title: Protective Effects of Glutamine Antagonist 6-Diazo-5-Oxo-l-Norleucine in Mice with Alphavirus Encephalomyelitis.

text: UNLABELLED Inflammation is a necessary part of the response to infection but can also cause neuronal injury in both infectious and autoimmune diseases of the central nervous system (CNS). A neurovirulent strain of Sindbis virus (NSV) causes fatal paralysis in adult C57BL/6 mice during clearance of infectious virus from the CNS, and the virus-specific immune response is implicated as a mediator of neuronal damage. Previous studies have shown that survival is improved in T-cell-deficient mice and in mice with pharmacological inhibition of the inflammatory response and glutamate excitotoxicity. Because glutamine metabolism is important in the CNS for the generation of glutamate and in the immune system for lymphocyte proliferation, we tested the effect of the glutamine antagonist DON (6-diazo-5-oxo-l-norleucine) on the outcome of NSV infection in mice. DON treatment for 7 days from the time of infection delayed the onset of paralysis and death. Protection was associated with reduced lymphocyte proliferation in the draining cervical lymph nodes, decreased leukocyte infiltration into the CNS, lower levels of inflammatory cytokines, and delayed viral clearance. In vitro studies showed that DON inhibited stimulus-induced proliferation of lymphocytes. When in vivo treatment with DON was stopped, paralytic disease developed along with the inflammatory response and viral clearance. These studies show that fatal NSV-induced encephalomyelitis is immune mediated and that antagonists of glutamine metabolism can modulate the immune response and protect against virus-induced neuroinflammatory disease. IMPORTANCE Encephalomyelitis due to infection with mosquito-borne alphaviruses is an important cause of death and of long-term neurological disability in those who survive infection. This study demonstrates the role of the virus-induced immune response in the generation of neurological disease. DON, a glutamine antagonist, inhibited the proliferation of lymphocytes in response to infection, prevented the development of brain inflammation, and protected mice from paralysis and death during treatment. However, because DON inhibited the immune response to infection, clearance of the virus from the brain was also prevented. When treatment was stopped, the immune response was generated, brain inflammation occurred, virus was cleared, and mice developed paralysis and died. Therefore, more definitive treatment for alphaviral encephalomyelitis should inhibit virus replication as well as neuroinflammatory damage.


How to Rapidly Determine First-in-Children Dosing for COVID-19 Therapeutics.


title: Distinct Zika Virus Lineage in Salvador, Bahia, Brazil.

text: Sequencing of isolates from patients in Bahia, Brazil, where most Zika virus cases in Brazil have been reported, resulted in 11 whole and partial Zika virus genomes. Phylogenetic analyses revealed a well-supported Bahia-specific Zika virus lineage, which indicates sustained Zika virus circulation in Salvador, Bahia's capital city, since mid-2014.


title: Comparison of cyanoacrylate closure and radiofrequency ablation for the treatment of incompetent great saphenous veins: 36-Month outcomes of the VeClose randomized controlled trial.

text: OBJECTIVE To evaluate the 36-month efficacy and safety of cyanoacrylate closure for the treatment of incompetent great saphenous veins in comparison with radiofrequency ablation. METHODS In this multicenter, prospective, randomized controlled trial, 222 symptomatic subjects with incompetent great saphenous veins were assigned to either cyanoacrylate closure or radiofrequency ablation. The primary endpoint, complete closure of the target great saphenous vein, was determined using duplex ultrasound examination starting from three-month visit. RESULTS At month 36, the great saphenous vein closure rates were 94.4% for the cyanoacrylate closure group and 91.9% for the radiofrequency ablation group. Stable improvement in symptoms and quality of life was observed in both groups. Adverse event rates between the 24- and 36-month visits were similar between the groups as were serious adverse events which were infrequent and judged unrelated to either the device or the procedure in both groups. CONCLUSIONS This trial continues to demonstrate the safety and efficacy of cyanoacrylate closure for the treatment of great saphenous vein incompetence with great saphenous vein closure rate at 36 months similar to that of radiofrequency ablation, indicating non-inferiority of cyanoacrylate closure to radiofrequency ablation. The improvement in quality of life outcomes were also sustained and similar between the two treatment groups.


title: Development and validation of an indirect competitive ELISA for quantification of recombinant staphylokinase in rabbit plasma: Application to pharmacokinetic study.

text: The relatively short circulatory half-life (2-3 min) of staphylokinase is a major drawback in the development of SAK- (staphylokinase) based thrombolytic drug. A rapid and sensitive method, based on indirect competitive ELISA, was developed and validated for quantitative determination of SAK in rabbit plasma. The dynamic range of the assay varied between 0.41 ± 0.16 μg/L and 9.03 ± 0.38 μg/L (R(2) = 0.98) for SAK in rabbit plasma. There were no dilution linearity issues apparent with this assay. The precision (% CV) ranged from 4.6-9.7% for the intraassay and from 17.1-19.3% for interassay. This validated method was successfully employed for evaluation of various pharmacokinetic parameters of SAK in rabbit.


title: Lifestyle Intervention and Medical Management With vs Without Roux-en-Y Gastric Bypass and Control of Hemoglobin A1c, LDL Cholesterol, and Systolic Blood Pressure at 5 Years in the Diabetes Surgery Study.

text: Importance The Roux-en-Y gastric bypass is effective in achieving established diabetes treatment targets, but durability is unknown. Objective To compare durability of Roux-en-Y gastric bypass added to intensive lifestyle and medical management in achieving diabetes control targets. Design, Setting, and Participants Observational follow-up of a randomized clinical trial at 4 sites in the United States and Taiwan, involving 120 participants who had a hemoglobin A1c (HbA1c) level of 8.0% or higher and a body mass index between 30.0 and 39.9 (enrolled between April 2008 and December 2011) were followed up for 5 years, ending in November 2016. Interventions Lifestyle-intensive medical management intervention based on the Diabetes Prevention Program and LookAHEAD trials for 2 years, with and without (60 participants each) Roux-en-Y gastric bypass surgery followed by observation to year 5. Main Outcomes and Measures The American Diabetes Association composite triple end point of hemoglobin A1c less than 7.0%, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood pressure less than 130 mm Hg at 5 years. Results Of 120 participants who were initially randomized (mean age, 49 years [SD, 8 years], 72 women [60%]), 98 (82%) completed 5 years of follow-up. Baseline characteristics were similar between groups: mean (SD) body mass index 34.4 (3.2) for the lifestyle-medical management group and 34.9 (3.0) for the gastric bypass group and had hemoglobin A1c levels of 9.6% (1.2) and 9.6% (1.0), respectively. At 5 years, 13 participants (23%) in the gastric bypass group and 2 (4%) in the lifestyle-intensive medical management group had achieved the composite triple end point (difference, 19%; 95% CI, 4%-34%; P = .01). In the fifth year, 31 patients (55%) in the gastric bypass group vs 8 (14%) in the lifestyle-medical management group achieved an HbA1c level of less than 7.0% (difference, 41%; 95% CI, 19%-63%; P = .002). Gastric bypass had more serious adverse events than did the lifestyle-medical management intervention, 66 events vs 38 events, most frequently gastrointestinal events and surgical complications such as strictures, small bowel obstructions, and leaks. Gastric bypass had more parathyroid hormone elevation but no difference in B12 deficiency. Conclusions and Relevance In extended follow-up of obese adults with type 2 diabetes randomized to adding gastric bypass compared with lifestyle and intensive medical management alone, there remained a significantly better composite triple end point in the surgical group at 5 years. However, because the effect size diminished over 5 years, further follow-up is needed to understand the durability of the improvement. Trial Registration clinicaltrials.gov Identifier: NCT00641251.


title: Human bocavirus respiratory infections in children.

text: Human bocavirus (HBoV) was recently identified in respiratory samples from patients with acute respiratory infections and has been reported in different regions of the world. To the best of our knowledge, HBoV has never been reported in respiratory infections in Brazil. Nasopharyngeal aspirates were collected from patients aged <5 years hospitalized in 2005 with respiratory infections in Ribeirão Preto, southeast Brazil, and tested by polymerase chain reaction (PCR) for HBoV. HBoV-positive samples were further tested by PCR for human respiratory syncytial virus, human metapneumovirus, human coronaviruses 229E and OC43, human influenza viruses A and B, human parainfluenza viruses 1, 2 and 3, human rhinovirus and human adenovirus. HBoV was detected in 26/248 (10.5%) children of which 21 (81%) also tested positive for other respiratory viruses. Despite the high rates of co-infections, no significant differences were found between HBoV-positive patients with and without co-infections with regard to symptoms.


title: Femoral vascular closure device use, bivalirudin anticoagulation, and bleeding after primary angioplasty for STEMI: results from the HORIZONS-AMI trial.

text: OBJECTIVE To assess the relationship of femoral vascular closure device (VCD) use to bleeding and ischemic events in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) via different anticoagulation strategies. BACKGROUND It is unknown whether femoral VCD reduce major bleeding after primary PCI for STEMI using bivalirudin anticoagulation. METHODS We compared VCD-treated patients with propensity-matched controls in the HORIZONS-AMI trial with respect to net adverse clinical events (NACE), defined as the composite of major bleeding unrelated to coronary artery bypass graft surgery (CABG) and major adverse cardiac events (comprised of death, reinfarction, ischemia-driven target vessel revascularization, and stroke), at 30 days and 1 year. RESULTS Among 3,602 patients enrolled in HORIZONS-AMI, 2,948 underwent primary PCI via femoral arterial access and 896 (30%) received VCDs, of whom 642 were included in our model along with 642 propensity-matched controls. At 30 days, VCD-treated patients had significantly less NACE (6.7% vs. 10.8%, HR: 0.61, 95% CI: 0.42-0.89, P = 0.009), driven by a lower rate of non-CABG related major bleeding (5.0% vs. 8.1%, HR: 0.61, 95% CI: 0.39-0.94, P = 0.02). Bleeding reduction was maintained at one year and consistent in magnitude regardless of randomization to bivalirudin or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor (P for interaction = 0.84). CONCLUSION In patients undergoing transfemoral primary PCI for STEMI, VCD use was associated with significantly lower non-CABG major bleeding irrespective of anticoagulation strategy.


