title: The CDK inhibitor p57Kip2 enhances the activity of the transcriptional coactivator FHL2.

text: The eukaryotic cell cycle is negatively regulated by cyclin-dependent kinase inhibitors (CKIs). p57Kip2 is a member of the Cip/Kip family of CKIs and frequently inactivated by genomic mutations associated with human overgrowth disorders. There is increasing evidence for p57 to control cellular processes in addition to cell cycle and CDK regulation including transcription, apoptosis, migration or development. In order to obtain molecular insights to unknown functions of p57, we performed a protein interaction screen. We identified the transcription regulator four-and-a-half LIM-only protein 2 (FHL2) as a novel p57-binding protein. Co-immunoprecipitation and reporter gene assays were used to elucidate the physiological and functional relevance of p57/FHL2 interaction. We found in cancer cells that endogenous p57 and FHL2 are in a complex. We observed a substantial induction of established FHL2-regulated gene promoters by p57 in reporter gene experiments and detected strong induction of the intrinsic transactivation activity of FHL2. Treatment of cells with histone deacetylase (HDAC) inhibitors and binding of exogenous FHL2 to HDACs indicated repression of FHL2 transcription activity by HDACs. In the presence of the HDAC inhibitor sodium butyrate activation of FHL2 by p57 is abrogated suggesting that p57 shares a common pathway with HDAC inhibitors. p57 competes with HDACs for FHL2 binding which might partly explain the mechanism of FHL2 activation by p57. These results suggest a novel function of p57 in transcription regulation.


title: Video-assisted thoracoscopic surgery right upper posterior segmentectomywith systemic mediastinal lymph node dissection.

text: Video-assisted thoracoscopic surgery (VATS) segmentectomy is a promising treatment option for rigorously selected patients with earlystage non-small cell lung cancer. In the presented video, a 66-year-old male with a 1.6 cm suspicious nodule located at the posterior segment of the right upper lobe was treated with anatomic segmentectomy and systemic mediastinal lymph node (LN) dissection successfully.


title: Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, double-blind, placebo-controlled phase 2 study.

text: BACKGROUND The interleukin-23 pathway is implicated genetically and biologically in the pathogenesis of Crohn's disease. We aimed to assess the efficacy and safety of risankizumab (BI 655066, Boehringer Ingelheim, Ingelheim, Germany), a humanised monoclonal antibody targeting the p19 subunit of interleukin-23, in patients with moderately-to-severely active Crohn's disease. METHODS In this randomised, double-blind, placebo-controlled phase 2 study, we enrolled patients at 36 referral sites in North America, Europe, and southeast Asia. Eligible patients were aged 18-75 years, with a diagnosis of Crohn's disease for at least 3 months, assessed as moderate-to-severe Crohn's disease at screening, defined as a Crohn's Disease Activity Index (CDAI) of 220-450, with mucosal ulcers in the ileum or colon, or both, and a Crohn's Disease Endoscopic Index of Severity (CDEIS) of at least 7 (≥4 for patients with isolated ileitis) on ileocolonoscopy scored by a masked central reader. Patients were randomised 1:1:1 using an interactive response system to a double-blind investigational product, and stratified by previous exposure to TNF antagonists (yes vs no). Patients received intravenous 200 mg risankizumab, 600 mg risankizumab, or placebo, at weeks 0, 4, and 8. The primary outcome was clinical remission (CDAI <150) at week 12 (intention-to-treat population). Safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02031276. FINDINGS Between March, 2014, and September, 2015, 213 patients were screened, and 121 patients randomised. At baseline, 113 patients (93%) had been previously treated with at least one tumour necrosis factor (TNF) antagonist (which had failed in 96 [79%]). At week 12, 25 (31%) of 82 risankizumab patients (pooled 41 patients in 200 mg and 41 patients in 600 mg arms) had clinical remission versus six (15%) of 39 placebo patients (difference vs placebo 15·0%, 95% CI 0·1 to 30·1; p=0·0489). Ten (24%) of 41 patients who received 200 mg risankizumab had clinical remission (9·0%, -8·3 to 26·2; p=0·31) and 15 (37%) of 41 who received the 600 mg dose (20·9%, 2·6 to 39·2; p=0·0252). 95 (79%) patients had adverse events (32 in the placebo group, 32 randomised to 200 mg risankizumab, 31 randomised to 600 mg risankizumab); 18 had severe adverse events (nine, six, three); 12 discontinued (six, five, one); 24 had serious adverse events (12, nine, three). The most common adverse event was nausea and most common serious adverse event was worsening of underlying Crohn's disease. No deaths occurred. INTERPRETATION In this short-term study, risankizumab was more effective than placebo for inducing clinical remission in patients with active Crohn's disease. Therefore, selective blockade of interleukin-23 via inhibition of p19 might be a viable therapeutic approach in Crohn's disease. FUNDING Boehringer Ingelheim.


title: Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience.

text: BACKGROUND The effects of convalescent plasma (CP) infusion, one of the treatment options for severe Middle East respiratory syndrome coronavirus (MERS-CoV) infections, have not yet been evaluated. METHODS Serological responses of CP-infused MERS patients during the 2015 Korean MERS outbreak at a tertiary care centre were evaluated. Serological activity was evaluated with anti-MERS-CoV enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig)G, ELISA IgA, immunofluorescence assay IgM and plaque reduction neutralization test (PRNT). Donor plasma and one or two recipient's serum samples per week of illness including one taken the day after each CP infusion were evaluated. For sensitivity and specificity analysis of ELISA IgG in predicting neutralization activity, a data set of 138 previously evaluated MERS-CoV-infected patients was used. RESULTS Three of thirteen MERS patients with respiratory failure received four CP infusions from convalesced MERS-CoV-infected patients, and only two of them showed neutralizing activity. Donor plasma with a PRNT titre 1:80 demonstrated meaningful serological response after CP infusion, while that with a PRNT titre 1:40 did not. ELISA IgG predicted neutralization activity of a PRNT titre ≥1:80 with more than 95% specificity at a cutoff optical density (OD) ratio of 1.6, and with 100% specificity at an OD ratio of 1.9. CONCLUSIONS For effective CP infusion in MERS, donor plasma with a neutralization activity of a PRNT titre ≥1:80 should be used. ELISA IgG could substitute for the neutralization test in resource-limited situations.


title: Comparing endoscopic ultrasound-guided core biopsies of solid pancreatic and extrapancreatic lesions: a large single-operator experience with a new fine-needle biopsy needle.

text: Background There has been a paradigm shift in tertiary centers from endoscopic ultrasound (EUS) fine-needle aspiration to EUS fine-needle biopsy (EUS-FNB) for tissue acquisition in solid lesions. While data exists on the use of FNB needles in solid pancreatic lesions, very few studies looked at the utility of FNB in solid extrapancreatic lesions. Our aim was to study and compare the technical success and feasibility of EUS-FNB in evaluating solid pancreatic and extrapancreatic lesions using a novel FNB needle. Methods We performed a retrospective cohort study of patients with solid masses or lesions needing EUS-guided core biopsy at the University of Utah between May 2016 and November 2017. All core biopsies were obtained using an Acquire™Fine Needle Biopsy Device (Boston Scientific Corporation, Natick MA, USA). Rapid on-site evaluation was performed by a board-certified cytopathologist in all cases. Results One hundred thirty-two patients (87 male) were included. Ninety-nine (73.3%) of the lesions were located in the pancreas. All needle sizes (19 G, 22 G and 25 G) had similar yield. The mean number of passes needed was 2.28±0.7. EUS-FNB of the pancreatic lesions had a diagnostic accuracy of 97.9%, comparable to the 97.2% for the biopsied extra-pancreatic lesions. Only 3 of 132 cases needed re-biopsy at a later date. No immediate adverse events were reported. Conclusion In this large, single-center study, EUS-FNB with a novel Franseen-design needle was proven to be an effective modality for tissue acquisition from both pancreatic and extrapancreatic solid lesions.


title: Methicillin-resistant staphylococcus aureus screening and eradication in the surgical intensive care unit: Is it worth it?

text: BACKGROUND The problem of intensive care unit methicillin-resistant Staphylococcus aureus (MRSA) infections has led to routine surveillance and eradication strategies. METHODS Our surgical intensive care unit (SICU) admissions receive MRSA nares cultures and if positive are isolated followed by eradication treatment. This strategy was retrospectively reviewed. RESULTS Our nares-positive culture rate was 21% (30/145), and the sputum positive (sputum+) rate was 18% (26/145). Positive nares culture (Nares+) was eradicated in 63%. The rate of sputum+ in Nares+ patients was 36% (9/25). The rate of sputum+ in Nares- was 10% (12/115; P = .003). The sputum+ SICU length of stay (LOS) (18 ± 12 days in 23 S+ patients) is longer than in sputum- (10 ± 9 days in 69 S-patients, P = .0002). CONCLUSIONS This SICU has high rates of both nares and sputum MRSA cultures. Our data suggest eradicating nares colonization may prevent pneumonia and might decrease SICU LOS.


title: Viral deubiquitinases: role in evasion of anti-viral innate immunity.

text: Host anti-viral innate-immune signalling pathways are regulated by a variety of post-translation modifications including ubiquitination, which is critical to regulate various signalling pathways for synthesis of anti-viral molecules. A homeostasis of host immune responses, induced due to viral infection and further ubiquitination, is maintained by the action of deubiquitinases (DUB). Infecting viruses utilize the process of deubiquitination for tricking host immune system wherein viral DUBs compete with host DUBs for inhibition of innate-immune anti-viral signalling pathways, which instead of maintaining an immune homeostasis bring about virus-mediated pathogenesis. This suggests that viruses co-evolve with their hosts to acquire similar machinery for tricking immune surveillance and establishing infection.


title: Access to Endovascular Treatment in Remote Areas: Analysis of the Reperfusion Treatment Registry of Catalonia.

text: BACKGROUND AND PURPOSE Since demonstration of the benefit of endovascular treatment (EVT) in acute ischemic stroke patients with proximal arterial occlusion, stroke care systems need to be reorganized to deliver EVT in a timely and equitable way. We analyzed differences in the access to EVT by geographical areas in Catalonia, a territory with a highly decentralized stroke model. METHODS We studied 965 patients treated with EVT from a prospective multicenter population-based registry of stroke patients treated with reperfusion therapies in Catalonia, Spain (SONIIA). Three different areas were defined: (A) health areas primarily covered by Comprehensive Stroke Centers, (B) areas primarily covered by local stroke centers located less than hour away from a Comprehensive Stroke Center, and (C) areas primarily covered by local stroke centers located more than hour away from a Comprehensive Stroke Center. We compared the number of EVT×100 000 inhabitants/year and time from stroke onset to groin puncture between groups. RESULTS Baseline characteristics were similar between groups. Throughout the study period, there were significant differences in the population rates of EVT across geographical areas. EVT rates by 100 000 in 2015 were 10.5 in A area, 3.7 in B, and 2.7 in C. Time from symptom onset to groin puncture was 82 minutes longer in group B (312 minutes [245-435]) and 120 minutes longer in group C (350 minutes [284-408]) compared with group A (230 minutes [160-407]; P<0.001). CONCLUSIONS Accessibility to EVT from remote areas is hampered by lower rate and longer time to treatment compared with areas covered directly by Comprehensive Stroke Centers.


