title: TMPRSS2 is a host factor that is essential for pneumotropism and pathogenicity of H7N9 influenza A virus in mice.

text: UNLABELLED Cleavage of the hemagglutinin (HA) by host proteases is essential for the infectivity of influenza viruses. Here, we analyzed the role of the serine protease TMPRSS2, which activates HA in the human respiratory tract, in pathogenesis in a mouse model. Replication of the human H7N9 isolate A/Anhui/1/13 and of human H1N1 and H3N2 viruses was compared in TMPRSS2 knockout (TMPRSS2(-/-)) and wild-type (WT) mice. Knockout of TMPRSS2 expression inhibited H7N9 influenza virus replication in explants of murine tracheas, bronchi, and lungs. H1N1 virus replication was also strongly suppressed in airway explants of TMPRSS2(-/-) mice, while H3N2 virus replication was only marginally affected. H7N9 and H1N1 viruses were apathogenic in TMPRSS2(-/-) mice, whereas WT mice developed severe disease with mortality rates of 100% and 20%, respectively. In contrast, all H3N2 infected TMPRSS2(-/-) and WT mice succumbed to lethal infection. Cleavage analysis showed that H7 and H1 are efficiently activated by TMPRSS2, whereas H3 is less susceptible to the protease. Our data demonstrate that TMPRSS2 is a host factor that is essential for pneumotropism and pathogenicity of H7N9 and H1N1 influenza virus in mice. In contrast, replication of H3N2 virus appears to depend on another, not yet identified protease, supporting the concept that human influenza viruses differ in protease specificity. IMPORTANCE Cleavage of the hemagglutinin (HA) by host proteases is essential for the infectivity of influenza virus, but little is known about its relevance for pathogenesis in mammals. Here, we show that knockout mice that do not express the HA-activating protease TMPRSS2 are resistant to pulmonary disease with lethal outcome when infected with influenza A viruses of subtypes H7N9 and H1N1, whereas they are not protected from lethal H3N2 virus infection. These findings demonstrate that human influenza viruses differ in protease specificity, and that expression of the appropriate protease in respiratory tissues is essential for pneumotropism and pathogenicity. Our observations also demonstrate that HA-activating proteases and in particular TMPRSS2 are promising targets for influenza therapy.


title: Bidirectional barbed suture in laparoscopic myomectomy: clinical features.

text: OBJECTIVE To compare bidirectional knotless barbed suture versus standard sutures, with either extracorporeal or intracorporeal knots, and to assess the feasibility, safety, and rapidity in repairing a uterine wall defect after laparoscopic myomectomy. SUBJECTS AND METHODS This was a randomized clinical study having a Canadian Task Force Classification of I. In tertiary-care university-based teaching hospitals, 117 women who underwent laparoscopic myomectomy were enrolled. In accord with randomization, uterine wall defects were closed with either extracorporeal (poliglecaprone 25; Monocryl™-1; Ethicon Inc., Somerville, NJ) or intracorporeal (polyglactin 910; Vicryl™-1; Ethicon Inc.) knots or a bidirectional knotless barbed suture (Quill™-0; Angiotech Pharmaceuticals, Inc., Vancouver, BC, Canada). RESULTS Time required to suture was significantly lower in the group operated on with a bidirectional suture than in groups with traditional sutures (P<.001). No significant difference was observed in operative time among the study groups. The degree of surgical difficulty was significantly lower in the Quill group than in the other groups. CONCLUSIONS Use of barbed sutures reduces the time required to repair a uterine wall defect during laparoscopic myomectomy. In a follow-up of patients carried out at 3 months, 6 months, and 1 year after the surgery, there were no wound dehiscence, no bleeding, and no other potential major complications.


title: The value of iterative metal artifact reduction algorithms during antenna positioning for CT-guided microwave ablation.

text: Objectives: To compare image quality between filtered back projection (FBP) and iterative reconstruction algorithm and dedicated metal artifact reduction (iMAR) algorithms during antenna positioning for computed tomography-guided microwave ablation (MWA).Materials and methods: An MWA antenna was positioned in the liver of five pigs under CT guidance. Different exposure settings (120kVp/200mAs-120kVp/50mAs) and image reconstruction techniques (FBP, iterative reconstruction with and without iMAR) were applied. Quantitative image analysis included density measurements in six positions (e.g., liver in extension of the antenna [ANTENNA] and liver >3 cm away from the antenna [LIVER-1]). Qualitative image analysis included assessment of overall quality, image noise, artifacts at the antenna tip, artifacts in liver parenchyma bordering antenna tip and newly generated artifacts. Two independent observers performed the analyses twice and interreader agreement was compared with Bland-Altman analysis.Results: For all exposure and reconstruction settings, density measurements for ANTENNA were significantly higher for the I30-1 iMAR compared with FBP and I30-1 (e.g., 8.3-17.2HU vs. -104.5 to 155.1HU; p ≤ 0.01, respectively). In contrast, for all exposure settings, density measurements for LIVER-1 were comparable between FBP and I30-1 iMAR (e.g., 49.4-50.4HU vs. 50.1-52.5U, respectively). For all exposure and reconstruction settings, subjective image quality for LIVER-1 was better for the I30-1 iMAR algorithm compared with FBP and I30-1. Bland-Altman interobserver agreement was from -0.2 to 0.2 for FBP and iMAR, and Cohen's kappa was 0.74.Conclusion: Iterative algorithms I30-1 with iMAR algorithm improves image quality during antenna positioning and placement for CT-guided MWA and is applicable over a range of exposure settings.


title: In vivo electroporation of developing mouse retina.

text: The functional characterization of genes expressed during mammalian retinal development remains a significant challenge. Gene targeting to generate constitutive or conditional loss of function knockouts remains cost and labor intensive, as well as time consuming. Adding to these challenges, retina expressed genes may have essential roles outside the retina leading to unintended confounds when using a knockout approach. Furthermore, the ability to ectopically express a gene in a gain of function experiment can be extremely valuable when attempting to identify a role in cell fate specification and/or terminal differentiation. We present a method for the rapid and efficient incorporation of DNA plasmids into the neonatal mouse retina by electroporation. The application of short electrical impulses above a certain field strength results in a transient increase in plasma membrane permeability, facilitating the transfer of material across the membrane (1,2,3,4). Groundbreaking work demonstrated that electroporation could be utilized as a method of gene transfer into mammalian cells by inducing the formation of hydrophilic plasma membrane pores allowing the passage of highly charged DNA through the lipid bilayer (5). Continuous technical development has resulted in the viability of electroporation as a method for in vivo gene transfer in multiple mouse tissues including the retina, the method for which is described herein (6, 7, 8, 9, 10). DNA solution is injected into the subretinal space so that DNA is placed between the retinal pigmented epithelium and retina of the neonatal (P0) mouse and electrical pulses are applied using a tweezer electrode. The lateral placement of the eyes in the mouse allows for the easy orientation of the tweezer electrode to the necessary negative pole-DNA-retina-positive pole alignment. Extensive incorporation and expression of transferred genes can be identified by postnatal day 2 (P2). Due to the lack of significant lateral migration of cells in the retina, electroporated and non-electroporated regions are generated. Non-electroporated regions may serve as internal histological controls where appropriate. Retinal electroporation can be used to express a gene under a ubiquitous promoter, such as CAG, or to disrupt gene function using shRNA constructs or Cre-recombinase. More targeted expression can be achieved by designing constructs with cell specific gene promoters. Visualization of electroporated cells is achieved using bicistronic constructs expressing GFP or by co-electroporating a GFP expression construct. Furthermore, multiple constructs may be electroporated for the study of combinatorial gene effects or simultaneous gain and loss of function of different genes. Retinal electroporation may also be utilized for the analysis of genomic cis-regulatory elements by generating appropriate expression constructs and deletion mutants. Such experiments can be used to identify cis-regulatory regions sufficient or required for cell specific gene expression (11). Potential experiments are limited only by construct availability.


title: A score to estimate 30-day mortality after intensive care admission after cardiac surgery.

text: OBJECTIVE Several risk-scoring systems have been developed to predict surgical mortality and complications in cardiac surgical patients, but none of the current systems include factors related to the intraoperative period. The purpose of this study was to develop a score that incorporates both preoperative and intraoperative factors so that it could be used for patients admitted to a cardiac surgical intensive care unit (ICU) immediately after surgery. METHOD Preoperative and intraoperative data from 30,350 patients in four hospitals were used to build a multiple logistic regression model estimating 30-day mortality after cardiac surgery. Sixty percent of the patients were used as a derivation group and forty percent as a validation group. RESULTS Mortality occurred in 2.6% of patients (n = 790). Preoperative factors identified in the model were age, female sex, emergency status, pulmonary hypertension, peripheral vascular disease, renal dysfunction, diabetes, peptic ulcer disease, history of alcohol abuse, and refusal of blood products. Intraoperative risk factors included the need for an intra-aortic balloon pump, ventricular assist device or extracorporeal membrane oxygenation leaving the operating room, presence of any intraoperative complication reported by the surgeon, the use of inotropes, high-dose vasopressors, red blood cell transfusion, and cardiopulmonary bypass time. When used after surgery at ICU admission, the model had C-statistics of 0.86 in both derivation and validation sets to estimate the 30-day mortality. CONCLUSIONS Preoperative and intraoperative variables can be used on admission to a cardiac surgical ICU to estimate 30-day mortality. The score could be used for risk stratification after cardiac surgery and evaluation of performance of cardiac surgical ICUs.