Urinalysis parameters for predicting severity in coronavirus disease 2019 (COVID-19).


title: [Fitting and forecasting the trend of COVID-19 by SEIR(+ CAQ) dynamic model].

text: Objectives: Fitting and forecasting the trend of COVID-19 epidemics. Methods: Based on SEIR dynamic model, considering the COVID-19 transmission mechanism, infection spectrum and prevention and control procedures, we developed SEIR(+ CAQ) dynamic model to fit the frequencies of laboratory confirmed cases obtained from the government official websites. The data from January 20, 2020 to February 7, 2020 were used to fit the model, while the left data between February 8-12 were used to evaluate the quality of forecasting. Results: According to the cumulative number of confirmed cases between January 29 to February 7, the fitting bias of SEIR(+ CAQ) model for overall China (except for cases of Hubei province), Hubei province (except for cases of Wuhan city) and Wuhan city was less than 5%. For the data of subsequent 5 days between February 8 to 12, which were not included in the model fitting, the prediction biases were less than 10%. Regardless of the cases diagnosed by clinical examines, the numbers of daily emerging cases of China (Hubei province not included), Hubei Province (Wuhan city not included) and Wuhan city reached the peak in the early February. Under the current strength of prevention and control, the total number of laboratory- confirmed cases in overall China will reach 80 417 till February 29, 2020, respectively. Conclusions: The proposed SEIR(+ CAQ) dynamic model fits and forecasts the trend of novel coronavirus pneumonia well and provides evidence for decision making.


title: Development of an efficient qRT-PCR assay for quality control and cellular quantification of respiratory samples.

text: BACKGROUND Sample quality is a fundamental parameter for the successful diagnosis of respiratory viruses. This parameter depends upon the concentration of epithelial cells. Respiratory samples are usually heterogeneous, which makes relative quantification of the viral load, against the quantity of cells, the most suitable measurement. The quantification of viral load in the field of respiratory viruses is a vital piece of information. Quantification is required from RNA or DNA viral genomes extracted. OBJECTIVES To design (RT-)PCR assays for reference genes, which show stable expression during viral infection, to be used as cellular controls and cellular quantification tools. STUDY DESIGN Assays were designed for two reference genes: hypoxanthine phosphoribosyltransferase 1 (HPRT1) and ubiquitin C (UBC). The glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) was used as a reference for this study. The transcriptional activity of the three genes was studied during infection with respiratory syncytial virus and adenovirus. The HPRT1 q(RT-)PCR assay was used on clinical samples. RESULTS All the analysis methods concluded that the three reference genes were stably expressed during viral infection. The HPRT1 q(RT-)PCR assay indicated that the majority of clinical samples (n=301, 69%) had a cellular load of between 100 and 10,000 cells/PCR. The data showed that the concentration decreased as the age of patient increased. CONCLUSIONS A new tool has been developed and commercialized for quality control and evaluation of cellular concentration in respiratory samples.


title: Thermochemical valorization and characterization of household biowaste.

text: Valorization of municipal solid waste (MSW), by means of energy and material recovery, is considered to be a crucial step for sustainable waste management. A significant fraction of MSW is comprised from food waste, the treatment of which is still a challenge. Therefore, the conventional disposal of food waste in landfills is being gradually replaced by recycling aerobic treatment, anaerobic digestion and waste-to-energy. In principle, thermal processes like combustion and gasification are preferred for the recovery of energy due to the higher electrical efficiency and the significantly less time required for the process to be completed when compared to biological process, i.e. composting, anaerobic digestion and transesterification. Nonetheless, the high water content and the molecular structure of biowaste are constraining factors in regard to the application of thermal conversion pathways. Investigating alternative solutions for the pre-treatment and more energy efficient handling of this waste fraction may provide pathways for the optimization of the whole process. In this study, by means of utilizing drying/milling as an intermediate step, thermal treatment of household biowaste has become possible. Household biowaste has been thermally processed in a bench scale reactor by means of torrefaction, carbonization and high temperature pyrolysis. According to the operational conditions, fluctuating fractions of biochar, bio-oil (tar) and syngas were recovered. The thermochemical properties of the feedstock and products were analyzed by means of Simultaneous Thermal Analysis (STA), Ultimate and Proximate analysis and Attenuated Total Reflectance (ATR). The analysis of the products shows that torrefaction of dried household biowaste produces an energy dense fuel and high temperature pyrolysis produces a graphite-like material with relatively high yield.


Six months of coronavirus: the mysteries scientists are still racing to solve.


title: NAT2 variants and toxicity related to anti-tuberculosis agents: a systematic review and meta-analysis.

text: BACKGROUND Tuberculosis (TB) patients receiving anti-tuberculosis treatment may experience serious adverse drug reactions (ADRs) such as hepatotoxicity. Variants of the N-acetyltransferase 2 (NAT2) gene may increase the risk of experiencing such toxicity events. OBJECTIVE To provide a comprehensive evaluation of the evidence base for associations between NAT2 variants and anti-tuberculosis drug-related toxicity. METHOD This was a systematic review and meta-analysis. We searched for studies in Medline, PubMed, EMBASE, BIOSIS and Web of Science. We included data from 41 articles (39 distinct cohorts of patients). We pooled effect estimates for each genotype on each outcome using meta-analyses stratified by country. RESULTS We assessed the quality of the included studies, which was variable, with many areas of concern. Slow/intermediate NAT2 acetylators were statistically significantly more likely to experience hepatotoxicity than rapid acetylators (OR 1.59, 95%CI 1.26-2.01). Heterogeneity was not detected in the overall pooled analysis (I² = 0%). NAT2 acetylator status was significantly associated with the likelihood of experiencing anti-tuberculosis drug-related hepatotoxicity. CONCLUSION We encountered several challenges in performing robust syntheses of data from pharmacogenetic studies, and we outline recommendations for the future reporting of pharmacogenetic studies to enable high-quality systematic reviews and meta-analyses to be performed.


title: Inflammatory reaction and neotissue maturation in the early host tissue incorporation of polypropylene prostheses.

text: PURPOSE The use prosthetic materials for the surgical repair of abdominal wall defects has become almost standard practice. This study was designed to assess the expression of different growth factors (VEGF/TGF-β1) and macrophages during the early host tissue incorporation of several polypropylene lightweight (PP-LW)-including one partially absorbable-and heavyweight (PP-HW) prosthetic meshes. METHODS Ventral defects were created in the anterior abdominal wall of New Zealand rabbits and repaired by fixing PP-LW meshes of different pore size and a low porosity PP-HW mesh to the edges of the defect. Following killing 14 days after implant, specimens were taken to examine TGF-β1/VEGF gene and protein expression by qRT-PCR and immunohistochemistry. The macrophage response was also assessed. RESULTS All the materials showed good host tissue incorporation, with a more severe inflammatory reaction and greater numbers of macrophages recorded in the partially absorbable LW implants. Relative amounts of VEGF mRNA were significantly lower for the LW partially absorbable implants compared with the remaining LW meshes. Protein expression of VEGF showed undetectable or minimum staining in the different groups. TGF-β1 mRNA levels were also lower in the partially absorbable group compared with one of PP-LW type of mesh. Gene expression patterns were consistent with the TGF-β1 protein levels detected. CONCLUSIONS The results suggest that VEGF and TGF-β1 expression were independent of mesh pore size. The expression of both growth factors and the macrophage response were correlated with the presence of biodegradable material in the mesh. The presence of absorbable material in the LW mesh gave rise to a more intense inflammatory reaction and the reduced synthesis of growth factors known to contribute to neotissue maturation.


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title: Impact of a nationwide COVID-19 lockdown on acute coronary syndrome referrals.


title: Progressive versus Nonprogressive Intracranial Dural Arteriovenous Fistulas: Characteristics and Outcomes.

text: BACKGROUND AND PURPOSE A minority of intracranial dural arteriovenous fistulas progress with time. We sought to determine features that predict progression and define outcomes of patients with progressive dural arteriovenous fistulas. MATERIALS AND METHODS We performed a retrospective imaging and clinical record review of patients with intracranial dural arteriovenous fistula evaluated at our hospital. RESULTS Of 579 patients with intracranial dural arteriovenous fistulas, 545 had 1 fistula (mean age, 45 ± 23 years) and 34 (5.9%) had enlarging, de novo, multiple, or recurrent fistulas (mean age, 53 ± 20 years; P = .11). Among these 34 patients, 19 had progressive dural arteriovenous fistulas with de novo fistulas or fistula enlargement with time (mean age, 36 ± 25 years; progressive group) and 15 had multiple or recurrent but nonprogressive fistulas (mean age, 57 ± 13 years; P = .0059, nonprogressive group). Whereas all 6 children had fistula progression, only 13/28 adults (P = .020) progressed. Angioarchitectural correlates to chronically elevated intracranial venous pressures, including venous sinus dilation (41% versus 7%, P = .045) and pseudophlebitic cortical venous pattern (P = .048), were more common in patients with progressive disease than in those without progression. Patients with progressive disease received more treatments than those without progression (median, 5 versus 3; P = .0068), but as a group, they did not demonstrate worse clinical outcomes (median mRS, 1 and 1; P = .39). However, 3 young patients died from intracranial venous hypertension and intracranial hemorrhage related to progression of their fistulas despite extensive endovascular, surgical, and radiosurgical treatments. CONCLUSIONS Few patients with dural arteriovenous fistulas follow an aggressive, progressive clinical course despite treatment. Younger age at initial presentation and angioarchitectural correlates to venous hypertension may help identify these patients prospectively.


title: The pharmacokinetics and pharmacodynamics of the injectable anaesthetic alfaxalone in the horse.

text: OBJECTIVE To determine the pharmacokinetics and pharmacodynamics of the neurosteroidal anaesthetic, alfaxalone, in horses after a single intravenous (IV) injection of alfaxalone, following premedication with acepromazine, xylazine and guaiphenesin. STUDY DESIGN Prospective experimental study. ANIMALS Ten (five male and five female), adult, healthy, Standardbred horses. METHODS Horses were premedicated with acepromazine (0.03 mg kg(-1) IV). Twenty minutes later they received xylazine (1 mg kg(-1) IV), then after 5 minutes, guaiphenesin (35 mg kg(-1) IV) followed immediately by IV induction of anaesthesia with alfaxalone (1 mg kg(-1) ). Cardiorespiratory variables (pulse rate, respiratory rate, pulse oximetry) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and plasma concentrations of alfaxalone were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis. The quality of anaesthetic induction and recovery was scored on a scale of 1-5 (1 very poor, 5 excellent). RESULTS The median (range) induction and recovery scores were 4 (3-5) (good: horse slowly and moderately gently attained recumbency with minimal or no rigidity or paddling) and 4 (1-5) (good: horse stood on first attempt with some knuckling and ataxia) respectively. The monitored cardiopulmonary variables were within the range expected for clinical equine anaesthesia. The mean ± SD durations of anaesthesia from induction to sternal recumbency and from induction to standing were 42.7 ± 8.4 and 47 ± 9.6 minutes, respectively. The mean ± SD plasma elimination half life (t(1/2) ), plasma clearance (Clp) and volume of distribution (V(d) ) for alfaxalone were 33.4 minutes, 37.1 ± 11.1 mL minute(-1) kg(-1) and 1.6 ± 0.4 L kg(-1) , respectively. CONCLUSIONS AND CLINICAL RELEVANCE Alfaxalone, in a 2-hydroxypropyl-beta-cyclodextrin formulation, provides anaesthesia with a short duration of recumbency that is characterised by a smooth induction and satisfactory recovery in the horse. As in other species, alfaxalone is rapidly cleared from the plasma in the horse.