title: Changing practice patterns: the impact of a randomized clinical trial on surgeons preference for treatment of type 3 supracondylar humerus fractures.

text: BACKGROUND A recent prospective randomized clinical trial (RCT) for comparison of medial and lateral entry pins with lateral entry pins for treatment of Gartland type 3 supracondylar humerus fractures (SCHF) was published, validating the national trend toward treatment of this injury with only lateral entry pins. But have surgeons actually changed their practice as a result of these recent data? The purpose of this study was to compare pin configuration, loss of reduction and rate of nerve injuries before and after the RCT. METHODS This was a retrospective review of patients with Gartland type 3 SCHF who were treated before the RCT (April 2000 to April 2003: 141 patients) and after the trial (April 2006 to April 2009: 126 patients). Eight surgeons were included. Patient demographic data, pin configuration, neurovascular status, and radiographic results were compared. Comparisons between the pretrial cohort and the posttrial cohort as a group as well as for each individual surgeon were performed. Comparisons included the choice of pin configuration, incidence of loss of radiographic reduction, iatrogenic nerve injuries, return to the operating room, and infection before and after the clinical trial. RESULTS There was a statistically different pin configuration in the pretrial group compared with the posttrial group (P<0.0001) with the posttrial group having a much higher percentage of bicolumnar lateral entry only pins. Five out of 8 surgeons individually had a statistically significant change in their practice pattern for pin configuration. There was no difference from pretrial to posttrial in loss of radiographic reduction, infection rate, iatrogenic nerve injuries, or return to the operating room. CONCLUSIONS Data showing change in surgeon practice have been relatively sparse. In this group of surgeons who participated in an RCT, there was a statistically significant change in pin configuration for treatment of Gartland type 3 SCHF after the results of the RCT were known. The change in clinical practice did not have an effect on outcomes. LEVEL OF EVIDENCE Level III.


docid: ncefkcap

title: Learning curve of transumbilical single incision laparoscopic cholecystectomy (SILS): a preliminary study of 80 selected patients with benign gallbladder diseases.

text: BACKGROUND Transumbilical single incision laparoscopic surgery (SILS) is a new laparoscopic procedure in which only one transumbilical incision is made, demonstrated as a scarless procedure. Here we report a single-center preliminary experience of transumbilical single incision laparoscopic cholecystectomy (SILC) in the treatment of benign gallbladder diseases, defining a single surgeon's learning curve. METHODS A total of 80 patients underwent SILC successfully by a single experienced laparoscopic surgeon. The operation was performed following the routine LC procedure. Then the perioperative demographics were recorded and the operative time was used to define the learning curve. RESULTS The study group included 27 male and 53 female patients with gallstones (56 cases), cholesterol polyps (16 cases), an adenomatous polyp (3 cases), adenomyomatosis (1 case), or complex diseases (4 cases), and all consented to undergo SILC. No patient was converted to normal LC or open surgery. There were no perioperative port-related or surgical complications. The average operative time was 46.9 ± 14.6 min. The average postoperative hospital stay was 1.8 ± 1.3 days. The learning curve of the SILC procedures for this series of selected patients confirmed that SILC is a feasible, safe, and effective approach to the treatment of benign gallbladder diseases. CONCLUSIONS For experienced laparoscopic surgeons, SILC is an easy and safe procedure. Patients benefit from milder pain, a lower incidence of port-related complications, better cosmesis, and fast recovery. The SILC procedure may become another option for the treatment of benign gallbladder diseases for selected patients.


Protecting society. Biological security and dual-use dilemma in the life sciences--status quo and options for the future.


docid: fqknallb

title: Equid herpesvirus type 4 uses a restricted set of equine major histocompatibility complex class I proteins as entry receptors.

text: Equid herpesvirus type 1 (EHV-1) was shown to use an unusual receptor for cellular entry - MHC-I molecules. Here, we demonstrated that the closely related EHV, EHV-4, also uses this strategy for cellular invasion, both in equine cells in culture and in the heterologous, non-permissive murine mastocytoma cell line (P815) after stable transfection with horse MHC-I genes. Using a panel of P815 cell lines transfected with individual horse MHC-I genes, we provided support for the hypothesis that EHV-1 and EHV-4 target classical polymorphic MHC-I molecules as viral entry receptors. All known equine MHC-I molecules from the two principal classical polymorphic loci specify alanine at position 173 (A173), whilst other MHC-I loci encoded different amino acids at this position and did not permit viral entry. Site-directed mutagenesis of position 173 diminished or enhanced viral entry, depending upon the initial amino acid. However, there were other, as yet undefined, constraints to this process: MHC-I genes from two non-classical loci carried A173 but did not enable viral entry in P815 transfectants. Our study suggested that the capacity to bind MHC-I molecules arose in the common ancestor of EHV-1 and EHV-4. The widespread occurrence of A173 in classical polymorphic horse MHC-I molecules indicated that horses of most MHC haplotypes should be susceptible to infection via this entry portal.


title: Perceived vaccination status in ecotourists and risks of anthropozoonoses.

text: Anthropozoonotic (human to nonhuman animal) transmission of infectious disease poses a significant threat to wildlife. A large proportion of travelers to tropical regions are not protected against vaccine-preventable illnesses, and a majority of these travelers demonstrate poor recall of actual vaccination status. Here we characterize self-perceived vaccination status among a large sample of ecotourists at the Sepilok Orangutan Rehabilitation Centre, Sabah, Malaysia. Despite their recognized travel itinerary to view endangered animals, tourists at wildlife sanctuaries are not adequately protected against vaccine-preventable illnesses. Of 633 surveys, over half reported being currently vaccinated against tuberculosis, hepatitis A, hepatitis B, polio, and measles. Fewer participants reported current vaccination status for influenza, rabies, and chickenpox. Despite the fact that the majority of visitors to Sepilok are from temperate regions where influenza is relatively more prevalent, 67.1% of those surveyed with medical-related occupations reported not being currently vaccinated for influenza. Ecotourists concerned about environmental protection are themselves largely unaware of their potential contribution to the spread of diseases to animals. The risks of negatively affecting animal populations must be communicated to all concerned parties, and this may begin by urging travelers to examine their actual vaccination status, particularly as the ecotourism industry continues its rapid expansion, and is seen increasingly as a possible tool to save great ape populations from extinction.


title: Time-series analysis of the relationship of antimicrobial use and hand hygiene promotion with the incidence of healthcare-associated infections.

text: We analyzed the effect of antimicrobial use and implementation of a hand hygiene program on the incidence of healthcare-associated infections (HAIs) and healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) infections at the Chung Shan Medical University Hospital (Taichung, Taiwan). Monthly data were retrospectively reviewed from January 2004 to December 2010. Use of antimicrobials and alcohol-based hand cleaner were separately regressed against the incidences of HAIs and HA-MRSA infections. Infection incidence was expressed as persons per 1000 patient days (PDs), monthly use of i.v. antibiotics was expressed as defined daily doses per 1000 PDs and monthly alcohol-based hand cleaner use was expressed as bottle per 1000 PDs. Multivariate analysis indicated that use of hand cleaner was associated with reduced incidence of HAIs (P=0.0001) and HA-MRSA infections (P<0.0001). Time-series analysis indicated that increased use of hand cleaner was significantly associated with significant decreases in the incidences of HAIs and HA-MRSA infections. Total antibiotic use had no significant effect on HAIs, but was associated with more HA-MRSA infections. In addition, the use of J01CR01 antibiotics (combinations of penicillins, including β-lactamase inhibitors) in particular was correlated with significantly increased incidence of HA-MRSA infections. Our forecasting model demonstrates the efficacy of a hand hygiene program and the need to limit the use of certain restricted antimicrobials in order to reduce the incidence of HAIs and HA-MRSA infections.


title: P2Y6 receptor inhibition aggravates ischemic brain injury by reducing microglial phagocytosis.

text: INTRODUCTION Clearance of damaged cells and debris is beneficial for the functional recovery after ischemic brain injury. However, the specific phagocytic receptor that mediates microglial phagocytosis after ischemic stroke is unknown. AIM To investigate whether P2Y6 receptor-mediated microglial phagocytosis is beneficial for the debris clearance and functional recovery after ischemic stroke. RESULTS The expression of the P2Y6 receptor in microglia increased within 3 days after transient middle cerebral artery occlusion. Inhibition of microglial phagocytosis by the selective inhibitor MRS2578 enlarged the brain atrophy and edema volume after ischemic stroke, subsequently aggravated neurological function as measured by modified neurological severity scores and Grid walking test. MRS2578 treatment had no effect on the expression of IL-1α, IL-1β, IL-6, IL-10, TNF-α, TGF-β, and MPO after ischemic stroke. Finally, we found that the expression of myosin light chain kinase decreased after microglial phagocytosis inhibition in the ischemic mouse brain, which suggested that myosin light chain kinase was involved in P2Y6 receptor-mediated phagocytosis. CONCLUSION Our results indicate that P2Y6 receptor-mediated microglial phagocytosis plays a beneficial role during the acute stage of ischemic stroke, which can be a therapeutic target for ischemic stroke.


title: Structural and Mechanistic Insights into Protein Translocation.

text: Many proteins are translocated across the endoplasmic reticulum (ER) membrane in eukaryotes or the plasma membrane in prokaryotes. These proteins use hydrophobic signal sequences or transmembrane (TM) segments to trigger their translocation through the protein-conducting Sec61/SecY channel. Substrates are first directed to the channel by cytosolic targeting factors, which use hydrophobic pockets to bind diverse signal and TM sequences. Subsequently, these hydrophobic sequences insert into the channel, docking into a groove on the outside of the lateral gate of the channel, where they also interact with lipids. Structural data and biochemical experiments have elucidated how channel partners, the ribosome in cotranslational translocation, and the eukaryotic ER chaperone BiP or the prokaryotic cytosolic SecA ATPase in posttranslational translocation move polypeptides unidirectionally across the membrane. Structures of auxiliary components of the bacterial translocon, YidC and SecD/F, provide additional insight. Taken together, these recent advances result in mechanistic models of protein translocation.