Ethics and Resource Scarcity: ASCO Recommendations for the Oncology Community During the COVID-19 Pandemic.


title: Evaluating developmental motor plasticity with paired afferent stimulation.

text: AIM Brain plasticity mechanisms are probably different in children but remain poorly understood. Paired afferent stimulation (PAS) combines peripheral sensory stimulation with transcranial magnetic stimulation (TMS) of primary motor cortex to induce rapid, reversible, topographically specific increases in primary motor cortex excitability suggestive of long-term potentiation in adults. Our aim was to determine frequency, characteristics, age effects, and reproducibility of PAS in school-age children. METHOD Typically developing right-handed children (6-18y) were recruited. Median nerve stimulation was delivered 25ms before suprathreshold primary motor cortex stimulation (0.2Hz, 7.5min). Primary outcome was changed in the amplitude of motor evoked potentials (MEPs) at five time points after PAS (0, 15, 30, 45, 75min) expressed as area under the curve. Reproducibility was evaluated. Secondary outcomes included stimulus response curves and safety/tolerability. RESULTS Of 28 children (20 males, mean age 12y), 64% demonstrated PAS effects (11 definite, seven probable). PAS effects were sustained across all time points to 75min (p=0.004). Stimulus response curve scores increased after PAS (n=9, p=0.02). PAS effect and age were not correlated. PAS was highly reproducible (p=0.925, r=0.283). Tolerability was favorable without adverse events. INTERPRETATION PAS effects are present and reproducible in children. Pediatric PAS paradigms appear safe and tolerable. PAS may provide insight into endogenous developmental plasticity, informing future studies in children with cerebral palsy and other motor disorders.


title: Culture Matters in Communicating the Global Response to COVID-19.

text: Current communication messages in the COVID-19 pandemic tend to focus more on individual risks than community risks resulting from existing inequities. Culture is central to an effective community-engaged public health communication to reduce collective risks. In this commentary, we discuss the importance of culture in unpacking messages that may be the same globally (physical/social distancing) yet different across cultures and communities (individualist versus collectivist). Structural inequity continues to fuel the disproportionate impact of COVID-19 on black and brown communities nationally and globally. PEN-3 offers a cultural framework for a community-engaged global communication response to COVID-19.


title: The potential impacts of obesity on COVID-19.

text: Obese patients are at increased risk of exacerbations from viral respiratory infections. During the H1N1 pandemic, obesity was associated with an increased risk of influenza-associated intensive care unit (ICU) admission and death, longer duration of mechanical ventilation, and longer duration of ICU and hospital length of stay compared with the non-obese. These observations have raised a concern about the correlation between obesity and the current COVID-19 pandemic. In this review, we have outlined the potential impacts of obesity on respiratory physiology and the function of both innate and adaptive immune responses. Also, it has been clearly illustrated that obese patients are potentially more vulnerable to COVID-19 and more contagious than lean patients. The comorbidities associated with obesity were found to be correlated with a severe clinical course of COVID-19 and increased mortality and high BMI has been shown to be correlated with hospitalisation, the need for mechanical ventilation and non-survival. The review also sheds light on the challenges that obese patients pose for healthcare providers inside and outside ICUs.


title: Renal denervation in patients with resistant hypertension: six-month results.

text: INTRODUCTION Increased activation of the sympathetic nervous system plays a central role in the pathophysiology of hypertension (HTN). Catheter-based renal denervation (RDN) was recently developed for the treatment of resistant HTN. AIM To assess the safety and efficacy of RDN for blood pressure (BP) reduction at six months in patients with resistant HTN. METHODS In this prospective registry of patients with essential resistant HTN who underwent RDN between July 2011 and May 2013, the efficacy of RDN was defined as ≥ 10 mm Hg reduction in office systolic blood pressure (SBP) six months after the intervention. RESULTS In a resistant HTN outpatient clinic, 177 consecutive patients were evaluated, of whom 34 underwent RDN (age 62.7 ± 7.6 years; 50.0% male). There were no vascular complications, either at the access site or in the renal arteries. Of the 22 patients with complete six-month follow-up, the response rate was 81.8% (n=18). The mean office SBP reduction was 22 mm Hg (174 ± 23 vs. 152 ± 22 mm Hg; p<0.001) and 9 mm Hg in diastolic BP (89 ± 16 vs. 80 ± 11 mm Hg; p=0.006). The number of antihypertensive drugs (5.5 ± 1.0 vs. 4.6 ± 1.1; p=0.010) and pharmacological classes (5.4 ± 0.7 vs. 4.6 ± 1.1; p=0.009) also decreased significantly. Of the 24-hour ambulatory BP monitoring and echocardiographic parameters analyzed, there were significant reductions in diastolic load (45 ± 29 vs. 27 ± 26%; p=0.049) and in left ventricular mass index (174 ± 56 vs. 158 ± 60 g/m(2); p=0.014). CONCLUSION In this cohort of patients with resistant HTN, RDN was safe and effective, with a significant BP reduction at six-month follow-up.


Attitude to telemedicine in the times of COVID 19 pandemic: Opinion of medical practitioners from India.


title: Pressure stability with CPAP devices: A bench evaluation.

text: BACKGROUND Continuous positive airway pressure (CPAP) maintains a constant pressure to reduce the patient's work of breathing (WOB). The aim of this study was to measure the additional WOB imposed by four current CPAP devices during simulation of a difficult but commonly encountered clinical situation. METHOD Flow contour, respiratory system compliance and total lung-airway resistance of a patient under CPAP were simulated. The devices were tested at a CPAP of 15cm H(2)O with a heated humidifier and a nasal pillow, which increased circuitry resistance and with and without a simulated unintentional leak. RESULTS With no leak, positive end-expiratory pressure (PEEP) at the interface varied across devices from 14.0 to 15.3cm H(2)O. With a leak of 1L/s, PEEP varied from 11.5 to 17.1cm H(2)O. Imposed inspiratory WOB ranged from less than 0.1J/min to 0.45J/min with no leak, and the range broadened with leaking. Findings were similar for the imposed expiratory WOB. CONCLUSION The performances of CPAP devices are variable. The device that calibrated for the pressure loss in the circuitry under dynamic conditions and made appropriate pressure adjustments outperformed the other devices.


title: Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis.

text: OBJECTIVE To evaluate the efficacy and safety of artificial pancreas treatment in non-pregnant outpatients with type 1 diabetes. DESIGN Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES Medline, Embase, Cochrane Library, and grey literature up to 2 February 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomised controlled trials in non-pregnant outpatients with type 1 diabetes that compared the use of any artificial pancreas system with any type of insulin based treatment. Primary outcome was proportion (%) of time that sensor glucose level was within the near normoglycaemic range (3.9-10 mmol/L). Secondary outcomes included proportion (%) of time that sensor glucose level was above 10 mmol/L or below 3.9 mmol/L, low blood glucose index overnight, mean sensor glucose level, total daily insulin needs, and glycated haemoglobin. The Cochrane Collaboration risk of bias tool was used to assess study quality. RESULTS 40 studies (1027 participants with data for 44 comparisons) were included in the meta-analysis. 35 comparisons assessed a single hormone artificial pancreas system, whereas nine comparisons assessed a dual hormone system. Only nine studies were at low risk of bias. Proportion of time in the near normoglycaemic range (3.9-10.0 mmol/L) was significantly higher with artificial pancreas use, both overnight (weighted mean difference 15.15%, 95% confidence interval 12.21% to 18.09%) and over a 24 hour period (9.62%, 7.54% to 11.7%). Artificial pancreas systems had a favourable effect on the proportion of time with sensor glucose level above 10 mmol/L (-8.52%, -11.14% to -5.9%) or below 3.9 mmol/L (-1.49%, -1.86% to -1.11%) over 24 hours, compared with control treatment. Robustness of findings for the primary outcome was verified in sensitivity analyses, by including only trials at low risk of bias (11.64%, 9.1% to 14.18%) or trials under unsupervised, normal living conditions (10.42%, 8.63% to 12.2%). Results were consistent in a subgroup analysis both for single hormone and dual hormone artificial pancreas systems. CONCLUSIONS Artificial pancreas systems are an efficacious and safe approach for treating outpatients with type 1 diabetes. The main limitations of current research evidence on artificial pancreas systems are related to inconsistency in outcome reporting, small sample size, and short follow-up duration of individual trials.


title: Hepatocellular carcinoma: concomitant sorafenib promotes necrosis after radiofrequency ablation--propensity score matching analysis.

text: PURPOSE To retrospectively compare radiofrequency ablation (RFA) combined with the multikinase inhibitor sorafenib (hereafter, sorafenib-RFA) and RFA alone in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. Between January 2007 and December 2011, 16 patients (mean age, 72.8 years; age range 52-84 years; 10 men, six women) with HCC tumors less than 3 cm in diameter were included in the sorafenib-RFA group, and 136 patients (mean age, 72.1 years; age range, 51-86 years; 92 men, 44 women) with HCC tumors less than 3 cm in diameter were included in the RFA alone (control) group. Mean diameters of the greatest long-axis dimensions of HCC were 22.8 mm ± 4.6 (standard deviation) in the sorafenib-RFA group and 18.1 mm ± 4.4 in the control group. RFA was performed immediately after the 7-day administration of sorafenib. Propensity score matching analysis was used to adjust for potential biases. RESULTS Fifteen of the 16 patients in the sorafenib-RFA group and 30 of the 136 patients in the control group were selected during propensity score matching. No significant differences between the sorafenib-RFA group (n = 15) and the control group (n = 30) were observed with regard to age, sex, etiology, Child-Pugh class, tumor size, puncture number, needle size, location at the liver margin, or location adjacent to a main vessel. The respective mean diameters of the greatest long- and short-axis dimensions of the RFA-induced ablated area were 46.3 mm ± 10.3 and 33.0 mm ± 6.9 in the sorafenib-RFA group and 32.9 mm ± 7.6 and 25.6 mm ± 5.7 in the control group; both of these dimensions were significantly larger in the sorafenib-RFA group (both P < .001). CONCLUSION Sorafenib-RFA may be superior to standard RFA alone in the treatment of HCC tumors smaller than 3 cm in diameter.


title: Does targeted neonatal echocardiography affect hemodynamics and cerebral oxygenation in extremely preterm infants?

text: OBJECTIVE To investigate the effect of targeted neonatal echocardiography (TnEcho) on heart rate, arterial oxygen saturation (SPO2), cerebral regional oxygen saturation (CrSO2) and cerebral fractional oxygen extraction (CFOE) in extremely preterm infants during the first 3 postnatal days. STUDY DESIGN s a nested study in a prospective observational study, we acquired continuous data on heart rate, SPO2, CrSO2 and CFOE. Data averaged for the duration of TnEcho study were compared with the data collected during a baseline period immediately before the start of echocardiography. The duration of the baseline and study periods was the same. TnEcho evaluation included assessment of preload, afterload, contractility, left and right ventricular output, patent ductus arteriosus and foramen ovale. RESULT We analyzed 138 data pairs before and during TnEcho in 22 extremely preterm infants (gestational age 25.9 ± 1.2 weeks; range 23 to 27). There was no significant difference in heart rate between baseline and TnEcho period. There was a statistical, but clinically negligible, difference between baseline and TnEcho in SPO2 (median (quartile) 91.4% (88.9, 94.2) vs 91.3% (88.9, 94), P = 0.048), CrSO2 (76.8% (70.7, 81.5) vs 74.9% (69.5, 80.1), P<0.0001) and CFOE (15.8% (9.8, 23.6) vs 17.5% (11.3, 24.7), P<0.0001). The changes in the parameters monitored were similar in preterm infants who developed peri/intraventricular hemorrhage and in those who did not. CONCLUSION Although there were statistically significant changes in SPO2, CrSO2 and CFOE, the alterations were minimal and unlikely of clinical relevance. Thus, cerebral hemodynamics and systemic and cerebral oxygenation are not perturbed during TnEcho and the procedure is well tolerated by the extremely preterm infants during the postnatal transitional period.


