhibitors of dipeptidyl peptidase (DPP) IV are a class of oral hypoglycemic agents that increase glucagon-like peptide-1 (GLP-1) levels by inhibiting its degradation. OBJECTIVE This study evaluated the pharmacokinetics, pharmacodynamics, and tolerability of DA-1229, which is a newly developed DPP IV inhibitor. This study was planned as part of a product development project at the request of the Korean regulatory agency. METHODS A 7 parallel arm dose-escalation study was conducted in healthy Korean male volunteers. A single oral dose of DA-1229 or placebo was given to 10 subjects (8 active + 2 placebo) in each dose group of 1.25, 2.5, 5, 10, 20, 40, or 60 mg. To assess the effects of food, the subjects in the 10-mg dose group received a single dose of DA-1229 10 mg after a high-fat meal, crossing over from the administration of DA-1229 under a fasting state, after a 7-day washout period. Serial blood samples were collected up to 120 hours after drug administration for pharmacokinetic analysis and the assessment of DPP IV activity, and blood samples were collected up to 2 hours after each meal until the next morning of drug administration to evaluate active GLP-1, glucose, and insulin levels. RESULTS Seventy-two subjects, aged 20 to 39 years and weighing 52.1 to 79.8 kg, participated in this study. Twenty-one adverse events were reported; all were mild, and all subjects recovered spontaneously. DA-1229 reached a peak at 3.0 to 5.5 hours after a single oral dose and the concentrations declined, with a terminal t(½) from 32.5 to 39.8 hours. The %CV of C(max) and AUC(0-last) ranged from 11.1% to 54.6%. Dose-proportional pharmacokinetics were confirmed within the dose range by using a linear regression analysis, and the 95% CIs of the slope of the log-transformed C(max) and AUC(0-last) included 1.0. The pharmacokinetics of DA-1229 were unchanged by food. The degree of DPP IV inhibition was dependent on the dose, and groups receiving ≥10 mg exhibited >80% DPP IV inhibition for >24 hours. The %CV of the time of the last quantifiable concentration ranged from 4.6% to 15.2%. C(max) of active GLP-1 was achieved at 30 minutes after meal intake. The active GLP-1 levels were enhanced in groups receiving ≥5 mg. There were no changes in the glucose and insulin levels after DA-1229 administration. CONCLUSIONS DA-1229 was well tolerated within the dose range of 1.25 to 60 mg. DA-1229 pharmacokinetics suggested dose proportionality, and dose-dependent DPP IV inhibition was exhibited. ClinicalTrials.gov identifier: NCT00961025.


title: Identification of H209 as Essential for pH 8-Triggered Receptor-Independent Syncytium Formation by S Protein of Mouse Hepatitis Virus A59.

text: The spike glycoprotein (S) of murine coronavirus mouse hepatitis virus (MHV) strain A59 uses murine carcinoembryonic antigen-related cell adhesion molecule 1a as its receptor for cell entry, but S protein can also be triggered in the absence of receptor by pH 8.0 alone at 37°C. The mechanism by which conformational changes of this S glycoprotein can be triggered by pH 8.0 has not yet been determined. Here, we show that MHV-A59 S protein is triggered by pH 8.0 at 37°C to induce receptor-independent syncytium (RIS) formation on 293T cells, and that the conformational changes in S proteins triggered by pH 8.0 are very similar to those triggered by receptor binding. We systemically mutated each of 15 histidine residues in S protein and found that H209 is essential for pH 8.0-triggered RIS formation, while H179, H441, H643, and H759 also play important roles in this process. Replacement of H209 with Ala had no effect on receptor binding, but in murine 17Cl.1 cells mutant H209A MHV-A59 showed delayed growth kinetics and was readily outcompeted by wild-type virus when mixed together, indicating that the H209A mutation caused a defect in virus fitness. Finally, the H209A mutation significantly increased the thermostability of S protein in its prefusion conformation, which may raise the energy barrier for conformational change of S protein required for membrane fusion and lead to a decrease in virus fitness in cell culture. Thus, MHV-A59 may have evolved to lower the stability of its S protein in order to increase virus fitness.IMPORTANCE Enveloped viruses enter cells through fusion of viral and cellular membranes, and the process is mediated by interactions between viral envelope proteins and their host receptors. In the prefusion conformation, viral envelope proteins are metastable, and activation to the fusion conformation is tightly regulated, since premature activation would lead to loss of viral infectivity. The stability of viral envelope proteins greatly influences their activation and virus fitness. Here, we report that, similar to the A82V mutation in Ebola glycoprotein, in the S glycoprotein of murine coronavirus MHV-A59, the histidine residue at position of 209 significantly affects the thermal stability of the S protein, determines whether S protein can be activated at 37°C by either pH 8.0 alone or by receptor binding, and affects viral fitness in cell culture. Thus, the spike glycoprotein of MHV-A59 has evolved to retain histidine at position 209 to optimize virus fitness.


title: In vivo characterization of a new type of biodegradable starch microsphere for transarterial embolization.

text: Transarterial embolization is an established minimally invasive treatment for solid tumors. Unintended inflammation, foreign body reactions and ischemia-triggered neoangiogenesis are clinical drawbacks of permanent embolic materials. The aim of the current study was to characterize a new type of biodegradable starch microsphere with regard to angiographic and histopathological features such as patterns of acute arterial occlusion as well as induction of tissue necrosis, microsphere biodegradation, and inflammation and foreign body reactions during follow-up. Key characteristics of both biodegradable prototypes (L1 and L2; prototype groups) were as follows: microspheres are biodegradable by serum α-amylase, produced from chemically crosslinked potato starch to different extents, in a diameter range of ∼300-800 µm, differing in size distribution and featuring a microsphere deformation of ∼1%. In vivo transarterial embolization with L1 and L2, while applying clinical standard techniques, was performed and compared with clinically established permanent microspheres (Embosphere®500-700 and Embosphere®700-900; control groups). Twenty-four pig kidneys were embolized with the different embolic materials by following the study protocol, and there were no technical failures or complications. Parenchymal necrosis with interstitial calcification was observed in all kidneys independent of the type of embolic material used. Compared with the permanent embolic materials, biodegradable microspheres showed complete (L1) or partial (L2) biodegradation within one week after transarterial embolization, and induced a comparable (L1) or a lower (L2) degree of arterial wall necrosis and a lower degree of inflammation and foreign body reactions. In conclusion, the presented new type of biodegradable microsphere is promising, and could be further evaluated in terms of clinical translation.


title: Implementation of clinical practice guidelines for ventilator-associated pneumonia: a multicenter prospective study.

text: OBJECTIVE Ventilator-associated pneumonia is an important cause of morbidity and mortality in critically ill patients. Evidence-based clinical practice guidelines for the prevention, diagnosis, and treatment of ventilator-associated pneumonia may improve outcomes, but optimal methods to ensure implementation of guidelines in the intensive care unit are unclear. Hence, we determined the effect of educational sessions augmented with reminders, and led by local opinion leaders, as strategies to implement evidence-based ventilator-associated pneumonia guidelines on guideline concordance and ventilator-associated pneumonia rates. DESIGN Two-year prospective, multicenter, time-series study conducted between June 2007 and December 2009. SETTING Eleven ICUs (ten in Canada, one in the United States); five academic and six community ICUs. PATIENTS At each site, 30 adult patients mechanically ventilated >48 hrs were enrolled during four data collection periods (baseline, 6, 15, and 24 months). INTERVENTION Guideline recommendations for the prevention, diagnosis, and treatment of ventilator-associated pneumonia were implemented using a multifaceted intervention (education, reminders, local opinion leaders, and implementation teams) directed toward the entire multidisciplinary ICU team. Clinician exposure to the intervention was assessed at 6, 15, and 24 months after the introduction of this intervention. MEASUREMENTS AND MAIN RESULTS The main outcome measure was aggregate concordance with the 14 ventilator-associated pneumonia guideline recommendations. One thousand three hundred twenty patients were enrolled (330 in each study period). Clinician exposure to the multifaceted intervention was high and increased during the study: 86.7%, 93.3%, 95.8%, (p < .001), as did aggregate concordance (mean [SD]): 50.7% (6.1), 54.4% (7.1), 56.2% (5.9), 58.7% (6.7) (p = .007). Over the study period, ventilator-associated pneumonia rates decreased (events/330 patients): 47 (14.2%), 34 (10.3%), 38 (11.5%), 29 (8.8%) (p = .03). CONCLUSIONS A 2-yr multifaceted intervention to enhance ventilator-associated pneumonia guideline uptake was associated with a significant increase in guideline concordance and a reduction in ventilator-associated pneumonia rates.