title: Perspective on COVID-19: Finally, Telemedicine at Center Stage.

text: The new world order caused by COVID-19 virus, associated with severe acute respiratory syndrome, multiple organ failure, and very high mortality, has brought about many changes to our world. Suddenly, the medical community, and those who finance the health care sector, realized that telemedicine and telepresence are applicable, desirable, acceptable, and much sought after by our patients and we can manage just about every disease and condition. Although, by and large, telemedicine has faced challenges and perhaps some resistance, despite its great potential, it has become evident that telemedicine can provide rapid, safe, and high-quality care remotely during this pandemic, the largest one since 1918. Perhaps one benefit of suffering through the COVID-19 pandemic will be the establishment of a new virtual medical world order, and that telemedicine has taken its deserving place in health care: prime time and a center stage.


title: COVID-19, Australia: Epidemiology Report 3 (Reporting week ending 19:00 AEDT 15 February 2020).

text: This is the third epidemiological report for coronavirus disease 2019 (COVID-19), previously known as novel coronavirus (2019-nCoV), from the virus now known as SARS-CoV-2, reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 15 February 2020. It includes data on the COVID-19 Australian cases, the international situation and current information on the severity, transmission and spread.


title: The impact of COVID-19 related lockdown on ophthalmology training programs in India - Outcomes of a survey.

text: Purpose In 2020, in response to the emergence and global spread of the disease COVID-19, caused by a new variant of coronavirus 2019-nCoV, the government of India ordered a nationwide lockdown for 21 days, which was then extended to a total of over 50 days. The aim of this study is to assess the effect of the lockdown on ophthalmic training programs across India. Methods An online survey was sent across to trainee ophthalmologists across India through various social media platforms. Results In all, 716 trainees responded; the average age was 29.1 years. Results showed that majority of the respondents were enrolled in residency programs (95.6%; 685/716) and the others were in fellowship programs. About 24.6% (176/716) of the trainees had been deployed on 'COVID-19 screening' duties. Nearly 80.7% (578/716) of the trainees felt that the COVID-19 lockdown had negatively impacted their surgical training. Furthermore, 54.8% (392/716) of the trainees perceived an increase in stress levels during the COVID-19 lockdown and 77.4% (554/716) reported that their family members had expressed an increased concern for their safety and wellbeing since the lockdown began. In all, 75.7% (542/716) of the respondents felt that online classes and webinars were useful during the lockdown period. Conclusion Our survey showed that majority ophthalmology trainees across the country felt that the COVID-19 lockdown adversely affected their learning, especially surgical training. While most found online classes and webinars useful, the trainees' perceived stress levels were higher than normal during the lockdown. Training hospitals should take cognizance of this and reassure trainees; formulate guidelines to augment training to compensate for the lost time as well as mitigate the stress levels upon resumption of regular hospital services and training. Going ahead, permanent changes such as virtual classrooms and simulation-based training should be considered.


What If I Told You the COVID-19 Pandemic Is Not Entirely Bad?


title: In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses.

text: Background/Aims As the coronavirus disease-2019 global pandemic progresses, screening of antiviral agents effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed. In addition, considering the viral load kinetics of SARS-CoV-2, which peaks early in the illness, and the massive burden of the disease, which may increase in the near future, identifying well-tolerated oral antivirals becomes increasingly important. We examined the in vitro activity of lopinavir/ritonavir and hydroxychloroquine on SARS-CoV-2, at concentrations which can be used to treat coronavirus-19 patients with little concern of toxicity. Methods Lopinavir/ritonavir (7/1.75 μg/mL), hydroxychloroquine base (1 or 2 μg/mL), or a combination thereof were administered 1 hour after the inoculation of SARS-CoV-2 to Vero cells at a multiplicity of infection of 0.05. We examined cytopathic effects of virus 48 hours after administration of the respective treatments and measured viral loads at three time points (0, 24, and 48 hours post-treatment) by quantitative real-time reverse-transcription polymerase chain reaction, and compared the results obtained from the different antiviral regimens tested. Results The severity of cytopathic effects was lower in lopinavir/ritonavir-treated cells, and viral load was significantly reduced in this group compared with the control group (p < 0.001). However, hydroxychloroquine did not show significant inhibitory effects on anti-SARS-CoV-2-mediated cytotoxicity or on viral load at either concentration. Conclusions Lopinavir/ritonavir showed significant inhibitory effects on SARS-CoV-2 in vitro at its usual plasma concentration. However, the in vitro antiviral activity of hydroxychloroquine at concentrations commonly used in humans was minimal, whether used alone or in combination with lopinavir/ritonavir.


title: Novel TRAIL sensitizer Taraxacum officinale F.H. Wigg enhances TRAIL-induced apoptosis in Huh7 cells.

text: TRAIL (TNF-related apoptosis inducing ligand) is a promising anti-cancer drug target that selectively induces apoptosis in cancer cells. However, many cancer cells are resistant to TRAIL-induced apoptosis. Therefore, reversing TRAIL resistance is an important step for the development of effective TRAIL-based anti-cancer therapies. We previously reported that knockdown of the TOR signaling pathway regulator-like (TIPRL) protein caused TRAIL-induced apoptosis by activation of the MKK7-c-Jun N-terminal Kinase (JNK) pathway through disruption of the MKK7-TIPRL interaction. Here, we identified Taraxacum officinale F.H. Wigg (TO) as a novel TRAIL sensitizer from a set of 500 natural products using an ELISA system and validated its activity by GST pull-down analysis. Furthermore, combination treatment of Huh7 cells with TRAIL and TO resulted in TRAIL-induced apoptosis mediated through inhibition of the MKK7-TIPRL interaction and subsequent activation of MKK7-JNK phosphorylation. Interestingly, HPLC analysis identified chicoric acid as a major component of the TO extract, and combination treatment with chicoric acid and TRAIL induced TRAIL-induced cell apoptosis via JNK activation due to inhibition of the MKK7-TIPRL interaction. Our results suggest that TO plays an important role in TRAIL-induced apoptosis, and further functional studies are warranted to confirm the importance of TO as a novel TRAIL sensitizer for cancer therapy. © 2015 Wiley Periodicals, Inc.


title: Mind and Brain: Consciousness in Unresponsive Subjects.

text: A new study shows that subjects rendered unresponsive with sedatives do not exhibit a stereotypic 'unconscious' response to direct cortical stimulation; instead, agent-specific effects are seen that can distinguish between unresponsiveness with and without consciousness.


Covid-19: how a virus is turning the world upside down.


NS1 is the fluid for "flu-transmission".


title: Impact of procedural time on clinical and angiographic outcomes in patients with acute ischemic stroke receiving endovascular treatment.

text: BACKGROUND Procedural time in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy may affect clinical outcomes. We performed a pooled analysis of the effect of procedural time on clinical outcomes using data from three prospective endovascular treatment trials. OBJECTIVE To examine the relationship between endovascular procedural time and clinical outcomes of patients with AIS following endovascular treatment. METHODS We analyzed data from SWIFT, STAR, and SWIFT PRIME studies, including baseline characteristics: National Institutes of Health Stroke Scale (NIHSS) score on admission, intracranial hemorrhage rates, and modified Rankin Scale score at 3 months. The Thrombolysis in Cerebral Infarction (TICI) scale was used to grade postprocedure recanalization. We recorded two procedural time intervals: (1) symptom onset to groin puncture and (2) groin puncture to angiographic recanalization. A multivariate analysis was performed using a logistic regression model to analyze predictors of unfavorable outcome. RESULTS We analyzed 301 patients who had undergone endovascular treatment and had near-complete or complete recanalization (TICI 2b or 3). At 3 months, 122 patients (40.5%) had unfavorable outcomes. The rate of favorable outcomes was significantly higher when the procedural time was <60 min compared with ≥60 min (62% vs 45%, p=0.020). Predictors of unfavorable outcome at 3 months were age (unit 10 years, OR=0.62, 95% CI 0.46 to 0.82, p<0.001), onset to groin puncture time (unit hour, OR=0.61, 95% CI 0.48 to 0.77, p<0.001), groin puncture to recanalization (unit 10 min, OR=0.89, 95% CI 0.80 to 0.99, p=0.032), baseline NIHSS score (20-28 vs 8-10, OR=0.17, 95% CI 0.05 to 0.62, p=0.018), and collaterals (OR=1.48, 95% CI 1.04 to 2.10, p=0.029). CONCLUSION Procedural time in patients with stroke undergoing mechanical thrombectomy may be an important determinant of favorable outcomes in those with recanalization.


docid: tldnnbyk

title: Evaluation of a new energy device for parenchymal transection in laparoscopic liver resection.

text: INTRODUCTION THUNDERBEAT (TB) is a novel device that uses both ultrasonic and advanced bipolar energies for hemostasis. Several recent human studies have proved the safety and efficacy of TB in different surgical procedures, but there have been no similar studies about its efficacy in hepatic parenchymal transection. Therefore, the aim of the study was to assess the safety and efficacy of the TB device in laparoscopic liver resection. METHODS This retrospective study compared TB and ultrasonic Harmonic devices in 80 patients who underwent laparoscopic liver resection from 2010 to 2016 in our institution. To reduce the selection bias, the two groups were matched in a 1-to-2 ratio on the basis of propensity scores. RESULTS There were no differences in the preoperative patient characteristics between the two groups. The extent of liver resection was comparable between the groups. Although the Harmonic group's intraoperative blood loss and operative time were less than that of the TB group, the differences were not statistically significant (P = 0.08, P = 0.32, respectively). Postoperative complications, mortality within 90 days, and hospital stay were comparable between the two groups. CONCLUSION TB is as safe and effective for parenchymal transection in laparoscopic hepatectomy as ultrasonic devices, but it is not a superior alternative.


title: Revival of the identification of cytotoxic T-lymphocyte epitopes for immunological diagnosis, therapy and vaccine development.

text: Immunogenic T-cell epitopes have a central role in the cellular immunity against pathogens and tumors. However, in the early stage of cellular immunity studies, it was complicated and time-consuming to identify and characterize T-cell epitopes. Currently, the epitope screening is experiencing renewed enthusiasm due to advances in novel techniques and theories. Moreover, the application of T-cell epitope-based diagnoses for tuberculosis and new data on epitope-based vaccine development have also revived the field. There is a growing knowledge on the emphasis of epitope-stimulated T-cell immune responses in the elimination of pathogens and tumors. In this review, we outline the significance of the identification and characterization of T-cell epitopes. We also summarize the methods and strategies for epitope definition and, more importantly, address the relevance of cytotoxic T-lymphocyte epitopes to clinical diagnoses, therapy and vaccine development.


