title: Unprecedented pace and partnerships: the story of and lessons learned from one Ebola vaccine program.

text: INTRODUCTION The Ebola epidemic in West Africa from 2014 to 2016 was unique in its size, location, and duration; this article reviews the experiences and lessons learned for one vaccine candidate developed during the outbreak and discusses critical gaps that still exist today which will need to be addressed for successful end to end emerging infectious disease vaccine product development in the future. AREAS COVERED Through the formation of numerous international partnerships, the rVSVΔG-ZEBOV-GP vaccine advanced through Phase I/II/III clinical trials which resulted in favorable Phase III efficacy results. Key lessons learned that could be used to facilitate future vaccine development efforts include sufficient preclinical work in relevant animal models, innovative partnerships created to pool resources and expertise, and 'hyper' coordination and communication among partners to build trust and ensure an adequate regulatory package needed to license a vaccine. EXPERT COMMENTARY As evidenced by the 2014-2016 outbreak in West Africa as well as the two other most recent outbreaks in the Democratic Republic of the Congo in 2018, there is an urgent need to develop new models for emerging infection vaccine development where trusted partners come together and where the development of vaccines is a shared responsibility conducted in advance of the next crisis.


RFID technology may improve contrast agent safety.


Implementation Science Workshop: Implementation of an Electronic Referral System in a Large Academic Medical Center.


title: Shifting hierarchies of interleukin-10-producing T cell populations in the central nervous system during acute and persistent viral encephalomyelitis.

text: Interleukin-10 (IL-10) mRNA is rapidly upregulated in the central nervous system (CNS) following infection with neurotropic coronavirus and remains elevated during persistent infection. Infection of transgenic IL-10/green fluorescent protein (GFP) reporter mice revealed that CNS-infiltrating T cells were the major source of IL-10, with minimal IL-10 production by macrophages and resident microglia. The proportions of IL-10-producing cells were initially similar in CD8(+) and CD4(+) T cells but diminished rapidly in CD8(+) T cells as the virus was controlled. Overall, the majority of IL-10-producing CD8(+) T cells were specific for the immunodominant major histocompatibility complex (MHC) class I epitope. Unlike CD8(+) T cells, a large proportion of CD4(+) T cells within the CNS retained IL-10 production throughout persistence. Furthermore, elevated frequencies of IL-10-producing CD4(+) T cells in the spinal cord supported preferential maintenance of IL-10 production at the site of viral persistence and tissue damage. IL-10 was produced primarily by the CD25(+) CD4(+) T cell subset during acute infection but prevailed in CD25(-) CD4(+) T cells during the transition to persistent infection and thereafter. Overall, these data demonstrate significant fluidity in the T-cell-mediated IL-10 response during viral encephalitis and persistence. While IL-10 production by CD8(+) T cells was limited primarily to the time of acute effector function, CD4(+) T cells continued to produce IL-10 throughout infection. Moreover, a shift from predominant IL-10 production by CD25(+) CD4(+) T cells to CD25(-) CD4(+) T cells suggests that a transition to nonclassical regulatory T cells precedes and is retained during CNS viral persistence.


title: Postcontrast susceptibility-weighted imaging: a novel technique for the detection of arteriovenous shunting in vascular malformations of the brain.

text: BACKGROUND AND PURPOSE The purpose of this study was to determine the utility of postcontrast susceptibility-weighted MRI (PCSWI) in the evaluation of vascular malformations of the brain (BVM). METHODS We retrospectively evaluated PCSWI and digital subtraction angiography data from 16 consecutive patients with known or suspected BVM, which had been entered into a prospectively maintained database during a 1-year period. There had been no intervening treatment or change in patients' symptoms between the PCSWI and digital subtraction angiography studies. The use of PCSWI in the detection of arteriovenous shunting was compared with that of routine noncontrast susceptibility-weighted imaging, time-of-flight MR angiography, and contrast-enhanced MR angiography using digital subtraction angiography results as the reference standard. The presence of arteriovenous shunting in PCSWI or susceptibility-weighted imaging sequences was defined by the presence of abnormal signal hyperintensity in the venous structures adjacent to the BVM. RESULTS A total of 17 BVMs were identified by digital subtraction angiography (9 newly diagnosed arteriovenous malformations, 3 dural arteriovenous fistulas, 4 treated arteriovenous malformations with residual arteriovenous shunting, and 1 complex developmental venous anomaly). PCSWI was 100% sensitive and 100% specific with 100% positive predictive value and 100% negative predictive value for the detection of arteriovenous shunting in these BVMs. The PCSWI/susceptibility-weighted imaging signal intensity ratio in the most prominent early draining venous structure was 1.2±0.32. CONCLUSIONS PCSWI appears to be superior to susceptibility-weighted imaging, time-of-flight MR angiography, and contrast-enhanced MR angiography in detecting arteriovenous shunting in BVMs and may be useful in the initial diagnosis and follow-up of patients with BVMs.


title: Transvaginal natural-orifice transluminal endoscopic surgery (NOTES) in adnexal procedures.

text: From August 2010 to June 2011, 10 consecutive patients underwent transvaginal NOTES of the adnexa, including tubal sterilization in 3, salpingectomy because of ectopic pregnancy in 3, and ovarian tumor enucleation in 4. The mean (SD; 95% CI) age of the patients was 34.8 (9.7; 27.9-41.8) years, and their body mass index was 21.6 (2.8; 19.4-23.8). In 9 of the 10 patients, the procedure was completed. The 3 tubal sterilization procedures were completed in 18 to 30 minutes, with negligible blood loss. Operative time for the 3 salpingectomies because of ectopic pregnancy was 62 to 116 minutes. One of these procedures included management of 2000 mL hemoperitoneum. Three of the 4 attempts at ovarian enucleation were successfully completed within 64 to 162 minutes, with estimated blood loss ≤ 50 mL. One NOTES procedure failed because of a misdiagnosed peritoneal mucinous tumor located anterior to the uterus and inaccessible, leading to subsequent conversion to transabdominal laparoscopy. Our preliminary results show that purely transvaginal NOTES is feasible and safe for use in performing uterine adnexal procedures in selected patients. However, the procedure cannot be used in patients with cul-de-sac disease, and could have limited use in treating lesions located anterior to the uterus.


Primary Respiratory Bacterial Coinfections in Patients with COVID-19.


title: The use of inflammatory markers as a diagnostic and prognostic approach in neonatal calves with septicaemia.

text: The objective of this study was to evaluate the usefulness of inflammatory markers as a diagnostic and prognostic approach in neonatal calves with septicaemia. The study material consisted of 13 neonatal calves with septicaemia (septicaemic calves, SC) and ten healthy neonatal calves (control calves, CC). Blood samples were collected for biochemical, haematological and microbiological analyses. In addition, faecal samples were collected for microbiological and virological analyses. Three of neonatal calves with septicaemia were positive for E. coli (E. coli O157 serotype) by microbiological examination, but all neonatal calves with septicaemia were negative for rota- and coronaviruses. By haematological examination, there were no significant differences between SC and CC for white blood cell (WBC) and neutrophil (NEU) counts (P > 0.05). NEU counts were higher on day 0 than on day 15 in SC (P < 0.05). Red blood cell (RBC) counts and packed cell volume (PCV) values were higher on day 0 in the SC than in the CC (P < 0.05). By biochemical analyses, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), procalcitonin (PCT), haptoglobin (Hp), and fibrinogen (Fb) concentrations were higher on day 0 in the SC than in the CC (P < 0.05). After treatment (on day 15), the serum IL-6, PCT, Hp, and Fb concentrations were significantly decreased in the SC compared to the CC (P < 0.05). The serum iron (Fe) concentrations were lower on day 0 in the SC than in the CC (P < 0.05), and were higher on day 15 than on day 0 in the SC (P < 0.05). The study revealed that inflammatory markers could be used for determining the diagnosis and prognosis in neonatal calves with septicaemia.


title: Recommendations for the management of critically ill adult patients with COVID-19.

text: Except for pregnant women, the management of critically ill patients with COVID-19 during the pandemic includes the standard procedures that are used for any patient that requires to be attended to at the intensive care unit, as well as limited administration of crystalloid solutions, orotracheal intubation, invasive mechanical ventilation in the event of patient clinical deterioration, and muscle relaxants continuous infusion only if necessary. Non-invasive mechanical ventilation and high-flow oxygen therapy are not recommended due to the generation of aerosol (associated with risk of viral spread among health personnel), and neither is extracorporeal membrane oxygenation or the use of steroids. So far, there is no specific antiviral treatment for patients with COVID-19, and neither are there results of controlled trials supporting the use of any.


While Normal Life is Halting, Aging is Not.


title: Phage display-mediated discovery of novel tyrosinase-targeting tetrapeptide inhibitors reveals the significance of N-terminal preference of cysteine residues and their functional sulfur atom.

text: Tyrosinase, a key copper-containing enzyme involved in melanin biosynthesis, is closely associated with hyperpigmentation disorders, cancer, and neurodegenerative diseases, and as such, it is an essential target in medicine and cosmetics. Known tyrosinase inhibitors possess adverse side effects, and there are no safety regulations; therefore, it is necessary to develop new inhibitors with fewer side effects and less toxicity. Peptides are exquisitely specific to their in vivo targets, with high potencies and relatively few off-target side effects. Thus, we systematically and comprehensively investigated the tyrosinase-inhibitory abilities of N- and C-terminal cysteine/tyrosine-containing tetrapeptides by constructing a phage-display random tetrapeptide library and conducting computational molecular docking studies on novel tyrosinase tetrapeptide inhibitors. We found that N-terminal cysteine-containing tetrapeptides exhibited the most potent tyrosinase-inhibitory abilities. The positional preference of cysteine residues at the N terminus in the tetrapeptides significantly contributed to their tyrosinase-inhibitory function. The sulfur atom in cysteine moieties of N- and C-terminal cysteine-containing tetrapeptides coordinated with copper ions, which then tightly blocked substrate-binding sites. N- and C-terminal tyrosine-containing tetrapeptides functioned as competitive inhibitors against mushroom tyrosinase by using the phenol ring of tyrosine to stack with the imidazole ring of His263, thus competing for the substrate-binding site. The N-terminal cysteine-containing tetrapeptide CRVI exhibited the strongest tyrosinase-inhibitory potency (with an IC50 of 2.7 ± 0.5 μM), which was superior to those of the known tyrosinase inhibitors (arbutin and kojic acid) and outperformed kojic acid-tripeptides, mimosine-FFY, and short-sequence oligopeptides at inhibiting mushroom tyrosinase.