title: Early Fluid Overload Prolongs Mechanical Ventilation in Children With Viral-Lower Respiratory Tract Disease.

text: OBJECTIVES Viral-lower respiratory tract disease is common in young children worldwide and is associated with high morbidity. Acute respiratory failure due to viral-lower respiratory tract disease necessitates PICU admission for mechanical ventilation. In critically ill patients in PICU settings, early fluid overload is common and associated with adverse outcomes such as prolonged mechanical ventilation and increased mortality. It is unclear, however, if this also applies to young children with viral-lower respiratory tract disease induced acute respiratory failure. In this study, we aimed to investigate the relation of early fluid overload with adverse outcomes in mechanically ventilated children with viral-lower respiratory tract disease in a retrospective dataset. DESIGN Retrospective cohort study. SETTING Single, tertiary referral PICU. PATIENTS One hundred thirty-five children (< 2 yr old) with viral-lower respiratory tract disease requiring mechanical ventilation admitted to the PICU of the Academic Medical Center, Amsterdam between 2008 and 2014. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The cumulative fluid balance on day 3 of mechanical ventilation was compared against duration of mechanical ventilation (primary outcome) and daily mean oxygen saturation index (secondary outcome), using uni- and multivariable linear regression. In 132 children, the mean cumulative fluid balance on day 3 was + 97.9 (49.2) mL/kg. Higher cumulative fluid balance on day 3 was associated with a longer duration of mechanical ventilation in multivariable linear regression (β = 0.166; p = 0.048). No association was found between the fluid status and oxygen saturation index during the period of mechanical ventilation. CONCLUSIONS Early fluid overload is an independent predictor of prolonged mechanical ventilation in young children with viral-lower respiratory tract disease. This study suggests that avoiding early fluid overload is a potential target to reduce duration of mechanical ventilation in these children. Prospective testing in a clinical trial is warranted to support this hypothesis.


title: Long-term use of inhaled corticosteroids and risk of upper respiratory tract infection in chronic obstructive pulmonary disease: a meta-analysis.

text: Recent studies have suggested that inhaled corticosteroids (ICS) may be associated with higher risks of tuberculosis and pneumonia in patients with COPD. However, it is not known whether ICS increases the risk of upper respiratory tract infection (URTI). Aim of this study was to explore the relationship between ICS and URTI. Through a comprehensive literature search of PubMed, EMBASE, Cochrane Library, and Google Scholar from inception to March 2016, we identified randomized controlled trials of ICS therapy lasting at least 6 months. A meta-analysis by the Peto approach was also conducted to generate summary estimates comparing ICS with non-ICS treatment on the risk of URTI. A total of 14 studies involving 19,777 subjects were considered in the meta-analysis. Compared with non-ICS treatment, ICS were associated with a significantly increased risk of URTI (Peto OR: 1.16; 95% CI: 1.05-1.29; I2 = 9%; p = .004). Subgroup analyzes were performed for different dose, high-dose ICS was associated with a significantly increased risk of URTI (Peto OR: 1.19; 95% CI: 1.05-1.34; I2 = 0%; p = .005), whereas low-dose ICS showed a non-significant increased risk of URTI (Peto OR: 1.10; 95% CI: 0.91-1.33; I2 = 0%; p = .32). Moreover, fluticasone was observed with an increased risk of URTI but not mometasone; high-dose fluticasone treatment was associated with a significantly higher risk of URTI but not low-dose. These results suggested to us that ICS use may increase the risk of URTI in patients with COPD, but it should be further investigated.


Do Not Minimize the Impact of Cellular Immunity in the Development of Vaccines and Therapeutics for COVID-19.


title: Cognitive Frailty as a Risk Factor for Incident Disability During Late Life: A 24-Month Follow-Up Longitudinal Study.

text: OBJECTIVES Association between cognitive frailty as identified by a new operational definition and incident disability in the community setting remains unclear. This will be the catalyst for preventive interventions designed to treat adverse health problems among elderlies. DESIGN A 24-month follow-up longitudinal study on a community-based cohort. SETTING Community-setting. PARTICIPANTS Participants included a total of 9,936 older adults aged 65 years or older. MEASUREMENTS Frailty was characterized as slow walking speed or/and muscle weakness represented by grip strength. Cognitive function was assessed according to several tests. Cognitive impairment was defined below the age-education reference threshold. Participants were categorized into the four groups: robust, cognitive impairment alone, frailty alone, and cognitive frailty (both frail and cognitive impairment). Incident disability data was extracted from the Japanese Long-Term Care system. RESULTS The prevalence of cognitive frailty was 11.2%. The cumulative incidence rates of incident disability in each group were also estimated (robust, 9.6/1,000 person-years (95% CI 7.9 to 11.7); cognitive impairment, 21.3/1,000 person years (95% CI 16.3 to 27.7); frailty, 45.4/1,000 person years (95% CI 39.5 to 52.3); and cognitive frailty, 79.9/1,000 person years (95% CI 68.6 to 93.1)). Adjusted Cox proportional hazard model revealed that the cognitive frailty group had the highest hazard ratio (HR 3.86, 95%CI 2.95 - 5.05, P < 0.001). CONCLUSIONS A proper operational definition was developed to determine cognitive frailty among elderlies. Cognitive frailty is more associated with incident disability in community-setting than cognitive impairment or physical frailty alone.


Identifying a biomarker for acute kidney injury: an illusory quest?


title: Effect of immunologic solutions on sows and gilts on time to stability, and production losses in breeding herds infected with 1-7-4 PRRSv.

text: Porcine reproductive and respiratory syndrome virus (PRRSv) is an economically significant swine pathogen causing production losses in the global swine industry. Clinical impact depends on many factors including the virus itself. One method to sub-type PRRSv is using restriction fragment length polymorphism (RFLP). The RFLP pattern 1-7-4 emerged within the United States swine industry in 2014 and has become prevalent since then. This was a field study that prospectively followed 1-7-4-infected breeding herds (n=107) and compared time to stability (TTS), time to baseline production (TTBP) and total loss per 1000 sows between herds using modified-live virus vaccine (MLV) on sows and gilts (MLV-MLV), MLV on sows and MLV in addition to field virus exposure on gilts (MLV-MLV/FVE) or not deliberately exposing sows or gilts to PRRSv (Natural-Natural). Analyses were done in SAS 9.4 and results were adjusted by selected co-variates (duration of herd closure, number of previous PRRSv outbreaks of last 3 years, weaning frequency/week, gilt development unit location, herd size and production system). Survival analysis was conducted on TTS and TTBP and regression analysis on total loss. Herds in the Natural-Natural group achieved TTS and TTBP before other herds. Herds in the MLV-MLV/FVE had the longest TTS and TTBP. The total loss was numerically least in MLV-MLV herds (1194 pigs/1000 sows) compared to MLV/MLV-FVE (1810/1000 sows) and Natural-Natural (2671/1000 sows). This study provided additional information to assist veterinarians deciding between methods of exposure to manage PRRSv infection from breeding herds.


title: COVID-19 mortality rates in the European Union, Switzerland, and the UK: effect of timeliness, lockdown rigidity, and population density.

text: BACKGROUND To date the European experience with COVID-19 mortality has been different to the observed in China and Asia. We aimed to forecast mortality trends in the 27 countries of the European Union (EU), plus Switzerland and the United Kingdom (UK), where lockdown dates and confinement interventions have been heterogeneous, and to explore its determinants. METHODS We have adapted our predictive model of COVID-19-related mortality, which rested on the observed mortality within the first weeks of the outbreak and the date of the respective lockdown in each country. It was applied in a training set of three countries (Italy, Germany and Spain), and then applied to the EU plus the UK and Switzerland. In addition, we explored the effects of timeliness and rigidity of the lockdown (on a five-step scale) and population density in our forecasts. We report r2, and percent variation of expected versus observed deaths, all following TRIPOD guidance. RESULTS We identified a homogeneous distribution of deaths, and found a median of 24 days after lockdown adoption to reach the maximum daily deaths. Strikingly, cumulative deaths up to April 25th, 2020 observed in Europe separated countries in three waves, according to the time lockdown measures were adopted following the onset of the outbreak: after a week, within a week, or even prior to the outbreak (r2=0.876). In contrast, no correlation neither with lockdown rigidity nor population density were observed. CONCLUSIONS The European experience confirms that early, effective interventions of 86 lockdown are fundamental to minimizing the COVID-19 death toll.