title: Initial experience with a new distal intermediate and aspiration catheter in the treatment of acute ischemic stroke: clinical safety and efficacy.

text: PURPOSE To describe our initial experience with the novel 5 F SOFIA (Soft Torqueable catheter Optimized For Intracranial Access) intermediate and aspiration catheter for endovascular treatment of patients with acute ischemic stroke. METHODS A retrospective review was performed in three centers of prospectively collected data of all stroke patients who underwent endovascular therapy using the SOFIA catheter. Patients were enrolled between November 2013 and December 2014. The primary endpoint of the study was accessibility of the thrombus with the SOFIA catheter. As a secondary endpoint, the study assessed recanalization success (Thrombolysis In Cerebral Infarction (TICI) ≥2b). Clinical presentation on admission and discharge was also documented. In addition, catheter- and procedure-related complications (particularly thromboembolic complications) were recorded. RESULTS The SOFIA catheter was used in 115 acute stroke procedures. In 110 cases (96%) the catheter could be advanced to the occlusion site. After mechanical thrombectomy, successful recanalization (TICI ≥2b) was documented in 86.9%. There were no complications related to positioning of the catheter. Distal thrombus migration into a new vascular territory occurred in three patients following thrombectomy with a stent retriever (2.6%). The mean NIH Stroke Scale (NIHSS) score on admission was 16.8±6 and at discharge the mean NIHSS score was 8.2±7.7. Sixteen patients died. CONCLUSIONS The SOFIA catheter is a safe and efficient catheter for endovascular stroke therapy.


title: Are we fully utilizing the functionalities of modern operating room ventilators?

text: PURPOSE OF REVIEW The modern operating room ventilators have become very sophisticated and many of their features are comparable with those of an ICU ventilator. To fully utilize the functionality of modern operating room ventilators, it is important for clinicians to understand in depth the working principle of these ventilators and their functionalities. RECENT FINDINGS Piston ventilators have the advantages of delivering accurate tidal volume and certain flow compensation functions. Turbine ventilators have great ability of flow compensation. Ventilation modes are mainly volume-based or pressure-based. Pressure-based ventilation modes provide better leak compensation than volume-based. The integration of advanced flow generation systems and ventilation modes of the modern operating room ventilators enables clinicians to provide both invasive and noninvasive ventilation in perioperative settings. Ventilator waveforms can be used for intraoperative neuromonitoring during cervical spine surgery. SUMMARY The increase in number of new features of modern operating room ventilators clearly creates the opportunity for clinicians to optimize ventilatory care. However, improving the quality of ventilator care relies on a complete understanding and correct use of these new features. VIDEO ABSTRACT: http://links.lww.com/COAN/A47.


docid: viajeomc

title: From feedback loop transitions to biomarkers in the psycho-immune-neuroendocrine network: Detecting the critical transition from health to major depression.

text: BACKGROUND Biological pathways underlying major depressive disorder (MDD) can be viewed as systems biology networks. The psycho-immune-neuroendocrine (PINE) network comprises central nervous, immune, endocrine and autonomic systems, integrating biological mechanisms of MDD. Such networks exhibit recurrent motifs with specific functions, including positive and negative feedback loops, and are subject to critical transitions, influenced by feedback loop transitions (FLTs). AIMS We aim to identify critical feedback loops and their FLTs, as well sentinel network nodes (SNNs), key network nodes that drive FLTs, within the PINE network. Examples of biomarkers are provided which may reflect early warning signs of impending critical transition to MDD. RESULTS Disruption of homeostatic feedback loops reflects the physiological transition to MDD. Putative FLTs are identified within hypothalamic-pituitary-adrenal (HPA) and sympathetic-parasympathetic axes, the kynurenine pathway, gut function and dysbiosis. CONCLUSIONS Progression from health to disease is driven by FLTs in the PINE network, which is likely to undergo changes characteristic of system instability. Biomarkers of system instability may effectively predict the critical transition to MDD.


title: Expert Opinion on the Management and Follow-up of Uveitis Patients during SARS-CoV-2 Outbreak.

text: INTRODUCTION Routine medical and ophthalmic care is being drastically curtailed in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Uveitis patients require particular attention because of their theoretical risk of viral infection, in the context of therapeutic immunosuppression. AREAS COVERED This collaborative work proposes practical management and follow-up criteria for uveitis patients in the context of the ongoing SARS-CoV-2 pandemic. EXPERT OPINION Management should proceed as usual when access to healthcare is possible in patients who do not belong to a group at high risk of severe SARS-CoV-2 infection; and in uncontrolled uveitis cases. In case of reduced access to eye clinics or high risk of SARS-CoV-2 infection, patients' management should be stratified based on their clinical presentation. In non-severe uveitis cases, the use of systemic steroids should be avoided, and local steroids preferred whenever possible. In uncontrolled situations where there is real risk of permanent visual loss, high-dose intravenous steroids and/or systemic immunosuppressants and/or biotherapies can be administered depending on the severity of eye disease. Immunosuppressive therapy should not be withheld, unless the patient develops SARS-CoV2 infection.


docid: opesjbhe

title: Concerns about injectable naltrexone for opioid dependence.


title: Video. Laparoscopic distal pancreatectomy and splenectomy for splenic artery aneurysm.

text: BACKGROUND Large splenic artery aneurysms are rare but comprise 60% of all visceral artery aneurysms. Most are found incidentally and rupture in the nonpregnant patient has an approximate 25 to 36% mortality rate. Historically these have been managed with an open surgical approach for resection. METHODS We present the case of a 43-year-old man with a recent episode of bacterial endocarditis with an incidental finding of a large 6-cm splenic artery aneurysm. There was noted to be splenic vein occlusion and multiple splenic infarcts versus abscesses on preoperative imaging. There were concerns that this represented a mycotic aneurysm. He underwent laparoscopic en bloc splenic artery aneurysm resection with splenectomy and distal pancreatectomy with preoperative prophylactic balloon catheter placement. RESULTS His large splenic artery aneurysm was adjacent to the splenic hilum. Due to the splenic vein occlusion, there were large collateral vessels complicating the dissection. Additionally, the aneurysm had dense adhesions to the tail of the pancreas from a desmoplastic reaction. To safely remove the aneurysm, a distal pancreatectomy was included with resection of the spleen. The specimen was successfully removed intact using the laparoscopic approach. The patient had an uneventful recovery and was discharged home on postoperative day 2. Final pathology revealed no evidence of bacterial etiology. CONCLUSIONS Laparoscopic distal pancreatectomy with splenectomy is an appropriate minimally invasive option for the treatment of splenic artery aneurysms. This video demonstrates the technical challenges and management options for successfully completing a distal pancreatectomy and splenectomy in the face of a splenic artery aneurysm.


title: Business Intelligence applied to Emergency Medical Services in the Lombardy region during SARS-CoV-2 epidemic.

text: BACKGROUND AND AIM OF THE WORK On the 21st of February, the first patient was tested positive for SARS-CoV-2 at Codogno hospital in the Lombardy region. From that date, the Regional Emergency Medical Services (EMS) Trust (AREU) of the Lombardy region decided to apply Business Intelligence (BI) to the management of EMS during the epidemic. The aim of the study is to assess in this context the impact of BI on EMS management outcomes. METHODS Since the beginning of the COVID-19 outbreak, AREU is using BI daily to track the number of first aid requests received from 112. BI analyses the number of requests that have been classified as respiratory and/or infectious episodes during the telephone dispatch interview. Moreover, BI allows identifying the numerical trend of episodes in each municipality (increasing, stable, decreasing). RESULTS AREU decides to reallocate in the territory the resources based on real-time data recorded and elaborated by BI. Indeed, based on that data, the numbers of vehicles and personnel have been implemented in the municipalities that registered more episodes and where the clusters are supposed to be. BI has been of paramount importance in taking timely decisions on the management of EMS during COVID-19 outbreak. Conclusions: Even if there is little evidence-based literature focused on BI impact within the health care, this study suggests that BI can be usefully applied to promptly identify clusters and patterns of the SARS-CoV-2 epidemic and, consequently, make informed decisions that can improve the EMS management response to the outbreak.


Novel treatment targets for COVID-19: Contribution from molecular psychiatry.


title: The Amyloid-beta rich CNS environment alters myeloid cell functionality independent of their origin.

text: Microglia, the innate immune cells of the central nervous system (CNS) survey their surroundings with their cytoplasmic processes, phagocytose debris and rapidly respond to injury. These functions are affected by the presence of beta-Amyloid (Aβ) deposits, hallmark lesions of Alzheimer's disease (AD). We recently demonstrated that exchanging functionally altered endogenous microglia with peripheral myeloid cells did not change Aβ-burden in a mouse model mimicking aspects of AD at baseline, and only mildly reduced Aβ plaques upon stimulation. To better characterize these different myeloid cell populations, we used long-term in vivo 2-photon microscopy to compare morphology and basic functional parameters of brain populating peripherally-derived myeloid cells and endogenous microglia. While peripherally-derived myeloid cells exhibited increased process movement in the non-diseased brain, the Aβ rich environment in an AD-like mouse model, which induced an alteration of surveillance functions in endogenous microglia, also restricted functional characteristics and response to CNS injury of newly recruited peripherally-derived myeloid cells. Our data demonstrate that the Aβ rich brain environment alters the functional characteristics of endogenous microglia as well as newly recruited peripheral myeloid cells, which has implications for the role of myeloid cells in disease and the utilization of these cells in Alzheimer's disease therapy.


title: Endotracheal bioimpedance cardiography improves immediate postoperative outcome: a case-control study in off-pump coronary surgery.

text: The feasibility and clinical utility of the endotracheal cardiac output monitor (ECOM) to optimize intraoperative hemodynamics and improve short-term outcome in off-pump coronary artery bypass grafting (OPCAB) is unknown. We aimed to compare ECOM with a standard of care in that specific surgical setting. Twenty consecutive adult ECOM-monitored patients undergoing OPCAB were prospectively included (ECOM group) and retrospectively compared to 42 patients scheduled for similar surgery without ECOM monitoring (Control group). The primary endpoint was the global rate of postoperative admission to the intensive care unit (ICU). Secondary endpoints were the time to extubation, the length of stay in ICU and in hospital, the postoperative levels of lactate and troponin and the feasibility of ECOM. The rate of postoperative admission to the ICU was 38/42 (90%) in the Control group versus 11/20 (55%) in the ECOM group, P = 0.008. None unexpected admission for hemodynamic instability was observed in the ECOM group. The time to extubation, the length of stay in ICU, and both troponin level at admission and lactate level at H6 were all significantly decreased in the ECOM group. On a scale ranging from 0 to 5, convenience and satisfaction regarding ECOM were 4.30 ± 1.17 and 3.45 ± 0.68, respectively. The systematic use of ECOM is associated with a significant reduction in the rate of admission to the ICU and an improvement in immediate outcome in OPCAB.