title: Cellular poly(c) binding proteins 1 and 2 interact with porcine reproductive and respiratory syndrome virus nonstructural protein 1β and support viral replication.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) infection of swine results in substantial economic losses to the swine industry worldwide. Identification of cellular factors involved in PRRSV life cycle not only will enable a better understanding of virus biology but also has the potential for the development of antiviral therapeutics. The PRRSV nonstructural protein 1 (nsp1) has been shown to be involved in at least two important functions in the infected hosts: (i) mediation of viral subgenomic (sg) mRNA transcription and (ii) suppression of the host's innate immune response mechanisms. To further our understanding of the role of the viral nsp1 in these processes, using nsp1β, a proteolytically processed functional product of nsp1 as bait, we have identified the cellular poly(C)-binding proteins 1 and 2 (PCBP1 and PCBP2) as two of its interaction partners. The interactions of PCBP1 and PCBP2 with nsp1β were confirmed both by coimmunoprecipitation in infected cells and/or in plasmid-transfected cells and also by in vitro binding assays. During PRRSV infection of MARC-145 cells, the cytoplasmic PCBP1 and PCBP2 partially colocalize to the viral replication-transcription complexes. Furthermore, recombinant purified PCBP1 and PCBP2 were found to bind the viral 5' untranslated region (5'UTR). Small interfering RNA (siRNA)-mediated silencing of PCBP1 and PCBP2 in cells resulted in significantly reduced PRRSV genome replication and transcription without adverse effect on initial polyprotein synthesis. Overall, the results presented here point toward an important role for PCBP1 and PCBP2 in regulating PRRSV RNA synthesis.


title: 1,8-Cineole potentiates IRF3-mediated antiviral response in human stem cells and in an ex vivo model of rhinosinusitis.

text: The common cold is one of the most frequent human inflammatory diseases caused by viruses and can facilitate bacterial superinfections, resulting in sinusitis or pneumonia. The active ingredient of the drug Soledum, 1,8-cineole, is commonly applied for treating inflammatory diseases of the respiratory tract. However, the potential for 1,8-cineole to treat primary viral infections of the respiratory tract remains unclear. In the present study, we demonstrate for the first time that 1,8-cineole potentiates poly(I:C)-induced activity of the antiviral transcription factor interferon regulatory factor 3 (IRF3), while simultaneously reducing proinflammatory nuclear factor (NF)-κB activity in human cell lines, inferior turbinate stem cells (ITSCs) and in ex vivo cultivated human nasal mucosa. Co-treatment of cell lines with poly(I:C) and 1,8-cineole resulted in significantly increased IRF3 reporter gene activity compared with poly(I:C) alone, whereas NF-κB activity was reduced. Accordingly, 1,8-cineole- and poly(I:C) treatment led to increased nuclear translocation of IRF3 in ITSCs and a human ex vivo model of rhinosinusitis compared with the poly(I:C) treatment approach. Nuclear translocation of IRF3 was significantly increased in ITSCs and slice cultures treated with lipopolysaccharide (LPS) and 1,8-cineole compared with the LPS-treated cells mimicking bacterial infection. Our findings strongly suggest that 1,8-cineole potentiates the antiviral activity of IRF3 in addition to its inhibitory effect on proinflammatory NF-κB signalling, and may thus broaden its field of application.


COVID-19 and Kawasaki Disease: Finding the Signal in the Noise.


title: The Prognostic Value of Anticholinergic Burden Measures in Relation to Mortality in Older Individuals: A Systematic Review and Meta-Analysis.

text: Background Greater anticholinergic burden (ACB) increases the risk of mortality in older individuals, yet the strength of this association varies between studies. One possible explanation for this variance is the use of different approaches to quantify ACB. This systematic review (PROSPERO number CRD42019115918) assessed the prognostic utility of ACB-specific measures on mortality in older individuals. Methods Multiple cross-disciplinary databases were searched from 2006-2018. Observational studies assessing the association between ACB and mortality utilizing ≥1 ACB measure, involving persons aged ≥65 years were included. Screening and data extraction were performed by two independent reviewers, with disagreements resolved by a third independent reviewer. Risk of bias and quality of evidence were assessed using Quality in Prognosis Studies (QUIPS) and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. Meta-analysis was conducted where appropriate. Results Of 19,224 titles, 20 articles describing 18 cohort studies involving 498,056 older individuals were eligible. Eight anticholinergic-specific measures were identified; the Anticholinergic Cognitive Burden Scale (ACBS, n=9) and Anticholinergic Risk scale (ARS, n=8) were most frequently reported. The evidence base was of poor quality, with moderate to high risk of bias. Meta-analysis showed increased mortality risk. Conclusions There was a modest association between some ACB measures and mortality, with most evidence derived from the ACBS. Studies comparing different measures within the same population were lacking. Analysis was limited by poor generalizability between studies, specifically regarding heterogeneity in methodology and reporting, as well as high risk of bias for most studies in the evidence base.


title: Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation: 1-Year follow-up outcome data of the EWOLUTION trial.

text: BACKGROUND Left atrial appendage (LAA) occlusion with WATCHMAN has emerged as viable alternative to vitamin K antagonists in randomized controlled trials. OBJECTIVE EWOLUTION was designed to provide data in routine practice from a prospective multicenter registry. METHODS A total of 1025 patients scheduled for a WATCHMAN implant were prospectively and sequentially enrolled at 47 centers. Indication for LAA closure was based on European Society of Cardiology guidelines. Follow-up and transesophageal echocardiography (TEE) were performed per local practice. RESULTS The baseline CHA2DS2-VASc score was 4.5 ± 1.6; the mean age was 73.4 ± 9 years; previous transient ischemic attack/ischemic stroke was present in 312 (30.5%), 155 (15.1%) had previous hemorrhagic stroke, and 320 (31.3%) had a history of major bleeding; and 750 (73%) were deemed unsuitable for oral anticoagulation therapy. WATCHMAN implant succeeded in 1005 (98.5%) of patients, without leaks >5 mm in 1002 (99.7%) with at least 1 TEE follow-up in 875 patients (87%). Antiplatelet therapy was used in 784 (83%), while vitamin K antagonists were used in only 75 (8%). At 1 year, mortality was 98 (9.8%), reflecting the advanced age and comorbidities in this population. Device thrombus was observed in 28 patients at routine TEE (3.7%) and was not correlated with the drug regimen (P = .14). Ischemic stroke rate was 1.1% (relative risk 84% vs estimated historical data); the major bleeding rate was 2.6% and was predominantly (2.3%) nonprocedure/device related. CONCLUSION LAA closure with the WATCHMAN device has a high implant and sealing success. This method of stroke risk reduction appears to be safe and effective with an ischemic stroke rate as low as 1.1%, even though 73% of patients had a contraindication to and were not using oral anticoagulation.


docid: sjvkutzd

title: Common Carotid Artery Ligation to Minimize Blood Loss During Oral and Maxillofacial Surgery.

text: Oral and maxillofacial surgery in veterinary medicine carries the risk of severe hemorrhage due to the great vascular supply of the head. Temporary hemostasis can be achieved with the application of pressure or hemostatic agents, but more definitive treatment may be needed to ensure bleeding will not resume once the patient is awake and normotensive. 1 , 2 Actively bleeding vessels encountered during maxillofacial surgery may be inaccessible, and vessels may recoil into bone, sometimes preventing definitive ligation. These scenarios may require ligation of the common carotid artery. 1 The purpose of this paper is to describe how to perform ligation of the common carotid artery in a step-by-step fashion. Both temporary and permanent ligation techniques are described.


title: Submental Intubation.

text: Acquisition of a secure airway is an essential element of the operative management of maxillofacial trauma. Of the options available, submental intubation is an alternative to tracheostomy. The access should be accomplished via a midline approach rather than lateral through the mylohyoid, an armored endotracheal tube utilized to prevent kinking, and the passage facilitated by use of wound dilators obtained from a percutaneous tracheostomy set.


title: The identification of pathogens associated with periprosthetic joint infection in two-stage revision.

text: OBJECTIVE Identification of periprosthetic joint infection (PJI)-related pathogens is crucial to decide what is the correct surgical strategies and the most secure timing to re-implant in case of two-stage revision. The purpose of the present study is to review the literature to identify the features of each exams which are used to identify the pathogens associated with PJI, to evaluate which are the most sensitive and specific and to set up an algorithm to decide when, in the field of two-stage revision, it's the ideal timing to re-implant. MATERIALS AND METHODS We did a systematic review of the literature to look for peer-reviewed papers of any evidence level focusing on: (1) Microbiological and molecular exams for identification of PJI-related pathogens. (2) Nuclear imaging methods, which can help in the identification of a PJI. Special attention was focused to analyse which is the sensitivity and specificity of these exams. RESULTS Overall, 64 manuscripts met the criteria of the systematic search at point 1 and 7 manuscripts at point 2. Among microbiological and molecular exams, the average of sensitivity and specificity were respectively 65.6% and 94.4% for cultural exams, 74.1% and 95.2% for molecular diagnosis and 86.9% and 96% for MicroDTTect. Among nuclear imaging methods, the average of sensitivity and specificity were respectively 94% and 69 % for three-phase bone scintigraphy and 100% and 62.5% for [18F] Fluoro-2-deoxyglucose-positron emission tomography/computed tomography. CONCLUSIONS In two-stage revision after PJI, taking into account the sensitivity and specificity values, just a few microbiological and molecular exams and nuclear imaging methods should be considered in the decision process to re-implant the components.


title: [The treatment proposal for the patients with breast diseases in the central epidemic area of 2019 coronavirus disease].

text: Currently, the epidemic of 2019 coronavirus disease (COVID-19) is still ongoing. The characteristics including high contagiousness, herd susceptibility and clinical phenotype diversity, made a serious influence on people's daily life and rountine therapy for other diseases. Breast dieases are clinical common diseases. In the central epidemic area of COVID-19, Hubei province, especially Wuhan, the clinical specialists of breast diseases should consider all of the following factors comprehensively: the prevention of COVID-19, the diagnosis and treatment of breast diseases and the accessibility of medical resources. Besides, we should select the appropriate therapy and optimize treatment process so as to prevent the propagation and cross infection of COVID-19 as well as manage the breast diseases without delay. Therefore, we carried out some management proposals of the patients with breast diseases in the central epidemic area during the epidemic of COVID-19 on the basis of conventional treatment guidelines and clinical experiences. The suggestions and corrections from colleagues will be welcomed.


title: Experiences of single incision cholecystectomy.

text: PURPOSE Single incision laparoscopic surgery in suitable cases is preferred today because it results in less postoperative pain, a more rapid recovery period, more comfort, and a better cosmetic appearance from smaller incisions. This study aims to present our experiences with single incision laparoscopic cholecystectomy to evaluate the safety and feasibility of this procedure. METHODS A total of 150 patients who underwent single incision laparoscopic cholecystectomy between January 2009 and December 2011 were evaluated retrospectively. In this serial, two different access techniques were used for single incision laparoscopy. RESULTS Single incision laparoscopic cholecystectomy was performed successfully on 150 patients. Median operative time was 29 (minimum-maximum=5-66) minutes. Median duration of hospital stay was found to be 1.33 (minimum-maximum=1-8) days. Patients were controlled on the seventh postoperative day. Bilier complication was not seen in the early period. Five patients showed port site hernia complications. Other major complications were not seen in the 36-month follow-up period. CONCLUSION Operation time of single incision laparoscopic cholecystectomy is significantly shortened with the learning curve. Single incision laparoscopic cholecystectomy seems a safe method.