title: Perianal fistula imaging: a comparison between two-channel superficial Flex coil and eight-channel body coil.

text: Purpose Perianal fistula is an important health problem with devastating morbidity. For diagnosis and prevention of recurrence, perianal fistula imaging (PFI) is crucial. The aim of this study was to investigate if a Flex-M superficial coil images would provide more information than images obtained with a phased-array body coil in PFI. Material and methods Thirty-one fistulas of 29 patients were prospectively evaluated with magnetic resonance imaging. A phased-array body coil was used in all patients as in routine practice, and sequences with Flex-M coil were also obtained. Afterwards, images were evaluated by two experienced radiologists who were blinded to the patients, coil and also to each other. The site of internal and external openings, and presence or absence of abscess and secondary tracts were recorded. Results The conspicuity of images was better with the Flex-M coil. Both radiologists saw more internal openings with the Flex-M coil. Cohen's κ value was 0.100 (p = 0.201) for Reader 1 and 0.110 (p = 0.361) for Reader 2 between these two coils. Additionally, numerically more internal/external openings and secondary tracts were seen by both readers. Interobserver variability was not statistically significant, and Cohen's κ values signifyied good concordance between readers. Conclusions In our study we showed that multichannel superficial phased-array coils improved imaging quality in PFI. We think that Flex-M coil can easily be used in routine clinical practice to gather better images of perianal fistulas.


Challenges in oral radiology teaching during COVID-19 pandemic.


Role of immunosuppressive therapy in rheumatic diseases concurrent with covid-19.


title: Clinical experience with repository corticotropin injection in patients with multiple sclerosis experiencing mood changes with intravenous methylprednisolone: a case series.

text: The elevated prevalence of neuropsychiatric symptoms and disorders among patients with multiple sclerosis (MS) is well recognized, as are potential neuropsychiatric side effects of treatment with corticosteroids. Both methylprednisolone (MP) and repository corticotropin injection (HP Acthar(®) gel) have demonstrated efficacy in reducing short-term disability after exacerbations of MS. Although historical data are limited, repository corticotropin injection has not generally been associated with detrimental neuropsychiatric effects. We describe six cases of patients with relapsing-remitting MS who had previously experienced detrimental mood changes with MP treatment. Some of these patients had previous histories of mood disorders or other neuropsychiatric symptoms prior to MS diagnosis. All six patients were subsequently treated with repository corticotropin injection for MS exacerbations and each demonstrated improvements in MS symptoms. This clinical experience suggests that repository corticotropin injection should be considered as an alternative for patients who do not tolerate corticosteroids or have difficulties associated with intravenous medication. Furthermore, the rate of neuropsychiatric side effects observed in these patients was low. These observations support repository corticotropin injection as a viable alternative for the treatment of acute exacerbations of MS, particularly in patients who have a history of neuropsychiatric disorders or symptoms either independently or in response to MP treatment. In reviewing both the published data and our own clinical experience regarding potential neuropsychiatric adverse events with treatment for MS exacerbations, we hope to stimulate further research into the potential efficacy and safety of repository corticotropin injection among patients with some form of neuropsychiatric complications that must be considered when establishing a treatment plan for MS.


title: Combating COVID-19 Pandemic in Nepal: Ethical Challenges in an Outbreak.

text: Pandemic outbreak of COVID-19 is the largest of its kind of this century. All countries throughout the globe are trying their best to contain the disease and eliminate at the earliest. Efforts are continuing to improve the outcome of the infection in terms of minimizing the morbidity and mortality. As a public health strategy every state has the responsibility of protecting the health of the community and such measures includes the preventive measures like social distancing or even lockdown of the state as a whole restricting the movement of the people, diagnostic measures like testing the suspects, contact tracing and isolation of the patients. Treatment of the infected requires decisions in resource constraint situation particularly ICU beds and ventilators. In the meantime, protecting doctors, nurses, other health workers as well as frontline workers need personal protective equipment which is a scarce commodity. While doing so there might be a compromise in the individual autonomy, privacy, confidentiality, and social justice for the beneficence for the larger community. This is an attempt to explore the ethical quandaries in relation to combating COVID-19 in Nepal by relating the issues with the principles of biomedical ethics.


title: Fatal pneumonia cases caused by human adenovirus 55 in immunocompetent adults.

text: BACKGROUND Adenovirus is a frequent cause of mild self-limiting upper respiratory tract infection, gastroenteritis, and conjunctivitis. Severe or fatal infection mostly occurs in newborn, elderly or immunocompromised persons. METHODS Fatal adenovirus pneumonia in three immunocompetent adults was identified. The clinical data and virological findings were reported from patients. Additional review of recently recorded fatal patients with adenovirus infection was carried out. RESULTS The patients presented with sudden onset respiratory distress that progressed rapidly to respiratory failure and death. Human adenovirus (HAdV)-55 was detected in both nasopharyngeal aspirates and serum samples in all three cases, and moreover detected in lung, liver, and kidney in one case. In another case, remarkably elevated aspartate aminotransferase, alanine transaminase, and lactate dehydrogenase were identified. Three HAdV-55 strains were isolated and genome sequencing revealed a high similarity with other strains from mild infection. CONCLUSIONS Fatal infection with HAdv-55 might occur in otherwise healthy adults. Diagnosis of adenovirus infection should be considered in patients with severe pneumonia yielding negative bacterial culture and presenting no response to antibiotic therapy.


title: The early autophagic pathway is activated by hepatitis B virus and required for viral DNA replication.

text: Autophagy is a catabolic process by which cells remove long-lived proteins and damaged organelles for recycling. Viral infections may also induce autophagic response. Here we show that hepatitis B virus (HBV), a pathogen that chronically infects approximately 350 million people globally, can enhance autophagic response in cell cultures, mouse liver, and during natural infection. This enhancement of the autophagic response is not coupled by an increase of autophagic protein degradation and is dependent on the viral X protein, which binds to and enhances the enzymatic activity of phosphatidylinositol 3-kinase class III, an enzyme critical for the initiation of autophagy. Further analysis indicates that autophagy enhances HBV DNA replication, with minimal involvement of late autophagic vacuoles in this process. Our studies thus demonstrate that a DNA virus can use autophagy to enhance its own replication and indicate the possibility of targeting the autophagic pathway for the treatment of HBV patients.


Time to Endovascular Thrombectomy for Acute Stroke.


title: Housing and care of laboratory cats: from requirements to practice.

text: Increased public awareness of the welfare and well-being of laboratory animals in biomedical research and related ethical considerations inspired us to review recent developments and recommendations for the care and housing of laboratory cats. The present review focuses on the practical requirements for maintaining domestic cats as laboratory animals - from the construction of animal shelters to the termination of an experiment. An excellent standard of housing and care will reduce the bias of experimental results due to stress. To provide cats with living conditions that best meet their natural physical requirements and permit natural social behaviour, laboratories should spare no effort to achieve high housing standards. Hence, the present report not only aims to be a practical reference for those who are involved in the care and husbandry of cats, but it also aims to motivate researchers to improve their knowledge in this field and to provide humane conditions for all cats kept for scientific purposes.