title: Enhancing a sedation score to include truly noxious stimulation: the Extended Observer's Assessment of Alertness and Sedation (EOAA/S).

text: BACKGROUND Although the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) is frequently used in sedation-related drug and device studies, a major shortcoming is that it does not differentiate between lighter and deeper levels of general anaesthesia because the only noxious stimulus of the MOAA/S is a trapezius squeeze. The primary aim of this investigation was to expand the MOAA/S score to include truly noxious stimulation, thereby extending the dynamic range of the assessment to include sedation states consistent with deeper levels of general anaesthesia. METHODS Twenty healthy volunteers received target controlled infusions of fentanyl (target=0.8 ng ml(-1)) and propofol (starting at 0.5 µg ml(-1) and gradually increasing to 5 µg ml(-1)). At each propofol concentration, a MOAA/S score was obtained before and after tetanic electrical stimulation. The tetanic electrical stimulation current was gradually increased until the subject responded or until 50 mA was delivered without a response. A pharmacodynamic model was constructed to characterize the concentration-effect relationship between propofol and the MOAA/S scores. RESULTS All subjects required a significantly higher propofol concentration to produce unresponsiveness to tetanic electrical stimulation at 50 mA compared with a standardized trapezius squeeze. The pharmacodynamic model adequately characterized the concentration-effect relationship. CONCLUSIONS The Extended Observer's Assessment of Alertness and Sedation (or EOAA/S) extends the range of the widely used MOAA/S score to include truly noxious stimulation, thereby enabling the identification of drug-induced central nervous system depression representative of surgical anaesthesia.


title: Disruption of Inferior Longitudinal Fasciculus Microstructure in Parkinson's Disease: A Systematic Review of Diffusion Tensor Imaging Studies.

text: Parkinson's disease (PD) is a neurodegenerative disorder accompanied by a series of pathological mechanisms which contribute to a variety of motor and non-motor symptoms. Recently, there has been an increasing interest in structural diffusion tensor imaging (DTI) in PD which has shed light on our understanding of structural abnormalities underlying PD symptoms or its associations with pathological mechanisms. One of the white matter tracts shown to be disrupted in PD with a possible contribution to some PD symptoms is the inferior longitudinal fasciculus (ILF). On the whole, lower ILF integrity contributes to thought disorders, impaired visual emotions, cognitive impairments such as semantic fluency deficits, and mood disorders. This review outlines the microstructural changes in ILF associated with systemic inflammation and various PD symptoms like cognitive decline, facial emotion recognition deficit, depression, color discrimination deficit, olfactory dysfunction, and tremor genesis. However, few studies have investigated DTI correlates of each symptom and larger studies with standardized imaging protocols are required to extend these preliminary findings and lead to more promising results.


title: High respiratory virus oropharyngeal carriage rate during Kingella kingae osteoarticular infections in children.

text: AIM Kingella kingae osteoarticular (KKO) infections are frequently associated with upper respiratory tract infections. However, no comparative studies detecting respiratory viruses had ever been performed between KKO and non-KKO (NKO). PATIENTS & METHODS Eighteen viruses were searched by FilmArray(®) Respiratory Panel (BioFire Diagnostics, UT, USA) in the oropharynx of 6-to-48-month-children admitted for KKO and NKO in 2013. RESULTS At least one virus was detected in the oropharynx of 19/21 (90.5%) KKO and 3/8 (37.5%) NKO cases (p = 0.008). In KKO group, human rhinovirus was predominant (12/21; 57.1%), especially during winter (7/11; 63.6%) despite its low concomitant circulation (<10%). Human rhinovirus was found in 2/8 (25%) in NKO group. CONCLUSION Higher prevalence of respiratory virus in oropharynx was observed in KKO than NKO, strengthening their putative role in KKO pathophysiology.


title: Morphologic characteristics of macroscopic peritoneal finding in patients with peritoneal dialysis.

text: Peritoneal dialysis (PD) has been an attractive treatment for end-stage kidney disease. Long-term exposure to the PD solution creates functional and morphological alterations, and these alterations diminish the efficacy of PD. It is important to establish an evaluation of the changes in PD patients and strategies for the prevention of PD damage and encapsulating peritoneal sclerosis (EPS). We determined the relationship between clinical findings and macroscopic morphological findings by laparoscopy in patients receiving PD. Macroscopic intraperitoneal findings were recorded at the PD catheter removal in 23 PD patients. We examined macroscopic morphological findings such as fibrin deposition, peritoneal turbidity, vasculopathy, adhesion and calcification in both parietal and visceral peritoneum of upper and lower peritoneal cavities, and assessed the score semi-quantitatively. We then evaluated the relationship between the morphological score and clinical findings, especially observational parts and findings in EPS patients. The total macroscopic score increased with PD duration. Peritoneal turbidity, fibrin deposition, and calcification were observed in the whole peritoneal cavity. Scores of fibrin deposition, turbidity, and calcification increased with PD duration. Vasculopathy in the parietal peritoneum was more serious compared with that in the visceral peritoneum, but there was no difference in the vasculopathy between the upper and lower areas. A characteristic of the macroscopic findings in EPS patients was peritoneal calcification in this study. It appears that macroscopic findings using laparoscopy is significant in evaluating the degree of the peritoneum damage and predicting EPS development.


title: Pathophysiological approach to bowel dysfunction after segmental colorectal resection for deep endometriosis infiltrating the rectum: a preliminary study.

text: BACKGROUND Colorectal segmental resection is performed worldwide in a majority of women presenting with symptomatic deep endometriosis infiltrating the rectum. The aim of the present study was to investigate the pathophysiological mechanisms involved in post-operative digestive dysfunction. METHODS We selected patients managed by colorectal resection for rectal endometriosis, who had developed post-operative severe constipation and whose follow up was superior to 24 months. To assess the mechanisms involved in the pathogenesis of this complaint, we performed a step-by-step work up including: low digestive tract endoscopy, colonic transit time measurement and when appropriate anorectal manometry, electromyography and defecographic evaluation. RESULTS Five out of 25 (20%) patients, whose age ranged from 27 to 41 years, were investigated for severe post-operative terminal constipation. Four different mechanisms responsible for terminal constipation were identified: tight stenosis of the colorectal anastomosis, post-operative neurological sequelae, colonic intussusception through the colorectal anastomosis and transit constipation that developed post surgery. CONCLUSIONS Post-operative constipation is a frequent complaint in women managed by colorectal resection for rectal endometriosis. A multidisciplinary approach is mandatory as pathophysiologic mechanisms may vary and prove difficult to understand. The risk of post-operative bowel dysfunction following colorectal endometriosis must be taken into account whenever this technique is proposed in young women presenting with a benign disease such as deep endometriosis.


title: Preclinical Testing of a Novel Thin Film Nitinol Flow-Diversion Stent in a Rabbit Elastase Aneurysm Model.

text: BACKGROUND AND PURPOSE Thin film nitinol can be processed to produce a thin microporous sheet with a low percentage of metal coverage (<20%) and high pore attenuation (∼70 pores/mm(2)) for flow diversion. We present in vivo results from the treatment of experimental rabbit aneurysms by using a thin film nitinol-based flow-diversion device. MATERIALS AND METHODS Nineteen aneurysms in the rabbit elastase aneurysm model were treated with a single thin film nitinol flow diverter. Devices were also placed over 17 lumbar arteries to model perianeurysmal branch arteries of the intracranial circulation. Angiography was performed at 2 weeks (n = 7), 1 month (n = 8), and 3 months (n = 4) immediately before sacrifice. Aneurysm occlusion was graded on a 3-point scale (grade I, complete occlusion; grade II, near-complete occlusion; grade III, incomplete occlusion). Toluidine blue staining was used for histologic evaluation. En face CD31 immunofluorescent staining was performed to quantify neck endothelialization. RESULTS Markedly reduced intra-aneurysmal flow was observed on angiography immediately after device placement in all aneurysms. Grade I or II occlusion was noted in 4 (57%) aneurysms at 2-week, in 6 (75%) aneurysms at 4-week, and in 3 (75%) aneurysms at 12-week follow-up. All 17 lumbar arteries were patent. CD31 staining showed that 75% ± 16% of the aneurysm neck region was endothelialized. Histopathology demonstrated incorporation of the thin film nitinol flow diverter into the vessel wall and no evidence of excessive neointimal hyperplasia. CONCLUSIONS In this rabbit model, the thin film nitinol flow diverter achieved high rates of aneurysm occlusion and promoted tissue in-growth and aneurysm neck healing, even early after implantation.


title: Cumulative effect of indoor temperature on cardiovascular disease-related emergency department visits among older adults in Taiwan.

text: Studies have demonstrated that exposure to extreme outdoor temperatures increases cardiovascular disease mortality and morbidity. However, people spend 80%-90% of their time indoors, and the cumulative effects of exposure to high or low temperature on the risk of cardiovascular diseases had not been considered. This study investigated the cumulative effects of high or low indoor temperature exposure on the risk of cardiovascular diseases. We estimated indoor temperatures by using a prediction model of indoor temperature from a previous study and further calculated the cumulative degree hours at different indoor temperature ranges. Samples of emergency department visits due to cardiovascular diseases were collected from the Longitudinal Health Insurance Database (LHID) from 2000 to 2014 in Taiwan. We used a distributed lag nonlinear model to analyze the data. Our data demonstrated a significant risk of emergency department visits due to cardiovascular diseases at 27, 28, 29, 30, and 31 °C when cooling cumulative degree hours exceeded 62, 43, 16, 1, and 1 during the hot season (May to October), respectively, and at 19, 20, 21, 22, and 23 °C when heating cumulative degree hours exceeded 1, 1, 1, 11, and 33 during the cold season (November to April), respectively. Cumulative degree hours were different according to gender and age groups. Policymakers should further consider the cumulative effects to prevent hot- or cold-related cardiovascular diseases for populations.