Funders' Efforts: Aging And Health, COVID-19.


title: Serology for SARS-CoV-2: Apprehensions, opportunities, and the path forward.

text: Serological testing for SARS-CoV-2 has enormous potential to contribute to COVID-19 pandemic response efforts. However, the required performance characteristics of antibody tests will critically depend on the use case (individual-level vs. population-level).


Reply: S-shaped brachioplasty: an effective technique to correct excess skin and fat of the upper arm.


title: How does an inventor find an investor or partner? Raising funds to start a company.

text: Rudy Mazzocchi has over 25 years of senior executive management, technology and intellectual property development, and financing experience in the medical-technology/biotechnology industries. He serves currently as cofounder/chief executive officer of ELENZA, Inc, an ophthalmology company that has developed an electro-active, autofocusing, implantable lens; executive chairman of Establishment Labs; executive chairman of LAFORGE Optical; and executive chairman of OptiSTENT, Inc. He served previously as managing director of Accuitive Medical Ventures and The Innovation Factory; cofounder/chief executive officer of Image-Guided NEUROLOGICS, acquired by Medtronic in 2005; and founding chief executive officer of MICROVENA Corporation, which became "eV3," acquired by Covidien. He was formerly cofounder/director of Vascular Science, acquired by St Jude Medical in 1996, and cofounder/chairman of CytoGenesis, one of the first United States stem cell companies that was merged with BresaGen and listed on the Australian public exchange. He is the recipient of the Technology Leadership Award, the Businessman of the Year Award, the Ernst & Young Entrepreneur of the Year Award in Healthcare, and Global Entrepreneur of the Year Award. He has also authored more than 70 patents; 2 published, award-winning novels (medical thrillers); and a top-selling business book on entrepreneurism.


title: Optimal number of samples to test for institutional respiratory infection outbreaks in Ontario.

text: The objective of this study was to determine the optimal number of respiratory samples per outbreak to be tested for institutional respiratory outbreaks in Ontario. We reviewed respiratory samples tested for respiratory viruses by multiplex PCR as part of outbreak investigations. We documented outbreaks that were positive for any respiratory viruses and for influenza alone. At least one virus was detected in 1454 (85∙2%) outbreaks. The ability to detect influenza or any respiratory virus increased as the number of samples tested increased. When analysed by chronological order of when samples were received at the laboratory, percent positivity of outbreaks testing positive for any respiratory virus including influenza increased with the number of samples tested up to the ninth sample, with minimal benefit beyond the fourth sample tested. Testing up to four respiratory samples per outbreak was sufficient to detect viral organisms and resulted in significant savings for outbreak investigations.


title: Near-infrared spectroscopy can predict the onset of cerebral hyperperfusion syndrome after carotid endarterectomy.

text: BACKGROUND Cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy (CEA) is a potential life-threatening complication. Therefore, early identification and treatment of patients at risk is essential. CHS can be predicted by a doubling of postoperative transcranial Doppler (TCD)-derived mean middle cerebral artery blood velocity (V(mean)) compared to preoperative values. However, in approximately 15% of CEA patients, an adequate TCD signal cannot be obtained due to an insufficient temporal bone window. Moreover, the use of TCD requires specifically skilled personnel. An alternative and promising technique of noninvasive cerebral monitoring is relative frontal lobe oxygenation (rSO(2)) measured by near-infrared spectroscopy (NIRS), which offers on-line information about cerebral oxygenation without the need for specialized personnel. In this study, we assess whether NIRS and perioperative TCD are related to the onset CHS following CEA. METHODS Patients who underwent CEA under general anesthesia and had a sufficient TCD window were prospectively included. The V(mean) and rSO(2) measured before induction of anesthesia were compared to measurements performed in the first postoperative hour (ΔV(mean), ΔrSO(2), respectively). Logistic regression analysis was performed to determine the relationship between ΔV and ΔrSO(2) and the occurrence of CHS. Subsequently, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values. Diagnostic values were shown as positive and negative predictive values (PPV and NPV). RESULTS In total, 151 patients were included, of which 7 patients developed CHS. The ΔV(mean) and ΔrSO(2) differed between CHS and non-CHS patients (median, interquartile range), i.e. 74% (67-103) versus 16% (-2 to 41), p = 0.001, and 7% (4-15) versus 1% (-6 to 7), p = 0.009, respectively. The mean arterial blood pressure did not change. Postoperative ΔV(mean) and ΔrSO(2) were significantly related to the occurrence of CHS [odds ratio (OR) 1.40 (95% CI 1.02-1.93) per 30% increase in V(mean) and OR 1.82 (95% CI 1.11-2.99) per 5% increase in rSO(2)]. ROC curve analysis showed an area under the curve of 0.88 (p = 0.001) for ΔV(mean) and an optimal cutoff value of 67% increase (PPV 38% and NPV 99%), and an area under the curve of 0.79 (p = 0.009) for ΔrSO(2) and an optimal cutoff value of 3% rSO(2) increase (PPV 11% and NPV 100%). The combination of both monitoring techniques provided a PPV of 58% and an NPV of 99%. CONCLUSIONS Both TCD and NIRS measurements can be used to safely identify patients not at risk of developing CHS. It appears that NIRS is a good alternative when a TCD signal cannot be obtained.


title: Anterior lumbar interbody fusion using recombinant human bone morphogenetic protein-2: a prospective study of complications.

text: OBJECT The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in anterior lumbar interbody fusion (ALIF) is controversial regarding the reported complication rates and cost. The authors aimed to assess the complication rates of performing ALIF using rhBMP-2. METHODS This is a prospective study of consecutive patients who underwent ALIF performed by a single spine surgeon and a single vascular surgeon between 2009 and 2012. All patients underwent placement of a polyetheretherketone (PEEK) cage filled with rhBMP-2 and a separate anterior titanium plate. Preoperative clinical data, operative details, postoperative complications, and clinical and radiographic outcomes were recorded for all patients. Clinical outcome measures included back and leg pain visual analog scale scores, Oswestry Disability Index (ODI), and SF-36 Physical and Mental Component Summary (PCS and MCS) scores. Radiographic assessment of fusion was performed using high-definition CT scanning. Male patients were screened pre- and postoperatively regarding sexual dysfunction, specifically retrograde ejaculation (RE). RESULTS The study comprised 131 patients with a mean age of 45.3 years. There were 67 men (51.1%) and 64 women (48.9%). Of the 131 patients, 117 (89.3%) underwent ALIF at L5-S1, 9 (6.9%) at L4-5, and 5 (3.8%) at both L4-5 and L5-S1. The overall complication rate was 19.1% (25 of 131), with 17 patients (13.0%) experiencing minor complications and 8 (6.1%) experiencing major complications. The mean estimated blood loss per ALIF level was 115 ml. There was 1 incidence (1.5%) of RE. No significant vascular injuries occurred. No prosthesis failure occurred with the PEEK cage and separate anterior screw-plate. Back and leg pain improved 57.2% and 61.8%, respectively. The ODI improved 54.3%, with PCS and MCS scores improving 41.7% and 21.3%, respectively. Solid interbody fusion was observed in 96.9% of patients at 12 months. CONCLUSIONS Anterior lumbar interbody fusion with a vascular access surgeon and spine surgeon, using a separate cage and anterior screw-plate, provides a very robust and reliable construct with low complication rates, high fusion rates, and positive clinical outcomes, and it is cost-effective. The authors did not experience the high rates of RE reported by other authors using rhBMP-2.


title: Test Agreement Between Roche Cobas 6800 and Cepheid GeneXpert Xpress SARS-CoV-2 Assays at High Cycle Threshold Ranges.

text: The SARS-CoV-2 pandemic has changed the face of the globe and upended the daily lives of billions.….


title: Communicable and non-communicable disease risks at the Grand Magal of Touba: The largest mass gathering in Senegal.

text: BACKGROUND An estimated 4-5 million individuals gather each year in the holy city of Touba, Senegal during the Grand Magal religious pilgrimage. Pilgrims come from across Senegal and the surrounding countries, as well as from countries outside Africa. It is the largest mass gathering (MG) of the Mouride community and the largest Muslim religious MG in West Africa. METHOD A cross-sectional study was conducted on all patients who attended a public healthcare structure during the November 2015 Grand Magal. RESULT Data were collected on a total of 32,229 healthcare contacts. The most frequent reasons for consultation were trauma, followed by fatigue and heatstroke. Infectious diseases were also prevalent with, notably, a high rate of febrile systemic illnesses and malaria, diarrheal diseases, and respiratory tract infections. Such results are likely to be linked to overcrowding and climatic conditions, the relative lack of sanitary facilities, and limited medical resources available during the event. CONCLUSION The context of the Grand Magal MG is unique, given its location in a tropical developing country and its international component which may favor the globalization of locally endemic diseases. As such, it warrants investment in modern methods for public health surveillance and planning of the event.


title: Early outcomes of two-stage minimally invasive oesophagectomy in an Australian institution.

text: BACKGROUND Minimally invasive oesophagectomy (MIO) has a steep learning curve. We report our outcomes of a standardized 25 mm circular-stapled anastomosis using a trans-orally placed anvil (Orvil™). The objective of this study is to report the initial experience of introducing two-stage MIO to an Australian tertiary health service. METHODS We describe our consecutive case series of all MIOs performed from a prospectively maintained database. We assessed the morbidity and mortality of MIO at our institution. We compared our first 30 cases to the second cohort of 32 cases. RESULTS There were 62 two-stage MIOs performed from 2011 to 2015. The average age was 65 years. Median length of stay was 13 days (5-72 days). Median number of total lymph nodes was 14. Conversion occurred in three patients (5%). Major morbidity was 45%. Delayed gastric emptying 6% (n = 4), pneumonia 6% (n = 4), chyle leak 6% (n = 4), pulmonary embolus 2% (n = 1) and grade II or III anastomotic leak 5% (n = 4). One conduit ischaemia (2%) required reoperation and formation of oesophagostomy. There was one post-operative death within 30 days. There were five post-oesophagectomy hiatal hernias requiring re-operation (8%). There was a significant improvement in operative time (minutes) from the first to second cohort 588 versus 464 (P-value 0.01). CONCLUSION The introduction of two-stage MIO to the Australian setting can be safely instituted. Our unit was still within a learning curve after 30 cases.


title: Comparison of air-sealing characteristics of tapered- vs. cylindrical-shaped high-volume, low-pressure tube cuffs.