HIV/Hepatitis C Virus Co-infection among Adults Beginning Antiretroviral Therapy, Malawi.


title: Surgical treatment of large incisional hernias by intraperitoneal insertion of Parietex® composite mesh with an associated aponeurotic graft (280 cases).

text: AIMS OF THE STUDY To evaluate post-operative complications and the recurrence rate after repair of large ventral incisional hernia with an open technique using intraperitoneal composite mesh and an associated aponeurotic overlay. PATIENTS AND METHODS This prospective study included a total of 280 patients who underwent repair of large incisional hernia using Parietex(®) composite mesh. RESULTS The post-operative mortality rate was 0.35%. Six patients (2%) developed subcutaneous surgical site infection without infection of the prosthesis. Six other patients (2%) developed a deep-seated infection; in three cases, the mesh had to be removed. Nine patients (3.2%) developed recurrent incisional hernia. CONCLUSION Large ventral incisional hernias can be effectively treated by the intraperitoneal placement of Parietex(®) composite mesh overlaid by an aponeurotic graft; the incidence of complications in this prospective study was very low.


title: Single-incision thoracoscopic surgery for primary spontaneous pneumothorax using the SILS port compared with conventional three-port surgery.

text: BACKGROUND Single-incision thoracoscopic surgery (SITS) is postulated to cause less incisional pain, less paresthesia, and less wound scarring than the conventional three-port approach. The difficulties performing the technique have prevented it from being widely accepted. This study shows how the authors overcame the difficulties by using the SILS port and proved it to be a safe and useful procedure for the treatment of primary spontaneous pneumothorax (PSP). METHODS The same surgeon operated on all the patients using the three-port technique (n = 13) and SITS (n = 27) under the same procedural and management policy. The two groups were retrospectively compared in terms of operation time, postoperative complications, hospital stay, pain score, residual paresthesia, satisfaction regarding the wound scar, and surgical material cost. RESULTS The mean age, sex ratio, and previous pneumothorax episodes were similar between the two groups. The uniport and three-port groups did not differ statistically in terms of mean operation time (74.6 ± 22.8 vs 72.4 ± 20.2 min; p = 0.77), hospital stay (2.3 ± 0.7 vs 2.5 ± 0.8 days; p = 0.72), visual analog pain scale (on the day of surgery: 4.1 ± 1.7 vs 4.8 ± 2.2, p = 0.26; on day 1: 3.2 ± 1.4 vs 2.8 ± 1.4, p = 0.33; on day 2: 2.7 ± 1.0 vs 2.6 ± 1.1, p = 0.61), or total surgical material cost (US$1,810 ± $320 vs $1,741 ± $329; p = 0.58). However, the uniport group had a lower incidence of paresthesia than the three-port group (33.3 vs 76.9%; p = 0.01) and showed a higher satisfaction rate regarding wound scarring (70.4 vs 30.7%; p = 0.03). CONCLUSIONS Compared with the three-port approach, SITS using the SILS port in PSP patients proved to be a safe and feasible procedure that can be clinically implemented without additional economic burden or operation time. Additionally, SITS showed better cosmesis with minimized neurologic sequelae, which contributed to higher satisfaction among patients. Progress in uniport instruments and surgical experience will lead to wider applications of SITS.


European Resuscitation Council Guidelines for Resuscitation 2015: Section 6. Paediatric life support.


title: A Novel Technique for Endovascular Removal of Large Volume Right Atrial Tumor Thrombus.

text: Venous thromboembolic disease is a significant cause of morbidity and mortality, particularly in the setting of large volume pulmonary embolism. Thrombolytic therapy has been shown to be a successful treatment modality; however, its use somewhat limited due to the risk of hemorrhage and potential for distal embolization in the setting of large mobile thrombi. In patients where either thrombolysis is contraindicated or unsuccessful, and conventional therapies prove inadequate, surgical thrombectomy may be considered. We present a case of percutaneous endovascular extraction of a large mobile mass extending from the inferior vena cava into the right atrium using the Angiovac device, a venovenous bypass system designed for high-volume aspiration of undesired endovascular material. Standard endovascular methods for removal of cancer-associated thrombus, such as catheter-directed lysis, maceration, and exclusion, may prove inadequate in the setting of underlying tumor thrombus. Where conventional endovascular methods either fail or are unsuitable, endovascular thrombectomy with the Angiovac device may be a useful and safe minimally invasive alternative to open resection.


title: Randomized Electronic Promotion of Lung Cancer Screening: A Pilot.

text: PURPOSE Screening for lung cancer with low-dose computed tomography is endorsed by the US Preventive Services Task Force, but many eligible patients have yet to be offered screening. Major barriers to the implementation of screening are physician and system related-the requirement for a detailed smoking history, including pack-years, to determine eligibility. We conducted this pilot to determine the feasibility of lung cancer screening (LCS) promotion that would offer screening to eligible persons and patient completion of smoking history to estimate the size of the population of former smokers who may be eligible for LCS in a single health care system. PATIENTS AND METHODS Two hundred participants were randomly selected from former smokers who were seen at the University of Minnesota Health in the past 2 years and assigned to control (usual care) and electronic promotion, stratified by age. Electronic messages to promote LCS were sent to an intervention group, including a link to complete a detailed smoking history in the electronic health record. RESULTS Of 99 participants, 66 (67%) in the intervention group read the message, 24 (36%) of 66 responded, and 19 (79%) of 24 respondents completed the smoking history. Ten intervention participants and 13 usual care participants were eligible for screening on the basis of pack-year history. Four eligible participants underwent screening in the intervention group compared with one participant in the usual care group. CONCLUSION Electronic promotion may help identify patients who are eligible for LCS but will not reliably reach all patients because of low response rates. In this sample of former smokers, the majority are ineligible for LCS on the basis of pack-year history. Electronic methods can improve documentation of smoking history.


title: Percutaneous radiofrequency ablation of a small renal mass complicated by appendiceal perforation.

text: Percutaneous radiofrequency ablation (RFA) has gained wide acceptance as nephron-sparing therapy for small renal masses in select patients. Generally, it is a safe procedure with minor morbidity and acceptable short-term oncologic outcome. However, as a result of the close proximity of vital structures, such as the bowel, ureter, and large vessels, to the ablative field, complications regarding these structures may occur. This is the first article describing appendiceal perforation as a complication of computed tomography-guided RFA despite hydrodissection. When performing this innovative and promising procedure one should be aware of the possibility of particular minor and even major complications.


title: Nutritional Recovery after Open and Laparoscopic Distal Gastrectomy for Early Gastric Cancer: A Prospective Multicenter Comparative Trial (CCOG1204).

text: BACKGROUND Little information from prospective clinical trials is available on the influences of surgical approaches on postoperative body compositions and nutritional status. We designed a prospective non-randomized trial to compare postoperative chronological changes in body composition and nutritional status between laparoscopic and open distal gastrectomy for stage I gastric cancer (GC). METHODS Body compositions and nutritional indicators in blood tests were measured at the baseline and at the 1st, 3rd, 6th, and 12th postoperative months (POM). The primary end point was the decrease relative to the baseline in the body muscle mass at POM 6. RESULTS Ninety-six patients for the laparoscopic group and 52 for the open group were eligible for data analysis. No significant differences were found in any baseline demographics, body compositions, and nutritional indicators between the groups. The changes of body muscle mass at POM 6 were similar in both groups. Overall, no significant differences between the groups were observed in any of the body composition and nutritional indicators during the first year after surgery. CONCLUSIONS Postoperative body compositions and nutritional status were not affected by surgical approaches during the first 12 months after surgery in patients who underwent distal gastrectomy for stage I GC.


title: Gastroesophageal reflux related to respiratory inhibition after crying and feeding hypoxemia in infants.

text: OBJECTIVE To determine the relationships between gastroesophageal reflux (GER) and both respiratory inhibition after crying (RIAC) and feeding hypoxemia in infants. METHODS We screened for RIAC and feeding hypoxemia among infants with a gestational age of 36 weeks or greater using pulse oximetry. We investigated the infants who showed hypoxemia with a decrease in SpO2 to less than 70% and bradycardia with a heart rate of less than 100 beats per minute caused by GER. We then evaluated the relationships between these events and both RIAC and feeding hypoxemia. RESULTS We examined 250 infants in the present study. RIAC and feeding hypoxemia were observed in 35 (14.0%), and 30 (12.0%) infants, respectively. Ten infants showed hypoxemia and bradycardia caused by GER. These events were correlated with RIAC (p = 0.006) and feeding hypoxemia (p = 0.031). CONCLUSIONS In the infants with RIAC and feeding hypoxemia, some show severe hypoxemia and bradycardia caused by GER. Medical staff caring for infants should note the presence of RIAC and feeding hypoxemia.


title: Alcohol Consumption Reported during the COVID-19 Pandemic: The Initial Stage.