title: Evaluation of erythrocyte antioxidant mechanisms: antioxidant enzymes, lipid peroxidation, and serum trace elements associated with progressive anemia in ovine malignant theileriosis.

text: Ovine malignant theileriosis is a fatal disease that is characterized by severe progressive anemia. In order to elucidate the underlying mechanisms involved in anemia, this study was designed to assess the antioxidant status and erythrocyte oxidative injuries in Iranian fat-tailed sheep that suffered from malignant theileriosis. The infected animals (infected group), composed of 50 Iranian sheep about 1-2 years old, naturally infected with Theileria sp., were divided into three subgroups according to parasitemia rates (<1%, 1-3%, 3-5%), and ten non-infected animals were also selected as the control group. Blood samples were taken and hematological parameters, the activities of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase, erythrocyte osmotic fragility, and serum concentrations of some trace elements (copper, iron, zinc, manganese, and selenium), were measured. As an index of lipid peroxidation, the level of malondialdehyde (MDA) was also determined. According to the results, a significant decrease in red blood cell (RBC) count, packed cell volume, the activities of SOD, GPX, and catalase (P <0.001), and also serum concentrations of Cu, Zn, Mn, and Se (P < 0.05) were evident in the infected sheep. In contrast, significantly increased levels of MDA and erythrocyte osmotic fragility (P < 0.001) as well as serum concentration of iron (P < 0.05) were recorded in the infected animals. The significant decrease in antioxidant enzyme activities and substantial elevated levels of lipid peroxidation and erythrocyte osmotic fragility associated with the increase in parasitemia indicate increased exposure of RBCs to oxidative damage. Also, it appears that disturbed antioxidant defense mechanisms can promote the development of anemia in ovine theileriosis.


title: Evaluation of the Seegene Allplex™ Respiratory Panel for diagnosis of acute respiratory tract infections.

text: OBJECTIVES The Seegene AllplexTM Respiratory panel was retrospectively challenged using a collection of quality control samples (QCMD) and clinical samples previously analysed with validated routine methods. METHODS A collection of 111 samples [43 QCMD samples, 13 bronchoalveolar lavage fluids and 55 nasopharyngeal aspirates/swabs] was tested with Seegene AllplexTM. The clinical samples were tested previously using either FTD® Respiratory Pathogens 21 qPCR assay (Fast Track Diagnostics), an in-house multiplex PCR for Bordetella, or BioGX Sample-ReadyTM Atypical pneumo panel (Becton Dickinson). Samples were stored at -80°C prior to analysis with Seegene Allplex™, nucleic acids were automatically extracted with NucliSENS Easymag (bioMérieux). Samples returning discordant results were subjected to repeat testing and/or additional testing by reference laboratories. RESULTS Seegene correctly identified 41/43 QCMD samples (95.4%); two samples positive for respiratory syncytial virus (RSV) and human metapneumovirus, respectively, were only correctly identified following repeat testing. In the 56 clinical samples, overall, 97 pathogens were identified: 65 pathogens (67.0%) were detected both by routine methods and Seegene, 24 pathogens (24.7%) only by routine methods, and 8 pathogens (8.2%) only by Seegene. The majority of discordant results was detected in samples with low pathogen load (22/32, 68.8%) and in samples containing multiple pathogens (25/32, 78.1%). Full agreement between methods was observed for influenza, RSV, adenovirus, Bordetella (para)pertussis and Chlamydia pneumoniae. Discordance was observed for human metapneumovirus, coronavirus OC43, bocavirus and parainfluenza virus, mainly type 4. CONCLUSION Overall, the Seegene AllplexTM assay performed well for routine detection of important respiratory targets. Acceptable agreement was observed between Seegene and other routine assays.


title: About the origin of the first two Sars-CoV-2 infections in Italy: inference not supported by appropriate sequence analysis.

text: In the 5th February 2020 issue of Journal of Medical Virology a paper was published by Giovannetti et al., entitled "The first two cases of 2019-nCoV in Italy: where they come from?"1 . In this paper a phylogenetic and evolutionary analysis was applied to the virus identified in the first two subjects diagnosed in Italy with 2019-nCoV infection, recently renamed SARS-CoV-22 , two Chinese spouses arrived in Italy for tourism. The diagnosis was performed by the virology team under direction of Maria R. Capobianchi, at the National Institute of Infectious Diseases (INMI) in Rome, Italy, where the patients are currently hospitalized. This article is protected by copyright. All rights reserved.


docid: tvgnovil

title: Differences in dry-bulb temperature do not influence moderate-duration exercise performance in warm environments when vapor pressure is equivalent.

text: PURPOSE Recent studies have determined that ambient humidity plays a more important role in aerobic performance than dry-bulb temperature does in warm environments; however, no studies have kept humidity constant and independently manipulated temperature. Therefore, the purpose of this study was to determine the contribution of dry-bulb temperature, when vapor pressure was matched, on the thermoregulatory, perceptual and performance responses to a 30-min cycling work trial. METHODS Fourteen trained male cyclists (age: 32 ± 12 year; height: 178 ± 6 cm; mass: 76 ± 9 kg; [Formula: see text]: 59 ± 9 mL kg-1 min-1; body surface area: 1.93 ± 0.12 m2; peak power output: 393 ± 53 W) volunteered, and underwent 1 exercise bout in moderate heat (MOD: 34.9 ± 0.2 °C, 50.1 ± 1.1% relative humidity) and 1 in mild heat (MILD: 29.2 ± 0.2 °C, 69.4 ± 0.9% relative humidity) matched for vapor pressure (2.8 ± 0.1 kPa), with trials counterbalanced. RESULTS Despite a higher weighted mean skin temperature during MOD (36.3 ± 0.5 vs. 34.5 ± 0.6 °C, p < 0.01), none of rectal temperature (38.0 ± 0.3 vs. 37.9 ± 0.4 °C, p = 0.30), local sweat rate (1.0 ± 0.3 vs. 0.9 ± 0.4 mg cm-2 min-1, p = 0.28), cutaneous blood flow (283 ± 116 vs. 287 ± 105 PU, p = 0.90), mean power output (206 ± 37 vs. 205 ± 41 W, p = 0.87) or total work completed (371 ± 64 vs. 369 ± 70 kJ, p = 0.77) showed any difference between environments during the work trial. However, all perceptual measures (perceived exertion, thermal discomfort, thermal sensation, skin wettedness, pleasantness, all p < 0.05) were affected detrimentally during MOD compared to MILD. CONCLUSION In a warm and compensable environment, dry-bulb temperature did not influence high-intensity cycling performance when vapor pressure was maintained, whilst the perceptual responses were affected.


title: Initial Results of the Use of a Standardized Diagnostic Criteria for Chest Computed Tomography Findings in Coronavirus Disease 2019.

text: OBJECTIVE The objective of this study was to assess the initial results of chest computed tomography (CT) standardized diagnostic criteria proposed by the Radiological Society of North America in coronavirus disease 2019 (COVID-19) compared with reverse transcription-polymerase chain reaction (RT-PCR). METHODS Seventy-one patients who underwent RT-PCR test for COVID-19 and chest CT within an interval of 4 days or less were included. Seventy-five CTs were reviewed and classified as typical, indeterminate, or atypical appearance or negative for pneumonia by 2 radiologists. With RT-PCR as reference standard, the performance of the CT diagnostic criteria in diagnosing COVID-19 was assessed. RESULTS The prevalence of positive RT-PCR was 45.1%. It was obtained a sensitivity of 83% (95% confidence interval [CI], 78%-89%), a specificity of 97% (95% CI, 92%-99%), an accuracy of 91% (95% CI, 85%-96%), a positive predictive value of 97% (95% CI, 91%-99%), and a negative predictive value of 86% (95% CI, 80%-92%). The diagnostic performance was excellent, considering the area under the curve of 0.92 (95% CI, 0.84-0.99). CONCLUSIONS Chest CT standardized diagnostic criteria had high specificity and positive predictive value for the diagnosis of COVID-19 when presenting a typical appearance.


How to restructure the management of Italian oncological patients during and after COVID-19 pandemic?


title: The uncertainty of UTCI due to uncertainties in the determination of radiation fluxes derived from measured and observed meteorological data.

text: In the present study, we investigate the determination accuracy of the Universal Thermal Climate Index (UTCI). We study especially the UTCI uncertainties due to uncertainties in radiation fluxes, whose impacts on UTCI are evaluated via the mean radiant temperature (Tmrt). We assume "normal conditions", which means that usual meteorological information and data are available but no special additional measurements. First, the uncertainty arising only from the measurement uncertainties of the meteorological data is determined. Here, simulations show that uncertainties between 0.4 and 2 K due to the uncertainty of just one of the meteorological input parameters may be expected. We then analyse the determination accuracy when not all radiation data are available and modelling of the missing data is required. Since radiative transfer models require a lot of information that is usually not available, we concentrate only on the determination accuracy achievable with empirical models. The simulations show that uncertainties in the calculation of the diffuse irradiance may lead to Tmrt uncertainties of up to ±2.9 K. If long-wave radiation is missing, we may expect an uncertainty of ±2 K. If modelling of diffuse radiation and of longwave radiation is used for the calculation of Tmrt, we may then expect a determination uncertainty of ±3 K. If all radiative fluxes are modelled based on synoptic observation, the uncertainty in Tmrt is ±5.9 K. Because Tmrt is only one of the four input data required in the calculation of UTCI, the uncertainty in UTCI due to the uncertainty in radiation fluxes is less than ±2 K. The UTCI uncertainties due to uncertainties of the four meteorological input values are not larger than the 6 K reference intervals of the UTCI scale, which means that UTCI may only be wrong by one UTCI scale. This uncertainty may, however, be critical at the two temperature extremes, i.e. under extreme hot or extreme cold conditions.


