title: Standardized adult-gerontology acute care nurse practitioner point-of-care ultrasound training: A new perspective in the age of a pandemic.

text: Our health care landscape is rapidly changing. With the aging population and seemingly increasing outbreak of communicable diseases, it is expected that there will be a continued demand for inpatient/critical care providers. The current COVID-19 pandemic provides a glimpse of a health care system in severe provider shortage. Adult-gerontology acute nurse practitioners (GACNPs) can play a vital part in relieving that shortage. But with the increased role, there is an increased responsibility and need for expansion of AGACNP skill set. This includes the training and utilization of point-of-care ultrasound (POCUS). The case reports and data available from countries that have already combated COVID-19 outbreak show POCUS can play a key part in managing critically ill patients on isolation precautions. This article provides my perspective on POCUS training and competency achievement for AGACNPPs.


title: Contraception during Coronavirus-Covid 19 pandemia. Recommendations of the Board of the Italian Society of Contraception.

text: Purpose: The Italian Society of Contraception identified as one of its priorities the need to give recommendations on management of contraception during Coronavirus-Covid 19 pandemiaMaterials and methods: A concise communication was produced which summarises in an easy-to-read format suitable for clinicians the management of the different contraceptives mostly used. Information how to manage contraception in different conditions is presented.Results: Women may, in general, continue to use either intrauterine and or hormonal contraceptives. The use of condom should be added to any hormonal contraceptive, when the contraceptive efficacy is reduced or when women stop the contraceptive method.Conclusion: At the present time, during the Coronavirus-Covid 19 pandemia, no data contraindicate the use of intrauterine or hormonal contraceptives. Conversely the use of an appropriate contraception is advocate to prevent unintended pregnancies.


title: Hypertension in older adults in Africa: A systematic review and meta-analysis.

text: BACKGROUND Hypertension is the leading driver of cardiovascular disease deaths in Africa. Its prevalence is highest in older populations. Yet, this group has received little attention in many African countries. We conducted a systematic review and meta-analysis (PROSPERO registration: CRD42017056474) to estimate the prevalence of hypertension in older adults living in Africa. METHODS We searched grey literature and major electronic databases including PubMed and Embase for population-based studies and published between 1 January 1980 to 28 May 2018 reporting the prevalence of hypertension for adults aged ≥50 years living in Africa. We employed a random effects model to estimate the pooled prevalence across included studies. FINDINGS We screened 10,719 articles and retrieved 103 full-text articles to evaluate for inclusion in the review. Thirty-four unique studies providing 37 data points on 43,025 individuals in 15 African countries were analyzed. The prevalence of hypertension ranged from 22.3% to 90.0% from the individual studies while the overall pooled prevalence was 57.0% (95% CI 52%-61%). The prevalence was not statistically significantly different by sex, residence, or African sub-region. In individual studies, older age and overweight/obesity were independently associated with hypertension. Twenty-nine (78%) data points were deemed to be of low- or moderate-risk of bias. Eliminating high-risk bias studies made little difference to the pooled estimate of hypertension. Sensitivity analyses, omitting one study at a time, identified three studies with significant but relatively small impact on the pooled estimate. We observed substantial heterogeneity (I2 = 98.9%) across the studies which was further explored by meta-regression analyses. Overall, the GRADE assessment suggested moderate quality evidence in the results. CONCLUSION The persistent high prevalence of hypertension among older adults in Africa, even in rural populations warrants more attention to the cardiovascular health of this group by public health authorities.


Occipital artery: a not so poor artery for the embolization of lateral sinus dural arteriovenous fistulas with Onyx.


title: Identification of a Bovine Enteric Calicivirus, Kırklareli Virus, Distantly Related to Neboviruses, in Calves with Enteritis in Turkey.

text: A calicivirus was detected in neonatal calves with enteritis in Kırklareli, Thrace, Turkey. In the full-length genome, Kırklareli virus was related (48% nucleotide identity) to bovine enteric caliciviruses (Nebovirus genus). The virus was also detected in a herd in Ankara, Central Anatolia, but not in other Turkish prefectures.


title: From Infections to Anthropogenic Inflicted Pathologies: Involvement of Immune Balance.