COVID Blindness.


title: Treatment with ACE inhibitors or ARBs and risk of severe/lethal COVID-19: a meta-analysis.

text: OBJECTIVE It has been hypothesised that the use of ACE inhibitors and angiotensin receptor blockers (ARBs) might either increase or reduce the risk of severe or lethal COVID-19. The findings from the available observational studies varied, and summary estimates are urgently needed to elucidate whether these drugs should be suspended during the pandemic, or patients and physicians should be definitely reassured. This meta-analysis of adjusted observational data aimed to summarise the existing evidence on the association between these medications and severe/lethal COVID-19. METHODS We searched MedLine, Scopus and preprint repositories up to 8 June 2020 to retrieve cohort or case-control studies comparing the risk of severe/fatal COVID-19 (either mechanical ventilation, intensive care unit admission or death), among hypertensive subjects treated with: (1) ACE inhibitors, (2) ARBs and (3) both, versus untreated subjects. Data were combined using a random-effect generic inverse variance approach. RESULTS Ten studies, enrolling 9890 hypertensive subjects were included in the analyses. Compared with untreated subjects, those using either ACE inhibitors or ARBs showed a similar risk of severe or lethal COVID-19 (summary OR: 0.90; 95% CI 0.65 to 1.26 for ACE inhibitors; 0.92; 95% CI 0.75 to 1.12 for ARBs). The results did not change when both drugs were considered together, when death was the outcome and excluding the studies with significant, divergent results. CONCLUSION The present meta-analysis strongly supports the recommendation of several scientific societies to continue ARBs or ACE inhibitors for all patients, unless otherwise advised by their physicians who should thus be reassured.


Clinical and health policy challenges in responding to the COVID-19 pandemic.


Coronavirus: limit short-term economic damage.


title: Telomere- and telomerase-interacting protein that unfolds telomere G-quadruplex and promotes telomere extension in mammalian cells.

text: Telomere extension by telomerase is essential for chromosome stability and cell vitality. Here, we report the identification of a splice variant of mammalian heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2), hnRNP A2*, which binds telomeric DNA and telomerase in vitro. hnRNP A2* colocalizes with telomerase in Cajal bodies and at telomeres. In vitro assays show that hnRNP A2* actively unfolds telomeric G-quadruplex DNA, exposes 5 nt of the 3' telomere tail and substantially enhances the catalytic activity and processivity of telomerase. The expression level of hnRNP A2* in tissues positively correlates with telomerase activity, and overexpression of hnRNP A2* leads to telomere elongation in vivo. Thus, hnRNP A2* plays a positive role in unfolding telomere G-quadruplexes and in enhancing telomere extension by telomerase.


title: Monitoring the level of hypnosis using a hierarchical SVM system.

text: Monitoring level of hypnosis is a major ongoing challenge for anesthetists to reduce anesthetic drug consumption, avoiding intraoperative awareness and prolonged recovery. This paper proposes a novel automated method for accurate assessing of the level of hypnosis with sevoflurane in 17 patients using the electroencephalogram signal. In this method, a set of distinctive features and a hierarchical classification structure based on support vector machine (SVM) methods, is proposed to discriminate the four levels of anesthesia (awake, light, general and deep states). The first stage of the hierarchical SVM structure identifies the awake state by extracting Shannon Permutation Entropy, Detrended Fluctuation Analysis and frequency features. Then deep state is identified by extracting the sample entropy feature; and finally light and general states are identified by extracting the three mentioned features of the first step. The accuracy of the proposed method of analyzing the brain activity during anesthesia is 94.11%; which was better than previous studies and also a commercial monitoring system (Response Entropy Index).


title: Subcutaneous single injection digital block with epinephrine.

text: The aim of this study was to investigate the anesthetic effect and risk of epinephrine for subcutaneous single injection digital block. Either 3.0 mL 1.0% Lidocaine or a 3.0 mL 1.0% Lidocaine with (1 : 100,000) epinephrine was injected into the subcutaneous space at the middle point of the palmar digital crease of the 18 middle fingers of 9 healthy volunteers. The SpO(2) of the fingers decreased to a maximum of 97. No subjects showed any symptoms of ischemic injury. The time to anesthesia for the fingers was significantly shorter (P < 0.05), and the duration of anesthesia was significantly longer (P < 0.01) for the fingers in the epinephrine group. In conclusion, a subcutaneous single injection digital blocks with 3.0 mL of 1.0% Lidocaine and (1 : 100,000) epinephrine were safe, reducing the time to the onset of anesthesia, while also markedly prolonging the anesthesia.


title: Biodegradable Magnesium Stent Treatment of Saccular Aneurysms in a Rat Model - Introduction of the Surgical Technique.

text: The steady progess in the armamentarium of techniques available for endovascular treatment of intracranial aneurysms requires affordable and reproducable experimental animal models to test novel embolization materials such as stents and flow diverters. The aim of the present project was to design a safe, fast, and standardized surgical technique for stent assisted embolization of saccular aneurysms in a rat animal model. Saccular aneurysms were created from an arterial graft from the descending aorta.The aneurysms were microsurgically transplanted through end-to-side anastomosis to the infrarenal abdominal aorta of a syngenic male Wistar rat weighing >500 g. Following aneurysm anastomosis, aneurysm embolization was performed using balloon expandable magnesium stents (2.5 mm x 6 mm). The stent system was retrograde introduced from the lower abdominal aorta using a modified Seldinger technique. Following a pilot series of 6 animals, a total of 67 rats were operated according to established standard operating procedures. Mean surgery time, mean anastomosis time, and mean suturing time of the artery puncture site were 167 ± 22 min, 26 ± 6 min and 11 ± 5 min, respectively. The mortality rate was 6% (n=4). The morbidity rate was 7.5% (n=5), and in-stent thrombosis was found in 4 cases (n=2 early, n=2 late in stent thrombosis). The results demonstrate the feasibility of standardized stent occlusion of saccular sidewall aneurysms in rats - with low rates of morbidity and mortality. This stent embolization procedure combines the opportunity to study novel concepts of stent or flow diverter based devices as well as the molecular aspects of healing.


title: An ovine model of cerebral catheter venography for implantation of an endovascular neural interface.

text: OBJECTIVE Neural interface technology may enable the development of novel therapies to treat neurological conditions, including motor prostheses for spinal cord injury. Intracranial neural interfaces currently require a craniotomy to achieve implantation and may result in chronic tissue inflammation. Novel approaches are required that achieve less invasive implantation methods while maintaining high spatial resolution. An endovascular stent electrode array avoids direct brain trauma and is able to record electrocorticography in local cortical tissue from within the venous vasculature. The motor area in sheep runs in a parasagittal plane immediately adjacent to the superior sagittal sinus (SSS). The authors aimed to develop a sheep model of cerebral venography that would enable validation of an endovascular neural interface. METHODS Cerebral catheter venography was performed in 39 consecutive sheep. Contrast-enhanced MRI of the brain was performed on 13 animals. Multiple telescoping coaxial catheter systems were assessed to determine the largest wide-bore delivery catheter that could be delivered into the anterior SSS. Measurements of SSS diameter and distance from the motor area were taken. The location of the motor area was determined in relation to lateral and superior projections of digital subtraction venography images and confirmed on MRI. RESULTS The venous pathway from the common jugular vein (7.4 mm) to the anterior SSS (1.2 mm) was technically challenging to selectively catheterize. The SSS coursed immediately adjacent to the motor cortex (< 1 mm) for a length of 40 mm, or the anterior half of the SSS. Attempted access with 5-Fr and 6-Fr delivery catheters was associated with longer procedure times and higher complication rates. A 4-Fr catheter (internal lumen diameter 1.1 mm) was successful in accessing the SSS in 100% of cases with no associated complications. Complications included procedure-related venous dissection in two major areas: the torcular herophili, and the anterior formation of the SSS. The bifurcation of the cruciate sulcal veins with the SSS was a reliable predictor of the commencement of the motor area. CONCLUSIONS The ovine model for cerebral catheter venography has generalizability to the human cerebral venous system in relation to motor cortex location. This novel model may facilitate the development of the novel field of endovascular neural interfaces that may include preclinical investigations for cortical recording applications such as paralysis and epilepsy, as well as other potential applications in neuromodulation.


The Coronavirus Pandemic - Lessons Learned?


title: Contact intervals, survival analysis of epidemic data, and estimation of R(0).

text: We argue that the time from the onset of infectiousness to infectious contact, which we call the "contact interval," is a better basis for inference in epidemic data than the generation or serial interval. Since contact intervals can be right censored, survival analysis is the natural approach to estimation. Estimates of the contact interval distribution can be used to estimate R(0) in both mass-action and network-based models. We apply these methods to 2 data sets from the 2009 influenza A(H1N1) pandemic.


title: Clinical and histologic description of ocular anatomy in captive black-tailed prairie dogs (Cynomys ludovicianus).

text: OBJECTIVE To describe the clinical and histologic ocular anatomy of the black-tailed prairie dog (PD). ANIMALS STUDIED Seventeen captive black-tailed PDs (11 males and six females), ranging in age from approximately 4 months to 4.5 years. PROCEDURES Complete ocular examinations, including slit-lamp biomicroscopy, direct and indirect ophthalmoscopy, were performed under isoflurane anesthesia. The globes (n = 2) of one black-tailed PD were harvested immediately after euthanasia and processed after formalin fixation. Staining with hematoxylin-eosin, cytokeratin AE1/AE3, glial fibrillary acidic protein, chromogranin A, claudin-5, smooth muscle actin, and vimentin was performed for light microscopic evaluation. RESULTS A thick mucinous precorneal tear film was present on the ocular surface. A vestigial nictitating membrane was identified in the medial canthus area. The limbus was heavily pigmented, the iris was a dark homogenous brown, and the pupil was round. Funduscopically, there was no tapetum lucidum, the retinal vascular pattern was holangiotic, and a horizontally elongated optic disk was visualized. The most common ocular abnormalities were acquired eyelid margin defects, present in seven eyes of six black-tailed PDs (35.3%). On histologic examination, the retina was asymmetric, thicker below the optic disk and thinner above it. CONCLUSIONS The black-tailed PD fundus is atapetal with a holangiotic retinal vessel pattern and a horizontally elongated optic disk. Acquired lesions of the peri-ocular and eyelid region were the most common documented abnormality. Unique anatomic features of the globe and adnexa were confirmed with histologic and immunohistochemical analysis.


title: Percutaneous thermal ablation for the treatment of colorectal liver metastases and hepatocellular carcinoma: a comparison of local therapeutic efficacy.

text: AIM This study aimed to compare the local therapeutic efficacy of percutaneous thermal ablation for colorectal liver metastases (CRLM) and hepatocellular carcinoma (HCC). METHODS One hundred sixty-one CRLM nodules in 101 patients and 122 HCC nodules in 97 patients were treated with thermal ablation. Complications and local efficacy were retrospectively compared. RESULTS Major complications were observed in two (2.0%) patients in the CRLM group and one (1.0%) in the HCC group (p = 1.000). The complete ablation (CA) rate of lesions ≤ 3 cm was lower in the CRLM group than in the HCC group (p = 0.018). After a mean follow-up period of 21.1 ± 20.7 months in the CRLM group and 22.1 ± 17.6 months in the HCC group, the local tumour progression (LTP) rate of lesions > 3 cm was higher in the CRLM group than in the HCC group (p = 0.036). The multivariate analysis revealed that only safety margin (≤ 0.5 cm/> 0.5 cm) was a significant predictor of LTP in both CRLM and HCC. CONCLUSIONS To achieve better local tumour control, thermal ablation should be more aggressive for CRLM than for HCC, especially for large tumours in clinical.