title: A Comparison of Clinical Outcomes for Diabetic and Nondiabetic Patients Following Directional Atherectomy in the DEFINITIVE LE Claudicant Cohort.

text: PURPOSE To report a subset analysis that evaluated the hypothesis that directional atherectomy for peripheral artery disease in diabetic claudicants has noninferior primary patency at 12 months compared with nondiabetic claudicants. METHODS DEFINITIVE LE, a US/European multicenter study, assessed the effectiveness of directional atherectomy using SilverHawk/TurboHawk systems for treatment of peripheral artery disease in the superficial femoral, popliteal, and infrapopliteal arteries. Of the 800 patients enrolled in the study, only the 598 claudicant patients (mean age 69.5±10.4 years; 336 men) who were classified at baseline as Rutherford category 1-3 were eligible for this subset analysis. Of these, 46.8% (280/598) had diabetes. Follow-up to 12 months included duplex ultrasound examination, functional assessments, and adverse event evaluations. Independent angiographic and duplex ultrasound core laboratories assessed primary patency and secondary endpoints; a clinical events committee adjudicated adverse events. RESULTS Although diabetics had significantly more baseline comorbidities, 12-month primary patency (77.0%) was no different than for nondiabetics (77.9%; superiority p=0.98; noninferiority p<0.001) across all anatomic territories treated. Freedom from clinically driven target lesion revascularization was no different between diabetics (83.8%) and nondiabetics (87.5%) overall (p=0.19) or by lesion locations. Secondary clinical outcomes (Rutherford category, ankle-brachial index, and walking impairment) improved at 12 months for both diabetics and nondiabetics. CONCLUSION Noninferior 12-month patency rates demonstrate that directional atherectomy is an effective treatment in diabetic as well as nondiabetic claudicants. Directional atherectomy remains an attractive treatment option, improving luminal diameters without stents, which preserves future treatment options for both diabetic and nondiabetic patients with progressive, diffuse vascular disease.


title: Late emergence of contrast-enhancing fat necrosis mimicking tumor seeding after renal cryoablation.

text: Defining radiographic treatment success after percutaneous renal ablation is challenging due to variable ablation zone imaging findings over time. The present report describes two cases of progressively more evident enhancing soft-tissue nodules in the perinephric fat more than 2 years after cryoablation. Despite features concerning for tumor recurrence on computed tomography and magnetic resonance imaging, biopsies revealed fat necrosis in both cases. Renal ablation zone soft-tissue nodules can appear long after ablation, enhance with contrast medium, mimic applicator tract or ablation zone tumor seeding, and may require biopsy for confirmation of benignity.


title: Assessing the Methodological Quality of Glaucoma Clinical Practice Guidelines and Their Recommendations on Microinvasive Glaucoma Surgery: A Systematic Review.

text: INTRODUCTION Clinical practice guidelines (CPG) are regarded by many as critical communications providing guidance within specific medical fields. Over a decade ago, the first microinvasive glaucoma surgical (MIGS) procedures were introduced. Since then, a number of these novel intraocular pressure controlling surgical options have been approved worldwide. Governing bodies and health care administration often utilize CPGs when considering funding for newer technologies. This highlights the importance of well-written, accurate, and up-to-date CPGs in the rapidly evolving field of MIGS. If CPGs are unable to fill this role, their use in treatment decision-making is doing a disservice to patients, who will be denied currently available and potentially superior care. To determine the overall value of a CPG, the methodological quality with which it was developed, in addition to the current relevance and appropriateness of its recommendations, should be evaluated. The objective of the present study was to assess the methodological quality of currently available international glaucoma CPGs, as well as their coverage of MIGS as a surrogate marker of relevance and appropriateness to policy-makers and ophthalmologists alike. MATERIALS AND METHODS To identify potentially relevant CPGs, a predefined search strategy was used to search the following databases: Medline, EMBASE, BIOSIS, and Web of Science. All CPGs related to adult glaucoma and published in English were included. CPG methodological quality was assessed by 3 individuals using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Studies were then assessed for coverage of MIGS devices and procedures. RESULTS Search strategy and subsequent screening identified 11 CPGs for analysis. Eight were of high quality according to the AGREE II criteria. Three included basic information on MIGS, but none provided specific recommendations regarding their indications or which patient populations would benefit most. CONCLUSIONS Many international glaucoma CPGs are of high methodological quality. However, coverage of MIGS is sparse, nonspecific and in many instances, absent. This causes CPGs to be a suboptimal source in guiding physicians and health policy-makers in areas characterized by novel and/or rapidly evolving technologies. Mechanisms to incorporate updated evidence in CPGs would have to be considered before they can be used as a source of contemporary clinical decision-making.


title: First human magnetic resonance visualisation of prosthetics for laparoscopic large hiatal hernia repair.

text: PURPOSE Mesh repair of large hiatal hernias has increasingly gained popularity to reduce recurrence rates. Integration of iron particles into the polyvinylidene fluoride mesh-based material allows for magnetic resonance visualisation (MR). METHODS In a pilot prospective case series eight patients underwent surgical repair of hiatal hernias repair with pre-shaped meshes, which were fixated with fibrin glue. An MR investigation with a qualified protocol was performed on postoperative day four and 3 months postoperatively to evaluate the correct position of the mesh by assessing mesh appearance and demarcation. The total MR-visible mesh surface area of each implant was calculated and compared with the original physical mesh size to evaluate potential reduction of the functional mesh surfaces. RESULTS We documented no mesh migrations or dislocations but we found a significant decrease of MR-visualised total mesh surface area after release of the pneumoperitoneum compared to the original mesh size (mean 78.9 vs 84 cm(2); mean reduction of mesh area = 5.1 cm(2), p < 0.001). At 3 months postoperatively, a further reduction of the mesh surface area could be observed (mean 78.5 vs 78.9 cm(2); mean reduction of mesh area = 0.4 cm(2), p < 0.037). CONCLUSION Detailed mesh depiction and accurate assessment of the surrounding anatomy could be successfully achieved in all cases. Fibrin glue seems to provide effective mesh fixation. In addition to a significant early postoperative decrease in effective mesh surface area a further reduction in size occurred within 3 months after implantation.


title: What Should Health Science Journalists Do in Epidemic Responses?

text: Journalists have long covered outbreaks of infectious disease. In the history of global health journalism-from the 1721 Boston smallpox epidemic to the 2002-2003 SARS outbreak in China and Singapore and to recent outbreaks of Ebola in West Africa and the Democratic Republic of the Congo-newsrooms have wielded their power both responsibly and irresponsibly. This article examines journalism practice during the 2013-2016 Ebola epidemic and recommends strategies for improving epidemic reporting.


Nigeria responds to COVID-19; first case detected in sub-Saharan Africa.


CMR versus SPECT for diagnosis of coronary heart disease.


title: Revisional surgery for failed vertical-banded gastroplasty.

text: Vertical-banded gastroplasty (VBG) was once a common bariatric procedure. It has fallen out of favor due to the emergence of the adjustable gastric band and late complications including band erosion and stenosis. Options for revision include conversion to a Roux-en-Y gastric bypass (RYGB) or VBG reversal via gastrogastrostomy. Patients undergoing revision of a previous VBG were identified. VBG reversal was performed laparoscopically. Conversion to RYGB was performed by both laparotomy and laparoscopy. Perioperative outcomes and long-term weight loss were evaluated. A total of 34 patients with a previous open VBG underwent revision over a nearly 8-year period (January 2003 to September 2010). Conversion to RYGB was performed in 25 (four laparoscopically) and VBG reversal in nine patients. Mean age for all patients was 56.3 years (range 36-70), and VBG had been performed 23 years previously (range 16-30). Patients to undergo VBG reversal were more likely to be male and less likely to be morbidly obese at the time of revision. Operative time and length of stay were shorter for laparoscopic procedures. Complication rates did not differ based on technique or procedure. Patients with a previous VBG may present with complications and obesity decades after the primary procedure. Revisional surgery can be accomplished laparoscopically. Following VBG reversal, most patients gain weight and many become morbidly obese again. Conversion to RYGB is associated with weight loss and resolution of morbid obesity in most patients. When feasible, laparoscopic conversion to RYGB may offer the best outcomes.


A preliminary report on the effectiveness of nanotechnology anti-microbial spray dressing in preventing Tenckhoff catheter exit-site infection.


title: Stabilized (111)in-labeled sCCK8 analogues for targeting CCK2-receptor positive tumors: synthesis and evaluation.

text: Radiolabeled cholecystokinin-8 (CCK8) peptide analogues can be used for peptide receptor radionuclide imaging and therapy for tumors expressing CCK2/gastrin receptors. Earlier findings indicated that sulfated CCK8 (sCCK8, Asp-Tyr(OSO(3)H)-Met-Gly-Trp-Met-Asp-Phe-NH(2)) may have better characteristics for peptide receptor radionuclide therapy (PRRT) than gastrin analogues. However, sCCK8 contains an easily hydrolyzable sulfated tyrosine residue and two methionine residues which are prone to oxidation. Here, we describe the synthesis of stabilized sCCK8 analogues, resistant to hydrolysis and oxidation. Hydrolytic stability was achieved by replacement of the Tyr(OSO(3)H) moiety by a robust isosteric sulfonate, Phe(p-CH(2)SO(3)H). Replacement of methionine by norleucine (Nle) or homopropargylglycine (HPG) avoided undesired oxidation side-reactions. The phenylalanine analogue Phe(p-CH(2)SO(3)H) of l-tyrosine, synthesized by a modification of known synthetic routes, was incorporated in three peptides: sCCK8[Phe(2)(p-CH(2)SO(3)H),Met(3,6)], sCCK8[Phe(2)(p-CH(2)SO(3)H),Nle(3,6)], and sCCK8[Phe(2)(p-CH(2)SO(3)H),HPG(3,6)]. All peptides were N-terminally conjugated with the macrocyclic chelator DOTA (1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) and radiolabeled with In-111. In vitro binding assays on CCK2R-expressing HEK293 cells revealed that all three peptides showed specific binding and receptor-mediated internalization, with binding affinity values (IC(50)) in the nanomolar range. In vitro oxidation studies demonstrated that peptides with Nle or HPG indeed were resistant to oxidation. In vivo targeting studies in mice with AR42J tumors showed that tumor uptake was highest for (111)In-DOTA-sCCK8 and (111)In-DOTA-sCCK8[Phe(2)(p-CH(2)SO(3)H),Nle(3,6)] (4.78 +/- 0.64 and 4.54 +/- 1.15%ID/g, respectively, 2 h p.i.). The peptide with the methionine residues replaced by norleucine ((111)In-DOTA-sCCK8[Phe(2)(p-CH(2)SO(3)H), Nle(3,6)]) showed promising in vivo characteristics and will be further investigated for radionuclide imaging and therapy of CCK2R-expressing tumors.