Antibody-dependent enhancement and COVID-19: Moving toward acquittal.


title: Is there a role for prophylactic mesh in abdominal wall closure after emergency laparotomy? A systematic review and meta-analysis.

text: BACKGROUND Incisional hernias are a common complication of emergency laparotomy and are associated with significant morbidity. Recent studies have found a reduction in incisional hernias when mesh is placed prophylactically during abdominal closure in elective laparotomies. This systematic review will assess the safety and efficacy of prophylactic mesh placement in emergency laparotomy. METHODS A systematic review was performed according to the PROSPERO registered protocol (CRD42018109283). Papers were dual screened for eligibility, and included when a comparison was made between closure with prophylactic mesh and closure with a standard technique, reported using a comparative design (i.e. case-control, cohort or randomised trial), where the primary outcome was incisional hernia. Bias was assessed using the Cochrane risk of bias in non-randomised studies tool. A meta-analysis of incisional hernia rate was performed to estimate risk ratio using a random effects model (Mantel-Haenszel approach). RESULTS 332 studies were screened for eligibility, 29 full texts were reviewed and 2 non-randomised studies were included. Both studies were biased due to confounding factors, as closure technique was based on patient risk factors for incisional hernia. Both studies found significantly fewer incisional hernias in the mesh groups [3.2% vs 28.6% (p < 0.001) and 5.9% vs 33.3% (p = 0.0001)]. A meta-analysis of incisional hernia risk favoured prophylactic mesh closure [risk ratio 0.15 (95% CI 0.6-0.35, p < 0.001)]. Neither study found an association between mesh and infection or enterocutaneous fistula. CONCLUSION This review found that there are limited data to assess the effect or safety profile of prophylactic mesh in the emergency laparotomy setting. The current data cannot reliably assess the use of mesh due to confounding factors, and a randomised controlled trial is required to address this important clinical question.


title: Wound complications in joint arthroplasty: comparing traditional and modern methods of skin closure.

text: Various methods of skin closure exist in joint replacement surgery. Although subcuticular skin closure techniques offer an aesthetic advantage over conventional skin stapling, no measurable differences have been reported. Furthermore, newer barbed sutures, such as the V-Loc absorbable suture (Covidien, Mansfield, Massachusetts), theoretically distribute tension evenly through the wound and help decrease knot-related complications. The purpose of this study was to evaluate whether wound complication rates were (1) lower in V-Loc closure cases as theoretically suggested, (2) lower for subcuticular closure vs staples, and (3) significantly different for knee and hip joint reconstruction.A retrospective chart review was conducted of 278 consecutive cases of primary joint reconstruction performed by a single surgeon (L.P.). The study group comprised 106 men and 161 women. Average patient age at surgery was 63 years (range, 18-92 years), and average body mass index of the cohort was 33.7 kg/m(2) (range, 25-51 kg/m(2)). Skin was closed via staple gun or subcuticular stitch (3-0 Biosyn [Covidien] vs V-Loc). Seven (3.9%) wound complications occurred in 181 cases closed with staples. Four (7.8%) wound complications occurred in 51 cases closed via subcuticular Biosyn suture. Six (13.0%) wound complications occurred in 46 cases closed with V-Loc suture. The staple group had a lower rate of complications when compared with the suture group as a whole (P=.033) and when compared specifically with the V-Loc suture group (P=.017).


title: Long-Term Outcomes of Roux-en-Y Gastric Bypass Conversion of Failed Laparoscopic Gastric Band.

text: BACKGROUND Laparoscopic adjustable gastric band (LAGB) carries a high rate of failure and reoperation. Laparoscopic conversion of failed LAGB to Roux-en-Y gastric bypass (RYGB) has been shown to be safe and feasible, but long-term follow-up data is still limited. OBJECTIVES The aim of this study is to evaluate the safety and effectiveness of RYGB after failed LAGB in our patient population. SETTING The setting was the University Hospital, Beirut, Lebanon. METHODS Using a prospectively collected database, we retrospectively reviewed data of patients who underwent LAGB revision to RYGB at our institution between 2006 and 2014. RESULTS A total of 58 patients underwent RYGB after failed LAGB in our institution between 2006 and 2014. Of those, 20 patients (34.5%) had concomitant band removal while the rest underwent a two-stage RYGB after a mean of 30 months after band removal. A follow-up was achieved in 84.5, 82, 83, 95, and 76% of patients at 1, 2, 3, 4, and 5 years after RYGB. Percentage of excess weight loss (%EWL) was 62.8, 68.1, 64.2, 63.8, and 61.3% at 1, 2, 3, 4, and 5 years, respectively, while percentage of total weight loss (%TWL) was 28.4, 30.7, 29.4, 28.9, and 28.6% at the corresponding time periods. The most common short-term complications were abscesses/leaks (5.2%) while the most common long-term complications were symptomatic gallstones necessitating laparoscopic cholecystectomy (5.2%), incisional hernias (5.2%), and small-bowel obstruction (3.4%). No surgery-related mortality was recorded. CONCLUSIONS RYGB is a safe procedure with favorable weight loss outcomes at 5 years and can be considered a good rescue procedure after failed LAGB.


title: A Novel Technique for Synchronous Laparoscopic Splenectomy and Azygoportal Disconnection With Hepatectomy.

text: BACKGROUND Liver resection was not formerly recommended in patients with both hepatocellular carcinoma (HCC) and portal hypertension because of difficult perioperative bleeding control and postoperative liver failure. Splenectomy is a proven method with which to overcome these problems. To investigate the safety and feasibility of synchronous laparoscopic splenectomy and azygoportal disconnection with hepatectomy (LSDH) for treatment of portal hypertension accompanied with HCC, we describe a clinical cohort of 10 patients who underwent a new technique of synchronous LSDH. METHODS A cohort of 10 cirrhotic patients with HCC, esophageal/gastric variceal bleeding, and hypersplenism received LSDH. A 6-port method was used for LSDH. This procedure comprises 5 steps: laparoscopic splenectomy, intraoperative splenic blood salvage, laparoscopic azygoportal disconnection, laparoscopic partial hepatectomy, and removal of spleen and liver specimens. Intraoperative autologous cell salvage was performed before hepatectomy. RESULTS LSDH was successful in all patients. There was no conversion to open operations. The operative time was 220.5 ± 19.8 minutes, blood loss was 264.0 ± 160.3 mL, and postoperative hospital stay was 10.2 ± 1.8 days. CONCLUSIONS Selective synchronous LSDH is a feasible, effective, and safe surgical procedure with satisfactory short-term efficacy. It is a promising minimally invasive treatment option for patients with cirrhotic HCC and portal hypertension.


title: Contrast enhanced ultrasonography (CEUS) to detect abdominal microcirculatory disorders in severe cases of COVID-19 infection: First experience.

text: In the hands of experienced examiners, the contrast enhanced sonography (CEUS) offers the possibility to analyze dynamic microcirculatory disturbances in real time dynamically without any risk for kidneys and thyroid gland even in severe progressing disease bedside. Based on severe COVID-19 infections, first experiences with abdominal CEUS examinations are presented. In the stage of an imminent organ failure with significantly reduced kidney and liver function, CEUS can be used to show a narrowing of the organ-supplying arteries, as well as a delayed capillary filling of vessels near the capsule, a regional reduced parenchymal perfusion or an inflammatory hyperemia with capillary hypercirculation. It is possible to quickly rule out organ infarction and to dynamically record the mesenteric arterial and venous blood flow.


Safe Handling of Containers of Expressed Human Milk in all Settings During the SARS-CoV-2 (COVID-19) Pandemic.


title: Usefulness of mean corpuscular volume as a surrogate marker for monitoring thiopurine treatment in inflammatory bowel disease.

text: BACKGROUND Thiopurines are commonly used drugs in inflammatory bowel disease. Intracellular levels of thiopurine metabolites [i.e. 6-thioguaninenucleotides (6-TGN)] are associated with efficacy and toxicity. Because 6-TGN measurement is not globally available, the mean corpuscular volume (MCV) has been proposed as a surrogate marker for monitoring thiopurine therapy. AIMS To analyze the relationship between MCV and efficacy of thiopurines, defined as either response to therapy or 6-TGN levels. METHODS A systematic search on PubMed was performed. RESULTS Fifteen studies were included. In six studies, a positive association was found between ΔMCV and 6-TGN. In four studies, it was suggested that ΔMCV can be used to predict clinical remission. In five articles, no association was found. CONCLUSION In the majority of articles, it was reported that ΔMCV is useful in guiding intracellular metabolite levels. However, there is insufficient evidence showing that ΔMCV can predict clinical remission.


title: A Critical Needs Assessment for Research in Companion Animals and Livestock Following the Pandemic of COVID-19 in Humans.

text: Problem: The emergence of novel coronavirus (SARS-CoV-2) in Wuhan, China, in November 2019 and a growing body of information compel inquiry regarding the transmissibility of infection between humans and certain animal species. Although there are a number of issues to be considered, the following points are most urgent: The potential for domesticated (companion) animals to serve as a reservoir of infection contributing to continued human-to-human disease, infectivity, and community spread. The ramifications to food security, economy, and trade issues should coronavirus establish itself within livestock and poultry. The disruption to national security if SARS-CoV-2 and its fairly well-established effects on smell (hyposmia/anosmia) to critical military service animals including explosive detector dog, narcotics detector dog, specialized search dog, combat tracker dog, mine detection dog, tactical explosive detector dog, improvised explosive device detector dog, patrol explosive detector dog, and patrol narcotics detector dog, as well as multipurpose canines used by special operations such as used by the U.S. customs and border protection agency (e.g., Beagle Brigade). This article presents in chronological order data that both individually (as received independently from multiple countries) and collectively urge studies that elucidate the following questions. 1.What animal species can be infected with SARS-CoV-2, the likely sources of infection, the period of infectivity, and transmissibility between these animals and to other animal species and humans? 2.What are the best diagnostic tests currently available for companion animals and livestock? 3.What expressions of illness in companion and other animal species can serve as disease markers? Although it is recognized that robust funding and methodology need to be identified to apply the best scientific investigation into these issues, there may be easily identifiable opportunities to capture information that can guide decision and study. First, it may be possible to quickly initiate a data collection strategy using in-place animal gatekeepers, such as zookeepers, veterinarians, kennel owners, feed lots, and military animal handlers. If provided a simple surveillance form, their detection of symptoms (lethargy, hyposmia, anosmia, and others) might be quickly reported to a central data collection site if one were created. Second, although current human COVID-19 disease is aligning around areas of population density and cluster events, it might be possible to overlay animal species density or veterinary reports that could signal some disease association in animals with COVID-19 patients. Unfortunately, although companion animals and zoo species have repeatedly served as sentinels for emerging infectious diseases, they do not currently fall under the jurisdiction of any federal agency and are not under surveillance.


Frugal solutions for the operating room during the COVID-19 pandemic.