text: Physical health is not the only area affected by the outbreak of the SARS-CoV-2 virus pandemic. There are also other consequences that have globally affected many millions at other levels, namely: Societal, political, economic, and cultural. This study aims to survey alcohol drinking throughout the pandemic so as to investigate those factors considered most relevant; i.e., sociodemographic and clinical. A longitudinal study was designed. The first (or initial) stage was completed between April 10-20 2020 on 443 subjects during the enforcement of the "Lockdown" in Poland. The second stage will be due in June 2020. As well as an in-house questionnaire, the study used: The Alcohol Use Disorder Identification Test (AUDIT), General Health Questionnaire (GHQ-28), Perceived Stress Scale (PSS-10), and the Brief COPE Inventory (Mini COPE). Alcohol was the most commonly used psychoactive substance (73%) identified. More than 30% changed their drinking habits because of the pandemic, with 16% actually drinking less, whilst 14% did so more. The former group was significantly younger than the latter. Amongst the stress-related coping strategies, it was found that current alcohol drinkers were significantly less able to find anything positive about the pandemic situation (positive reframing) and were mentally less able to cope. Those drinking more now were found to have been drinking more intensively before the pandemic started.


title: A single centre experience of zero-ischaemia laparoscopic partial nephrectomy in Ireland.

text: BACKGROUND Nephron-sparing surgery in the form of partial nephrectomy is increasingly becoming the standard of care in patients with small renal tumours. Oncological outcomes for partial nephrectomy are equivalent to radical nephrectomy, however, clamping of the hilar vessels to allow resection of tumours during partial nephrectomy may cause ischaemic damage to the kidney and result in long-term renal impairment. AIM We carried out a retrospective review of 43 patients undergoing laparoscopic partial nephrectomy (LPN) and assessed functional and oncological outcomes. METHODS The operative technique initially utilised a thulium laser, with later cases using the LigaSure™ vessel sealing device. All patients underwent preoperative cross sectional imaging and anatomical classification accordingly. RESULTS Forty three patients underwent LPN in our unit from 2006 to 2014. The mean (range) tumour diameter on preoperative cross sectional imaging was 28.2 (12-49) mm. All cases had a warm ischaemia time of zero, as hilar vessels were not clamped in any case. The mean (range) preoperative estimated glomerular filtration rate (eGFR) was 73 (37 to >90) ml/min/1.73 m2 and was not significantly different to the post-operative mean (range) eGFR of 71 (31 to >90) ml/min/1.73 m2. 34 (79%) of the tumours were found to be malignant. Positive surgical margins were found in one case. The mean (range) follow-up time in our cohort was 61.6 (24-127) months and no patient has had a local or distant recurrence. CONCLUSION Zero ischaemia laparoscopic partial nephrectomy appears to be a safe and oncologically satisfactory procedure for the management of small localised kidney tumours.


title: [Drug interaction monitoring of lopinavir / ritonavir in COVID-19 patients with cancer].

text: 新型冠状病毒肺炎治疗药物洛匹那韦/利托那韦（LR）是多种细胞色素P(450)（CYP(450)）酶的抑制剂，又是多种CYP(450)酶底物，此外还是P糖蛋白的抑制剂、葡萄糖醛酸转移酶诱导剂，与很多抗肿瘤药物存在药物相互作用。药品说明书仅列举了少数抗肿瘤药物与LR的相互作用，提供参考信息严重不足。本文系统总结了抗肿瘤药物及常用辅助药物和LR的相互作用及处理建议。.


title: Alphacoronavirus transmissible gastroenteritis virus nsp1 protein suppresses protein translation in mammalian cells and in cell-free HeLa cell extracts but not in rabbit reticulocyte lysate.

text: The nsp1 protein of transmissible gastroenteritis virus (TGEV), an alphacoronavirus, efficiently suppressed protein synthesis in mammalian cells. Unlike the nsp1 protein of severe acute respiratory syndrome coronavirus, a betacoronavirus, the TGEV nsp1 protein was unable to bind 40S ribosomal subunits or promote host mRNA degradation. TGEV nsp1 also suppressed protein translation in cell-free HeLa cell extract; however, it did not affect translation in rabbit reticulocyte lysate (RRL). Our data suggested that HeLa cell extracts and cultured host cells, but not RRL, contain a host factor(s) that is essential for TGEV nsp1-induced translational suppression.


title: Collective trauma and community support: Lessons from Detroit.

text: The COVID-19 crisis can be defined as a collective trauma, which contributes to an upheaval of community connection and functioning. The current pandemic has also illuminated disparities in mental health supports. In this commentary, we highlight one community organization, located in metro Detroit, that has responded to the trauma by bolstering resources and supports for residents, many of whom are ethnoracial minorities. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models.

text: Griffithsin (GRFT) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 (HIV-1), HIV-2, and other enveloped viruses, including hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Ebola virus. GRFT displays no human T-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines. However, despite the growing evidence showing the broad-spectrum nanomolar or better antiviral activity of GRFT, no study has reported a comprehensive assessment of GRFT safety as a potential systemic antiviral treatment. The results presented in this work show that minimal toxicity was induced by a range of single and repeated daily subcutaneous doses of GRFT in two rodent species, although we noted treatment-associated increases in spleen and liver mass suggestive of an antidrug immune response. The drug is systemically distributed, accumulating to high levels in the serum and plasma after subcutaneous delivery. Further, we showed that serum from GRFT-treated animals retained antiviral activity against HIV-1-enveloped pseudoviruses in a cell-based neutralization assay. Overall, our data presented here show that GRFT accumulates to relevant therapeutic concentrations which are tolerated with minimal toxicity. These studies support further development of GRFT as a systemic antiviral therapeutic agent against enveloped viruses, although deimmunizing the molecule may be necessary if it is to be used in long-term treatment of chronic viral infections.


title: Surgical risk and benefits of laparoscopic surgery for elderly patients with gastric cancer: a multicenter prospective cohort study.

text: BACKGROUND Laparoscopic gastrectomy (LG) might have greater clinical benefits for elderly patients as less invasive surgery; however, there is still little evidence to support its benefit. We evaluated the surgical outcomes of elderly patients in a nationwide prospective cohort study. METHODS One hundred and sixty-nine participating institutions were identified by stratified random sampling, and were adjusted for hospital volume, type and location. During 1 year from 2014 to 2015, consecutive patients who underwent gastrectomy for gastric cancer were prospectively enrolled. 'Elderly' was defined as ≥ 75 years of age, based on the prevalence of comorbidities and the activities of daily living of patients of this age. We compared the surgical outcomes of LG to those of open gastrectomy (OG) in non-elderly and elderly patients. The primary outcome was the incidence of severe morbidities (Grade ≥ 3). RESULTS Eight thousand nine hundred and twenty-seven patients were enrolled [non-elderly, n = 6090 (OG, n = 2602; LG, n = 3488); elderly, n = 2837 (OG, n = 1471; LG, n = 1366)]. Grade ≥ 3 complications occurred in 161 (10.9%) patients who underwent OG and 98 (7.2%) who underwent LG (p < 0.001). After adjusting for confounding factors, we confirmed that laparoscopic surgery was not an independent risk factor (odds ratio = 0.81, 0.60-1.09). OG was associated with a significantly longer median length of postoperative stay in comparison to LG (16 versus 12 days, p < 0.001). There were no significant differences in the incidence of other postoperative comorbidities. CONCLUSION The safety of LG in elderly patients was demonstrated. LG shortened the length of postoperative hospital stay.


title: Peritoneal adhesion formation and reformation tracked by sequential laparoscopy: optimizing the time point for adhesiolysis.