title: Safety and Feasibility of Repeatable Hepatic Vascular Isolation Chemotherapy: A Pilot Study.

text: BACKGROUND The authors herein describe a novel method of repeatable hepatic isolation using an implantable access system allowing simultaneous control of hepatic arterial and portal flows by multiple endovascular catheters. PURPOSE The aim of this study was to assess the feasibility and safety of the system and to compress standard intravenous chemotherapy into 4 weeks of targeted intra-arterial delivery. METHODS An arterial access system was implanted to the axillary artery via an anastomosis. Infusions of oxaliplatin were performed biweekly for 4 weeks, using balloon catheters to achieve hepatic isolation and segmental selectivity for 20-25 min. Fifty-seven treatments under general anesthetic were performed in ten patients with inoperable chemotherapy-refractory metastatic colorectal cancer. Systemic, intrahepatic, and hepatic venous pressures were recorded to assess vascular isolation, and platinum levels were measured to assess chemotherapy distribution. RESULTS Pressure verified, multiple day-only hepatic vascular isolation infusions were achieved in nine of ten patients, with a single patient receiving multiple hepatic arterial infusions. Positron emission tomography-computed tomography (PET-CT) imaging confirmed partial response in three of ten patients and stable disease in three of ten patients. Systemic toxicity was minimal as all treatment-related gastrointestinal and neuropathic symptoms reported throughout the 4 weeks were grades 1-2. CONCLUSIONS Intra-arterial chemotherapy infusions with hepatic vascular isolation can be achieved repeatedly with targeted selectivity and minimal complications using an implantable multicatheter access system. Oxaliplatin infusions over a 4-week period may achieve tumor response in selected patients in the salvage setting. The technique should be further assessed in a phase Ib/II study.


Cultivating Deliberate Resilience During the Coronavirus Disease 2019 Pandemic.


title: Hepatic artery stenosis angioplasty and implantation of Wingspan neurovascular stent: A case report and discussion of stenting in tortuous vessels.

text: BACKGROUND Hepatic artery stenosis is a complication of orthotopic liver transplant occurring in 3.1%-7.4% of patients that can result in graft failure and need for re-transplantation. Endovascular therapy with angioplasty and stenting has been used with a high degree of technical success and good clinical outcomes, but tortuous hepatic arteries present a unique challenge for intervention. Suitable stents for this application should be maneuverable and conformable while also exerting adequate radial force to maintain a patent lumen. CASE SUMMARY Herein we report our experience with a neurovascular Wingspan stent system in a challenging case of recurrent hepatic artery stenosis and discuss the literature of stenting in tortuous transplant hepatic arteries. CONCLUSION Wingspan neurovascular stent is self-expanding, has good conformability, and adequate radial resistance and as such it could be added to the armamentarium of interventionalists in the setting of a tortuous and stenotic transplant hepatic artery.


title: Cutaneous metastases in renal cell carcinoma: a systematic review and a case report.

text: Objective: Cutaneous metastases of renal cell carcinoma (C.M.R.C.C.) are rare and associated with a poor prognosis. The aim of this study is to evaluate the incidence and the prognosis of C.M.R.C.C. with a relevant case report. Materials and methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (P.R.I.S.M.A.) of existing literature in English and Scandinavian languages was used in the period 1902-2017 with a literature search in PubMed, Embase, and Cochrane Library. Results: Nine original articles were found where the incidence of a C.M.R.C.C. was 3.3% (168/5017). In order to estimate the prognosis of C.M.R.C.C., 161 articles were found with a total of 334 cases. Survival was described in 40% of all cases (132/334). In 31% (102/334) of the cases the final time of death was stated and in this group the mean survival was 10.9 months. Ninety-six per cent died within 36 months after being diagnosed with C.M.R.C.C. Conclusion: C.M.R.C.C. are rare with an incidence of 3.3%. The prognosis is poor with a high mortality. It is suggested that the skin should be examined in the diagnostic evaluation and follow-up for patients with renal cell carcinoma.


title: Identification of porcine reproductive and respiratory syndrome virus ORF1a-encoded non-structural proteins in virus-infected cells.

text: The porcine reproductive and respiratory syndrome virus (PRRSV) replicase gene consists of two large ORFs, ORF1a and ORF1b, the latter of which is expressed by ribosomal frameshifting. The ORF1a-encoded part of the resulting replicase polyproteins (pp1a and pp1ab) is predicted to be processed proteolytically into ten non-structural proteins (nsps), known as nsp1-8, with both the nsp1 and nsp7 regions being cleaved internally (yielding nsp1α and nsp1β, and nsp7α and nsp7β, respectively). The experimental verification of these predictions depends strongly on the ability to identify individual cleavage products with specific antibodies. In this study, a panel of monoclonal and polyclonal antibodies was generated, which together were able to recognize eight ORF1a-encoded PRRSV nsps. Using these reagents, replicase cleavage products were detected in PRRSV-infected MARC-145 cells using a variety of immunoassays. By immunofluorescence microscopy, most nsps could be detected by 6 h post-infection. During the early stages of infection, nsp1β, nsp2, nsp4, nsp7α, nsp7β and nsp8 co-localized in distinct punctate foci in the perinuclear region of the cell, which were determined to be the site of viral RNA synthesis by in situ labelling. Western blot and immunoprecipitation analysis identified most individual nsps and several long-lived processing intermediates (nsp3-4, nsp5-7, nsp5-8 and nsp3-8). The identification and subcellular localization of PRRSV nsps in virus-infected cells documented here provides a basis for the further structure-function studies. Thus, this PRRSV antibody panel will be an important tool for future studies on the replication and pathogenesis of this major swine pathogen.


title: Unilateral versus bilateral prostatic arterial embolization for lower urinary tract symptoms in patients with prostate enlargement.

text: PURPOSE This study was designed to compare baseline data and clinical outcome between patients with prostate enlargement/benign prostatic hyperplasia (PE/BPH) who underwent unilateral and bilateral prostatic arterial embolization (PAE) for the relief of lower urinary tract symptoms (LUTS). METHODS This single-center, ambispective cohort study compared 122 consecutive patients (mean age 66.7 years) with unilateral versus bilateral PAE from March 2009 to December 2011. Selective PAE was performed with 100- and 200-μm nonspherical polyvinyl alcohol (PVA) particles by a unilateral femoral approach. RESULTS Bilateral PAE was performed in 103 (84.4 %) patients (group A). The remaining 19 (15.6 %) patients underwent unilateral PAE (group B). Mean follow-up time was 6.7 months in group A and 7.3 months in group B. Mean prostate volume, PSA, International prostate symptom score/quality of life (IPSS/QoL) and post-void residual volume (PVR) reduction, and peak flow rate (Qmax) improvement were 19.4 mL, 1.68 ng/mL, 11.8/2.0 points, 32.9 mL, and 3.9 mL/s in group A and 11.5 mL, 1.98 ng/mL, 8.9/1.4 points, 53.8 mL, and 4.58 mL/s in group B. Poor clinical outcome was observed in 24.3 % of patients from group A and 47.4 % from group B (p = 0.04). CONCLUSIONS PAE is a safe and effective technique that can induce 48 % improvement in the IPSS score and a prostate volume reduction of 19 %, with good clinical outcome in up to 75 % of treated patients. Bilateral PAE seems to lead to better clinical results; however, up to 50 % of patients after unilateral PAE may have a good clinical outcome.


title: Preconditioning by portal vein embolization modulates hepatic hemodynamics and improves liver function in pigs with extended hepatectomy.

text: BACKGROUND Portal vein embolization is performed weeks before extended hepatic resections to increase the future liver remnant and prevent posthepatectomy liver failure. Portal vein embolization performed closer to the operation also could be protective, but worsening of portal hyper-perfusion is a major concern. We determined the hepatic hemodynamic effects of a portal vein embolization performed 24 hours prior to hepatic operation. METHODS An extended (90%) hepatectomy was performed in swine undergoing (portal vein embolization) or not undergoing (control) a portal vein embolization 24 hours earlier (n = 10/group). Blood tests, hepatic and systemic hemodynamics, hepatic function (plasma disappearance rate of indocyanine green), liver histology, and volumetry (computed tomographic scanning) were assessed before and after the hepatectomy. Hepatocyte proliferating cell nuclear antigen expression and hepatic gene expression also were evaluated. RESULTS Swine in the control and portal vein embolization groups maintained stable systemic hemodynamics and developed similar increases of portal blood flow (302 ± 72% vs 486 ± 92%, P = .13). Portal pressure drastically increased in Controls (from 9.4 ± 1.3 mm Hg to 20.9 ± 1.4 mm Hg, P < .001), while being markedly attenuated in the portal vein embolization group (from 11.4 ± 1.5 mm Hg to 16.1 ± 1.3 mm Hg, P = .061). The procedure also improved the preservation of the hepatic artery blood flow, liver function, and periportal edema. These effects occurred in the absence of hepatocyte proliferation or hepatic growth and were associated with the induction of the vasoprotective gene Klf2. CONCLUSION Portal vein embolization preconditioning represents a potential hepato-protective strategy for extended hepatic resections. Further preclinical studies should assess its medium-term effects, including survival. Our study also supports the relevance of hepatic hemodynamics as the main pathogenetic factor of post-hepatectomy liver failure.


title: Is there a role for blood purification therapies targeting cytokine storm syndrome in critically severe COVID-19 patients?

text: The coronavirus disease-19 (COVID-19) has spread over many countries and regions since the end of 2019, becoming the most severe public health event at present. Most of the critical cases developed multiple organ dysfunction, including acute kidney injury (AKI). Cytokine storm syndrome (CSS) may complicate the process of severe COVID-19 patients. This manuscript reviews the different aspects of blood purification in critically ill patients with AKI and increased inflammatory factors, and examines its potential role in severe COVID-19 treatment. Continuous renal replacement therapy (CRRT) has been practiced in many sepsis patients with AKI. Still, the timing and dosing need further robust evidence. In addition to the traditional CRRT, the high-throughput membrane with adsorption function and cytokine adsorption column are two representatives of recently emerging novel membrane technologies. Their potential in removing inflammatory factors and other toxins prospects for the treatment of severe COVID-19.