Does spitting in public play a role in transmitting SARS-CoV-2?


title: The effects of TNF-α on GLP-1-stimulated plasma glucose kinetics.

text: CONTEXT Glucagon-like peptide-1 (GLP-1) analogs have recently been promoted as antihyperglycemic agents in critically ill patients with systemic inflammation, but the effects of TNF-α on glucose metabolism during GLP-1 administration are unknown. OBJECTIVE The objective of the study was to determine whether the infusion of TNF-α at high physiological levels impairs GLP-1's effects on glucose metabolism. DESIGN This was a randomized, controlled, cross-over trial. SETTING The study was conducted at a hospital clinical research laboratory. PARTICIPANTS Twelve healthy males (aged 24 ± 3 y; body mass index 22.9 ± 1.3 kg/m(2)). INTERVENTIONS After an overnight fast, either saline (0.9%) or recombinant human TNF-α (1000 ng/m(2) · h) was infused from t = 0-6 hours. At t = 2 hours, GLP-1 infusion (0.5 pmol/kg · min) began. From t = 4-6 hours, the GLP-1 infusion rate was increased to 1.2 pmol/kg · min. Plasma glucose was clamped at 5 mmol/L throughout via a variable rate 20% dextrose infusion. Trials were 7-14 days apart. MAIN OUTCOME MEASURES Endogenous glucose production (EGP) was measured by the [6,6-(2)H2]glucose isotope tracer dilution method. RESULTS GLP-1 infusion suppressed plasma glucagon (P < .01), elevated plasma insulin, and C-peptide (P < .01) and suppressed EGP (P < .001) during the saline infusion. In contrast, the infusion of TNF-α increased plasma TNF-α and IL-6, elevated body temperature, and blunted the GLP-1-induced suppression of EGP during high-dose GLP-1 infusion (all P < .05, TNF-α vs saline). However, TNF-α infusion lowered plasma GLP-1 during high-dose GLP-1 infusion (P < .001). CONCLUSIONS TNF-α induces systemic inflammation and reduces plasma GLP-1, thereby reducing the suppression of EGP during GLP-1 infusion. This may have clinical relevance if GLP-1 analog drugs are used for the treatment of hyperglycemia in critically ill patients.


title: Treating Low Back Pain in Failed Back Surgery Patients with Multicolumn-lead Spinal Cord Stimulation.

text: Failed back surgery syndrome (FBSS) refers to persistent, chronic pain following spinal surgery. Spinal cord stimulation with dorsal epidural leads can be used to treat back and leg pain in FBSS patients. This paper presents a detailed protocol for using spinal cord stimulation with surgical leads in FBSS patients. In our department, with the patient under general anesthesia, we place the lead in the epidural space by means of a small laminectomy at the 10th thoracic level. Placement of the lead is followed by a 1 month trial period with an externalized lead. If pain relief is greater than 50% at the end of this 1 month stimulation trial (required by Belgian reimbursement criteria), an internal pulse generator is then placed under the skin and connected to the lead in a second surgical procedure. We have demonstrated that using this technique in rigorously selected FBSS patients can significantly improve back pain, leg pain, patient activity, and quality of life for a sustained period of time.


title: Use of a peripheral venous catheter in single-incision laparoscopic surgery.

text: BACKGROUND Getting the critical view in performing single-incision laparoscopic surgery (SILS) is challenging. In addition, visibility may be impaired by lens fogging and smoke accumulation in the abdomen produced by electrocautery or ultrasonic devices. METHODS In 12 patients undergoing single-incision laparoscopic cholecystectomy, a peripheral venous catheter (PVC) was introduced in the right upper quadrant under direct vision, and a three-way stopcock was screwed onto the catheter to allow controlled smoke evacuation. Cholangiography was attempted in all cases, four times by introducing a (CH5) feeding tube via PVC. RESULTS The described technique allowed controlled smoke evacuation via the PVC during SILS while reducing lens fogging and contamination by a constant air flow toward the venous catheter. Cholangiography was possible using a conventional cholangiography forceps (in 7 of 12 cases) or a feeding tube introduced via PVC (in 4 of 12 cases). Once, bleeding from an adjuvant vessel after incision of the cystic duct had to be controlled with clips, and no cholangiogram was achieved (in 1 of 12 cases). No procedure-related complications were observed. There was no conversion to conventional laparoscopic or open surgery. No visible scar was seen at the site of PVC introduction 5 weeks postoperatively. CONCLUSIONS Visibility can be improved in SILS using a PVC without leaving apparent scars. Cholangiography via PVC is technically feasible and allows complete assessment of the biliary tract.


title: Targeting and Enrichment of Viral Pathogen by Cell Membrane Cloaked Magnetic Nanoparticles for Enhanced Detection.

text: Attachment to cellular surfaces is a major attribute among infectious pathogens for initiating disease pathogenesis. In viral infections, viruses exploit receptor-ligand interactions to latch onto cellular exterior prior to subsequent entry and invasion. In light of the selective binding affinity between viral pathogens and cells, nanoparticles cloaked in cellular membranes are herein employed for virus targeting. Using the influenza virus as a model, erythrocyte membrane cloaked nanoparticles are prepared and modified with magnetic functionalities (RBC-mNP) for virus targeting and isolation. To maximize targeting and isolation efficiency, density gradient centrifugation and nanoparticle tracking analysis were applied to minimize the presence of uncoated particles and membrane vesicles. The resulting nanoparticles possess a distinctive membrane corona, a sialylated surface, and form colloidally stable clusters with influenza viruses. Magnetic functionality is bestowed to the nanoparticles through encapsulation of superparamagnetic iron-oxide particles, which enable influenza virus enrichment via magnetic extraction. Viral samples enriched by the RBC-mNPs result in significantly enhanced virus detection by multiple virus quantification methods, including qRT-PCR, immunnochromatographic strip test, and cell-based titering assays. The demonstration of pathogen targeting and isolation by RBC-mNPs highlights a biologically inspired approach toward improved treatment and diagnosis against infectious disease threats. The work also sheds light on the efficient membrane cloaking mechanism that bestows nanoparticles with cell mimicking functionalities.


Brain-spleen link tunes immunity.


title: Management of the artificial airway.

text: Management of the artificial airway includes securing the tube to prevent dislodgement or migration as well as removal of secretions. Preventive measures include adequate humidification and appropriate airway suctioning. Monitoring airway patency and removing obstruction are potentially life-saving components of airway management. Cuff pressure management is important for preventing aspiration and mucosal damage as well as assuring adequate ventilation. A number of new monitoring techniques have been introduced, and automated cuff pressure control is becoming more common. The respiratory therapist should be adept with all these devices and understand the appropriate application and management.


title: Case Report: Novel Coronavirus-A Potential Cause of Acute Pancreatitis?

text: A 32-year-old medical practitioner presented to the emergency department with complaints of severe abdominal pain, fever, and vomiting, 1 week after the diagnosis of COVID-19. The patient did not report any comorbid conditions, alcohol usage, or gallstone disease. Laboratory and radiological investigations revealed the diagnosis of acute pancreatitis. He underwent conservative management and was discharged after 3 days of hospital admission. This case highlights a possible association between COVID-19 and acute pancreatitis, and the need for clinicians to carefully evaluate patients presenting with gastrointestinal complaints during the current pandemic.


Rethinking the early intubation paradigm of COVID-19: time to change gears?


title: Outpatient management of community-acquired pneumonia.

text: PURPOSE OF REVIEW Although most patients with community-acquired pneumonia (CAP) are treated as outpatients, the majority of data regarding CAP management is provided by hospitals, either from emergency department or inpatients. This was already noted in the first CAP guidelines, published in 1993, and the challenges regarding the outpatient management of CAP persist nowadays. These include the uncertainty of the initial diagnosis and risk stratification, the empirical choice of antibiotics, the overgrowing of antibiotic resistance bacteria and the relative scarcity of novel antibiotics. RECENT FINDINGS New molecular biology methods have changed the etiologic perspective of CAP, unveiling the role of virus. Diagnostic uncertainty may lead to antibiotic overuse and bacteria resistance. Novel antibiotics along with diagnostic improvement, related to the use of lung ultrasound and point-of-care biomarkers testing, may help to improve CAP treatment. Prevention, especially the use of antipneumococcal vaccine, is instrumental in reducing the burden of disease. SUMMARY Most of CAP cases are managed in the outpatient setting. However, most research is focused on hospitalized severe patients. New and awaited advances might contribute to aid diagnosis, cause and assessment of patients with CAP in the community. This knowledge might prove decisive in improving outcomes, as well as to the execution of stewardship programs that maintain current antibiotics, safeguard future ones and reinforce prevention.


title: MOLECULAR IDENTIFICATION OF AVIAN VIRUSES IN NEOTROPIC CORMORANTS ( PHALACROCORAX BRASILIANUS) IN CHILE.

text: We identified two RNA (paramyxovirus and coronavirus) and two DNA (adenovirus and herpesvirus) viruses in a common aquatic bird, the Neotropic Cormorant ( Phalacrocorax brasilianus), and determined their phylogenetic relationships to other global circulating variants. We analyzed 104 cloacal swabs from individuals collected at locations in Central Chile. Sequences were obtained from amplicons using consensus primers targeting conserved genes of the virus families Paramyxoviridae, Coronaviridae, Adenoviridae, and Herpesviridae. A total of 20.2% of the samples was positive for coronavirus, 8.7% for adenovirus, and 3.8% for herpesvirus. No paramyxoviruses were detected. All coronaviruses were identified as viruses of the Gammacoronavirus genus, closely related to the infectious bronchitis virus clade (bootstrap clade support=75%). All adenovirus samples were identified as Aviadenovirus, related to a gull and falcon adenovirus (Bayesian posterior probability=0.86). The herpesviruses identified were related to the infectious laryngotracheitis virus ( Gallid herpesvirus 1) of the genus Iltovirus (bootstrap clade support=99%). We provide information about the diversity of viruses circulating among apparently healthy Neotropic Cormorants.


title: Comparison of antibiotic prescriptions in adults and children with upper respiratory tract infections in Bangka Tengah primary health care centers.

text: Background Inappropriate antibiotic therapy is accelerating the development of antimicrobial resistance (AMR). Upper respiratory tract infections (URTIs) are predominantly caused by viruses, resulting in the prescription of antibiotics to a few selected patients. Previous studies in primary health care centers (PHCCs) in Indonesia have shown a high percentage of antibiotic therapy for URTIs. This study tries to analyze the difference in profiles of antibiotic prescription in the treatment of children and adults with URTI in Bangka Tengah, Indonesia. Methods Random prescriptions from patients diagnosed with URTIs (sinusitis, bronchitis, common cold, and pharyngitis) from all PHCCs in Bangka Tengah were collected from January to February 2018. Prescriptions from patients with overlapping diagnoses, such as URTI with diarrhea or typhoid, were excluded. Results During the two months of data collection, 1348 prescriptions for adults and children with URTIs were studied. Children were 1.30 (95% CI, 1.03-1.58) times more likely to be treated with antibiotics compared to adults. Amoxicillin was the most commonly prescribed antibiotic both in children (92.3%) and adults (78.6%). Ciprofloxacin was commonly prescribed in adults (14.6%) but not in children (0.3%). Conclusions This study confirms the major antibiotic overuse in patients with URTI, especially in children. Owing to the fact that children are more likely to get URTI of viral origin, they receive high percentage of antibiotic therapy. These findings support the need for collaborated intervention to decrease unnecessary prescription of antibiotics in Bangka Tengah.