text: BACKGROUND This study aimed at comparing air-sealing characteristics of the new tapered-shaped tracheal tube cuffs with cylindrical tube cuffs. METHODS Tracheal tubes with tapered-shaped polyurethane (PU) and polyvinyl chloride (PVC) cuffs as well as standard cylindrical-shaped cuffs made of PU and PVC (Covidien, Athlone, Ireland) were investigated. A tracheal model attached to a test lung was intubated, and cuffs were inflated to 10, 15, 20, 25 and 30 cm H(2)O. The test lung was ventilated with intermittent positive pressure ventilation at peak inspiratory pressures (PIPs) of 20 and 25 cm H(2)O. Air leakage was assessed by spirometry and measurement of sevoflurane concentration passing the cuff at the upper cuff border using an anaesthetic gas analyser. Experiments were repeated four times with new tracheal tubes for each run. Statistical comparisons were done using Mann-Whitney U-test with level of significance at P < 0.05. RESULTS The tapered-shaped PVC tube cuff demonstrated a significantly lower air leakage determined by spirometry than the cylindrical-shaped cuff at both PIPs (20 and 25 cm H(2)O). Similarly, sevoflurane leakage was less with the tapered PVC cuff particularly at higher cuff pressures. With the PU cuff, reduction in air leakage by a tapered-shaped compared with a cylindrical-shaped tube cuff was not significant. CONCLUSIONS A tapered-shaped tube cuff considerably improves air-sealing characteristics of PVC tube cuffs and allows thereby reducing cuff pressure required for sufficient ventilation. In tube cuffs made of PU that exhibits superior sealing characteristics compared with PVC, a tapered shape failed to result in a further reduction of air leakage.


title: On the Pharmacy Radar: COViD-19 and Older People.

text: The COVID-19 pandemic presents many medical and social issues for older people. Presented here is a range of information arising from related areas that have impact upon the safety and efficacy of drug therapy in the context of COVID-19. Issues include pharmacy practice, clinical therapeutics, and possible new treatments for the virus. More information will be published in coming issues of The Senior Care Pharmacist.


title: Two-step conformational changes in a coronavirus envelope glycoprotein mediated by receptor binding and proteolysis.

text: The coronaviruses mouse hepatitis virus type 2 (MHV-2) and severe acute respiratory syndrome coronavirus (SARS-CoV) utilize proteases to enter host cells. Upon receptor binding, the spike (S) proteins of both viruses are activated for membrane fusion by proteases, such as trypsin, present in the environment, facilitating virus entry from the cell surface. In contrast, in the absence of extracellular proteases, these viruses can enter cells via an endosomal pathway and utilize endosomal cathepsins for S protein activation. We demonstrate that the MHV-2 S protein uses multistep conformational changes for membrane fusion. After interaction with a soluble form of the MHV receptor (CEACAM1a), the metastable form of S protein is converted to a stable trimer, as revealed by mildly denaturing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Liposome-binding assays indicate that the receptor-bound virions are associated with the target membrane through hydrophobic interactions. The exposure of receptor-bound S protein to trypsin or cathepsin L (CPL) induces the formation of six-helix bundles (6HB), the final conformation. This trypsin- or CPL-mediated conversion to 6HB can be blocked by a heptad repeat peptide known to block the formation of 6HB. Although trypsin treatment enabled receptor-bound MHV-2 to enter from the cell surface, CPL failed to do so. Interestingly, consecutive treatment with CPL and then chlorpromazine enabled a portion of the virus to enter from cell surface. These results suggest that trypsin suffices for the induction of membrane fusion of receptor-primed S protein, but an additional unidentified cellular factor is required to trigger membrane fusion by CPL.


Lung Pathology in COVID-19 Disease: We Must Be Aware!


Optimizing provision of extracorporeal life support during the COVID-19 pandemic: practical considerations for Canadian jurisdictions.


Money injection for public services.


title: The evolving WHO: implications for global health security.

text: The World Health Organization (WHO) is central to the international community's efforts to control infectious disease outbreaks. In recent years, however, the Organization's powers have undergone substantial revision following a series of interconnected global events including the 2003 severe acute respiratory syndrome outbreak, the revised International Health Regulations, the emergence and spread of avian influenza, and more recently, the 2009 H1N1 Swine Flu pandemic. This paper explores how the WHO's role, authority and autonomy have been shaped and re-shaped, and examines what this may mean for the future of global health security.


Striving as a nation to become an academic leader in the COVID-19 crisis.


title: [Study on issues for stomatological institutions responding to state public health emergencies].

text: Crisis management in emergent public health event is a global problem and a difficult thesis for researchers worldwide, highlighted by World Health Organization for its vital importance to public sanitation and health, life quality and survival. This article makes a brief analysis and reflection on the relevant legal issues faced and raised by oral medical institutions and practioners, taking cases from the emergent crisis caused by COVID-19 in China since December 2019, with the hope to provide legal help and guidance to the oral medical industry in dealing with public health emergencies.


title: Association Between High-Sensitivity Cardiac Troponin and Risk of Stroke in 96 702 Individuals: A Meta-Analysis.

text: Background and Purpose- Our study aim was to estimate risk of incident stroke based on levels of hs-cTn (high-sensitivity cardiac troponin), a specific biomarker indicating myocardial injury, in the general population, patients with atrial fibrillation, and patients with previous stroke. Methods- Embase, PubMed, and Web of Science were searched until March 14, 2019 to identify relevant articles. Randomized controlled trials and cohort studies assessing the risk of incident stroke based on hs-cTn were eligible. Pooled adjusted hazard ratios including 95% CI were calculated using a random-effects model due to study heterogeneity per population, coding of hs-cTn (categorical/continuous data), per hs-cTn subunit (T or I), for low risk of bias, and for all-cause and ischemic stroke separately. Results- We included 17 articles with 96 702 participants. In studies conducted in the general population (n=12; 77 780 participants), the pooled adjusted hazard ratio for incident stroke was 1.25 (CI, 1.10-1.40) for high versus low hs-cTn (as defined by included studies) during an average follow-up of 1 to 20 years (median 10). When categorical data were used, this was increased to 1.58 (CI, 1.26-1.90). The results were robust when accounting for stroke classification (all-cause stroke/ischemic stroke), hs-cTn subunit, risk of bias, and coding of hs-cTn. In patients with atrial fibrillation (4 studies; 18 725 participants), the pooled adjusted hazard ratio for incident stroke was 1.95 (CI, 1.29-2.62) for high versus low hs-cTn. Due to lack of data (one study, 197 participants), no meta-analysis could be performed in patients with previous stroke. Conclusions- This meta-analysis suggests that hs-cTn can be regarded as a risk marker for incident stroke, with different effect size in different subgroups. More research about the association between hs-cTn and incident stroke in high-risk populations is needed, especially in patients with history of ischemic stroke.


title: Otolaryngology Community Operating With Collaboration and Productive Resolve During the COVID-19 Pandemic.

text: In the wake of the tremendous fallout from the COVID-19 pandemic that was mostly negative, I find great optimism and encouragement from the ability of society at all levels to focus on a common problem with a collaborative and productive resolve to address this millennial event. The rapid response was made possible by marshaling the resources available from many sources, not the least of which was the medical association community. It has been particularly gratifying to work hand-in-hand with our specialty societies within and outside the otolaryngology family to produce educational and scientific information that is consistent and that has and will continue to affect policy favorably. The groups that enable these inspirational collaborative accomplishments through their dedication, innovation, and imagination are the practicing physicians who have given freely and generously of their time and talents to help the whole health care community provide the most up-to-date care possible.


title: Reflection on lower rates of COVID-19 in children: does childhood immunizations offer unexpected protection?

text: The incidence of COVID-19 in children and teenagers is only about 2% in China. Children had mild symptoms and hardly infected other children or adults. It is worth considering that children are the most vulnerable to respiratory pathogens, but fatal SARS-like virus had not caused severe cases among them. According to the pathological studies of COVID-19 and SARS, a sharp decrease in T lymphocytes leads to the breakdown of the immune system. The cellular immune system of children differs from that of adults may be the keystone of atypical clinical manifestations or even covert infection. The frequent childhood vaccinations and repeated pathogens infections might be resulting in trained immunity of innate immune cells, immune fitness of adaptive immune cells or cross-protection of antibodies in the children. Therefore, due to lack of specific vaccine, some vaccines for tuberculosis, influenza and pneumonia may have certain application potential for the front-line health workers in the prevention and control of COVID-19. However, for high-risk susceptible populations, such as the elderly with basic diseases such as hypertension and diabetes, it is necessary to explore the acclimatization effect of the planned immune process on their immunity to achieve the trained immunity or immune fitness, so as to improve their own antiviral ability.


title: Statewide Interventions and Covid-19 Mortality in the United States: An Observational Study.

text: BACKGROUND Social distancing is encouraged to mitigate viral spreading during outbreaks. However, the association between distancing and patient-centered outcomes in Covid-19 has not been demonstrated. In the United States social distancing orders are implemented at the state level with variable timing of onset. Emergency declarations and school closures were two early statewide interventions. METHODS To determine whether later distancing interventions were associated with higher mortality, we performed a state-level analysis in 55,146 Covid-19 non-survivors. We tested the association between timing of emergency declarations and school closures with 28-day mortality using multivariable negative binomial regression. Day 1 for each state was set to when they recorded ≥ 10 deaths. We performed sensitivity analyses to test model assumptions. RESULTS At time of analysis, 37 of 50 states had ≥ 10 deaths and 28 follow-up days. Both later emergency declaration (adjusted mortality rate ratio [aMRR] 1.05 per day delay, 95% CI 1.00 to 1.09, p=0.040) and later school closure (aMRR 1.05, 95% CI 1.01 to 1.09, p=0.008) were associated with more deaths. When assessing all 50 states and setting day 1 to the day a state recorded its first death, delays in declaring an emergency (aMRR 1.05, 95% CI 1.01 to 1.09, p=0.020) or closing schools (aMRR 1.06, 95% CI 1.03 to 1.09, p<0.001) were associated with more deaths. Results were unchanged when excluding New York and New Jersey. CONCLUSIONS Later statewide emergency declarations and school closure were associated with higher Covid-19 mortality. Each day of delay increased mortality risk 5 to 6%.


title: Respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants.

text: OBJECTIVE To investigate the prevalence of 14 viruses in infants with bronchiolitis and to study demographic and clinical differences in those with respiratory syncytial virus (RSV), human bocavirus (hBoV) and rhinovirus (RV) infection. METHODS 182 infants aged <12 months hospitalised for bronchiolitis were enrolled. Infants underwent nasal washing for the detection of RSV, influenza virus A and B, human coronavirus OC43, 229E, NL-63, HUK1, adenovirus, RV, parainfluenza 1-3, human metapneumovirus and hBoV. Demographic, clinical and laboratory data were obtained from parents and from patient medical files. Main outcome measurements were age, breastfeeding history, family smoking habits, family history for asthma and atopy, blood eosinophil count, chest radiological findings, clinical severity score and number of days of hospitalisation. RESULTS A virus was detected in 57.2% of the 182 infants. The most frequently detected viruses were RSV (41.2%), hBoV (12.2%) and RV (8.8%). Infants with dual infections (RSV and hBoV) had a higher clinical severity score and more days of hospitalisation than infants with RSV, RV and hBoV bronchiolitis (mean+/-SD: 4.7+2.4 vs 4.3+/-2.4 vs 3.0+/-2.0 vs 2.9+/-1.7, p<0.05; and 6.0+/-3.2 vs 5.3+/-2.4 vs 4.0+/-1.6 vs 3.9+/-1.1 days; p<0.05). Infants with RV infection had higher blood eosinophil counts than infants with bronchiolitis from RSV and hBoV (307+/-436 vs 138+/-168 vs 89+/-19 n/mm(3); p<0.05). CONCLUSIONS Although the major pathogen responsible for bronchiolitis remains RSV, the infection can also be caused by RV and hBoV. Demographic characteristics and clinical severity of the disease may depend on the number of viruses or on the specific virus detected.