title: Permissivity of Dipeptidyl Peptidase 4 Orthologs to Middle East Respiratory Syndrome Coronavirus Is Governed by Glycosylation and Other Complex Determinants.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes dipeptidyl peptidase 4 (DPP4) as an entry receptor. While bat, camel, and human DPP4 support MERS-CoV infection, several DPP4 orthologs, including mouse, ferret, hamster, and guinea pig DPP4, do not. Previous work revealed that glycosylation of mouse DPP4 plays a role in blocking MERS-CoV infection. Here, we tested whether glycosylation also acts as a determinant of permissivity for ferret, hamster, and guinea pig DPP4. We found that, while glycosylation plays an important role in these orthologs, additional sequence and structural determinants impact their ability to act as functional receptors for MERS-CoV. These results provide insight into DPP4 species-specific differences impacting MERS-CoV host range and better inform our understanding of virus-receptor interactions associated with disease emergence and host susceptibility.IMPORTANCE MERS-CoV is a recently emerged zoonotic virus that is still circulating in the human population with an ∼35% mortality rate. With no available vaccines or therapeutics, the study of MERS-CoV pathogenesis is crucial for its control and prevention. However, in vivo studies are limited because MERS-CoV cannot infect wild-type mice due to incompatibilities between the virus spike and the mouse host cell receptor, mouse DPP4 (mDPP4). Specifically, mDPP4 has a nonconserved glycosylation site that acts as a barrier to MERS-CoV infection. Thus, one mouse model strategy has been to modify the mouse genome to remove this glycosylation site. Here, we investigated whether glycosylation acts as a barrier to infection for other nonpermissive small-animal species, namely, ferret, guinea pig, and hamster. Understanding the virus-receptor interactions for these DPP4 orthologs will help in the development of additional animal models while also revealing species-specific differences impacting MERS-CoV host range.


title: Low-fidelity simulation of medical emergency and cardiac arrest responses in a suspected COVID-19 patient - an interim report.

text: BACKGROUND COVID-19 poses many challenges to healthcare systems and workers. Responding to medical emergencies in patients with suspected COVID-19 will require new guidelines and protocols. Simulation can support their development. METHODS We organised seven simulations involving patients with suspected COVID-19 for staff at Brighton and Sussex University Hospitals. Participants completed pre- and post-simulation questionnaires. RESULTS Fifty-six staff participated and they reported being significantly less prepared to respond to an emergency in a patient with suspected COVID-19 than in one in whom it is not suspected. The simulations significantly improved the participants' confidence in responding to emergencies in patients with suspected COVID-19. Numerous challenges were identified along the themes of equipment, personnel, communication and procedures. CONCLUSIONS Low-fidelity simulation can provide relevant and timely information on how prepared health systems and their workforce are to respond to emergencies. We urge NHS trusts nationally to implement simulations to identify problems and develop effective solutions.


title: Understanding the role of communities of practice in evidence-informed decision making in public health.

text: In this article we report on qualitative findings that describe public health practitioners' practice-based definitions of evidence-informed decision making (EIDM) and communities of practice (CoP), and how CoP could be a mechanism to enhance their capacity to practice EIDM. Our findings emerged from a qualitative descriptive analysis of group discussions and participant concept maps from two consensus-building workshops that were conducted with public health practitioners (N = 90) in two provinces in eastern Canada. Participants recognized the importance of EIDM and the significance of integrating explicit and tacit evidence in the EIDM process, which was enhanced by CoP. Tacit knowledge, particularly from peers and personal experience, was the preferred source of knowledge, with informal peer interactions being the favored form of CoP to support EIDM. CoP helped practitioners build relationships and community capacity, share and create knowledge, and build professional confidence and critical inquiry. Participants described individual and organizational attributes that were needed to enable CoP and EIDM.


title: Induced, selective proteolysis of MLK3 negatively regulates MLK3/JNK signalling.

text: MLK3 (mixed lineage kinase 3) is a MAP3K [MAPK (mitogen-activated protein kinase) kinase kinase] that activates multiple MAPK pathways, including the JNK (c-Jun N-terminal kinase) pathway. Immunoblotting of lysates from cells ectopically expressing active MLK3 revealed an additional immunoreactive band corresponding to a CTF (C-terminal fragment) of MLK3. In the present paper we provide evidence that MLK3 undergoes proteolysis to generate a stable CTF in response to different stimuli, including PMA and TNFalpha (tumour necrosis factor alpha). The cleavage site was deduced by Edman sequencing as between Gln251 and Pro252, which is within the kinase domain of MLK3. Based on our homology model of the kinase domain of MLK3, the region containing the cleavage site is predicted to reside on a flexible solvent-accessible loop. Site-directed mutagenesis studies revealed that Leu250 and Gln251 are required for recognition by the 'MLK3 protease', reminiscent of the substrate specificity of the coronavirus 3C and 3CL proteases. Whereas numerous mammalian protease inhibitors have no effect on MLK3 proteolysis, blockade of the proteasome through epoxomicin or MG132 abolishes PMA-induced production of the CTF of MLK3. This CTF is able to heterodimerize with full-length MLK3, and interact with the active form of the small GTPase Cdc42, resulting in diminished activation loop phosphorylation of MLK3 and reduced signalling to JNK. Thus this novel proteolytic processing of MLK3 may negatively control MLK3 signalling to JNK.


title: An anterior mediastinal mass: delayed airway compression and using a double lumen tube for airway patency.

text: Perioperative management of patients with an anterior mediastinal mass is difficult. We present a 35-year-old woman who showed delayed compression of the carina and left main bronchus despite no preoperative respiratory signs, symptoms, or radiologic findings due to an anterior mediastinal mass and uneventful stepwise induction of general anesthesia. Even use of a fiberoptic bronchoscope (FB) after induction of anesthesia was not helpful to predict delayed compression of the airway. Therefore, the anesthesiologist and the cardiothoracic surgeon must prepare for unexpected delayed compression of the airway, even in low risk patients who are asymptomatic or mildly symptomatic without postural symptoms or radiographic evidence of significant compression of structures. We also describe successful management for the compressed carina and left main bronchus with a double lumen tube (DLT) as a stent during surgery. FB guided DLT intubation is a possible solution to maintain airway patency.


docid: fbvqpgdg

title: As COVID-19 cases, deaths and fatality rates surge in Italy, underlying causes require investigation.

text: COVID-19 case fatalities surged during the month of March 2020 in Italy, reaching over 10,000 by 28 March 2020. This number exceeds the number of fatalities in China (3,301) recorded from January to March, even though the number of diagnosed cases was similar (85,000 Italy vs. 80,000 China). Case Fatality Rates (CFR) could be somewhat unreliable because the estimation of total case numbers is limited by several factors, including insufficient testing and limitations in test kits and materials, such as NP swabs and PPE for testers. Sero prevalence of SARS-CoV-2 antibodies may help in more accurate estimations of the total number of cases. Nevertheless, the disparity in the differences in the total number of fatalities between Italy and China suggests investigation into several factors, such as demographics, sociological interactions, availability of medical equipment (ICU beds and PPE), variants in immune proteins (e.g., HLA, IFNs), past immunity to related CoVs, and mutations in SARS-CoV-2, could impact survival of severe COVID-19 illness survival and the number of case fatalities.


docid: jmjsbktd

title: Image-Guided Surgical e-Learning in the Post-COVID-19 Pandemic Era: What Is Next?

text: The current unprecedented coronavirus 2019 (COVID-19) crisis has accelerated and enhanced e-learning solutions. During the so-called transition phase, efforts were made to reorganize surgical services, reschedule elective surgical procedures, surgical research, academic education, and careers to optimize results. The intention to switch to e-learning medical education is not a new concern. However, the current crisis triggered an alarm to accelerate the transition. Efforts to consider e-learning as a teaching and training method for medical education have proven to be efficient. For image-guided therapies, the challenge requires more effort since surgical skills training is combined with image interpretation training, thus the challenge is to cover quality educational content with a balanced combination of blended courses (online/onsite). Several e-resources are currently available in the surgical scenario; however, further efforts to enhance the current system are required by accelerating the creation of new learning solutions to optimize complex surgical education needs in the current disrupted environment.


title: Infectious Disease Risk and Vaccination in Northern Syria after 5 Years of Civil War: The MSF Experience.

text: Introduction In 2015, following an influx of population into Kobanê in northern Syria, Médecins Sans Frontières (MSF) in collaboration with the Kobanê Health Administration (KHA) initiated primary healthcare activities. A vaccination coverage survey and vaccine-preventable disease (VPD) risk analysis were undertaken to clarify the VPD risk and vaccination needs. This was followed by a measles Supplementary Immunization Activity (SIA). We describe the methods and results used for this prioritisation activity around vaccination in Kobanê in 2015. Methods We implemented a pre-SIA survey in 135 randomly-selected households in Kobanê using a vaccination history questionnaire for all children <5 years. We conducted a VPD Risk Analysis using MSF 'Preventive Vaccination in Humanitarian Emergencies' guidance to prioritize antigens with the highest public health threat for mass vaccination activities. A Measles SIA was then implemented and followed by vaccine coverage survey in 282 randomly-selected households targeting children <5 years. Results The pre-SIA survey showed that 168/212 children (79.3%; 95%CI=72.7-84.6%) had received one vaccine or more in their lifetime. Forty-three children (20.3%; 95%CI: 15.1-26.6%) had received all vaccines due by their age; only one was <12 months old and this child had received all vaccinations outside of Syria. The VPD Risk Analysis prioritised measles, Haemophilus Influenza type B (Hib) and Pneumococcus vaccinations. In the measles SIA, 3410 children aged 6-59 months were vaccinated. The use of multiple small vaccination sites to reduce risks associated with crowds in this active conflict setting was noted as a lesson learnt. The post-SIA survey estimated 82% (95%CI: 76.9-85.9%; n=229/280) measles vaccination coverage in children 6-59 months. Discussion As a result of the conflict in Syria, the progressive collapse of the health care system in Kobanê has resulted in low vaccine coverage rates, particularly in younger age groups. The repeated displacements of the population, attacks on health institutions and exodus of healthcare workers, challenge the resumption of routine immunization in this conflict setting and limit the use of SIAs to ensure sustainable immunity to VPDs. We have shown that the risk for several VPDs in Kobanê remains high. Conclusion We call on all health actors and the international community to work towards re-establishment of routine immunisation activities as a priority to ensure that children who have had no access to vaccination in the last five years are adequately protected for VPDs as soon as possible.