text: A temporal trend can be seen in recent human history where the dominant causes of death have shifted from infectious to chronic diseases in industrialized societies. Human influences in the current "Anthropocene" epoch are exponentially impacting the environment and consequentially health. Changing ecological niches are suggested to have created health transitions expressed as modifications of immune balance from infections inflicting pathologies in the Holocene epoch (12,000 years ago) to human behaviors inflicting pathologies beginning in the Anthropocene epoch (300 years ago). A review of human immune health and adaptations responding to environmental (biological, chemical, physical, and psychological) stresses, which are influenced by social conditions, emphasize the involvement of fluctuations in immune cell subsets affecting influential gene-environment interactions. The literature from a variety of fields (anthropological, immunological, and environmental) is incorporated to present an expanded perspective on shifts in diseases within the context of immune balance and function and environmental immunology. The influences between historical and contemporary human ecology are examined in relation to human immunity. Several examples of shifts in human physiology and immunity support the premise that increased incidences of chronic diseases are a consequence of human modification of environment and lifestyle. Although the development of better health care and a broader understanding of human health have helped with better life quality and expectancy, the transition of morbidity and mortality rates from infections to chronic diseases is a cause for concern. Combinations of environmental stressors/pollutants and human behaviors and conditions are modulating the immune-neuroendocrine network, which compromises health benefits.


title: [Early detection and disease assessment of patients with novel coronavirus pneumonia].

text: In December 2019, the outbreak of novel coronavirus (2019-nCoV) in Wuhan, China, attracting attention worldwidely. The novel coronavirus has the characteristics of rapid transmission, atypical clinical symptoms, and easy to affect both lungs, leading to missed diagnosis and misdiagnosis, as well as difficult to detection and assessment at early stage. Fever, cough, myalgia, weakness, dyspnea and imagings may be helpful for the early detection of novel coronavirus pneumonia. At the same time, the rate of disease progression, fever, CT manifestations, hypoxia degree, age, basic diseases, and laboratory indicators can also be used to evaluate the severity of the novel coronavirus pneumonia.


title: Prediction of COVID-19 spreading profiles in South Korea, Italy and Iran by data-driven coding.

text: This work applies a data-driven coding method for prediction of the COVID-19 spreading profile in any given population that shows an initial phase of epidemic progression. Based on the historical data collected for COVID-19 spreading in 367 cities in China and the set of parameters of the augmented Susceptible-Exposed-Infected-Removed (SEIR) model obtained for each city, a set of profile codes representing a variety of transmission mechanisms and contact topologies is formed. By comparing the data of an early outbreak of a given population with the complete set of historical profiles, the best fit profiles are selected and the corresponding sets of profile codes are used for prediction of the future progression of the epidemic in that population. Application of the method to the data collected for South Korea, Italy and Iran shows that peaks of infection cases are expected to occur before mid April, the end of March and the end of May 2020, and that the percentage of population infected in each city or region will be less than 0.01%, 0.5% and 0.5%, for South Korea, Italy and Iran, respectively.


title: Brain natriuretic peptide and acute hypobaric hypoxia in humans.

text: In animal models, the secretion of the cardiac hormone, brain natriuretic peptide (BNP), and its closely related peptide, atrial natriuretic peptide (ANP), are stimulated by acute hypoxia. There is extensive human evidence for a rise in ANP under acute hypoxic conditions but very little evidence regarding the BNP response to acute hypoxia in humans. We therefore subjected seven healthy subjects to an acute hypobaric hypoxic stimulus to examine if BNP secretion increases rapidly. Significant hypoxaemia (mean nadir oxygen saturation 62.3%) was induced but no significant rise in BNP occurred. This suggests that either such acute hypoxaemia is well tolerated by the healthy human heart or it is not a stimulus for BNP secretion.


title: Pre-discharge prognostic factors of physical function among older adults with hip fracture surgery: a systematic review.

text: INTRODUCTION To identify, organize, and assess the evidence level of pre-discharge prognostic factors of physical function beyond discharge after hip fracture surgery. METHODS We performed a systematic search of four databases (PubMed, Embase, CINAHL, PsycINFO) for longitudinal studies of prognostic factors of physical function at ≥ 1 month among older adults ≥ 50 years old with surgically treated hip fracture, complemented with hand-searching. Two reviewers independently screened papers for inclusion and assessed the quality of all the included papers using the Quality in Prognosis Studies (QUIPS) tool. We assigned the evidence level for each prognostic factor based on consistency in findings and study quality. RESULTS From 98 papers that met our inclusion criteria, we identified 107 pre-discharge prognostic factors and organized them into the following seven categories: demographic, physical, cognitive, psychosocial, socioeconomic, injury-related, and process of care. Potentially modifiable factors with strong or moderate evidence of an association included total length of stay, physical function at discharge, and grip strength. Factors with strong or moderate evidence of no association included gender, fracture type, and time to surgery. Factors with limited, conflicting, or inconclusive evidence included body-mass index, psychological resilience, depression, and anxiety. CONCLUSIONS Our findings highlight potentially modifiable prognostic factors that could be targeted and non-modifiable prognostic factors that could be used to identify patients who may benefit from more intensive intervention or to advise patients on their expectations on recovery. Examining the efficacies of existing interventions targeting these prognostic factors would inform future studies and whether any of such interventions could be incorporated into clinical practice.


title: Evaluation of the ablation margin of hepatocellular carcinoma using CEUS-CT/MR image fusion in a phantom model and in patients.