Total debranching thoracic endovascular aortic arch repair with inflow from the descending thoracic aorta.


title: During Infection, Theiler's Virions Are Cleaved by Caspases and Disassembled into Pentamers.

text: UNLABELLED Infected macrophages in spinal cords of mice persistently infected with Theiler's murine encephalomyelitis virus (TMEV) undergo apoptosis, resulting in restricted virus yields, as do infected macrophages in culture. Apoptosis of murine macrophages in culture occurs via the intrinsic pathway later in infection (>10 h postinfection [p.i.]) after maximal virus titers (150 to 200 PFU/cell) have been reached, with loss of most infectious virus (<5 PFU/cell) by 20 to 24 h p.i. Here, we show that BeAn virus RNA replication, translation, polyprotein processing into final protein products, and assembly of protomers and pentamers in infected M1-D macrophages did not differ from those processes in TMEV-infected BHK-21 cells, which undergo necroptosis. However, the initial difference from BHK-21 cell infection was seen at 10 to 12 h p.i., where virions from the 160S peak in sucrose gradients had incompletely processed VP0 (compared to that in infected BHK-21 cells). Thereafter, there was a gradual loss of the 160S virion peak in sucrose gradients, with replacement by a 216S peak that was observed to contain pentamers among lipid debris in negatively stained grids by electron microscopy. After infection or incubation of purified virions with activated caspase-3 in vitro, 13- and 17-kDa capsid peptide fragments were observed and were predicted by algorithms to contain cleavage sites within proteins by cysteine-dependent aspartate-directed proteases. These findings suggest that caspase cleavage of sites in exposed capsid loops of assembled virions occurs contemporaneously with the onset and progression of apoptosis later in the infection. IMPORTANCE Theiler's murine encephalomyelitis virus (TMEV) infection in mice results in establishment of virus persistence in the central nervous system and chronic inflammatory demyelinating disease, providing an experimental animal model for multiple sclerosis. Virus persistence takes place primarily in macrophages recruited into the spinal cord that undergo apoptosis and in turn may facilitate viral spread via infected apoptotic blebs. Infection of murine macrophages in culture results in restricted virus yields late in infection. Here it is shown that the early steps of the virus life cycle in infected macrophages in vitro do not differ from these processes in TMEV-infected BHK-21 cells, which undergo necroptosis. However, the findings late in infection suggest that caspases cleave sites in exposed capsid loops and possibly internal sites of assembled virions occurring contemporaneously with onset and progression of apoptosis. Mechanistically, this would explain the dramatic loss in virus yields during TMEV-induced apoptosis and attenuate the virus, enabling persistence.


A year without conferences? How the coronavirus pandemic could change research.


title: Ergonomics of and technologies for single-port lapaxroscopic surgery.

text: BACKGROUND There are a number of major constraints in ergonomics of and technologies for single port laparoscopic surgery. MATERIAL AND METHODS The review is based on a complete literature search through PubMed, Medline. Single port laparoscopic surgery (SPLS), single incision laparoscopic surgery (SILS), laparoscopic single-site surgery (LESS), ergonomics, technologies, robotic SPLS, SPLS or SILS operations were the keywords used for the literature search. RESULTS AND DISCUSSION The SPLS approach imposes several restrictions: Maintenance of sufficient exposure, sustained pneumoperitoneum, adequate retraction, collision between instruments (internal and external), collision between instruments and optics, and limited instrument manipulation and triangulation. Compensatory techniques such as using percutaneous sutures for retraction and employing coaxial, flexible, and articulating instruments have been used to improve triangulation. CONCLUSIONS The ergonomics imposed by this approach are different from those of multi-port laparoscopic surgery. Considerable progress in port and instruments for SPLS has been achieved in the last five years in order to overcome the constraints and problems facing the operating surgeon when using the SPLS approach. Further more advanced instrumentation such as hand-held manipulators with seven degrees of freedom (DOF) and robotic devices for SPLS is needed to realize the full potential of the SPLS approach.


Covid-19: hospitals brace for disaster as US surpasses China in number of cases.


title: Novel expression pattern of neuropeptide Y immunoreactivity in the peripheral nervous system in a rat model of neuropathic pain.

text: BACKGROUND Neuropeptide Y (NPY) has been implicated in the modulation of pain. Under normal conditions, NPY is found in interneurons in the dorsal horn of the spinal cord and in sympathetic postganglionic neurons but is absent from the cell bodies of sensory neurons. Following peripheral nerve injury NPY is dramatically upregulated in the sensory ganglia. How NPY expression is altered in the peripheral nervous system, distal to a site of nerve lesion, remains unknown. To address this question, NPY expression was investigated using immunohistochemistry at the level of the trigeminal ganglion, the mental nerve and in the skin of the lower lip in relation to markers of sensory and sympathetic fibers in a rat model of trigeminal neuropathic pain. RESULTS At 2 and 6 weeks after chronic constriction injury (CCI) of the mental nerve, de novo expression of NPY was seen in the trigeminal ganglia, in axons in the mental nerve, and in fibers in the upper dermis of the skin. In lesioned animals, NPY immunoreactivity was expressed primarily by large diameter mental nerve sensory neurons retrogradely labelled with Fluorogold. Many axons transported this de novo NPY to the periphery as NPY-immunoreactive (IR) fibers were seen in the mental nerve both proximal and distal to the CCI. Some of these NPY-IR axons co-expressed Neurofilament 200 (NF200), a marker for myelinated sensory fibers, and occasionally colocalization was seen in their terminals in the skin. Peptidergic and non-peptidergic C fibers expressing calcitonin gene-related peptide (CGRP) or binding isolectin B4 (IB4), respectively, never expressed NPY. CCI caused a significant de novo sprouting of sympathetic fibers into the upper dermis of the skin, and most, but not all of these fibers, expressed NPY. CONCLUSIONS This is the first study to provide a comprehensive description of changes in NPY expression in the periphery after nerve injury. Novel expression of NPY in the skin comes mostly from sprouted sympathetic fibers. This information is fundamental in order to understand where endogenous NPY is expressed, and how it might be acting to modulate pain in the periphery.


Audio Interview: Studying Potential Covid-19 Therapies.


title: High-dose-rate Interstitial Brachytherapy Boost with a Pedicled Latissimus Dorsi Myocutaneous Flap for Myxofibrosarcoma of the Arm.

text: SUMMARY A 71-year-old man was found to have a 7.4 × 2.9 × 7.0 cm myxofibrosarcoma of the right medial arm close to neurovascular structures. He received 50 Gray (Gy) of preoperative external beam radiation. Radical resection resulted in a 15 × 10 cm defect. Nine brachytherapy catheters were placed, and a pedicled latissimus dorsi myocutaneous flap was used in reconstruction. Final pathology confirmed myxofibrosarcoma, high grade. The tumor was <1 mm from 2 margins. A total of 17.5 Gy of brachytherapy was delivered to the surgical bed from postoperative days 7 to 9. The flap developed fat necrosis distally which eventually required surgical debridement on postoperative day 58. It subsequently healed well and maintained good function of the limb. The patient remains under surveillance without evidence of recurrence.


title: 2009 influenza pandemic impact on sick leave use in the Veterans Health Administration: framework for a health care provider-based national syndromic surveillance system.

text: OBJECTIVE To determine relations between sick leave use and the 2009 novel influenza A (H1N1) influenza pandemic among clinical and nonclinical staff in the Veterans Health Administration (VHA). METHODS Aggregate sick leave use for all VHA employees was monitored in near-real time during the 2009 H1N1 influenza pandemic and compared with historical data from 2004 to 2008. The ratio of sick leave use between clinical and nonclinical staff was examined. An autoregressive integrated moving average model was used to assess whether the pandemic had a significant effect on sick leave use. RESULTS The H1N1 influenza pandemic was associated with a significant effect on sick leave use in the VHA during the second wave of the pandemic. During this wave, the ratio of clinical to nonclinical sick leave use changed; clinical staff began taking more leave than nonclinical staff for 3 successive 2-week pay periods, with ratio measures of 1.004, 1.018, and 1.011, respectively. Using an autoregressive integrated moving average model with a pulse variable representing the pandemic, there was a significant effect on sick leave use. The average hours of sick leave used per full-time equivalent staff member per month increased by 0.3904 hours (P = .003) for clinical staff and 0.3898 hours (P = .01) for nonclinical staff over previous months during the first month of the second pandemic wave. CONCLUSIONS Work loss associated with a pandemic is an important indicator of disease activity and may be a more sensitive indicator of emerging strains than deaths. Monitoring sick leave use in near real time in a large national health care system may be an important early indicator of pandemic severity with practical implications that should be considered in addition to more traditional measures of influenza epidemic and pandemic severity.


title: Effect of hand hygiene on infectious disease risk in the community setting: a meta-analysis.

text: To quantify the effect of hand-hygiene interventions on rates of gastrointestinal and respiratory illnesses and to identify interventions that provide the greatest efficacy, we searched 4 electronic databases for hand-hygiene trials published from January 1960 through May 2007 and conducted meta-analyses to generate pooled rate ratios across interventions (N=30 studies). Improvements in hand hygiene resulted in reductions in gastrointestinal illness of 31% (95% confidence intervals [CI]=19%, 42%) and reductions in respiratory illness of 21% (95% CI=5%, 34%). The most beneficial intervention was hand-hygiene education with use of nonantibacterial soap. Use of antibacterial soap showed little added benefit compared with use of nonantibacterial soap. Hand hygiene is clearly effective against gastrointestinal and, to a lesser extent, respiratory infections. Studies examining hygiene practices during respiratory illness and interventions targeting aerosol transmission are needed.


title: Effect of laparoscopy by single-port endoscopic access in benign adnexal surgery: study protocol for a randomized controlled trial.

text: BACKGROUND Laparoscopic surgery has become the preferred surgical approach due to a reduction in postoperative pain, better recovery, shorter hospitalization, and improved esthetic outcomes. Laparoscopic surgery with single-port laparoscopy (SPL) is a laparoscopic surgery technique that is based on making a single parietal incision using a single trocar specifically designed to allow introduction of several instruments. The level of evidence regarding the advantages of SPL in terms of postoperative pain has remained low despite several randomized studies. Adult patients exhibiting a surgical indication for an a priori benign ovarian pathology or for prophylactic purposes that can be performed by laparoscopy will be randomized to receive conventional laparoscopy (CL) or SPL. The aim of our study is to evaluate whether SPL offers advantages over CL in benign adnexal surgery. METHODS The patients will be evaluated preoperatively to confirm their eligibility. The perioperative data up to 24 h after the intervention, as well as the postoperative data at day 7 and at one month from the intervention will be collected. The primary outcome for the study will be the postoperative pain at 24 h ± 2 h after the intervention. The pain will be assessed by a numeric rating scale of 0-10. Other outcomes will also be assessed, such as pain at other times, the consumption of analgesics, the operative time, perioperative bleeding, the number of additional trocars in the two groups, the incidence of laparoconversion, the esthetic criteria of the scar at one month, the incidence of complications, and the quality of life at one month. DISCUSSION If our hypothesis is confirmed, this study will provide evidence that the use of SPL can decrease postoperative pain in adnexal surgery. The standard surgical treatment of this condition would thus be modified. TRIAL REGISTRATION ClinicalTrials.gov, NCT02739724 . Registered on 12 April 2016.