title: Associative plasticity in the human motor cortex is enhanced by concurrently targeting separate muscle representations with excitatory and inhibitory protocols.

text: Paired associative stimulation (PAS) induces changes in the excitability of human sensorimotor cortex that outlast the procedure. PAS typically involves repeatedly pairing stimulation of a peripheral nerve that innervates an intrinsic hand muscle with transcranial magnetic stimulation over the representation of that muscle in the primary motor cortex. Depending on the timing of the stimuli (interstimulus interval of 25 or 10 ms), PAS leads to either an increase (PAS25) or a decrease (PAS10) in excitability. Both protocols, however, have been associated with an increase in excitability of nearby muscle representations not specifically targeted by PAS. Based on these spillover effects, we hypothesized that an additive, excitability-enhancing effect of PAS25 applied to one muscle representation may be produced by simultaneously applying PAS25 or PAS10 to a nearby representation. In different experiments prototypical PAS25 targeting the left thumb representation [abductor pollicis brevis (APB)] was combined with either PAS25 or PAS10 applied to the left little finger representation [abductor digiti minimi (ADM)] or, in a control experiment, with PAS10 also targeting the APB. In an additional control experiment PAS10 targeted both representations. The plasticity effects were quantified by measuring the amplitude of motor evoked potentials (MEPs) recorded before and after PAS. As expected, prototypical PAS25 was associated with an increase in MEP amplitude in the APB muscle. This effect was enhanced when PAS also targeted the ADM representation but only when a different interstimulus timing (PAS10) was used. These results suggest that PAS-induced plasticity is modified by concurrently targeting separate motor cortical representations with excitatory and inhibitory protocols.


title: Direct carotid artery puncture access for endovascular treatment of acute ischemic stroke: technical aspects, advantages, and limitations.

text: BACKGROUND Challenging anatomy for carotid artery access can result in a delay to achieve successful recanalization in patients with acute ischemic stroke. Our objective was to study emergent direct percutaneous carotid artery puncture as an alternative access approach for acute endovascular stroke interventions. METHODS We reviewed cases of acute ischemic stroke in which direct carotid artery puncture was used for access. We also reviewed current literature relevant to this subject. RESULTS We describe the technical aspects, limits, and potential complications associated with direct carotid artery puncture for intracranial acute ischemic stroke interventions, and present cases to illustrate the utility of this access approach. CONCLUSIONS Direct carotid artery puncture is a feasible alternative to transfemoral artery access in cases of stroke with difficult anatomy, including unfavorable arch type, carotid tortuosity, or an ostial lesion.


title: The role of pathogen genomics in assessing disease transmission.

text: Whole genome sequencing (WGS) of pathogens enables the sources and patterns of transmission to be identified during specific disease outbreaks and promises to transform epidemiological research on communicable diseases. This review discusses new insights into disease spread and transmission that have come from the use of WGS, particularly when combined with genomic scale phylogenetic analyses. These include elucidation of the mechanisms of cross species transmission, the potential modes of pathogen transmission, and which people in the population contribute most to transmission. Particular attention is paid to the ability of WGS to resolve individual patient to patient transmission events. Importantly, WGS data seem to be sufficiently discriminatory to target cases linked to community or hospital contacts and hence prevent further spread, and to investigate genetically related cases without a clear epidemiological link. Approaches to combine evidence from epidemiological with genomic sequencing observations are summarised. Ongoing genomic surveillance can identify determinants of transmission, monitor pathogen evolution and adaptation, ensure the accurate and timely diagnosis of infections with epidemic potential, and refine strategies for their control.


title: Off-clamp robot-assisted partial nephrectomy for complex renal tumors.

text: BACKGROUND AND PURPOSE Considering the potential impact of warm ischemia time (WIT) on renal functional outcomes after robot-assisted partial nephrectomy (RAPN), many techniques that reduce or eliminate WIT have been studied. We present our institutional experience and progression using one such technique-off-clamp RAPN-as well as the results of this technique in the management of complex cases. PATIENTS AND METHODS A retrospective chart review of 65 patients undergoing off-clamp RAPN was performed, 15 of whom underwent off-clamp RAPN for 26 complex tumors. Complex features included hilar location, completely endophytic growth, and ipsilateral multifocality. In all cases, hilar vessels were dissected but not clamped. RESULTS Mean tumor size was 2.5 cm (standard deviation; [SD]=1.4), while mean nephrometry score was 8.7 (SD=1.5). One (7%) intraoperative complication occurred. Mean estimated blood loss was 403 mL (SD=381), mean operative time was 190 minutes (SD=68), and WIT was 0 minutes in all cases. Mean length of stay was 1.8 days (SD=0.9), with one patient needing a postoperative blood transfusion (Clavien II complication). Final pathology results demonstrated clear-cell carcinoma (n=16), papillary carcinoma (n=4), angiomyolipoma (n=1), oncocytoma (n=2), and cystic nephroma (n=3). Margins were negative for tumor for 96% (25/26) of resected masses. Estimated glomerular filtration rate (eGFR) decreased by an average of 3.1 mL/min/1.73 m(2) (SD=9.8, P=0.24), at a mean follow-up of 177 days (SD=296). Five patients with radiographic follow-up of at least 6 months have no evidence of disease recurrence. CONCLUSIONS Off-clamp RAPN can be safely and effectively performed even in the case of complex tumors, but occurs with higher estimated blood loss. Minimal changes in eGFR were experienced by patients undergoing off-clamp RAPN at an average follow-up of roughly 6 months. Longer follow-up and direct comparison with conventional clamped RAPN technique are needed to establish the efficacy of off-clamp RAPN in complex cases.


title: What lies ahead: Elevated concerns for the ongoing suicide pandemic.

text: The genesis and global spread of coronavirus disease 2019 (COVID-19) has resulted in significant health concerns amid societies that were ill-equipped for such a formidable opponent. The COVID-19 pandemic has illuminated systemic health disparities and weaknesses within our health care and political systems. With aggressive but necessary interventions to thwart the instantaneous reproduction number, we have simultaneously introduced risk factors for new and exacerbated mental health concerns. Suicide, an ongoing pandemic whose rates are higher than they have been in the past 50 years, is one of these concerns as we navigate COVID-19 deaths and fears surrounding its spread. This article aims to briefly describe in retrospect some of the historical pandemics and their downstream consequences as well as present what may lie ahead in terms of anxiety, depression, and suicidal behaviors. This applies not only to frontline health care workers but also the public at large, who may very well experience long-term stressor- and trauma-related consequences through ongoing exposure to a virus that is not only potentially fatal but may have taken the lives of loved ones. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Endovascular Neuromodulation: Safety Profile and Future Directions.

text: Endovascular neuromodulation is an emerging technology that represents a synthesis between interventional neurology and neural engineering. The prototypical endovascular neural interface is the StentrodeTM, a stent-electrode array which can be implanted into the superior sagittal sinus via percutaneous catheter venography, and transmits signals through a transvenous lead to a receiver located subcutaneously in the chest. Whilst the StentrodeTM has been conceptually validated in ovine models, questions remain about the long term viability and safety of this device in human recipients. Although technical precedence for venous sinus stenting already exists in the setting of idiopathic intracranial hypertension, long term implantation of a lead within the intracranial veins has never been previously achieved. Contrastingly, transvenous leads have been successfully employed for decades in the setting of implantable cardiac pacemakers and defibrillators. In the current absence of human data on the StentrodeTM, the literature on these structurally comparable devices provides valuable lessons that can be translated to the setting of endovascular neuromodulation. This review will explore this literature in order to understand the potential risks of the StentrodeTM and define avenues where further research and development are necessary in order to optimize this device for human application.


docid: dxlpvyzn

title: The pandemic is challenging China's breakneck race to the top of science.


title: Innovation and discovery: the application of nucleic acid-based technology to avian virus detection and characterization.

text: Polymerase chain reaction (PCR)-based approaches to the detection, differentiation and characterization of avian pathogens continue to be developed and refined. The PCRs, or reverse transcriptase-PCRs, may be general, designed to detect all or most variants of a pathogen, or to be serotype, genotype or pathotype specific. Progress is being made with respect to making nucleic acid approaches more suitable for use in diagnostic laboratories. Robotic workstations are now available for extraction of nucleic acid from many samples in a short time, for routine diagnosis. Following general PCR, the DNA products are commonly analyzed by restriction endonuclease mapping (restriction fragment length polymorphism), using a small number of restriction endonucleases, based on a large body of sequence data. Increasingly, however, nucleotide sequencing is being used to analyze the DNA product, in part due to the expanding use of non-radioactive sequencing methods that are safe and enable high throughout. In this review, I highlight some recent developments with many avian viruses: Newcastle disease virus; circoviruses in canary and pigeon; infectious bursal disease virus (Gumboro disease virus); avian adenoviruses, including Angara disease/infectious hydropericardium virus, haemorrhagic enteritis virus of turkeys, and egg drop syndrome virus; avian herpesviruses, including infectious laryngotracheitis virus, duck plague virus, psittacine herpesvirus (Pacheco's parrot disease virus), Marek's disease virus and herpesvirus of turkeys; avian leukosis virus (associated with lymphoid leukosis or myeloid leukosis, and egg transmission); avian pneumoviruses (turkey rhinotracheitis virus); avian coronaviruses, including infectious bronchitis virus, turkey coronavirus and pheasant coronavirus; astrovirus, in the context of poult enteritis and mortality syndrome, and avian nephritis virus; and avian encephalomyelitis virus, a picornavirus related to hepatitis A virus.


Smart learning for urology residents during the COVID-19 pandemic and beyond: insights from a nationwide survey in Italy.