title: Synthesis and evaluation of in vitro antiviral activity of novel phenoxy acetic acid derivatives.

text: Several substituted phenoxy acetic acid derived pyrazolines were synthesized by the reaction between 2-{4-[3-(2,4-dihydroxyphenyl)-3-oxo-1-propenyl]-2-methoxyphenoxy} acetic acid and substituted acid hydrazides and were tested for their in vitro cytotoxicity and antiviral activity. None of the compounds showed any specific antiviral activity [50% antivirally effective concentration (EC(50)) > or = 5-fold lower than minimum cytotoxic concentration]. The most cytotoxic of the series was 2-{4-[3-(2,4-dihydroxyphenyl)-1-(2-hydroxybenzoyl-4,5-dihydro-1H-5-pyrazolyl]-2-methoxyphenoxy}acetic acid (3(j)), with a minimum cytotoxic concentration of 0.16 microg/mL in human embryonic lung (HEL) cells.


title: The in vivo stability of electrospun polycaprolactone-collagen scaffolds in vascular reconstruction.

text: To avoid complications of prosthetic vascular grafts, engineered vascular constructs have been investigated as an alternative for vascular reconstruction. The scaffolds for vascular tissue engineering remain a cornerstone of these efforts and yet many currently available options are limited by issues of inconsistency, poor adherence of vascular cells, or inadequate biomechanical properties. In this study, we investigated whether PCL/collagen scaffolds could support cell growth and withstand physiologic conditions while maintaining patency in a rabbit aortoiliac bypass model. Our results indicate that electrospun scaffolds support adherence and growth of vascular cells under physiologic conditions and that endothelialized grafts resisted adherence of platelets when exposed to blood. When implanted in vivo, these scaffolds were able to retain their structural integrity over 1 month of implantation as demonstrated by serial ultrasonography. Further, at retrieval, these scaffolds continued to maintain biomechanical strength that was comparable to native artery. This study suggests that electrospun scaffolds combined with vascular cells may become an alternative to prosthetic vascular grafts for vascular reconstruction.


title: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of advanced epithelial and recurrent ovarian carcinoma: a single center experience.

text: BACKGROUND With standard treatment of epithelial ovarian cancer (EOC), prognosis is very poor. The aim of this study is to show early and late results in patients who underwent cytoreductive surgery and intraperitoneal chemotherapy. PATIENTS AND METHODS This was a retrospective single centre study. All patients with advanced and recurrent ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) or modified early postoperative intraperitoneal chemotherapy (EPIC) were included in the study. RESULTS In the period 1995-2014, 116 patients were treated, 55 with primary EOC and 61 with recurrent EOC. The mean age was 59 years (26-74). Statistically, median survival time was significantly longer in the group with primary advanced cancer of the ovary (41.3 months) compared to relapsed ovarian cancer (27.3 months). Survival for the primary EOC was 65 and 24% at 3 and 5 years, respectively. Survival for recurrent EOC was 33 and 16% at 3 and 5 years, respectively. Mortality was 1/116 (0.8%). Morbidity was 11/116 (9.5%). Peritoneal cancer index (PCI) was ≤20 in 59 (51%) patients and statistically, their average survival was significantly longer than in the group of 57 (49%) patients with PCI >20 (p = 0.014). CONCLUSIONS In advanced or recurrent EOC, a curative therapeutic approach was pursued that combined optimal cytoreductive surgery and intraperitoneal chemotherapy. PCI and timing of the intervention (primary or recurrent) were the strongest independent prognostic factors.


title: Intra-arterial administration of papaverine during mechanical thrombectomy for acute ischemic stroke.

text: BACKGROUND The use of stent retrievers for mechanical thrombectomy in acute ischemic stroke may induce significant vasospasm, which at the early phases of reperfusion may be crucial for rethrombosis of the recanalized vessel. We aimed to study whether the use of intra-arterial papaverine in selected cases of vasospasm was associated with improved cerebral perfusion, arterial reocclusion, or increased hemorrhagic complications. METHODS We retrospectively studied 9 consecutive patients with large artery acute occlusion, treated with stent retriever and intra-arterial papaverine. Onset to administration of intravenous recombinant tissue-plasminogen activator time, baseline National Institute of Health Stroke Scale, time to reperfusion, number of passes of the stent retriever, modified Rankin Scale score at discharge, postprocedural hemorrhage, onset to reperfusion time, papaverine dose, and thrombolysis in cerebral infarction grade were recorded in all patients. RESULTS After papaverine administration, the caliber of the infused arteries and their flow was increased in all cases. In none of the treated cases a reocclusion occurred after papaverine infusion. In one of the studied patients (11%), a parenchymal bleeding occurred 36 hours postoperatively. CONCLUSIONS This small study suggests that intra-arterial infusion of papaverine for the treatment of cerebral vasospasm after mechanical thrombectomy in acute ischemic stroke is effective and safe.


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title: Differences in Alimentary Glucose Absorption and Intestinal Disposal of Blood Glucose After Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy.

text: BACKGROUND & AIMS Bariatric procedures, such as Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG), are the most effective approaches to resolve type 2 diabetes in obese individuals. Alimentary glucose absorption and intestinal disposal of blood glucose have not been directly compared between individuals or animals that underwent RYGB vs VSG. We evaluated in rats and humans how the gut epithelium adapts after surgery and the consequences on alimentary glucose absorption and intestinal disposal of blood glucose. METHODS Obese male rats underwent RYGB, VSG, or sham (control) operations. We collected intestine segments from all rats; we performed histologic analyses and measured levels of messenger RNAs encoding the sugar transporters SGLT1, GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5. Glucose transport and consumption were assayed using ex vivo jejunal loops. Histologic analyses were also performed on Roux limb sections from patients who underwent RYGB 1-5 years after surgery. Roux limb glucose consumption was assayed after surgery by positron emission and computed tomography imaging. RESULTS In rats and humans that underwent RYGB, the Roux limb became hyperplasic, with an increased number of incretin-producing cells compared with the corresponding jejunal segment of controls. Furthermore, expression of sugar transporters and hypoxia-related genes increased and the nonintestinal glucose transporter GLUT1 appeared at the basolateral membrane of enterocytes. Ingested and circulating glucose was trapped within the intestinal epithelial cells of rats and humans that underwent RYGB. By contrast, there was no hyperplasia of the intestine after VSG, but the intestinal absorption of alimentary glucose was reduced and density of endocrine cells secreting glucagon-like peptide-1 increased. CONCLUSIONS The intestine adapts differently to RYGB vs VSG. RYGB increases intestinal glucose disposal and VSG delays glucose absorption; both contribute to observed improvements in glycemia.


title: Hepatitis B virus (HBV) surface antigen interacts with and promotes cyclophilin a secretion: possible link to pathogenesis of HBV infection.

text: Cyclophilin A (CypA), predominantly located intracellularly, is a multifunctional protein. We previously reported decreased CypA levels in hepatocytes of transgenic mice expressing hepatitis B virus (HBV) surface antigen (HBsAg). In this study, we found that expression of HBV small surface protein (SHBs) in human hepatoma cell lines specifically triggered CypA secretion, whereas SHBs added extracellularly to culture medium did not. Moreover, CypA secretion was not promoted by the expression of a secretion deficient SHBs mutant, suggesting a close association between secretion of CypA and SHBs. Interaction between CypA and SHBs was observed by using coimmunoprecipitation and glutathione S-transferase pull-down assays. Hydrodynamic injection of the SHBs expression construct into C57BL/6J mice resulted in increased serum CypA levels and ALT/AST levels, as well as the infiltration of inflammatory cells surrounding SHBs-positive hepatocytes. The inflammatory response and serum ALT/AST level were reduced when the chemotactic effect of CypA was inhibited by cyclosporine and anti-CD147 antibody. Furthermore, higher serum CypA levels were detected in chronic hepatitis B patients than in healthy individuals. In HBV patients who had received liver transplantation, serum CypA levels declined dramatically after the loss of HBsAg as a consequence of liver transplantation. Taken together, these results indicate that expression and secretion of SHBs can promote CypA secretion, which may contribute to the pathogenesis of HBV infection.


title: A rapid bio-optical sensor for diagnosing Q fever in clinical specimens.

text: Recent zoonotic outbreaks, such as Zika, Middle East respiratory syndrome and Ebola, have highlighted the need for rapid and accurate diagnostic assays that can be used to aid pathogen control. Q fever is a zoonotic disease caused by the transmission of Coxiella burnetii that can cause serious illness in humans through aerosols and is considered a potential bioterrorism agent. However, the existing assays are not suitable for the detection of this pathogen due to its low levels in real samples. We here describe a rapid bio-optical sensor for the accurate detection of Q fever and validate its clinical utility. By combining a bio-optical sensor, that transduces the presence of the target DNA based on binding-induced changes in the refractive index on the waveguide surface in a label-free and real-time manner, with isothermal DNA amplification, this new diagnostic tool offers a rapid (<20 min), 1-step DNA amplification/detection method. We confirmed the clinical sensitivity (>90%) of the bio-optical sensor by detecting C. burnetii in 11 formalin-fixed, paraffin-embedded liver biopsy samples from acute Q fever hepatitis patients and in 16 blood plasma samples from patients in which Q fever is the cause of fever of unknown origin.


title: Impact of barbed suture in controlling the dorsal vein complex during laparoscopic radical prostatectomy.

text: OBJECTIVE To compare applications of unidirectional knotless barbed suture and traditional two single polyglactin sutures for dorsal vein complex (DVC) control during laparoscopic radical prostatectomy (LRP). MATERIAL AND METHODS This was a non-randomized, prospective matched-pair pilot study. Thirty-one LRP cases with barbed suture (V-Loc®) were match-paired with 31 LRP cases in which traditional two single polyglactin stitches according to patient's prostate volume and body mass index (BMI) were used. Time needed for DVC ligation, DVC control and operation time were recorded. Peri- and postoperative parameters were noted. Statistical analyses were performed. RESULTS Mean age was 65.4±6.3 years. Mean follow-up was 20.2±3.3 months. Mean BMI and prostate volume were similar in both groups. Mean preoperative clinical stage, Gleason score, and PSA were comparable between both groups. Mean DVC ligature time and mean DVC controlling time in group 1 were statistically shorter than in group 2 (p=0.04, p<0.001). Continence rates were significantly higher in group 1 than in group 2 in early follow-up (p=0.005).


title: Real-time Tracheal Ultrasound for the Confirmation of Endotracheal Intubations in the Intensive Care Unit: An Observational Study.