Covid-19 in Italy: A Lesson to be Learned.


title: Effect of amino acids on IGF1 gene expression in human myotubes and skeletal muscle.

text: OBJECTIVE Insulin-like growth factor I (IGF1) is an important regulator of collagen and extracellular matrix protein expression. We aimed to evaluate the effect of amino acids (AAs) on expression of IGF1 and IGF1-dependent genes in human myotubes and skeletal muscle and supposed that AAs administration increases IGF1 levels in blood and expression of IGF1 and IGF1-dependent genes in trained skeletal muscle, thereby reducing training-induced muscle damage. DESIGN Human myotubes were incubated with Arg and Leu for 24 h. Then, the effects of long-term branched chain AAs administration (10 weeks, 0.1 g/kg body mass/day) to volunteers (six subjects per AAs and placebo groups) performing large training volumes regularly (cross country skiers, training twice a day) were examined. RESULTS Incubating the myotubes with AAs increases expression of IGF1 mRNA isoforms and IGF1 secretion by 2-3 times. In athletes, long-term AAs administration increased basal blood levels of IGF1 (~50%) and expression of IGF1Ea mRNA slightly in skeletal muscle. There is no marked increase in expression of COL1A1, COL3A1, COL5A1, and LOX genes in skeletal muscle after AAs administration. However, expression of these genes in the combined group (placebo + AAs; n = 12) significantly correlated with the expression of IGF1Ea mRNA in muscle and did not correlate with IGF1 levels in the blood. CONCLUSIONS AAs administration increases IGF1 expression in vitro and in vivo. To obtain more pronounced changes in expression of IGF1 and IGF1-dependent genes in skeletal muscle, it may be necessary to increase the dose and/or duration of AAs administration.


Too many children miss out on education - but better data can help.


title: Evaluating the Effectiveness of Social Distancing Interventions to Delay or Flatten the Epidemic Curve of Coronavirus Disease.

text: By April 2, 2020, >1 million persons worldwide were infected with severe acute respiratory syndrome coronavirus 2. We used a mathematical model to investigate the effectiveness of social distancing interventions in a mid-sized city. Interventions reduced contacts of adults >60 years of age, adults 20-59 years of age, and children <19 years of age for 6 weeks. Our results suggest interventions started earlier in the epidemic delay the epidemic curve and interventions started later flatten the epidemic curve. We noted that, while social distancing interventions were in place, 20% of new cases and most hospitalizations and deaths were averted, even with modest reductions in contact among adults. However, when interventions ended, the epidemic rebounded. Our models suggest that social distancing can provide crucial time to increase healthcare capacity but must occur in conjunction with testing and contact tracing of all suspected cases to mitigate virus transmission.


title: Identification and characterization of genetically divergent members of the newly established family Mesoniviridae.

text: The recently established family Mesoniviridae (order Nidovirales) contains a single species represented by two closely related viruses, Cavally virus (CavV) and Nam Dinh virus (NDiV), which were isolated from mosquitoes collected in Côte d'Ivoire and Vietnam, respectively. They represent the first nidoviruses to be discovered in insects. Here, we report the molecular characterization of four novel mesoniviruses, Hana virus, Méno virus, Nsé virus, and Moumo virus, all of which were identified in a geographical region in Côte d'Ivoire with high CavV prevalence. The viruses were found with prevalences between 0.5 and 2.8%, and genome sequence analyses and phylogenetic studies suggest that they represent at least three novel species. Electron microscopy revealed prominent club-shaped surface projections protruding from spherical, enveloped virions of about 120 nm. Northern blot data show that the four mesoniviruses analyzed in this study produce two major 3'-coterminal subgenomic mRNAs containing two types of 5' leader sequences resulting from the use of different pairs of leader and body transcription-regulating sequences that are conserved among mesoniviruses. Protein sequencing, mass spectroscopy, and Western blot data show that mesonivirus particles contain eight major structural protein species, including the putative nucleocapsid protein (25 kDa), differentially glycosylated forms of the putative membrane protein (20, 19, 18, and 17 kDa), and the putative spike (S) protein (77 kDa), which is proteolytically cleaved at a conserved site to produce S protein subunits of 23 and 57 kDa. The data provide fundamental new insight into common and distinguishing biological properties of members of this newly identified virus family.


title: [Guide for the prevention and treatment of coronavirus disease 2019].

text: In December 2019, a novel coronavirus was identified in Wuhan City, Hubei Province, China and later the disease was named coronavirus disease 2019 (COVID-19) . On March 11, 2020, the World Health Organization (WHO) officially announced that COVID-19 had reached global pandemic status. This article summarized the understanding of the etiology, pathogenesis, epidemiology, clinical characteristics, diagnosis, treatment, rehabilitation, and prevention and control measures of COVID-19 based on the available data and anti-epidemic experience in China.


title: Impact of contrast-induced acute kidney injury on outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

text: PURPOSE The purpose of this study was to identify predictors of contrast-induced acute kidney injury (CI-AKI) and the effect of CI-AKI on cardiovascular outcomes after hospital discharge in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). METHODS AND MATERIALS We retrospectively reviewed 194 STEMI consecutive patients who underwent primary PCI to evaluate the predictors for CI-AKI and 187 survivors to examine all-cause mortality and cardiovascular events. Outcomes were compared between patients with CI-AKI and those without CI-AKI, which was defined as an increase >50% or >0.5mg/dl in serum creatinine concentration within 48hours after primary PCI. RESULTS CI-AKI occurred in 23 patients (11.9%). Multivariate analysis identified pre-procedural renal insufficiency as a predictor of CI-AKI, and this predictor was independent from hemodynamic instability and excessive contrast volume. Receiver-operator characteristics analysis demonstrated that patients with an estimated glomerular filtration rate (eGFR) of ≤43.6ml/min per 1.73m(2) had the potential for CI-AKI. Patients who developed CI-AKI had higher mortality and cardiovascular events than did those without CI-AKI (27.8% vs. 4.7%; log-rank P=.0003, 27.8% vs. 11.2%; log-rank P=.0181, respectively). Cox proportional hazards model analysis identified CI-AKI as the independent predictor of mortality and cardiovascular events [hazard ratio [HR]=5.36; P=.0076, HR=3.10; P=.0250, respectively]. CONCLUSIONS The risk of CI-AKI is increased in patients with pre-procedural renal insufficiency, and eGFR is clinically useful in the emergent setting for CI-AKI risk stratification before primary PCI.


title: Secondary omental torsion as a rare cause of acute abdomen in a child and the advantages of laparoscopic approach.

text: Omental torsion is an underdiagnosed cause of acute abdomen in children. Most cases occur in adults, with only 15% presenting in children. It is estimated that omental infarct is found in approximately 0.1 to 0.5% of children undergoing operations for appendicitis. It may present with various signs and symptoms, although the clinical presentation usually mimics that of acute appendicitis. Definitive diagnosis is often established during surgery. We report a case of a 9-year-old boy who came to our attention for acute abdomen. We performed a laparoscopy-assisted procedure suspecting acute appendicitis. We therefore identified a secondary omental torsion associated with patency of the right inguinal duct and herniated omentum. Laparoscopy allowed a correct diagnosis and therapy.


Commentary: Definitions of global health--the 2005 PBS series 'Rx for Survival' 's approach.


The time has come for an Australian Centre for Disease Control.


COVID-19, Urologists and Hospitals.


title: CXCR5+ CD8+ T Cells Indirectly Offer B Cell Help and Are Inversely Correlated with Viral Load in Chronic Hepatitis B Infection.

text: Treatment options for chronic hepatitis B (CHB) infection are extremely limited. CXCR5+ CD8+ T cell is a novel cell subtype and could possess strong cytotoxic properties in HIV infection. In this study, we investigated the role of CXCR5+ CD8+ T cells in CHB patients. Compared to healthy individuals, both CHB patients and hepatitis B virus (HBV)-infected hepatocellular carcinoma patients presented significant upregulation of CXCR5+ CD8+ T cells in peripheral blood, in which CXCR5+ CD8+ T cells were negatively correlated with the frequency of CXCR5+ CD4+ T cells in CHB patients. After PMA+ionomycin stimulation, CXCR5+ CD8+ T cells from CHB patients presented significantly higher transcription level of interferon gamma (IFN-γ), interleukin 10 (IL-10), and IL-21, as well as higher IL-10 and IL-21 protein secretion, than CXCR5- CD8+ T cells. Unlike CXCR5+ CD4+ T cells, when incubated with naive CD19+CD27- B cells, CXCR5+ CD8+ T cells alone did not upregulate IgM, IgG, and IgA secretion. However, addition of CXCR5+ CD8+ T cells in B cell-CXCR5+ CD4+ T cell coculture significantly increased the levels of secreted IgG and IgA, demonstrating that CXCR5+ CD8+ T cell could indirectly offer B cell help. Furthermore, high frequencies of CXCR5+ CD8+ T cells tended to associate with low HBV DNA load, and the frequency of CXCR5+ CD8+ T cells was negatively correlated with alanine aminotransferase (ALT) level. Together, these results suggested that CXCR5+ CD8+ T cells were involved in the antiviral immune responses in CHB and could potentially serve as a therapeutic candidate.


title: Planning irreversible electroporation in the porcine kidney: are numerical simulations reliable for predicting empiric ablation outcomes?