Degenerative myopia: myopic macular schisis and the posterior pole buckle.


title: Using evidence-based medicine to protect healthcare workers from pandemic influenza: Is it possible?

text: OBJECTIVE To use evidence-based principles to develop infection control algorithms to ensure the protection of healthcare workers and the continuity of health service provision during a pandemic. DESIGN : Evidence-based algorithms were developed from published research as well as "needs and values" assessments. Research evidence was obtained from 97 studies reporting the protectiveness of antiviral prophylaxis, seasonal vaccination, and mask use. Needs and values assessments were undertaken by international experts in pandemic infection control and local healthcare workers. Opportunity and resources costs were not determined. SETTING The Australian government commissioned the development of an evidence-based algorithm for inclusion in the 2008 revision of the Australian Health and Management Plan for Pandemic Influenza. PARTICIPANTS Two international infection control teams responsible for healthcare worker safety during the Severe Acute Respiratory Syndrome outbreak reviewed the evidence-based algorithms. The algorithms were then reviewed for needs and values by eight local clinicians who were considered key frontline clinicians during the contain and sustain phases. The international teams reviewed for practicability of implementation, whereas local clinicians reviewed for clinician compliance. RESULTS Despite strong evidence for vaccination and antiviral prophylaxis providing significant protection, clinicians believed they required the additional combinations of both masks and face shields. Despite the equivocal evidence for the efficacy of surgical and N95 masks and the provision of algorithms appropriate for the level of risk according to clinical care during a pandemic, clinicians still demanded N95 masks plus face shields in combination with prophylaxis and novel vaccination. CONCLUSIONS Conventional evidence-based principles could not be applied to formulate recommendations due to the lack of pandemic-specific efficacy data of protection tools and the inherent unpredictability of pandemics. As an alternative, evidence-based principles have been used to formulate recommendations while giving priority to the needs and values of healthcare workers over the research evidence.


title: An ethanol/sodium citrate locking solution compared to heparin to prevent hemodialysis catheter-related infections: a randomized pilot study.

text: PURPOSE The objective of this study was to compare the initial safety and efficacy of a novel 30% ethanol/4% sodium citrate catheter-locking solution to heparin in a hemodialysis population. METHODS This was a prospective, randomized, pilot study of 40 hemodialysis patients randomized to a 30% ethanol/4% sodium citrate or heparin 1000 units/mL locking solution. The primary outcome was identification of any serious adverse events over the study duration. Secondary outcomes included the rate per 1000 catheter days for catheter-related bloodstream infections (CRBSI), alteplase use, catheter dysfunction, and catheter removal. RESULTS Three serious adverse events were reported as possibly related to the catheter solutions. Only one CRBSI was observed during the study in the heparin arm. The rate of alteplase use was 1.5/1000 catheter days in the heparin arm compared to 2.8/1000 catheter days in the ethanol/citrate arm (rate ratio = 1.85, 90% CI 0.48, 7.07, p value = 0.45), while the rate of catheter dysfunction was 6.8/1000 catheter days in the heparin arm compared to 1.9/1000 catheter days in the ethanol citrate arm (rate ratio = 0.27, 90% CI 0.10, 0.74, p value = 0.04). Catheter survival to first catheter outcome was longer in the ethanol/citrate group compared to heparin and there were no catheter removals due to bacteremia or thrombosis. CONCLUSIONS The ethanol/sodium citrate locking solution was safely used in this study. It appears to prevent CRBSI and may improve catheter survival compared to heparin. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01394458.


title: Transanal minimally invasive surgery: an initial experience.

text: BACKGROUND Transanal minimally invasive surgery (TAMIS) is a novel approach used for the resection of rectal lesions. The purpose of this study was to review our initial experience with TAMIS. METHODS Between March 2012 and May 2012, we collected clinical data on patients who underwent the TAMIS procedure. This included patient demographics, tumour characteristics, operative technique, histological results and post-operative outcomes. RESULTS Three patients successfully underwent TAMIS resection of rectal lesions. All tumours were tubulovillous adenomas with high-grade dysplasia, with one also having a small focus of adenocarcinoma. Clear margins were achieved in all cases. One case was complicated by a post-operative bleed, requiring a return to theatre. CONCLUSIONS TAMIS is a feasible and cost-effective alternative to transanal endoscopic microsurgery for resection of rectal lesions. It may have a shorter learning curve, especially for laparoscopic surgeons already proficient in single-port procedures.


title: Exploratory subgroup analysis of patients with prior trastuzumab use in the ATTRACTION-2 trial: a randomized phase III clinical trial investigating the efficacy and safety of nivolumab in patients with advanced gastric/gastroesophageal junction cancer.

text: BACKGROUND Data on immune checkpoint inhibitor efficacy in patients with human epidermal growth factor receptor 2-positive (HER2+) advanced gastric/gastroesophageal junction (G/GEJ) cancer are lacking. Because HER2 status was not captured in the ATTRACTION-2 trial, we used patients with prior trastuzumab use (Tmab+) as surrogate for HER2 expression status to evaluate the efficacy and safety of nivolumab as third- or later-line therapy in these patients. METHODS In ATTRACTION-2, a randomized, double-blind, placebo-controlled, phase 3 multicenter trial, patients were randomized (2:1) to receive nivolumab (3 mg/kg) or placebo every 2 weeks until disease progression or toxicity requiring study discontinuation. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were assessed. RESULTS Of 493 enrolled patients, 81 (nivolumab, n = 59; placebo, n = 22) were Tmab+ and 412 (nivolumab, n = 271; placebo, n = 141) were Tmab-. In both groups, patients receiving nivolumab showed a longer median OS vs placebo (Tmab+, 8.3 [95% confidence interval, 5.3-12.9] vs 3.1 [1.9-5.3] months, hazard ratio, 0.38 [0.22-0.66]; P = 0.0006; Tmab-, 4.8 [4.1-6.0] vs 4.2 [3.6-4.9] months, 0.71 [0.57-0.88]; P = 0.0022). PFS was longer in both groups receiving nivolumab vs placebo (Tmab+, 1.6 [1.5-4.0] vs 1.5 [1.3-2.9] months, 0.49 [0.29-0.85]; P = 0.0111; Tmab-, 1.6 [1.5-2.4] vs 1.5 [1.5-1.5] months, 0.64 [0.51-0.80]; P = 0.0001). CONCLUSIONS Nivolumab was efficacious and safe as third- or later-line therapy regardless of prior trastuzumab use in patients with advanced G/GEJ cancer.


title: Cerebral foreign body reaction after carotid aneurysm stenting.

text: Flow diverter stents are new important tools in the treatment of large, giant, or wide-necked aneurysms. Their delivery and positioning may be difficult due to vessel tortuosity. Common adverse events include intracranial hemorrhage and ischemic stroke, which usually occurs within the same day, or the next few days after the procedure. We present a case where we encountered an unusual intracerebral complication several months after endovascular treatment of a large left internal carotid artery aneurysm, and where brain biopsy revealed foreign body reaction to hydrophilic polymer fragments distally to the stent site. Although previously described, embolization of polymer material from intravascular equipment is rare. We could not identify any other biopsy verified case in the literature, with this particular presentation of intracerebral polymer embolization--a multifocal inflammation spread out through the white matter of one hemisphere without hemorrhage or ischemic changes.


title: Active Surveillance of Influenza A and Other Respiratory Viruses in Children with Influenza-like-illness in Two Seasons.

text: INTRODUCTION The aim of this study was to asses the surveillance of influenza A/other respiratory viruses and risk factors in hospitalized children with the symptoms of influenza-like illness during two consecutive influenza seasons. METHODOLOGY All children hospitalized with adiagnosis of influenza-like illness had been investigated for Influenza A and other respiratory antigens in pharengeal/nasopharyngeal secretions. RESULTS A total of 132 hospitalized children between December 2013-May 2014 and December 2014-May 2015 were enrolled in this study. At least one respiratory virus was found to be positive by RT-PCR in 78 (59%) patients, influenza A (H3N2) was detected in only 8 (6%) patients. In 54 (41%) patients samples no respiratory viral pathogen was detected and in 70 (53%) patients, one non- influenza A virus was detected. The respiratory viral pathogens detected in decreasing rates were:RSV (n = 46, 35%), HCoV (n = 10, 7.5%), adenovirüs (n = 7, 5%), rhinovirüs (n = 6, 4.5%), HMPV (n = 5, 4%), Influenza B (n = 4, 3%) ve human Bocavirus (n = 2, 1.5%). In 10 patients, coinfection was detected, however none was with H3N2. In the H3N2 (+) group, the following risk factors were identified: age older than three years (p < 0.05), asthma history (p < 0.05) and chronic lung diseases (p < 0.05). CONCLUSION Influenza A virus was detected in 6% of hospitalized patients with influenza-like illness. Viruses other then Influenza, especially RSV, can cause similar symptoms compatible with Influenza-like-illness.


title: Comparison of endovascular treatment approaches for acute ischemic stroke: cost effectiveness, technical success, and clinical outcomes.

text: INTRODUCTION The use of mechanical thrombectomy for the treatment of acute ischemic stroke has significantly advanced over the last 5 years. Few data are available comparing the cost and clinical and angiographic outcomes associated with available techniques. The aim of this study is to compare the cost and efficacy of current endovascular stroke therapies. METHODS A single-center retrospective review was performed of the medical record and hospital financial database of all ischemic stroke cases admitted from 2009 to 2013. Three discrete treatment methodologies used during this time were compared: traditional Penumbra System (PS), stent retriever with local aspiration (SRLA) and A Direct Aspiration first Pass Technique (ADAPT). Statistical analyses of clinical and angiographic outcomes and costs for each group were performed. RESULTS 222 patients (45% men) underwent mechanical thrombectomy. Successful revascularization was defined as Thrombolysis In Cerebral Infarction (TICI) 2b/3 flow, which was achieved in 79% of cases with PS, 83% of cases with SRLA, and 95% of cases with ADAPT. The average total cost of hospitalization for patients was $51,599 with PS, $54,700 with SRLA, and $33 ,11 with ADAPT (p<0.0001). Average times to recanalization were 88 min with PS, 47 min with SRLA, and 37 min with ADAPT (p<0.0001). Similar rates of good functional outcomes were seen in the three groups (PS 36% vs SRLA 43% vs ADAPT 47%; p=0.4). CONCLUSIONS The ADAPT technique represents the most technically successful yet cost-effective approach to revascularization of large vessel intracranial occlusions.