text: OBJECTIVES Current methods to confirm endotracheal tube (ETT) placement have varying degrees of effectiveness and time to completion. We aimed to study the accuracy of real-time tracheal ultrasound (US) to confirm ETT placement in the intensive care unit (ICU) setting. METHODS This work was a prospective study completed at 2 academic tertiary care centers. Patients in the adult ICU requiring emergent intubation were enrolled in the trial. During the intubation process, a US team performed a tracheal US examination to determine, in real time, whether the ETT was placed into the trachea or the esophagus. RESULTS A total of 75 patients were enrolled in the study and were available for analysis. There were 12 (16%) esophageal intubations and 63 (84%) tracheal intubations. One hundred percent of the tracheal intubations and 83% of the esophageal intubations were correctly identified. The positive and negative predictive values of US to detect an esophageal intubation were 100% and 97%, respectively. CONCLUSIONS Tracheal US can be highly accurate in identifying the location of the ETT, in real time, in ICU patients undergoing emergent intubation. Although our study shows a great potential of real-time US use during emergent intubations, larger studies would be needed to further evaluate the accuracy of this technique.


title: Endovascular Treatment for Acute Ischemic Stroke: Considerations from Recent Randomized Trials.

text: BACKGROUND Despite increasing use of intravenous recombinant tissue plasminogen activator therapy, the large number of patients ineligible for treatment or for whom treatment is ineffective has become problematic. SUMMARY The number of endovascular treatments for acute ischemic stroke is increasing each year. This treatment provides higher recanalization rates for occluded vessels but may lead to hemorrhagic complications such as subarachnoid hemorrhage. Results were announced for three randomized controlled trials in 2013, with all failing to show the superiority of endovascular treatment. These results have had a major negative impact, but a new randomized controlled trial, the Multicenter Randomized CLinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN), showed that acute endovascular treatment was superior to standard medical treatment in terms of clinical outcomes. With this positive result, interim analyses from other randomized trials appear likely to show the effectiveness of endovascular treatment. KEY MESSAGE Clinical evidence of acute stroke intervention using mechanical devices might be established in the near future.


title: Recommendations for management of patients with neuroendocrine liver metastases.

text: Many management strategies exist for neuroendocrine liver metastases. These strategies range from surgery to ablation with various interventional radiology procedures, and include both regional and systemic therapy with diverse biological, cytotoxic, or targeted agents. A paucity of biological, molecular, and genomic information and an absence of data from rigorous trials limit the validity of many publications detailing management. This Review represents the views from an international conference, for which 15 expert working groups prepared evidence-based assessments addressing specific questions, and from which an independent jury derived final recommendations. The aim of the conference was to review the existing approaches to neuroendocrine liver metastases, assess the evidence on which management decisions were based, develop internationally acceptable recommendations for clinical practice (when evidence was available), and make recommendations for clinical and research endeavours. This report represents the final clinical statements and proposals for future research.


title: Development of a new analgesic index using nasal photoplethysmography.

text: Although surrogate measures to quantify pain intensity have been commercialised, there is a need to develop a new index with improved accuracy. The aim of this study was to develop a new analgesic index using nasal photoplethysmography data. The specially designed sensor was placed between the columella and the nasal septum to acquire nasal photoplethysmography in surgical patients. Nasal photoplethysmography and Surgical Pleth Index® (GE Healthcare) data were obtained for 14 min both in the absence (pre-operatively) or presence (postoperatively) of pain in a group of surgical patients, each patient acting as their own control. Various dynamic photoplethysmography variables were extracted to quantify pain intensity; the most accurate index was selected using logistic regression as a classifier. The area under the curve of the receiver-operating characteristic curve was measured to evaluate the accuracy of final model predictions. In total, 12,012 heart beats from 89 patients were used to develop a new Nasal Photoplethysmography Index for analgesic depth quantification. The two-variable model (a combination of diastolic peak point variation and heart beat interval variation) was most accurate in discriminating between the presence and absence of pain (numerical rating scale (NRS) ≥ 3). The accuracy and area under the curve of the receiver-operating characteristic curve for the Nasal Photoplethysmography Index were 75.3% and 0.8018, respectively, and 64.8% and 0.7034, respectively, for the Surgical Pleth Index. The Nasal Photoplethysmography Index clearly distinguished pain (NRS ≥ 3) in awake surgical patients with postoperative pain. The Nasal Photoplethysmography Index performed better than the Surgical Pleth Index. Further validation studies are needed to evaluate its feasibility to quantify pain intensity during general anaesthesia.


title: Biomechanics of the front abdominal wall as a potential factor leading to recurrence with laparoscopic ventral hernia repair.

text: BACKGROUND Intraabdominal pressure often is blamed as the cause of mesh-fascia junction failure after laparoscopic ventral hernia repair. Stretching of the mesh during a cough or defecation may lead to recurrence. Little is known about the movements of mesh in the abdominal cavity after this operation. This study investigated the front abdominal wall to describe its elasticity in vivo and searched for elongations that possibly stretched an implanted mesh, thereby causing fixation failure and subsequent recurrence. METHODS To measure front abdominal wall elongations, a model of fascia movements was created. Eight healthy volunteers were measured during exercise to determine the extent of elongations in their front abdominal wall. Videos were analyzed in three positions to create a mathematical shell structure. A computerized model based on the net movement of nodes was calculated to determine the axes and values for maximum elongations. RESULTS The largest average elongations were measured for the upper midline (32.08%) and the transverse line in the low lateral area (34.06%). The maximum values for these lines were larger than 100% for the middle line (133.78%) and exceeded 50% for the entire middle line. The values for the horizontal lines did not reach 10% at any level. According to these data, areas of both high and low elasticity were defined. CONCLUSIONS The presented experiment adds new parameters to the understanding of in vivo mesh behavior. Elongation of the front abdominal wall may stretch implanted mesh and could be a cause of recurrence in cases of insufficient fixation.


title: Human respiratory syncytial virus: prevalence, viral co-infections and risk factors for lower respiratory tract infections in children under 5 years of age at a general hospital in the Democratic Republic of Congo.

text: PURPOSE This study aimed to determine the prevalence of human respiratory syncytial virus (HRSV) acute respiratory infection (ARI) in children under the age of 5 years at the Provincial General Hospital of Bukavu (PGHB), and to analyse factors associated with the risk of ARI being diagnosed as lower respiratory tract infection (LRTI). METHODOLOGY A total of 146 children under 5 years visiting the PGHB for ARI between August and December 2016 were recruited, and socio-demographic information, clinical data and nasopharyngeal swabs were collected. The samples were analysed by a multiplex reverse transcriptase polymerase chain reaction targeting 15 different viruses. RESULTS Of 146 samples collected, 84 (57.5 %) displayed a positive result of at least one of the 15 viruses. The overall prevalence of HRSV was 21.2 %. HRSV A (30, 20.5 %) was the virus the most detected, followed by HRV (24, 16.4 %), PIV3 (20, 16.6) and ADV (7, 4.79 %). The other viruses were detected in three or fewer cases. There were only 11 (7.5 %) cases of co-infection. HRSV infection, malnutrition, younger age, rural settings, low income and mother illiteracy were associated with the risk of ARI being diagnosed as LRTI in bivariate analyses but, after adjusting for the confounding factors, only HRSV infection and younger age were independently associated with LRTI. CONCLUSION The prevalence of HRSV is high among children visiting the PGHB for ARI. HRSV infection and lower age are independently associated with the risk of ARI being diagnosed as LRTI.


title: Single port laparoscopic totally extraperitoneal hernioplasty: a comparative study of short-term outcome with conventional laparoscopic totally extraperitoneal hernioplasty.

text: BACKGROUND Recently, single port laparoscopic surgery has begun to develop as an extension of minimally invasive surgery, but there have been only a few reports of single port laparoscopic totally extraperitoneal (SPLTEP) hernioplasty. In addition, there are few comparative studies with conventional laparoscopic totally extraperitoneal (CLTEP) hernioplasty. The aim of the present study was to report our experience with SPLTEP hernioplasty and to compare short-term outcomes for SPLTEP hernioplasty with CLTEP hernioplasty. METHODS Data were prospectively collected for all patients undergoing SPLTEP hernioplasty for inguinal hernia at Incheon St. Mary's Hospital, Incheon, Korea. Data for the SPLTEP group (n = 76 patients enrolled between June 2010 and May 2011) were compared retrospectively with data for the CLTEP group (n = 93 patients enrolled between June 2009 and May 2010). RESULTS There were no significant differences in patient demographics. This study showed no significant difference in terms of operative time between the two groups (SPLTEP group 54.0 min vs. CLTEP group 47.8 min; p = 0.07). There were no conversions to conventional TEP hernioplasty or transabdominal preperitoneal hernioplasty or open surgery in SPLTEP hernioplasty. Morbidity rates were 7.9 % (n = 6) in the SPLTEP group and 10.8 % (n = 10) in the CLTEP group, and the difference was not significant. CONCLUSIONS Single port laparoscopic totally extraperitoneal hernioplasty is technically feasible and the short-term operative outcome is comparable to that of CLTEP hernioplasty. Future large-scale prospective controlled studies and long-term analysis are needed to establish the cosmetic outcomes, quality of life, long-term recurrence rate, and long-term complication rate of SPLTEP hernioplasty.


Extracorporeal Hemoadsorption: An Option for COVID-19 Associated Cytokine Storm Syndrome.


title: Renal Function-Adjusted D-Dimer Levels in Critically Ill Patients With Suspected Thromboembolism.

text: OBJECTIVES Diagnosing thromboembolic disease typically includes D-dimer testing and use of clinical scores in patients with low to intermediate pretest probability. However, renal dysfunction is often observed in patients with thromboembolic disease and was previously shown to be associated with increased D-dimer levels. We seek to validate previously suggested estimated glomerular filtration rate-adjusted D-dimer cutoff levels. Furthermore, we strive to explore whether the type of renal dysfunction affects estimated glomerular filtration rate-adjusted D-dimer test characteristics. DESIGN Single-center retrospective data analysis from electronic healthcare records of all emergency department patients admitted for suspected thromboembolic disease. SETTING Tertiary care academic hospital. SUBJECTS Exclusion criteria were as follows: age less than 16 years old, patients with active bleeding, and/or incomplete records. INTERVENTIONS Test characteristics of previously suggested that estimated glomerular filtration rate-adjusted D-dimer cutoff levels (> 333 µg/L [estimated glomerular filtration rate, > 60 mL/min/1.73 m], > 1,306 µg/L [30-60 mL/min/1.73 m], and > 1,663 µg/L [< 30 mL/min/1.73 m]) were validated and compared with the conventional D-dimer cutoff level of 500 µg/L. MAIN RESULTS A total of 14,477 patients were included in the final analysis, with 467 patients (3.5%) diagnosed with thromboembolic disease. Renal dysfunction was observed in 1,364 (9.4%) of the total population. When adjusted D-dimer levels were applied, test characteristics remained stable: negative predictive value (> 99%), sensitivity (91.2% vs 93.4%), and specificity (42.7% vs 50.7%) when compared with the conventional D-dimer cutoff level to rule out thromboembolic disease (< 500 µg/L). Comparable characteristics were also observed when adjusted D-dimer cutoff levels were applied in patients with acute kidney injury (negative predictive value, 98.8%; sensitivity, 95.8%; specificity, 39.2%) and/or "acute on chronic" renal dysfunction (negative predictive value, 98.0%; sensitivity, 92.9%; specificity, 48.5%). CONCLUSIONS D-Dimer cutoff levels adjusted for renal dysfunction appear feasible and safe assessing thromboembolic disease in critically ill patients. Furthermore, adjusted D-dimer cutoff levels seem reliable in patients with acute kidney injury and "acute on chronic" renal dysfunction. In patients with estimated glomerular filtration rate less than 60 mL/min/1.73 m, the false-positive rate can be reduced when estimated glomerular filtration rate-adjusted D-dimer cutoff levels are applied.