text: PURPOSE Numerical simulations are used for treatment planning in clinical applications of irreversible electroporation (IRE) to determine ablation size and shape. To assess the reliability of simulations for treatment planning, we compared simulation results with empiric outcomes of renal IRE using computed tomography (CT) and histology in an animal model. METHODS The ablation size and shape for six different IRE parameter sets (70-90 pulses, 2,000-2,700 V, 70-100 µs) for monopolar and bipolar electrodes was simulated using a numerical model. Employing these treatment parameters, 35 CT-guided IRE ablations were created in both kidneys of six pigs and followed up with CT immediately and after 24 h. Histopathology was analyzed from postablation day 1. RESULTS Ablation zones on CT measured 81 ± 18 % (day 0, p ≤ 0.05) and 115 ± 18 % (day 1, p ≤ 0.09) of the simulated size for monopolar electrodes, and 190 ± 33 % (day 0, p ≤ 0.001) and 234 ± 12 % (day 1, p ≤ 0.0001) for bipolar electrodes. Histopathology indicated smaller ablation zones than simulated (71 ± 41 %, p ≤ 0.047) and measured on CT (47 ± 16 %, p ≤ 0.005) with complete ablation of kidney parenchyma within the central zone and incomplete ablation in the periphery. CONCLUSION Both numerical simulations for planning renal IRE and CT measurements may overestimate the size of ablation compared to histology, and ablation effects may be incomplete in the periphery.


title: Nebulised amphotericin B to eradicate Candida colonisation from the respiratory tract in critically ill patients receiving selective digestive decontamination: a cohort study.

text: INTRODUCTION Colonisation of the lower respiratory tract with Candida species occurs in 25% of mechanically ventilated critically ill patients, and is associated with increased morbidity. Nebulised amphotericin B has been used to eradicate Candida as part of selective decontamination of the digestive tract (SDD) protocols, but its effectiveness is unknown. We aimed to determine the effectiveness of nebulised amphotericin B in eradicating Candida respiratory tract colonisation in patients receiving SDD. METHODS We included consecutive mechanically ventilated patients during a four-year period. Microbiological screening was performed upon admission and twice weekly thereafter according to a standardised protocol. A colonisation episode was defined as the presence of Candida species in two consecutive sputum samples taken at least one day apart. To correct for time-varying bias and possible confounding, we used a multistate approach and performed time-varying Cox regression with adjustment for age, disease severity, Candida load at baseline and concurrent corticosteroid use. RESULTS Among 1,819 patients, colonisation with Candida occurred 401 times in 363 patients; 333 of these events were included for analysis. Decolonisation occurred in 51 of 59 episodes (86%) and in 170 of 274 episodes (62%) in patients receiving and not receiving nebulised amphotericin B, respectively. Nebulised amphotericin B was associated with an increased rate of Candida eradication (crude HR 2.0; 95% CI 1.4 to 2.7, adjusted HR 2.2; 95% CI 1.6 to 3.0). Median times to decolonisation were six and nine days, respectively. The incidence rate of ventilator-associated pneumonia, length of stay and mortality did not differ between both groups. CONCLUSIONS Nebulised amphotericin B reduces the duration of Candida colonisation in the lower respiratory tracts of mechanically ventilated critically ill patients receiving SDD, but data remain lacking that this is associated with a meaningful improvement in clinical outcomes. Until more evidence becomes available, nebulised amphotericin B should not be used routinely as part of the SDD protocol.


title: Uniportal thoracoscopic treatment in bronchiectasis patients: preliminary experience.

text: Introduction Bronchiectasis is defined as a permanent and abnormal dilation of the bronchi due to destruction of the bronchial wall. The thoracoscopic approach is represented in the literature by a few reports, and multiple port incisions are observed in these studies. Aim To investigate the effectiveness and outcomes of the single port video-assisted thoracoscopic surgery (VATS) method in the surgical treatment of bronchiectasis. To our knowledge, this is the first study reporting surgical treatment of bronchiectasis via the uniportal thoracoscopic approach. Material and methods The medical records of 15 patients undergoing surgery for bronchiectasis between 2013 and 2017 were reviewed. The patients were evaluated with regard to age, gender, duration of symptoms, localization, types and duration of the surgery, presence of pleural adhesion, intraoperative complications, amount of intraoperative bleeding, conversion to open surgery, postoperative drainage amount, chest tube removal time, length of hospital stay, mortality and morbidity, follow-up period, duration of narcotic analgesic usage, pain according to visual analog scale evaluation and satisfaction score. Results A total of 15 patients initially underwent single port thoracoscopic resection and 14 procedures were completed thoracoscopically. In terms of anatomic resections, 6 patients underwent left lower lobectomy, 4 right lower lobectomy, 1 right upper lobectomy, 1 left lower lobectomy + lingulectomy, 1 right basal segmentectomy and 1 patient underwent lingulectomy. The mean operative time was 137.1 ±24.5 min and the mean length of hospital stay was 4.78 ±1.52 days. The mean postoperative analgesic requirement was 2.85 ±0.66 days. Conclusions We believe that uniportal VATS is a safe, feasible, and effective technique for selected bronchiectasis patients.


title: Validation of the SF-36 as a measure of postoperative recovery after colorectal surgery.

text: INTRODUCTION Surgery is evolving, and new techniques are introduced to improve "recovery." Postoperative recovery is complex, and evaluating the effectiveness of surgical innovations requires assessment of patient-reported outcomes. The Short-Form-36 (SF-36), a generic health-related quality of life questionnaire, is the most commonly used instrument in this context. The objective of this study was to contribute evidence for the validity of the SF-36 as a metric of postoperative recovery. METHODS Data from 128 patients undergoing planned colorectal surgery at one university hospital between 2005 and 2010 were analyzed. In the absence of a gold standard, the responsiveness and construct validity (known groups and convergent) of the SF-36 were evaluated. Standardized response means were computed for the former and non-parametric tests were used to assess the statistical significance of the changes observed. Multiple linear regression was used to determine whether the SF-36 discriminates between patients with versus without complications and between laparoscopic and open surgery (known groups); correlations between the SF-36 and the 6-min walk test, a measure of functional walking capacity (convergent) was investigated with Spearman's rank correlation. RESULTS The SF-36 was sensitive to clinically important changes. Scores on six of eight domains and the physical component summary score deteriorated postoperatively (SRM 0.86 for the PCS, p < 0.01) and improved to baseline thereafter. Patients with complications had significantly lower scores on five SF-36 domains (with differences from -9 (-18, -1), p = 0.04 to -18 (-32, -2), p = 0.03), and scores on all subscales were lower than those in a healthy population (p < 0.01 to p = 0.04). The SF-36 did not differentiate between laparoscopic and open surgery. Physical functioning scores correlated with 6MWT distance at 1 and 2 months (Spearman's r = 0.31 and 0.36, p < 0.01). CONCLUSIONS The SF-36 is responsive to expected physiological changes in the postoperative period, demonstrates construct validity, and thus constitutes a valid measure of postoperative recovery after planned colorectal surgery. The SF-36 did not, however, discriminate between recovery after laparoscopic and open surgery.


title: Optimizing the tissue anchoring performance of barbed sutures in skin and tendon tissues.

text: The focus of the current work was to study how the geometric design of a single barbed monofilament suture effects its biomechanical behavior. Different cut angles and cut depths of barbs were prepared and tested in vitro for their tensile and tissue anchoring properties by means of a novel suture/tissue pullout test. Experiments were also performed using bovine tendon and porcine skin tissues. The experimental results revealed that since tendon tissue has a higher modulus than skin it needs a more rigid barb to penetrate and anchor the surrounding tissue. A cut angle of 150 degrees and a cut depth of 0.18 mm are therefore recommended. On the other hand, for the softer skin tissue, a cut angle of 170 degrees and a cut depth of 0.18 mm provides a more flexible barb that gives superior skin tissue anchoring. These findings confirm that the future development of barbed suture technology requires a detailed understanding of the biomechanical properties of the tissue in which they are to be used. This will lead to the future development of a range of tissue-specific barbed sutures.


title: Cross-linking of porcine acellular dermal matrices negatively affects induced neovessel formation using platelet-rich plasma in a rat model of hernia repair.

text: The degree of cross-linking within acellular dermal matrices (ADM) seems to correlate to neovascularization when used in ventral hernia repair (VHR). Platelet-rich plasma (PRP) enhances wound healing through several mechanisms including neovascularization, but research regarding its effect on soft tissue healing in VHR is lacking. We sought to study the effect of cross-linking on PRP-induced neovascularization in a rodent model of bridging VHR. We hypothesized that ADM cross-linking would negatively affect PRP-induced neovessel formation. PRP was extracted and characterized from pooled whole blood. Porcine cross-linked (cADM) and non-cross-linked ADMs (ncADM) were implanted in a rat model of chronic VHR after treatment with saline (control) or PRP. Neovascularization of samples at 2, 4, and 6 weeks was assessed by hematoxylin and eosin and immunohistochemical staining of CD 31. Adhesion severity at necropsy was compared using a previously validated scale. Addition of PRP increased neovascularization in both cADM and ncADM at 2- and 4-week time points but appeared to do so in a dependent fashion, with significantly greater neovascularization in the PRP-treated ncADMs compared to cADMs. Omental adhesions were increased in all PRP-treated groups. Results indicate that, for 2-week measurements when compared with the cADM group without PRP therapy, the mean change in neovascularization due to ncADM was 3.27 (Z = 2.75, p = 0.006), PRP was 17.56 (Z = 14.77, p < 0.001), and the combined effect of ncADM and PRP was 9.41 (Z = 5.6, p < 0.001). The 4-week data indicate that the average neovascularization change due to ncADM was 0.676 (Z = 0.7, p = 0.484), PRP was 7.69 (Z = 7.95, p < 0.001), and combined effect of ncADM and PRP was 5.28 (Z = 3.86, p < 0.001). These findings validate PRP as a clinical adjunct to enhance the native tissue response to implantable biomaterials and suggest that ncADM is more amenable than cADM to induced neovascularization. PRP use could be advantageous in patients undergoing VHR where poor incorporation is anticipated and early-enhanced neovascularization is desired.


Patients with lupus are not protected from COVID-19.