text: BACKGROUND In a high proportion of patients, operatively lysed adhesions reform. Using a rabbit adhesiogenesis model, this study assessed the efficacy of adhesiolysis and examined how this relates to the tissue composition of adhesions at the time of lysis. METHODS Polypropylene meshes (5 x 3.5 cm) were implanted on the parietal peritoneum of New Zealand white rabbits. Some animals were killed 3, 7, 14, and 90 days postimplantation to obtain adhesion tissue. Adhesion formation/reformation was monitored by sequential laparoscopy in other animals kept for 90 days and in a separate experimental group subjected to adhesiolysis at 3 days postimplantation. Immune and inflammatory response markers were determined by immunohistochemical, Western blotting, and real-time reverse transcriptase polymerase chain reaction procedures in adhesion tissue; areas occupied by adhesions were quantified in meshes. RESULTS In animals undergoing adhesiolysis, mesh areas covered by adhesions were significantly decreased at each follow-up time and affected areas became mesothelialized. Increased transforming growth factor (TGF)-beta1 expression was detected in adhesions at 3 days. Greatest TGF-beta1 and vascular endothelial growth factor (VEGF) protein expressions were observed at 7 days, whereas genetic overexpression was noted at 14 days. Active inflammatory cells peaked at the 7-day time point. CONCLUSION Adhesions formed at 3 days; at this critical time, an adhesiolysis was effective in preventing reformation of future adhesions. TGF-beta1 gene and protein expression were increased in 3-day adhesions with respect to the omentum. Levels of active TGF-beta1 and VEGF were increased at 7 days, along with the inflammatory response at this time point related to tissue remodeling, which led to stabilization of adhesions.


title: A commentary on the Nigerian response to the COVID-19 pandemic.

text: In this commentary, we review the emergence of the COVID-19 pandemic in Nigeria and how aspects of the socioeconomic context and responses from the government and general public may contribute to its persistence. We also suggest mechanisms for the adverse mental health impacts of the pandemic and highlight the need for data and strengthening social infrastructure. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Upregulated expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in BALB/c mouse brain challenged with Japanese encephalitis virus.

text: BACKGROUND Uncontrolled immune responses in the nervous system are potentially damaging following Japanese encephalitis virus (JEV) infection. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) act together to control the proteolysis of extracellular matrix. Disbalances in the MMP/TIMP system during virally induced neurodegenerative processes and inflammations are responsive to changes in the progression of diseases. METHODS The expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-3 in JEV-infected mouse brain was analyzed by RT-PCR for semiquantitation and ELISA for estimation of protein along with brain histopathology at different days postinoculation (dpi). Gelatin gel zymography was performed for MMP-2 and MMP-9 activities. RESULTS In the virus-infected group, expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-3 was found to be increased from 1 dpi to 6 dpi as compared to controls by both RT-PCR and ELISA. The expressions of MMPs and TIMPs at mRNA and protein levels were in concordance with each other. Post hoc multiple comparison analysis between days revealed that, in the virus-infected groups, significant increases (p < 0.05) in MMP and TIMP levels were observed between various dpi at both mRNA and protein levels. Only the MMP-7 protein level at 6 dpi was not significant compared to 5 dpi (p = 0.99). CONCLUSION Overexpression of MMPs and TIMPs is associated with disease severity in the central nervous system (CNS) during JEV infection. Our results showed that JEV infection can alter the expression of MMPs and TIMPs in the CNS. Thus, assessing these important immune mediators in CNS infection appears to play an important role in the development of symptoms and may help to understand the JEV-induced neurological disorders. More studies are required on this important enzymatic system to study their role in immune mediated pathogenesis.


title: Delphi Survey of Clinical Nursing and Midwifery Research Priorities in the Eastern Mediterranean Region.

text: PURPOSE As the shortage of nurses and midwives is expected to worsen in the Eastern Mediterranean region concomitantly with a growing focus on achievement of universal health coverage, nurses and midwives are expected to fill major gaps in health care. Hence, the need for a solid evidence base for nursing practice and a clear direction for clinical nursing research are paramount. Therefore, a Delphi survey was conducted to determine clinical (research focused on patient outcomes) nursing and midwifery priorities for research within this region. DESIGN A Delphi survey, using iterative rounds of an online survey of regional clinical nursing and midwifery research experts, was conducted between January and April 2016. METHODS Consensus was determined by percentage agreement on level of priority for topics as determined by participants. Additionally, results were compared between countries within the region by income and mortality levels using Kendall's tau. FINDINGS Critical research topics were focused on public/community/primary care as well as emergency preparedness for disasters, and these priorities are well aligned with gaps in the literature for this region. There were statistically significant differences between priority level and country mortality group for geriatrics, self-management of disease, and sexually transmitted infections. CONCLUSIONS Critical research priorities should focus on population-based health topics. Between-country differences should be analyzed further. A clinical research database for the region may help improve research access for nurses and midwives. CLINICAL RELEVANCE Practicing nurses and midwives lack extensive evidence (including culturally relevant evidence) on which to practice. Increasing research in areas identified in this survey may improve patient outcomes and quality of care regionally.


title: Therapeutic Effects of Pretreatment with Tocovid on Oxidative Stress in Postischemic Mice Brain.

text: BACKGROUND Dietary supplement is an attempt to reduce the risk of ischemic stroke in high-risk population. A new mixed vitamin E-Tocovid that mainly contains tocotrienols other than tocopherol, attenuated the progression of white matter lesions by oral in humans. However, the effect of Tocovid on ischemic stroke has not been examined. In the present study, we assessed the therapeutic effects of Tocovid pretreatment on transient middle cerebral artery occlusion (tMCAO) in mice. MATERIALS AND METHODS After pretreatment with Tocovid (200 mg/kg/d) or vehicle for 1 month, 60-minute tMCAO was performed, and these mice were examined at 1 day, 3 days, and 7 days after reperfusion. We histologically assessed the effects of Tocovid pretreatment on the expressive changes of oxidative stress markers, cleaved caspase-3, and LC3-II after tMCAO in mice. RESULTS We observed that Tocovid pretreatment significantly improved the rotarod time, reduced infarct volume, decreased the number of 4-HNE, nitrotyrosine, and 8-OhdG positive cells, inhibited advanced glycation end products biomarkers RAGE, CMA, and CML expressions, and increased Nrf2 and MRP1 levels with GSSG/GSH ratio decrease. Furthermore, Tocovid pretreatment greatly decreased cleaved caspase-3 and LC3-II expressions after tMCAO. CONCLUSIONS The present study obviously demonstrated that Tocovid pretreatment showed neuroprotective effects against oxidative stress and at least in part by antiapoptotic/autophagic cell death in ischemic mice brain.


title: Efficacy of the Roux-en-Y gastric bypass compared to medically managed controls in meeting the American Diabetes Association composite end point goals for management of type 2 diabetes mellitus.

text: BACKGROUND The treatment goals recommended by the American Diabetes Association (ADA) for patients with type 2 diabetes mellitus include hemoglobin A1c (HbA1C) <7.0%, low-density lipoprotein (LDL) <100 mg/dL, and systolic blood pressure (SBP) <130 mmHg. Only 10% of conventionally treated patients reach these goals as a composite endpoint. The efficacy of the Roux-en-Y gastric bypass (RYGB) in meeting this composite endpoint has not been reported. METHODS We compared our database of patients with type 2 diabetes undergoing RYGB to a database of patients with medically managed type 2 diabetes and at least 2 years of follow-up data. RESULTS Ultimately, 152 RYGB patients were compared to 115 routine medical management (RMM) patients for whom data on the composite endpoint were available over 2 years. The results show significant decrease in body mass index (kilograms per square meter) in the RYGB group compared to the RMM group (P < 0.001). HbA1C, LDL cholesterol, and SBP all significantly improved in the RYGB group (all P ≤ 0.01) and did not demonstrate any significant change in the RMM group. Over 2 years, when evaluating all three endpoints, the RYGB group (10.5% to 38.2%, P < 0.001) demonstrated increased achievement of the ADA goals compared to the RMM group (13.9% to 17.4%, P = 0.47). There was a significant decrease in medication use in the RYGB cohort; however, discontinuation of medications was sometimes inappropriate. CONCLUSIONS RYGB achieves the ADA composite endpoint more frequently than conventional therapy and with less medication.