title: Evaluation of a laparoscopic liver resection in the setting of cirrhosis.

text: INTRODUCTION Patients presenting with cirrhosis and hepatic tumours represent a fragile group that have typically been avoided in early series of laparoscopic liver resection. This study was undertaken to evaluate the results of a laparoscopic hepatectomy in the setting of cirrhosis. METHODS Subgroup analysis of patients with cirrhosis within a series of 327 patients undergoing a laparoscopic resection was performed. Comparisons were made with patients without cirrhosis where appropriate to highlight differences in patient selection and outcomes. Specific variables assessed included operative details and short-term outcomes including length of stay (LOS), morbidity and mortality. Outcomes specific to hepatocellular carcinoma (HCC) were also assessed. RESULTS There were 52 patients with cirrhosis undergoing a laparoscopic hepatic resection. Ninety per cent of patients were Childs class A, with a median model for end-stage liver disease (MELD) score of 8. Hepatitis C was the most common cause of cirrhosis (88.5%), whereas the most common indication for an operation was HCC (71.2%). Resections were generally limited, with the median number of segments resected being 2 (range: 1-4). Complications occurred in 13 (25%) patients, with a 90-day mortality of 5.8%. The median LOS was 3 days. CONCLUSIONS A laparoscopic hepatectomy is safe in the setting of cirrhosis, provided the application of appropriate selection criteria and sufficient experience with the procedure.


title: Personality differences and COVID-19: are extroversion and conscientiousness personality traits associated with engagement with containment measures?

text: INTRODUCTION In December 2019, an outbreak of the novel coronavirus, the coronavirus disease 2019 (COVID-19) probably occurred in Wuhan, China. By March 2020, the World Health Organization (WHO) had declared a pandemic. Containment measures such as social distancing and hand hygiene were recommended. In this study, we start from the hypothesis that engaging with containment measures in a pandemic situation should be more comfortable for some people than for other people. Thus, individual differences should be associated with engagement with containment measures. OBJECTIVE To investigate to what extent two personality traits, extroversion and conscientiousness, are associated with engagement with two containment measures (social distancing and handwashing). METHODS The sample consisted of 715 Brazilian adults aged 18-78 years, who answered the Big Five Inventory 2 Short (BFI-2-S) and factors from the Dimensional Clinical Personality Inventory 2 (IDCP-2). RESULTS Higher scores for extroversion were associated with lower means for social distancing (p < 0.001) and higher scores for conscientiousness were associated with higher means for social distancing and handwashing (p < 0.05). CONCLUSION The findings indicate the importance of acknowledging extroversion and conscientiousness traits as relevant to people's engagement with the measures recommended for COVID-19 containment.


title: Viral Exploration of Negative Acute Febrile Cases Observed during Chikungunya Outbreaks in Gabon.

text: Non-malarial febrile illness outbreaks were documented in 2007 and 2010 in Gabon. After investigation, these outbreaks were attributed to the chikungunya and dengue viruses (CHIKV and DENV). However, for more than half of the samples analyzed, the causative agent was not identified. Given the geographical and ecological position of Gabon, where there is a great animal and microbial diversity, the circulation of other emerging viruses was suspected in these samples lacking aetiology. A total of 436 undiagnosed samples, collected between 2007 and 2013, and originating from 14 urban, suburban, and rural Gabonese locations were selected. These samples were used for viral isolation on newborn mice and VERO cells. In samples with signs of viral replication, cell supernatants and brain suspensions were used to extract nucleic acids and perform real-time RT-PCR targeting specific arboviruses, i.e., CHIKV, DENV, yellow fever, Rift Valley fever, and West Nile and Zika viruses. Virus isolation was conclusive for 43 samples either on newborn mice or by cell culture. Virus identification by RT-PCR led to the identification of CHIKV in 37 isolates. A total of 18 complete genomes and 19 partial sequences containing the E2 and E1 genes of CHIKV were sequenced using next-generation sequencing technology or the Sanger method. Phylogenetic analysis of the complete genomes showed that all the sequences belong to the East Central South Africa lineage. Furthermore, we identified 2 distinct clusters. The first cluster was made up of sequences from the western part of Gabon, whereas the second cluster was made up of sequences from the southern regions, reflecting the way CHIKV spread across the country following its initial introduction in 2007. Similar results were obtained when analyzing the CHIKV genes of the E2 and E1 structural proteins. Moreover, study of the mutations found in the E2 and E1 structural proteins revealed the presence of several mutations that facilitate the adaptation to the Aedes albopictus mosquito, such as E2 I211T and E1 A226V, in all the Gabonese CHIKV strains. Finally, sequencing of 6 additional viral isolates failed to lead to any conclusive identification.


title: Reducing surgical site infection in arthroplasty of the lower limb: A multi-disciplinary approach.

text: OBJECTIVES To review the current best surgical practice and detail a multi-disciplinary approach that could further reduce joint replacement infection. METHODS Review of relevant literature indexed in PubMed. RESULTS Surgical site infection is a major complication following arthroplasty. Despite its rarity in contemporary orthopaedic practice, it remains difficult to treat and is costly in terms of both patient morbidity and long-term health care resources. CONCLUSIONS Emphasis on education of patients and all members of the health-care team and raising awareness in how to participate in preventative efforts is imperative.


title: Demographics, Comorbidities, and Outcomes in Hospitalized Covid-19 Patients in Rural Southwest Georgia.

text: Background: There is limited data on outcomes in patients with coronavirus disease 2019 (Covid-19) in rural United States (US). This study aimed to describe the demographics, and outcomes of hospitalized Covid-19 patients in rural Southwest Georgia.Methods: Using electronic medical records, we analyzed data from all hospitalized Covid-19 patients who either diedor survived to discharge between March 2, 2020 and May 6, 2020.Results: Of the 522 patients, 92 died in hospital (17.6%). Median age was 63 years, 58% were females, and 87% African-Americans. Hypertension (79.7%), obesity (66.5%), and diabetes mellitus (42.3%) were the most common comorbidities. Males had higher overall mortality compared to females (23% v 13.8%). Immunosuppression [odds ratio (OR) 3.6; (confidence interval {CI): 1.52-8.47, p = 0.003)], hypertension (OR 3.36; CI:1.3-8.6, p = 0.01), age ≥65 years (OR 3.1; CI:1.7-5.6, p < 0.001), and morbid obesity (OR 2.29; CI:1.11-4.69, p = 0.02), were independent predictors of in-hospital mortality. Female gender was an independent predictor of decreased in-hospital mortality. Mortality in intubated patients was 67%. Mortality was 8.9% in <50 years, compared to 20% in ≥50 years.Conclusions: Immunosuppression, hypertension, age ≥65 years, and morbid obesity were independent predictors of mortality, whereas female gender was protective for mortality in hospitalized Covid-19 patients in rural Southwest Georgia. Key Messages:Patients hospitalized with Covid-19 in rural US have higher comorbidity burden.Immunosuppression, hypertension, age ≥65 years, and morbid obesity are independent predictors of increased mortality.Female gender is an independent predictor of reduced mortality.


title: Synergistic effect of modified Pd-based cobalt chromite and manganese oxide system towards NO-CO redox detoxification reaction.

text: Surface architecting of the catalyst is a hopeful method to expand the surface property of the impetus material for upgrading their response towards the chemical reaction. In the present study, designing of the catalyst was carried out using specific transition metals to boost the simultaneous NO-CO conversion reaction catalytically. These metal oxide systems have been prepared using the combustion and wet impregnation method. Prepared oxides were characterized using XRD, BET, XPS, SEM, and TEM. Further, the surface phenomenon of the catalyst was monitored through H2-TPR, O2-TPO, NO-TPD, and CO-TPD studies. The highly remarkable activity was perceived by Pd-based modified manganese oxide-cobalt chromite system as compared with simple Pd-based manganese oxide and Pd-based cobalt chromite. The catalyst showed the highest activity for NO-CO redox reaction with T100 at 170 °C. Also, good stability was observed with a runtime of 7 h.


title: Novel 2019-coronavirus on new year's Eve.

text: An ongoing apocalyptic outbreak of a new virus causing pneumonia-like clusters in Wuhan city, China, has gleamed the world. The outbreak, confirmed on the New Year's Eve 2020, has known no boundaries since then. The number has surpassed that of Severe Acute Respiratory Syndrome (SARS) and Middle East respiratory syndrome (MERS), and is uninterruptedly escalating. Being an RNA virus, it has a propensity to mutate due to the low proofreading capacity of RNA-dependent RNA polymerase. Step-wise mutations have led to the gradual spillover of virus and after crossing the inter-species interface, the virus has adapted itself for a stable human-to-human transmission. The disease caused by severe acute respiratory syndrome coronavirus (CoV)-2 (SARS-CoV-2) can prove deadlier if the so-called 'super-spreading events' emerge with time. Recent research has shown the maximum homology of 99% of SARS-CoV-2 to pangolins associated coronavirus, owing to which these can serve as potential intermediate host. India is responding swiftly to the emergency situation, and the whole of the country is under lockdown since 25 March 2020, to ensure social distancing. All the international flights are padlocked and the travellers are being screened at airports and seaports via thermal sensors, and quarantine for a period of 14 days is recommended. Three hundred and forty-five patients across the country tested positive with six fatalities as of 22 March 2020. No specific anti-CoV drugs are currently available. Patients are being treated with protease drugs are inhibitors, remdesivir, chloroquine, angiotensin-converting enzyme 2 inhibitors, ivermectin, sarilumab and tocilizumab, though none of these is Food and Drug Administration approved and are undergoing trials. Preventive measures such as social distancing, quarantine, cough etiquettes, proper hand washing, cleaning and decontaminating the surfaces are the mainstay for curbing the transmission of this virus. The present review highlights the update of novel SARS-CoV-2 in context to the Indian scenario.


title: High-order sliding-mode control for anesthesia.

text: Depth of anesthesia can be indirectly measured by Bispectral Index (BIS), therefore it is possible to administer propofol in a closed loop to maintain the optimal level of anesthesia while minimizing the dose to improve the postanesthesia recovery. High-Order Sliding-Mode control can be used to individualize drug dosing. In this study, the controller is tested with four in silico patients.