text: BACKGROUND To assess the accuracy of contrast-enhanced ultrasound (CEUS)-CT/MR image fusion in evaluating the radiofrequency ablative margin (AM) of hepatocellular carcinoma (HCC) based on a custom-made phantom model and in HCC patients. METHODS Twenty-four phantoms were randomly divided into a complete ablation group (n = 6) and an incomplete ablation group (n = 18). After radiofrequency ablation (RFA), the AM was evaluated using ultrasound (US)-CT image fusion, and the results were compared with the AM results that were directly measured in a gross specimen. CEUS-CT/MR image fusion and CT-CT / MR-MR image fusion were used to evaluate the AM in 37 tumors from 33 HCC patients who underwent RFA. RESULTS The sensitivity, specificity, and accuracy of US-CT image fusion for evaluating AM in the phantom model were 93.8, 85.7 and 91.3%, respectively. The maximal thicknesses of the residual AM were 3.5 ± 2.0 mm and 3.2 ± 2.0 mm in the US-CT image fusion and gross specimen, respectively. No significant difference was observed between the US-CT image fusion and direct measurements of the AM of HCC. In the clinical study, the success rate of the AM evaluation was 100% for both CEUS-CT/MR and CT-CT/MR-MR, and the duration was 8.5 ± 2.8 min (range: 4-12 min) and 13.5 ± 4.5 min (range: 8-16 min) for CEUS-CT/MR and CT-CT/MR-MR, respectively. The sensitivity, specificity, and accuracy of CEUS-CT/MR imaging for evaluating the AM were 100.0, 80.0, and 90.0%, respectively. CONCLUSIONS A phantom model composed of carrageenan gel and additives was suitable for the evaluation of HCC AM. CEUS-CT/MR image fusion can be used to evaluate HCC AM with high accuracy.


Re: The Magnetic Resonance Imaging in Active Surveillance (MRIAS) Trial: Use of Baseline Multiparametric Magnetic Resonance Imaging and Saturation Biopsy to Reduce the Frequency of Surveillance Prostate Biopsies.


title: Retroperitoneoscopic nephrectomy for symptomatic hydronephrosis using a SAND balloon catheter.

text: INTRODUCTION A retroperitoneoscopic nephrectomy (RN) for symptomatic hydronephrosis (SH) is a challenging procedure because of the limited working space. This report describes a specific technical modification for efficient and successful RN for SH by using the SAND balloon catheter. PATIENT AND METHODS A 38-year-old woman underwent RN for SH caused by extrinsic compression of the ureter by a pelvic endometriosis. The SAND balloon catheter was directly inserted into the expanded hydronephrotic sac, and the liquid was extracted, appropriately. Urine leakage from the hydronephrotic sac could be avoided because the puncture site was sealed firmly between the two adjacent balloons at the tip of the catheter. Disposal counter traction using the catheter facilitated the mobilization of the hydronephrotic sac. RESULTS The patient was discharged 3 days after undergoing this procedure. CONCLUSIONS This method improves the surgeon's vision and facilitates resection without causing any injury to the hydronephrotic sac wall during RN.


Patient perspective: Roger Boyes.


title: Total intracorporeal anastomosis during single-port laparoscopic right hemicolectomy for carcinoma of colon: a new step forward.

text: BACKGROUND Laparoscopic surgery is a feasible option for colonic carcinoma as short-and long-term results show. This technique is as safe and effective as the open approach. Single-port access surgery is considered a new minimally invasive approach in the search for better cosmetic results and less postoperative pain. One of the goals of single-port surgery is to preserve the satisfactory oncological results obtained by standard laparoscopy. This study presents the first single-port access right hemicolectomy for carcinoma of colon with intracorporeal anastomosis. METHODS The authors report a single-port access right hemicolectomy in a 59-year-old male patient with a neoplasm of the cecum stage IIA (T3, N0) according to the TNM classification. RESULTS A transumbilical single-port access right hemicolectomy was performed with no additional trocars and total intracorporeal anastomosis. Operative time was 140 minutes. No intraoperative or postoperative complications were reported. CONCLUSION Single-port access right hemicolectomy with intracorporeal anastomosis is a feasible and safe technique when performed by experienced laparoscopic surgeons. This approach must follow the basic principles of laparoscopic right hemicolectomy to achieve the same oncological results. The advantages of a total intracorporeal anastomosis include that there is no need to enlarge the umbilical incision and that avoid traction of the pedicle of the mesenterium of the transverse colon during the extracorporeal anastomosis.


title: COVID-19-A Novel Zoonotic Disease: A Review of the Disease, the Virus, and Public Health Measures.