Editorial: renal sympathetic denervation: a true lack of efficacy, or the victim of a "perfect storm"?


title: Whole-lung lavage complicated with pneumothorax: a case report.

text: A patient with pulmonary alveolar proteinosis underwent whole lung lavage of the right lung. Lavage of the left lung was not immediately possible because of severe hypoxemia. Three days later, after correction of hypoxemia, we re-attempted the left lung lavage. However, the patient had severe hypoxemia (SpO2 < 80%) within a few minutes of performing right one lung ventilation (OLV). On bronchoscopic examination, proper tube location was confirmed. Bronchodilator nebulization and steroid injection were attempted with no effect. While searching for the cause of the hypoxemia, we found that the breath sound from the right lung had become very weak and distant compared with that from initial auscultation. Right pneumothorax was diagnosed on chest X-ray and a chest tube was inserted. After confirming pneumothorax resolution, we re-tried right OLV and were able to proceed with the left lung lavage without signs of aggravating air leak, loss of tidal volume, or severe hypoxemia.


title: Prehospital Supraglottic Airway Was Associated With Good Neurologic Outcome in Cardiac Arrest Victims Especially Those Who Received Prolonged Cardiopulmonary Resuscitation.

text: OBJECTIVES We performed this study to investigate the association of prehospital supraglottic airway (SGA) on neurologic outcome in cardiac arrest victims with adjustment of postresuscitation variables as well as prehospital and resuscitation variables. METHODS This study was a retrospective study based on a multicenter prospective cohort registry from December 2013 to April 2016. According to the 28-day cerebral performance categories (CPCs) scale, patients were divided into the good-outcome group (CPC 1-2) and the poor-outcome group (CPC 3-5). We compared the two groups with respect to demographic variables, prehospital and in-hospital resuscitation variables, and postresuscitation variables. RESULTS A total of 869 cardiac arrest victims who received in-progress cardiopulmonary resuscitation (CPR) were delivered to the emergency department of three hospitals, and 310 patients were admitted to the intensive care unit. The use of a prehospital SGA was independently associated with 28-day good neurologic outcome (odds ratio [OR] = 7.88; 95% confidence interval [CI] = 1.33-46.53; p = 0.023] when postresuscitation variables were adjusted, although there were no significant association with the acquisition of sustained return of spontaneous circulation (OR = 0.992; 95% CI = 0.591-1.666; p = 0.976). Furthermore, a prehospital SGA was significantly associated with good neurologic outcome, especially in patients who received prolonged CPR (low flow time > 15 minutes; OR = 3.41; 95% CI = 1.23-9.45; p = 0.018) rather than in patients with nonprolonged CPR (OR = 4.50; 95% CI = 0.75-27.13; p = 0.101). CONCLUSIONS When postresuscitation variables were adjusted, the prehospital SGA was independently associated with 28-day good neurologic outcome in cardiac arrest victims.


title: Emergence of viral diseases: mathematical modeling as a tool for infection control, policy and decision making.

text: Mathematical modeling can be used for the development and implementation of infection control policy to combat outbreaks and epidemics of communicable viral diseases. Here an outline is provided of basic concepts and approaches used in mathematical modeling and parameterization of disease transmission. The use of mathematical models is illustrated, using the 2001 UK foot-and-mouth disease (FMD) epidemic, the 2003 global severe acute respiratory syndrome (SARS) epidemic, and human influenza pandemics, as examples. This provides insights in the strengths, limitations, and weaknesses of the various models, and demonstrates their potential for supporting policy and decision making.


How COVID-19 Rapidly Transformed Clinical Practice at the Harold Schnitzer Diabetes Health Center Now and for the Future.


title: Laparoscopic Resection of Cholecystocolic Fistula and Subtotal Cholecystectomy by Tri-Staple in a Type V Mirizzi Syndrome.

text: The Mirizzi syndrome (MS) is an impacted stone in the cystic duct or Hartmann's pouch that mechanically obstructs the common bile duct (CBD). We would like to report laparoscopic subtotal cholecystectomy (SC) and resection of cholecystocolic fistula by the help of Tri-Staple™ in a case with type V MS and cholecystocolic fistula, for first time in the literature. A 24-year-old man was admitted to emergency department with the complaint of abdominal pain, intermittent fever, jaundice, and diarrhea. Two months ago with the same complaint, ERCP was performed. Laparoscopic resection of cholecystocolic fistula and subtotal cholecystectomy were performed by the help of Tri-Staple. At the eight-month follow-up, he was symptom-free with normal liver function tests. In a patient with type V MS and cholecystocolic fistula, laparoscopic resection of cholecystocolic fistula and SC can be performed by using Tri-Staple safely.


title: Structural elucidation of in vitro metabolites of bavachinin in rat liver microsomes by LC-ESI-MSn and chemical synthesis.

text: 1. Bavachinin isolated from Psoralea corylifolia has various activities, such as antimicrobial, antiallergic, antitumor and so on. Our previous study showed that natural bavachinin exhibits peroxisome proliferator-activated receptor γ-agonist activity. 2. In vitro studies on bavachinin metabolism were conducted using rat liver microsomes incubated at 37 °C for 60 min. 3. Structures of eight metabolites of the incubation mixtures were cautiously characterized using electrospray tandem mass spectra and three synthetic compounds. The results indicated that eight metabolites of bavachinin were biotransformed mainly through oxidation. 4. The metabolic pathways of bavachinin were elucidated in vitro. These results contribute to the understanding of bavachinin's in vivo metabolism.


Dangerous interactions of gastrointestinal drugs with experimental treatments for COVID-19.


COVID-19 and obesity: links and risks.


title: Acute Ischemic Stroke Intervention.

text: Acute ischemic stroke (AIS) is the leading cause of disability worldwide and among the leading causes of mortality. Although intravenous tissue plasminogen activator (IV-rtPA) was approved nearly 2 decades ago for treatment of AIS, only a minority of patients receive it due to a narrow time window for administration and several contraindications to its use. Endovascular approaches to recanalization in AIS developed in the 1980s, and recently, 5 major randomized trials showed an overwhelming superior benefit of combining endovascular mechanical thrombectomy with IV-rtPA over IV-rtPA alone. In this paper, we discuss the evolution of catheter-based treatment from first-generation thrombectomy devices to the game-changing stent retrievers, results from recent trials, and the evolving stroke systems of care to provide timely access to acute stroke intervention to patients in the United States.


title: Patients with low Alberta Stroke Program Early CT Score (ASPECTS) but good collaterals benefit from endovascular recanalization.

text: BACKGROUND Benefit of thrombectomy in patients with a low initial Alberta Stroke Program Early CT Score (ASPECTS) is still uncertain. We hypothesized that, despite low ASPECTS, patients may benefit from endovascular recanalization if good collaterals are present. METHODS Ischemic stroke patients with large vessel occlusion in the anterior circulation and an ASPECTS of ≤5 were analyzed. Collateral status (CS) was assessed using a 5-point-scoring system in CT angiography with poor CS defined as CS=0-1. Clinical outcome was determined using the modified Rankin Scale (mRS) score after 90 days. Edema formation was measured in admission and follow-up CT by net water uptake. RESULTS 27/100 (27%) patients exhibited a CS of 2-4. 50 patients underwent successful vessel recanalization and 50 patients had a persistent vessel occlusion. In multivariable logistic regression analysis, collateral status (OR 3.0; p=0.003) and vessel recanalization (OR 12.2; p=0.009) significantly increased the likelihood of a good outcome (mRS 0-3). A 1-point increase in CS was associated with 1.9% (95% CI 0.2% to 3.7%) lowered lesion water uptake in follow-up CT . CONCLUSION Endovascular recanalization in patients with ASPECTS of ≤5 but good collaterals was linked to improved clinical outcome and attenuated edema formation. Collateral status may serve as selection criterion for thrombectomy in low ASPECTS patients.


title: Effect of Conscious Sedation vs General Anesthesia on Early Neurological Improvement Among Patients With Ischemic Stroke Undergoing Endovascular Thrombectomy: A Randomized Clinical Trial.