Hydroxychloroquine, Coronavirus Disease 2019, and QT Prolongation.


title: Semi-quantitative assessment of disease risks at the human, livestock, wildlife interface for the Republic of Korea using a nationwide survey of experts: A model for other countries.

text: Wildlife-associated diseases and pathogens have increased in importance; however, management of a large number of diseases and diversity of hosts is prohibitively expensive. Thus, the determination of priority wildlife pathogens and risk factors for disease emergence is warranted. We used an online questionnaire survey to assess release and exposure risks, and consequences of wildlife-associated diseases and pathogens in the Republic of Korea (ROK). We also surveyed opinions on pathways for disease exposure, and risk factors for disease emergence and spread. For the assessment of risk, we employed a two-tiered, statistical K-means clustering algorithm to group diseases into three levels (high, medium and low) of perceived risk based on release and exposure risks, societal consequences and the level of uncertainty of the experts' opinions. To examine the experts' perceived risk of routes of introduction of pathogens and disease amplification and spread, we used a Bayesian, multivariate normal order-statistics model. Six diseases or pathogens, including four livestock and two wildlife diseases, were identified as having high risk with low uncertainty. Similarly, 13 diseases were characterized as having high risk with medium uncertainty with three of these attributed to livestock, six associated with human disease, and the remainder having the potential to affect human, livestock and wildlife (i.e., One Health). Lastly, four diseases were described as high risk with high certainty, and were associated solely with fish diseases. Experts identified migration of wildlife, international human movement and illegal importation of wildlife as the three routes posing the greatest risk of pathogen introduction into ROK. Proximity of humans, livestock and wildlife was the most significant risk factor for promoting the spread of wildlife-associated diseases and pathogens, followed by high density of livestock populations, habitat loss and environmental degradation, and climate change. This study provides useful information to decision makers responsible for allocating resources to address disease risks. This approach provided a rapid, cost-effective method of risk assessment of wildlife-associated diseases and pathogens for which the published literature is sparse.


title: [Clinical outcomes of COVID-19 cases and influencing factors in Guangdong province].

text: Objective: To analyze the clinical courses and outcomes of COVID-19 cases and the influencing factors in Guangdong province and provide basis for the formulation or adjustment of medical care and epidemic control strategy for COVID-19. Methods: We collected demographic data, medical histories, clinical courses and outcomes of 1 350 COVID-19 patients reported in Guangdong as of 4 March 2020 via epidemiological investigation and process tracking. Disease severity and clinical course characteristics of the patients and influencing factors of severe illness were analyzed in our study. Results: Among 1 350 cases of COVID-19 cases in Guangdong, 72 (5.3%) and 1049 (77.7%) were mild and ordinary cases, 164 (12.1%) were severe cases, 58 (4.3%) were critical cases and 7 (0.5%) were fatal. The median duration of illness were 23 days (P(25)-P(75): 18-31 days) and the median length of hospitalization were 20 days (P(25)-P(75): 15-27 days). For severe cases, the median time of showing severe manifestations was on the 12th day after onset (P(25)-P(75): 9th to 15th days), and the median time of severe manifestation lasted for 8 days P(25)-P(75): 4-14 days). Among 1 066 discharged/fetal cases, 36.4% (36/99) and 1.0% (1/99) of the mild cases developed to ordinary cases and severe cases respectively after admission; and 5.2% (50/968) and 0.6% (6/968) of the ordinary cases developed to severe cases, and critical cases respectively after admission. In severe cases, 11.4% developed to critical cases (10/88). The influencing factors for severe illness or worse included male (aHR=1.87, 95%CI: 1.43-2.46), older age (aHR=1.67, 95%CI: 1.51-1.85), seeking medical care on day 2-3 after onset (aHR=1.73, 95%CI: 1.20-2.50) pre-existing diabetes (aHR=1.75, 95%CI: 1.12-2.73) and hypertension (aHR=1.49, 95%CI: 1.06-2.09). Conclusions: The course of illness and length of hospitalization of COVID-19 cases were generally long and associated with severity of disease clinical outcomes. The severe cases were mainly occurred in populations at high risk. In the epidemic period, classified management of COVID-19 cases should be promoted according to needs for control and prevention of isolation and treatment for the purpose of rational allocation of medical resources.


title: Hemodynamic Analysis of Postoperative Rupture of Unruptured Intracranial Aneurysms after Placement of Flow-Diverting Stents: A Matched Case-Control Study.

text: BACKGROUND AND PURPOSE Postoperative rupture of intracranial aneurysm has been reported as a fatal complication after flow-diverter placement. We assessed several hemodynamic variables to explore risk factors in the postoperative rupture process. MATERIALS AND METHODS We enrolled 10 patients with intracranial aneurysms, treated with flow diverters between September 2014 and December 2018, who experienced postoperative aneurysm rupture (postoperative aneurysm rupture group). We matched these subjects 1:2 with 20 patients with postoperative unruptured (postoperative unruptured group) intracranial aneurysms based on clinical and morphologic factors. Using computational fluid dynamics, we assessed hemodynamic changes pre- and posttreatment between the 2 groups on a number of qualitative and quantitative parameters. RESULTS In the postoperative aneurysm rupture group, the proportion of patients with aneurysms with an unstable flow pattern increased to 60.0% after treatment, while the proportion in the postoperative unruptured group decreased to 20.0%, a significant difference between the 2 groups (P = .028). Energy loss in the postoperative unruptured group decreased after treatment but increased in the postoperative aneurysm rupture group. The reduction ratio of energy loss showed a significant difference between the 2 groups (22.73% ± 53.59% for postoperative unruptured versus -158.81% ± 183.95% for postoperative aneurysm rupture, P = .02). Other parameters and changes of pre- and posttreatment hemodynamic parameters showed no significant difference between 2 groups. CONCLUSIONS Compared with pretreatment, unstable flow pattern and higher energy loss after Pipeline Embolization Device placement for intracranial aneurysm may be the important hemodynamic risk factors related to delayed aneurysm rupture.


title: Universal Testing for COVID-19 in Essential Orthopaedic Surgery Reveals a High Percentage of Asymptomatic Infections.

text: BACKGROUND The long incubation period and asymptomatic spread of COVID-19 present considerable challenges for health-care institutions. The identification of infected individuals is vital to prevent the spread of illness to staff and other patients as well as to identify those who may be at risk for disease-related complications. This is particularly relevant with the resumption of elective orthopaedic surgery around the world. We report the results of a universal testing protocol for COVID-19 in patients undergoing orthopaedic surgery during the coronavirus pandemic and to describe the postoperative course of asymptomatic patients who were positive for COVID-19. METHODS A retrospective review of adult operative cases between March 25, 2020, and April 24, 2020, at an orthopaedic specialty hospital in New York City was performed. Initially, a screening questionnaire consisting of relevant signs and symptoms (e.g., fever, cough, shortness of breath) or exposure dictated the need for nasopharyngeal swab real-time quantitative polymerase chain reaction (RT-PCR) testing for all admitted patients. An institutional policy change occurred on April 5, 2020, that indicated nasopharyngeal swab RT-PCR testing for all orthopaedic admissions. Screening and testing data for COVID-19 as well as relevant imaging, laboratory values, and postoperative complications were reviewed for all patients. RESULTS From April 5, 2020, to April 24, 2020, 99 patients underwent routine nasopharyngeal swab testing for COVID-19 prior to their planned orthopaedic surgical procedure. Of the 12.1% of patients who tested positive for COVID-19, 58.3% were asymptomatic. Three asymptomatic patients developed postoperative hypoxia, with 2 requiring intubation. The negative predictive value of using the signs and symptoms of disease to predict a negative test result was 91.4% (95% confidence interval [CI], 81.0% to 97.1%). Including a positive chest radiographic finding as a screening criterion did not improve the negative predictive value of screening (92.5% [95% CI, 81.8% to 97.9%]). CONCLUSIONS A protocol for universal testing of all orthopaedic surgery admissions at 1 hospital in New York City during a 3-week period revealed a high rate of COVID-19 infections. Importantly, the majority of these patients were asymptomatic. Using chest radiography did not significantly improve the negative predictive value of screening. These results have important implications as hospitals anticipate the resumption of elective surgical procedures. LEVEL OF EVIDENCE Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


title: [Efecto de un enfoque estandarizado para el manejo de lactantes hospitalizados por eventos aparentemente letales].

text: Introducción. Los eventos aparentemente letales (Apparent Life-Threatening Event, ALTE) son causa frecuente de hospitalización en lactantes. Hay poca información sobre el enfoque estandarizado para establecer su etiología, a pesar de que un diagnóstico causal correcto puede afectar la evolución clínica, la duración de la hospitalización y los recursos sanitarios.Objetivo. Comparar los efectos del enfoque diagnóstico estandarizado en lactantes hospitalizados por este tipo de eventos.Materiales y métodos. Se hizo un estudio retrospectivo de cohorte con base en los datos recolectados de las historias clínicas de lactantes hospitalizados por esta causa en el servicio de pediatría entre el 2002 y el 2009. Se analizaron dos cohortes de pacientes agrupados según su manejo: la cohorte 1, con guías clínicas, y la cohorte 2, con guías clínicas, protocolo de estudio y seguimiento ambulatorio. Se compararon los grupos en cuanto a la etiología, el tiempo de hospitalización y la tasa de nuevas hospitalizaciones.Resultados. De los 255 lactantes hospitalizados por eventos aparentemente letales, el 57,6 % integró la cohorte 1 y, el 42,3 %, la cohorte 2. No se observaron diferencias en cuanto a la edad y el sexo. En la cohorte 2 se observó un mayor porcentaje de causas atribuidas (63,9 Vs. 87,0; p<0,0001), y un menor tiempo de hospitalización (8,0 Vs. 5,0 días; p=0,0001). No hubo diferencias en cuanto a nuevas hospitalizaciones (10,5 Vs. 8,3 días; p=0,7435).Conclusiones. El enfoque del manejo de lactantes afectados por eventos aparente letales basado en protocolos, se asoció con un mayor porcentaje de reconocimiento de las causas atribuidas y con un menor período de hospitalización. A partir de estos resultados es posible sugerir la implementación de este tipo de estandarización para el manejo de dichos pacientes.


title: LigaSure for pancreatic sealing during distal pancreatectomy.

text: BACKGROUND Pancreatic fistula is an unresolved problem after distal pancreatectomy. The current study investigated the safety of LigaSure for distal pancreatic resection in a porcine model. METHODS A distal pancreatectomy was performed in 22 pigs. Animals were randomly assigned to undergo conventional scalpel transection with hand-sewn closure of the pancreatic remnant or pancreatic transection and sealing by LigaSure. Closed-suction drainage was collected daily. Animals were sacrificed on postoperative day (POD) 7 and the pancreatic remnant was sampled for histology. RESULTS Two grade A postoperative temporary pancreatic fistulas (ISGPF definition) developed after hand suturing but none after LigaSure sealing. Amylase and lipase levels in drainage fluid were higher in the suture group during the first postoperative days but showed no differences after the fourth day. All but two animals that had to be euthanized because of small bowel invagination survived until POD 7. No significant differences were found in macroscopic changes between groups at reexploration. Histology demonstrated focal, chronic granulating inflammation with minor necrosis in all animals. CONCLUSIONS The LigaSure sealing device provides a safe alternative to conventional hand-sewn closure of the pancreatic stump in distal pancreatectomy. This is the first study that investigated this effective and highly applicable technique for pancreatic transection.


Adapting the ordre public and morality exclusion of European patent law to accommodate emerging technologies.


title: COVID-19 highlights risks of healthcare and social care workers attending work while ill.

text: As COVID-19 affects healthcare and social care systems around the world, reports of infection among healthcare and social care workers continue to accumulate.