Will novel virus go pandemic or be contained?


title: Health care professionals and bedbugs: an ethical analysis of a resurgent scourge.

text: Many health care professionals (HCPs) are understandably reluctant to treat patients in environments infested with bedbugs, in part due to the risk of themselves becoming bedbug vectors to their own homes and workplaces. However, bedbugs are increasingly widespread in care settings, such as nursing homes, as well as in private homes visited by HCPs, leading to increased questions of how health care organizations and their staff ought to respond. This situation is associated with a range of ethical considerations including the duty of care, stigmatization, vulnerability, confidentiality, risks for third parties, and professional autonomy. In this article, we analyze these issues using a case study approach. We consider how patients whose living environments are infested with bedbugs can receive care in the community setting in a manner that supports their well-being, is consistent with fairness in care provision, and takes into account risks for HCPs and third parties. We also discuss limits and obstacles to the provision of care in these situations.


title: Nuclear medicine in SARS-CoV-2 pandemia: 18F-FDG-PET/CT to visualize COVID-19.

text: The current outbreak of coronavirus SARS-CoV-2 has reached multiple countries worldwide. While the number of newly diagnosed cases and fatalities is rising quickly, far-reaching measures were enacted to prevent further spread. Diagnosis relies on clinical presentation, exposure history, PCR using specimens from the respiratory tract together with computed tomography (CT) imaging. One of the hallmarks of a critical course of COVID-19 is the development of severe acute respiratory distress syndrome (ARDS). As management of COVID-19 can be considered a multi-disciplinary approach involving various medical specialties, we here review the first 18F-FDG-PET/CT scans of COVID-19 to discuss how Nuclear Medicine could contribute to management of this disease.


title: High-intensity Interval Exercise Promotes Motor Cortex Disinhibition and Early Motor Skill Consolidation.

text: Gamma-aminobutyric acid (GABA) inhibition shapes motor cortex output, gates synaptic plasticity in the form of long-term potentiation, and plays an important role in motor learning. Remarkably, recent studies have shown that acute cardiovascular exercise can improve motor memory, but the cortical mechanisms are not completely understood. We investigated whether an acute bout of lower-limb high-intensity interval (HIT) exercise could promote motor memory formation in humans through changes in cortical inhibition within the hand region of the primary motor cortex. We used TMS to assess the input-output relationship, along with inhibition involving GABAA and GABAB receptors. Measures were obtained before and after a 20-min session of HIT cycling (exercise group) or rest (control group). We then had the same participants learn a new visuomotor skill and perform a retention test 5 hr later in the absence of sleep. No differences were found in corticomotor excitability or GABAB inhibition; however, synaptic GABAA inhibition was significantly reduced for the exercise group but not the control group. HIT exercise was found to enhance motor skill consolidation. These findings link modification of GABA to improved motor memory consolidation after HIT exercise and suggest that the beneficial effects of exercise on consolidation might not be dependent on sleep.


docid: nhragpzn

title: Magnitude of blood pressure reduction and clinical outcomes in acute intracerebral hemorrhage: intensive blood pressure reduction in acute cerebral hemorrhage trial study.

text: UNLABELLED Evidence supports early intensive blood pressure (BP) lowering in acute intracerebral hemorrhage, but uncertainty persists over whether potential benefits and harms vary according to the magnitude of BP reduction. We aimed to determine whether larger systolic BP (SBP) reductions were associated with better outcomes in participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). INTERACT2 was an international, open, blinded end point, randomized controlled trial of patients with spontaneous intracerebral hemorrhage (<6 hours) and elevated SBP (150-220 mm Hg) assigned to intensive (target SBP <140 mm Hg) or guideline-recommended (SBP <180 mm Hg) treatment. Associations of BP reduction (baseline minus average of achieved SBP) during 3 time periods post randomization (15-60 minutes, 1-24 hours, and 2-7 days) on poor outcome (death or major disability) at 90 days were analyzed in multivariable logistic regression models with odds ratios and 95% confidence intervals. Larger SBP reductions within the first hour after randomization were associated with lower risks of poor outcome: compared with minimal reduction (<10 mm Hg), odds ratios were 0.80 (95% confidence interval, 0.63-1.02) for moderate (10-20 mm Hg) and 0.65 (0.52-0.82) for large (≥20 mm Hg) reductions (P trend <0.01). Similar associations were also observed for SBP reductions during 1 to 24 hours (P<0.01) and 2 to 7 days (P 0.02). No heterogeneity in associations for patients above or below baseline SBP 180 mm Hg was reported (P>0.30). Optimal recovery from intracerebral hemorrhage was observed in hypertensive patients who achieved the greatest SBP reductions (≥20 mm Hg) in the first hour and maintained for 7 days. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079.


title: Serum inflammatory biomarkers and clinical outcomes of COPD exacerbation caused by different pathogens.

text: BACKGROUND AND OBJECTIVE COPD exacerbation is characterized by worsening of symptoms, warranting change in treatment. Systemic and airway inflammation play roles in the pathogenesis of COPD exacerbation. We hypothesized whether increased serum inflammatory biomarkers are associated with the clinical outcomes of COPD exacerbation caused by different infectious pathogens. METHODS COPD patients with exacerbation were recruited from a hospital emergency department during 2014-2015. Serum procalcitonin (PCT) and C-reactive protein (CRP) were measured. Dyspnea, eosinopenia, consolidation, acidemia, and atrial fibrillation (DECAF) score was calculated for predicting mortality. Multiplex polymerase chain reaction was carried out for respiratory viral assay from nasopharyngeal swabs, and sputum bacterial culture was also performed. Hospital mortality, invasive mechanical ventilation requirement, and length of hospital stay (LOS) were evaluated, and their associations with clinical characteristics, DECAF score, and serum biomarkers were examined. RESULTS A total of 62 COPD patients were enrolled. These patients were classified as Global Initiative for Obstructive Lung Disease (GOLD) stage 2, 3, and 4 in 12.9%, 6.4%, and 80.7% of cases, respectively. Isolated bacterial exacerbation was recovered in 30.6% of exacerbation episodes: Klebsiella pneumoniae was the most commonly identified bacteria. Viral pathogens and coinfections were noted in 9.6% and 16.1% of exacerbated patients, respectively. Influenza was the most commonly detected viral pathogen. Serum biomarkers and DECAF score for viruses, bacteria, coinfection, and noninfectious causes of exacerbations were similar. Neither DECAF score nor serum biomarkers were able to differentiate patients with and without mortality or requiring mechanical ventilation. Increased serum PCT was noted in patients with LOS ≥7 days when compared with those with LOS <7 days (0.38 ng/mL vs 0.1 ng/mL; P=0.035). CONCLUSION Increased serum PCT is associated with longer LOS in COPD exacerbation. However, CRP and DECAF score play limited roles in predicting clinical outcome and lack an association with causes of exacerbation.


title: Registries as Tools for Clinical Excellence and the Development of the Pelvic Floor Disorders Registry.

text: Surgical device innovation has been less regulated than drug development, allowing integration of unproven techniques and materials into standard practice. Successful device registries gather information on patient outcomes and can provide postmarket surveillance of new technologies and allow comparison with currently established treatments or devices. The Pelvic Floor Disorders Registry was developed in collaboration with the Food and Drug Administration, device manufacturers, and other stakeholders to serve as a platform for industry-sponsored postmarket device surveillance, investigator-initiated research, and quality and effectiveness benchmarking, all designed to improve the care of women with pelvic floor disorders.


Differences and similarities between Severe Acute Respiratory Syndrome (SARS)-CoronaVirus (CoV) and SARS-CoV-2. Would a rose by another name smell as sweet?


title: Urinary Bladder Matrix Reinforcement for Laparoscopic Hiatal Hernia Repair.

text: Background and Objectives Synthetic mesh reinforcement during laparoscopic hiatal hernia repair (LHHR) reduces recurrence. Biologically derived mesh is also associated with reduced recurrence. Urinary bladder matrix (UBM), a biologically derived extracellular matrix mesh, has shown clinical success. We wanted to determine the safety and efficacy of LHHR with porcine UBM reinforcement. Methods This retrospective, single-surgeon study reviewed clinical data on patients who underwent LHHR from August 2009 through May 2014, with diaphragmatic reinforcement with porcine UBM mesh. Primary outcomes were (1) recurrence-a >2-cm defect above the diaphragm at 3 months; (2) intra- and postoperative complications; (3) pre- and postoperative esophageal reflux (GERD) or dysphagia; and (4) cessation of proton pump inhibitor (PPI). Results Sixty-two patients who had LHHR with UBM mesh were studied (mean age, 62 years, 53 women, mean body mass index 32.7 kg/m2) Before surgery 98% had GERD, 19% had dysphagia, and 98% were on PPI. Postoperative UGIS was performed on 66% 3 months after surgery, and 19% had a recurrence of >2 cm; 56% remained on PPI, and 16% (P < .001) remained symptomatic. Dysphagia improved in 75% (P = .05). No intraoperative complications were recorded. One postoperative mortality occurred secondary to an unrelated cardiac event. Conclusions UBM mesh was effective and safe for LHHR. In addition to reducing the rate of recurrence compared to unreinforced primary repair, the properties of UBM, including site-specific constructive tissue remodeling, may add benefits over other biologic products. This study represents an evaluation of UBM mesh in a large cohort of patients who underwent LHHR.


title: Thin-section computed tomography findings in 104 immunocompetent patients with adenovirus pneumonia.

text: Background To date, there has been no computed tomography (CT) evaluation of adenovirus pneumonia in a large number of immunocompetent patients. Purpose To describe the thin-section CT findings of immunocompetent patients with adenovirus pneumonia. Material and Methods We prospectively enrolled 104 patients with adenovirus pneumonia from a military hospital. CT scans of each patient were retrospectively and independently assessed by two radiologists for the presence of abnormalities, laterality and zonal predominance of the parenchymal abnormalities, and dominant imaging patterns and their anatomic distributions. Results CT findings included consolidation (n = 92), ground-glass opacity (GGO; n = 82), septal thickening (n = 34), nodules (n = 46), bronchial wall thickening (n = 32), pleural effusion (n = 16), and lymphadenopathy (n = 3). Eighty-four patients (81%) exhibited unilateral parenchymal abnormalities and 57 (57%) exhibited lower lung zone abnormalities. The most frequently dominant CT pattern was consolidation with surrounding GGO (n = 50), with subpleural (70%) and peribronchovascular (94%) distributions. Consolidation-the second-most common pattern (n = 33)-also exhibited subpleural (79%) and peribronchovascular (97%) distributions. The dominant nodule pattern (n = 14) exhibited mixed (64%) and peribronchovascular (100%) distributions. A dominant GGO pattern was only observed in four patients; none had central distribution. Conclusion Although the manifestations of adenovirus pneumonia on CT are varied, we found the most frequent pattern was consolidation with or without surrounding GGO, with subpleural and peribronchovascular distributions. Parenchymal abnormalities were predominantly unilateral and located in the lower lung zone. If dominant consolidation findings are present in immunocompetent patients during the early stages, adenovirus pneumonia should be considered.


title: The safety of biologic mesh for laparoscopic repair of large, complicated hiatal hernia.

text: BACKGROUND Biologic mesh is widely used for repair of large, complicated hiatal hernias. Recently, there have been reports of complications after its implantation. We studied the course of a large group of patients who had undergone hiatal hernia repair with use of biologic mesh to determine the rate of immediate and late complications related to its use. METHODS All patients who had biologic mesh placed at the hiatus and who had been followed for at least 1 year were included. Perioperative data were reviewed, and a questionnaire was administered, designed to identify symptoms of gastroesophageal reflux, other symptoms such as dysphagia, and all other operative or endoscopic interventions that occurred after mesh implantation. In addition, postoperative radiologic and endoscopic studies were reviewed to assess signs of complications related to use of mesh. RESULTS There were 126 patients eligible for the study. We were able to contact 73 of these patients, at median follow-up of 45 months. No mesh-related complications were found. The frequency and severity of heartburn, regurgitation, and dysphagia improved significantly compared with preoperative values, and 89% of the patients reported good to excellent results in terms of overall satisfaction. Six patients recorded worsening of dysphagia postoperatively, but after careful work-up and review of each individual case, no case seemed to be directly related to the mesh. No erosions, strictures, or other complications directly related to use of mesh were found. One patient required reoperation due to hiatal hernia recurrence with gastroesophageal reflux disease (GERD) symptoms. CONCLUSIONS Use of biologic mesh for laparoscopic repair of large, complicated hiatal hernias appears safe. There were no major complications related to the mesh, and overall satisfaction with the operation was very good.