text: Importance Optimal management of sedation and airway during thrombectomy for acute ischemic stroke is controversial due to lack of evidence from randomized trials. Objective To assess whether conscious sedation is superior to general anesthesia for early neurological improvement among patients receiving stroke thrombectomy. Design, Setting, and Participants SIESTA (Sedation vs Intubation for Endovascular Stroke Treatment), a single-center, randomized, parallel-group, open-label treatment trial with blinded outcome evaluation conducted at Heidelberg University Hospital in Germany (April 2014-February 2016) included 150 patients with acute ischemic stroke in the anterior circulation, higher National Institutes of Health Stroke Scale (NIHSS) score (>10), and isolated/combined occlusion at any level of the internal carotid or middle cerebral artery. Intervention Patients were randomly assigned to an intubated general anesthesia group (n = 73) or a nonintubated conscious sedation group (n = 77) during stroke thrombectomy. Main Outcomes and Measures Primary outcome was early neurological improvement on the NIHSS after 24 hours (0-42 [none to most severe neurological deficits; a 4-point difference considered clinically relevant]). Secondary outcomes were functional outcome by modified Rankin Scale (mRS) after 3 months (0-6 [symptom free to dead]), mortality, and peri-interventional parameters of feasibility and safety. Results Among 150 patients (60 women [40%]; mean age, 71.5 years; median NIHSS score, 17), primary outcome was not significantly different between the general anesthesia group (mean NIHSS score, 16.8 at admission vs 13.6 after 24 hours; difference, -3.2 points [95% CI, -5.6 to -0.8]) vs the conscious sedation group (mean NIHSS score, 17.2 at admission vs 13.6 after 24 hour; difference, -3.6 points [95% CI, -5.5 to -1.7]); mean difference between groups, -0.4 (95% CI, -3.4 to 2.7; P = .82). Of 47 prespecified secondary outcomes analyzed, 41 showed no significant differences. In the general anesthesia vs the conscious sedation group, substantial patient movement was less frequent (0% vs 9.1%; difference, 9.1%; P = .008), but postinterventional complications were more frequent for hypothermia (32.9% vs 9.1%; P < .001), delayed extubation (49.3% vs 6.5%; P < .001), and pneumonia (13.7% vs 3.9%; P = .03). More patients were functionally independent (unadjusted mRS score, 0 to 2 after 3 months [37.0% in the general anesthesia group vs 18.2% in the conscious sedation group P = .01]). There were no differences in mortality at 3 months (24.7% in both groups). Conclusions and Relevance Among patients with acute ischemic stroke in the anterior circulation undergoing thrombectomy, conscious sedation vs general anesthesia did not result in greater improvement in neurological status at 24 hours. The study findings do not support an advantage for the use of conscious sedation. Trial Registration clinicaltrials.gov Identifier: NCT02126085.


Covid-19: Test and trace system is not fit for purpose, says Independent SAGE.


title: Laboratory assessments of therapeutic platelet inhibition in endovascular neurosurgery: comparing results of the VerifyNow P2Y12 assay to thromboelastography with platelet mapping.

text: OBJECTIVEInhibition of platelet aggregation is vital to preventing thromboembolic complications related to stent placement in endovascular neurosurgery, but excessive inhibition potentiates hemorrhagic complications. Recent evidence suggests an ideal inhibition range of 70-150 P2Y12 response units (PRU) as measured on the VerifyNow assay, which relies on photometric measurements of platelet aggregation. Thromboelastography (TEG) with platelet mapping (PM) is an alternative assay that directly measures clot formation and mechanical strength. This study compares the results of PRU to TEG-PM.METHODSPatients with simultaneous or near-simultaneous PRU and TEG-PM results who underwent cervical carotid artery stenting, intracranial stent-assisted aneurysm coiling, or flow diversion at the authors' institution between August 2015 and November 2016 were identified. PRU results were compared with the TEG maximal amplitude (MA) attributable to adenosine diphosphate (ADP) activity (MA-ADP) as measured by TEG-PM. Platelet inhibition was considered therapeutic for MA-ADP values < 50 mm or PRU < 194. The Pearson correlation coefficient was calculated, and the sensitivity and specificity of PRU were calculated assuming that the results of TEG-PM reflected the true degree of platelet inhibition.RESULTSTwenty-three patients were identified with a total of 37 matched sets of TEG-PM and PRU. Three of these pairs were excluded due to anemia outside of the PRU manufacturer's recommended range. The Pearson correlation coefficient for these values was 0.50 (p = 0.0026). The prevalence of clopidogrel nonresponders determined by TEG-PM (9%) matched reported rates (5%-12%); PRU demonstrated much higher prevalence (39%). For detecting a therapeutic level of platelet inhibition, PRU demonstrated a sensitivity of 0.59, specificity of 0.50, positive predictive value of 0.95, and negative predictive value of 0.07. Ideal inhibition was concordant in only 25% of observations in which at least one of the results was ideal.CONCLUSIONSAgreement between TEG-PM and PRU regarding the degree of platelet inhibition is poor. PRU likely overestimates clopidogrel resistance, as 93% of patients with PRU > 194 demonstrate a therapeutic level of platelet inhibition on TEG.


title: Pulse Oximetry with Two Infrared Wavelengths without Calibration in Extracted Arterial Blood.

text: Oxygen saturation in arterial blood (SaO₂) provides information about the performance of the respiratory system. Non-invasive measurement of SaO₂ by commercial pulse oximeters (SpO₂) make use of photoplethysmographic pulses in the red and infrared regions and utilizes the different spectra of light absorption by oxygenated and de-oxygenated hemoglobin. Because light scattering and optical path-lengths differ between the two wavelengths, commercial pulse oximeters require empirical calibration which is based on SaO₂ measurement in extracted arterial blood. They are still prone to error, because the path-lengths difference between the two wavelengths varies among different subjects. We have developed modified pulse oximetry, which makes use of two nearby infrared wavelengths that have relatively similar scattering constants and path-lengths and does not require an invasive calibration step. In measurements performed on adults during breath holding, the two-infrared pulse oximeter and a commercial pulse oximeter showed similar changes in SpO₂. The two pulse oximeters showed similar accuracy when compared to SaO₂ measurement in extracted arterial blood (the gold standard) performed in intensive care units on newborns and children with an arterial line. Errors in SpO₂ because of variability in path-lengths difference between the two wavelengths are expected to be smaller in the two-infrared pulse oximeter.


title: [Medical rehabilitation of patients with pneumonia associated with the new COVID-19 coronavirus infection].

text: Effective medical rehabilitation of patients with pneumonia caused by the new SARS-CoV-2 coronavirus is critical for the recovery and optimization of emergency and specialty care outcomes. In this regard, it is relevant to develop a scientifically based medical rehabilitation program for patients with the coronavirus infectious disease COVID-19, whose composition and structure includes methods and tools that have proven effectiveness. AIM To develop evidence-based approaches to medical rehabilitation for patients with pneumonia associated with the new COVID-19 coronavirus infection. RESULTS The clinical effects and suggested mechanisms of action of rehabilitation technologies in patients with pneumonia, including those associated with the new COVID-19 coronavirus infection, are considered in Detail. The most studied of the physical methods that have a proven effect are physical exercises, breathing exercises, the complex effect of factors of resort therapy, hydrotherapy, which affect the main clinical manifestations of the underlying disease, astheno-neurotic syndrome and increasing immunity. Clinical recommendations for medical rehabilitation are proposed and its promising methods are considered. CONCLUSION Regular generalization and analysis of high-quality randomized controlled clinical trials to evaluate various physical methods of treatment of patients with pneumonia associated with the new COVID-19 coronavirus infection is Necessary, which serve as a basis for the development of future valid clinical recommendations. Timely and adequate specialized medical rehabilitation care is critical to maintaining the health, reducing disability and mortality of patients with pneumonia associated with the new COVID-19 coronavirus infection.


title: Vein mapping prior to endovenous catheter ablation of the great saphenous vein predicts risk of endovenous heat-induced thrombosis.

text: OBJECTIVE We investigate the value of vein mapping for predicting the risk of endovenous heat-induced thrombosis (EHIT) after endovenous laser treatment (EVLT) and radiofrequency ablation (RFA) of the great saphenous vein (GSV). METHODS In all, 355 consecutive vein mappings were retrospectively analyzed. A generalized estimating equations approach to linear logistic regression was used to evaluate the variables. RESULTS Among the 312 vein ablation of the GSV, 10 (3.2%) developed EHIT. When comparing the group of patients who developed EHIT versus no EHIT, the mean GSV diameter was 13.05 ± 5.59 mm versus 8.39 ± 3.38 mm (odds ratio [OR]: 1.25, P = .001), the presence of valvular incompetence at the saphenofemoral junction (SFJ) was 10.71% versus 0.44% (OR: 27.75, P =.001), and 3.09% in RFA versus 3.33% in EVLT (OR: 1.09, P = .89). CONCLUSIONS Patients with valvular insufficiency of the SFJ and a large proximal GSV diameter had a significantly higher risk of developing heat-induced thrombosis after endovenous catheter ablation.