Direct common carotid artery puncture for acute thrombectomy against ischemic stroke.


title: Is renal tissue oxygen desaturation during severe hypoxia underestimated? An observational study in term newborn piglets.

text: The kidney is an organ highly susceptible to injury by regional tissue oxygen desaturation during hypoxic episodes. Transcutaneous monitoring of renal tissue oxygen saturation is therefore of increasing interest. The aim of the present study was to compare renal tissue oxygen saturation measured by near-infrared spectroscopy (NIRS) during acute hypoxia in neonates directly on the kidney and transcutaneously. We hypothesized that transcutaneous renal tissue oxygen saturation measurements would be influenced by superficial tissue. Five term newborn piglets were anesthetized, instrumented and exposed to normocapnic hypoxia at an inspired oxygen concentration of 0.14. Regional tissue oxygen saturation (rSO₂) was simultaneously measured for comparison with the sensor of NIRS (Invos 5100, Somanetics Corp., Troy, MI, USA) applied directly on the left kidney (renaldirect rSO₂) and on the skin of right flank above the right kidney (renalskin rSO₂). Cerebral regional tissue oxygenation (cerebralskin rSO₂), arterial oxygen saturation, heart rate (HR) and mean arterial pressure (MAP) were also monitored. NIRS parameters were analyzed in 5 s intervals during first 2 min of hypoxia. Hypoxia was achieved with an arterial oxygen desaturation from median (range) 95.3% (86.8-98.0) to 23.5% (13.0-41.0) after 2 min. HR and MAP did not change significantly during hypoxia. There were pronounced and lower renaldirect rSO₂ readings when compared with those of renalskin rSO₂ with significant differences from 25 to 55 s after initiation of hypoxia. Changes of cerebralskin rSO₂ and renalskin rSO₂ were similar. Transcutaneous monitoring of renal tissue oxygen saturation may underestimate acute oxygen desaturation of the kidney during hypoxia in neonates.


title: ST-segment elevation myocardial infarction.

text: ST-segment elevation myocardial infarction (STEMI) is the most acute manifestation of coronary artery disease and is associated with great morbidity and mortality. A complete thrombotic occlusion developing from an atherosclerotic plaque in an epicardial coronary vessel is the cause of STEMI in the majority of cases. Early diagnosis and immediate reperfusion are the most effective ways to limit myocardial ischaemia and infarct size and thereby reduce the risk of post-STEMI complications and heart failure. Primary percutaneous coronary intervention (PCI) has become the preferred reperfusion strategy in patients with STEMI; if PCI cannot be performed within 120 minutes of STEMI diagnosis, fibrinolysis therapy should be administered to dissolve the occluding thrombus. The initiation of networks to provide around-the-clock cardiac catheterization availability and the generation of standard operating procedures within hospital systems have helped to reduce the time to reperfusion therapy. Together with new advances in antithrombotic therapy and preventive measures, these developments have resulted in a decrease in mortality from STEMI. However, a substantial amount of patients still experience recurrent cardiovascular events after STEMI. New insights have been gained regarding the pathophysiology of STEMI and feed into the development of new treatment strategies.


title: Optimal temperature zone for the dispersal of COVID-19

text: Abstract It is essential to know the environmental parameters within which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can survive to understand its global dispersal pattern. We found that 60.0% of the confirmed cases of coronavirus disease 2019 (COVID-19) occurred in places where the air temperature ranged from 5 °C to 15 °C, with a peak in cases at 11.54 °C. Moreover, approximately 73.8% of the confirmed cases were concentrated in regions with absolute humidity of 3 g/m3 to 10 g/m3. SARS-CoV-2 appears to be spreading toward higher latitudes. Our findings suggest that there is an optimal climatic zone in which the concentration of SARS-CoV-2 markedly increases in the ambient environment (including the surfaces of objects). These results strongly imply that the COVID-19 pandemic may spread cyclically and outbreaks may recur in large cities in the mid-latitudes in autumn 2020.


title: Detection of sentinel lymph nodes in minimally invasive surgery using indocyanine green and near-infrared fluorescence imaging for uterine and cervical malignancies.

text: OBJECTIVES Our primary objective was to assess the detection rate of sentinel lymph nodes (SLNs) using indocyanine green (ICG) and near-infrared (NIR) fluorescence imaging for uterine and cervical malignancies. METHODS NIR fluorescence imaging for the robotic platform was obtained at our institution in 12/2011. We identified all cases planned for SLN mapping using fluorescence imaging from 12/2011-4/2013. Intracervical ICG was the fluorophobe in all cases. Four cc (1.25mg/mL) of ICG was injected into the cervix alone divided into the 3- and 9-o'clock positions, with 1 cc deep into the stroma and 1 cc submucosally before initiating laparoscopic entry. Blue dye was concurrently injected in some cases. RESULTS Two hundred twenty-seven cases were performed. Median age was 60 years (range, 28-90 years). Median BMI was 30.2 kg/m(2) (range, 18-60 kg/m(2)). The median SLN count was 3 (range, 1-23). An SLN was identified in 216 cases (95%), with bilateral pelvic mapping in 179 (79%). An aortic SLN was identified in 21 (10%) of the 216 mapped cases. When ICG alone was used to map cases, 188/197 patients mapped, for a 95% detection rate compared to 93% (28/30) in cases in which both dyes were used (P=NS). Bilateral mapping was seen in 156/197 (79%) ICG-only cases and 23/30 (77%) ICG and blue dye cases (P=NS). CONCLUSIONS NIR fluorescence imaging with intracervical ICG injection using the robotic platform has a high bilateral SLN detection rate and appears favorable to using blue dye alone and/or other modalities. Combined use of ICG and blue dye appears unnecessary.


title: Molecular epidemiology of respiratory viruses among Malaysian Young children with a confirmed respiratory infection during 2014-2015.

text: Background In many developing countries, acute respiratory tract infections (ARTIs) are the main cause of morbidity and mortality among young children. This study aims to evaluate the molecular epidemiology of respiratory viruses among Malaysian children with confirmed respiratory infections between July 2014 and July 2015. Methods A total of 394 nasopharyngeal swabs were collected prospectively from children age 0-5 years old with ARTIs from hospitals in Kuala Lumpur. Respiratory viral panel (RVP) assay was used to identify the viral aetiology of respiratory infections. Results From a total of 394 samples, the positive detection rate was 79.9% (n=315). A total of 15 types of RNA viruses and a single type of DNA virus were detected. Enterovirus/rhinovirus (n=112, 28.4%), respiratory syncytial virus (RSV) (n=85, 21.6%), adenovirus (n=64, 16.2%), human bocavirus (n=34, 8.6%), and human metapneumovirus (n=29, 7.4%) were the five predominant viruses. Enterovirus/rhinovirus and RSV constituted most of the viral respiratory infections among young children, especially among children less than 1 year old. No coronavirus was detected among children between 3 and 5 years old. Co-infection caused by 2 or 3 respiratory viruses were detected in 52 patients (13.2%). Enterovirus/rhinovirus, adenovirus, and human bocavirus demonstrated pronounced seasonality. The infection rate peaked during mid-year, while the lowest activity occurred during early of the year. Conclusions The use of molecular assay as a routine diagnostic in the hospitals can improve the diagnosis and management of respiratory tract infections among children.


title: Cell-penetrating peptides: design, synthesis, and applications.

text: The intrinsic property of cell-penetrating peptides (CPPs) to deliver therapeutic molecules (nucleic acids, drugs, imaging agents) to cells and tissues in a nontoxic manner has indicated that they may be potential components of future drugs and disease diagnostic agents. These versatile peptides are simple to synthesize, functionalize, and characterize yet are able to deliver covalently or noncovalently conjugated bioactive cargos (from small chemical drugs to large plasmid DNA) inside cells, primarily via endocytosis, in order to obtain high levels of gene expression, gene silencing, or tumor targeting. Typically, CPPs are often passive and nonselective yet must be functionalized or chemically modified to create effective delivery vectors that succeed in targeting specific cells or tissues. Furthermore, the design of clinically effective systemic delivery systems requires the same amount of attention to detail in both design of the delivered cargo and the cell-penetrating peptide used to deliver it.


Creating a Global Health Risk Framework.


title: Thirty-seven patients treated with the C-seal: protection of stapled colorectal anastomoses with a biodegradable sheath.

text: PURPOSE The present study was performed to get a better insight in the incidence of anastomotic leakage leading to reintervention when using the C-seal: a biodegradable sheath that protects the stapled colorectal anastomosis from leakage. METHODS The C-seal is a thin walled tube-like sheath that forms a protective sheath within the bowel lumen. Thirty-seven patients undergoing surgery with creation of a stapled colorectal anastomosis with C-seal were analyzed. Follow-up was completed until 3 months after surgery. RESULTS One patient (3%) developed anastomotic leakage leading to reintervention. None of the 37 anastomoses was dismantled. One patient was diagnosed with a rectovaginal fistula. In three patients (8%), a perianastomotic abscess spontaneously drained. CONCLUSION The incidence of anastomotic leakage leading to reintervention when using the C-seal (3%) is lower than expected based on the literature (11%). We have currently set-up a multicenter randomized trial to confirm the efficiency of the C-seal (www.csealtrial.nl).


title: Barbed sutures versus conventional tenorrhaphy in flexor tendon repair: An ex vivo biomechanical analysis.

text: BACKGROUND The management of flexor tendon injuries has evolved in recent years through industrial improvements in suture materials, refinements of repair methods, and early rehabilitation protocols. However, there is no consensus on the ideal suture material and technique. This study was conducted to compare the tensile strength, repair time, and characteristics of 4-strand cruciate, modified Kessler, and 4-strand horizontal intrafiber barbed sutures for flexor tenorrhaphy with a 12-mm suture purchase length in an animal model. METHODS The right third deep flexors of 60 adult Leghorn chicken feet were isolated and repaired with a 12-mm suture purchase length. The tendons were randomly assigned to three groups of equal number (n=20 each). Groups 1 and 2 received 4-strand cruciate and modified Kessler repair with conventional suture materials, respectively. A 4-strand horizontal intrafiber barbed suture technique was used in group 3. The repaired tendons were biomechanically tested for tensile strength, 2-mm gap resistance, and mode of failure. Repair times were also recorded. RESULTS The maximum tensile strength until failure was 44.6±4.3 N in group 1, 35.7±5.2 N in group 2, and 56.7±17.3 N in group 3. The barbed sutures were superior to the other sutures in terms of the load needed for 2-mm gap formation (P<0.05). Furthermore, the barbed sutures showed the shortest repair time (P<0.05). CONCLUSIONS This study found that 4-strand horizontal intrafiber barbed suture repair with a 12-mm purchase length in a chicken flexor tendon injury model showed promising biomechanical properties and took less time to perform than other options.


title: Simulation-based training for thoracoscopic lobectomy: a randomized controlled trial: virtual-reality versus black-box simulation.

text: BACKGROUND Video-assisted thoracic surgery is gradually replacing conventional open thoracotomy as the method of choice for the treatment of early-stage non-small cell lung cancers, and thoracic surgical trainees must learn and master this technique. Simulation-based training could help trainees overcome the first part of the learning curve, but no virtual-reality simulators for thoracoscopy are commercially available. This study aimed to investigate whether training on a laparoscopic simulator enables trainees to perform a thoracoscopic lobectomy. METHODS Twenty-eight surgical residents were randomized to either virtual-reality training on a nephrectomy module or traditional black-box simulator training. After a retention period they performed a thoracoscopic lobectomy on a porcine model and their performance was scored using a previously validated assessment tool. RESULTS The groups did not differ in age or gender. All participants were able to complete the lobectomy. The performance of the black-box group was significantly faster during the test scenario than the virtual-reality group: 26.6 min (SD 6.7 min) versus 32.7 min (SD 7.5 min). No difference existed between the two groups when comparing bleeding and anatomical and non-anatomical errors. CONCLUSION Simulation-based training and targeted instructions enabled the trainees to perform a simulated thoracoscopic lobectomy. Traditional black-box training was more effective than virtual-reality laparoscopy training. Thus, a dedicated simulator for thoracoscopy should be available before establishing systematic virtual-reality training programs for trainees in thoracic surgery.


Managing passengers with stable respiratory disease planning air travel: British Thoracic Society recommendations.


Reply to O'Riordan et al.


Video Conferencing Impact on Facial Appearance: Looking Beyond the COVID-19 Pandemic.


title: Innate immune responses to duck Tembusu virus infection.

text: The disease caused by duck Tembusu virus (DTMUV) is characterized by severe egg-drop in laying ducks. Currently, the disease has spread to most duck-raising areas in China, leading to great economic losses in the duck industry. In the recent years, DTMUV has raised some concerns, because of its expanding host range and increasing pathogenicity, as well as the potential threat to public health. Innate immunity is crucial for defending against invading pathogens in the early stages of infection. Recently, studies on the interaction between DTMUV and host innate immune response have made great progress. In the review, we provide an overview of DTMUV and summarize current advances in our understanding of the interaction between DTMUV and innate immunity, including the host innate immune responses to DTMUV infection through pattern recognition receptors (PRRs), signaling transducer molecules, interferon-stimulated genes (ISGs), and the immune evasion strategies employed by DTMUV. The aim of the review is to gain an in-depth understanding of DTMUV pathogenesis to facilitate future studies.


title: Impact of the coronavirus disease 2019 (COVID-19) pandemic on pediatric oncology care in the Middle East, North Africa, and West Asia Region: A report from the Pediatric Oncology East and Mediterranean (POEM) Group.

text: BACKGROUND Childhood cancer is a highly curable disease when timely diagnosis and appropriate therapy are provided. A negative impact of the coronavirus disease 2019 (COVID-19) pandemic on access to care for children with cancer is likely but has not been evaluated. METHODS A 34-item survey focusing on barriers to pediatric oncology management during the COVID-19 pandemic was distributed to heads of pediatric oncology units within the Pediatric Oncology East and Mediterranean (POEM) collaborative group, from the Middle East, North Africa, and West Asia. Responses were collected on April 11 through 22, 2020. Corresponding rates of proven COVID-19 cases and deaths were retrieved from the World Health Organization database. RESULTS In total, 34 centers from 19 countries participated. Almost all centers applied guidelines to optimize resource utilization and safety, including delaying off-treatment visits, rotating and reducing staff, and implementing social distancing, hand hygiene measures, and personal protective equipment use. Essential treatments, including chemotherapy, surgery, and radiation therapy, were delayed in 29% to 44% of centers, and 24% of centers restricted acceptance of new patients. Clinical care delivery was reported as negatively affected in 28% of centers. Greater than 70% of centers reported shortages in blood products, and 47% to 62% reported interruptions in surgery and radiation as well as medication shortages. However, bed availability was affected in <30% of centers, reflecting the low rates of COVID-19 hospitalizations in the corresponding countries at the time of the survey. CONCLUSIONS Mechanisms to approach childhood cancer treatment delivery during crises need to be re-evaluated, because treatment interruptions and delays are expected to affect patient outcomes in this otherwise largely curable disease.


title: The K-Technique: A Novel Technique for Laparoscopic Apical Suspension Using Barbed Sutures.

text: OBJECTIVES Hysterectomy is among the most common gynecologic procedures performed for women, second only to cesarean sections, and the proportion of it performed laparoscopically continues to increase. Addressing apical support at the time of the hysterectomy is crucial to minimizing the risk of posthysterectomy prolapse. Barriers to addressing apical support include the lack of experience in laparoscopic suturing and knot tying that require advanced skills and dexterity. The K-technique is a novel modification of the uterosacral ligament suspension procedure using the knot-less barbed suture technology, rendering suturing easier and quicker to perform. METHOD The vaginal cuff epithelium is closed with 2 unidirectional barbed sutures that are started at the lateral fornices and ran until the midsection. The same sutures will then serially purchase the anterior and posterior vaginal endopelvic fascia and the midsegment of the uterosacral ligament. Two more passes are thrown through the same structures, yet farther laterally, back and forth. A video illustration of the procedure is attached. RESULTS Eighteen patients underwent the procedure with no urinary tract injuries documented by cystoscopy and no postoperative morbidity documented during the 6-week postoperative follow-up period. Limited short- and long-term follow-up data are reassuring, but more will be needed to confirm the efficacy of barbed sutures in prolapse repair. CONCLUSIONS The K-technique combines the conventional uterosacral ligament suspension concept with the ease, effectiveness, and safety of barbed sutures. The technique might aid the surgeon to add the apical vaginal support when indicated.


Pre-existing anti-PEG antibodies are associated with severe immediate allergic reactions to pegnivacogin, a PEGylated aptamer.


title: Potential Biomarkers for Radiation-Induced Renal Toxicity following 177Lu-Octreotate Administration in Mice.

text: UNLABELLED The kidneys are one of the main dose-limiting organs in peptide receptor radionuclide therapy and due to large inter-individual variations in renal toxicity, biomarkers are urgently needed in order to optimize therapy and reduce renal tissue damage. The aim of this study was to investigate the transcriptional, functional, and morphological effects on renal tissue after 177Lu-octreotate administration in normal mice, and to identify biomarkers for radiation induced renal toxicity. METHODS C57BL/6N mice were i.v. injected with 0, 30, 60, 90, 120, or 150 MBq 177Lu-octreotate (0, 16, 29, 40, 48, and 54 Gy to the kidneys). At 4, 8, and 12 months after administration, radiation-induced effects were evaluated in relation to (a) global transcriptional variations in kidney tissues, (b) morphological changes in the kidneys, (c) changes in white and red blood cell count as well as blood levels of urea, and (d) changes in renal function using 99mTc-DTPA/99mTc-DMSA scintigraphy. RESULTS In general, the highest number of differentially regulated transcripts was observed at 12 months after administration. The Cdkn1a, C3, Dbp, Lcn2, and Per2 genes displayed a distinct dose-dependent regulation, with increased expression level with increasing absorbed dose. Ifng, Tnf, and Il1B were identified as primary up-stream regulators of the recurrently regulated transcripts. Furthermore, previously proposed biomarkers for kidney injury and radiation damage were also observed. The functional investigation revealed reduced excretion of 99mTc-DTPA after 150 MBq, an increased uptake of 99mTc-DMSA at all dose levels compared with the controls, and markedly increased urea level in blood after 150 MBq at 12 months. CONCLUSION Distinct dose-response relationships were found for several of the regulated transcripts. The Cdkn1a, Dbp, Lcn2, and Per2 genes are proposed as biomarkers for 177Lu-octreotate exposure of kidney. Correlations to functional and morphological effects further confirm applicability of these genes as markers of radiation damage in kidney tissue.


title: Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) - United States, February 12-March 16, 2020.

text: Globally, approximately 170,000 confirmed cases of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) have been reported, including an estimated 7,000 deaths in approximately 150 countries (1). On March 11, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic (2). Data from China have indicated that older adults, particularly those with serious underlying health conditions, are at higher risk for severe COVID-19-associated illness and death than are younger persons (3). Although the majority of reported COVID-19 cases in China were mild (81%), approximately 80% of deaths occurred among adults aged ≥60 years; only one (0.1%) death occurred in a person aged ≤19 years (3). In this report, COVID-19 cases in the United States that occurred during February 12-March 16, 2020 and severity of disease (hospitalization, admission to intensive care unit [ICU], and death) were analyzed by age group. As of March 16, a total of 4,226 COVID-19 cases in the United States had been reported to CDC, with multiple cases reported among older adults living in long-term care facilities (4). Overall, 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths associated with COVID-19 were among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years. In contrast, no ICU admissions or deaths were reported among persons aged ≤19 years. Similar to reports from other countries, this finding suggests that the risk for serious disease and death from COVID-19 is higher in older age groups.