text: A cluster of cases of pneumonia of unknown etiology emerged in Wuhan, China, at the end of December 2019. The cluster was largely associated with a seafood and animal market. A novel Betacoronavirus was quickly identified as the causative agent, and it is shown to be related genetically to SARS-CoV and other bat-borne SARS-related Betacoronaviruses. The number of cases increased rapidly and spread to other provinces in China, as well as to another 4 countries. To help control the spread of the virus, a "cordon sanitaire" was instituted for Wuhan on January 23, 2020, and subsequently extended to other cities in Hubei Province, and the outbreak declared a Public Health Emergency of International Concern by the Director General of the World Health Organization on January 30, 2020. The virus was named SARS-CoV-2 by the International Committee for the Taxonomy of Viruses, and the disease it causes was named COVID-19 by the World Health Organization. This article described the evolution of the outbreak, and the known properties of the novel virus, SARS-CoV-2 and the clinical disease it causes, and the major public health measures being used to help control it's spread. These measures include social distancing, intensive surveillance and quarantining of cases, contact tracing and isolation, cancellation of mass gatherings, and community containment. The virus is the third zoonotic coronavirus, after SARS-CoV and MERS-CoV, but appears to be the only one with pandemic potential. However, a number of important properties of the virus are still not well understood, and there is an urgent need to learn more about its transmission dynamics, its spectrum of clinical severity, its wildlife origin, and its genetic stability. In addition, more research is needed on possible interventions, particularly therapeutic and vaccines.


title: Cross-neutralization of four paramyxoviruses by a human monoclonal antibody.

text: Broadly neutralizing antibodies reactive against most and even all variants of the same viral species have been described for influenza and HIV-1 (ref. 1). However, whether a neutralizing antibody could have the breadth of range to target different viral species was unknown. Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are common pathogens that cause severe disease in premature newborns, hospitalized children and immune-compromised patients, and play a role in asthma exacerbations. Although antisera generated against either HRSV or HMPV are not cross-neutralizing, we speculated that, because of the repeated exposure to these viruses, cross-neutralizing antibodies may be selected in some individuals. Here we describe a human monoclonal antibody (MPE8) that potently cross-neutralizes HRSV and HMPV as well as two animal paramyxoviruses: bovine RSV (BRSV) and pneumonia virus of mice (PVM). In its germline configuration, MPE8 is HRSV-specific and its breadth is achieved by somatic mutations in the light chain variable region. MPE8 did not result in the selection of viral escape mutants that evaded antibody targeting and showed potent prophylactic efficacy in animal models of HRSV and HMPV infection, as well as prophylactic and therapeutic efficacy in the more relevant model of lethal PVM infection. The core epitope of MPE8 was mapped on two highly conserved anti-parallel β-strands on the pre-fusion viral F protein, which are rearranged in the post-fusion F protein conformation. Twenty-six out of the thirty HRSV-specific neutralizing antibodies isolated were also found to be specific for the pre-fusion F protein. Taken together, these results indicate that MPE8 might be used for the prophylaxis and therapy of severe HRSV and HMPV infections and identify the pre-fusion F protein as a candidate HRSV vaccine.


title: Comparison of drug delivery with autoinjector versus manual prefilled syringe and between three different autoinjector devices administered in pig thigh.

text: Parenteral routes of drug administration are often selected to optimize actual dose of drug delivered, assure high bioavailability, bypass first-pass metabolism or harsh gastrointestinal environments, as well as maximize the speed of onset. Intramuscular (IM) delivery can be preferred to intravenous delivery when initiating intravenous access is difficult or impossible. Drugs can be injected intramuscularly using a syringe or an automated delivery device (autoinjector). Investigation into the IM delivery dynamics of these methods may guide further improvements in the performance of injection technologies. Two porcine model studies were conducted to compare differences in dispersion of injectate volume for different methods of IM drug administration. The first study compared the differences in the degree of dispersion and uptake of injectate following the use of a manual syringe and an autoinjector. The second study compared the spatial spread of the injected formulation, or dispersion volume, and uptake of injectate following the use of five different autoinjectors (EpiPen(®) [0.3 mL], EpiPen(®) Jr [0.3 mL], Twinject(®) [0.15 mL, 0.3 mL], and Anapen(®) 300 [0.3 mL]) with varying needle length, needle gauge, and force applied to the plunger. In the first study, the autoinjector provided higher peak volumes of injectate, indicating a greater degree of dispersion, compared with manual syringe delivery. In the second study, EpiPen autoinjectors resulted in larger dispersion volumes and higher initial dispersion ratios, which decreased rapidly over time, suggesting a greater rate of uptake of injectate than the other autoinjectors. The differences in dispersion and uptake of injectate are likely the result of different functional characteristics of the delivery systems. Both studies demonstrate that the functional characteristics of the method for delivering IM injections impact the dispersion and uptake of the material injected, which could significantly affect the pharmacokinetics and, ultimately, the effectiveness of the drug.


title: Pediatric COVID-19: Systematic review of the literature.

text: OBJECTIVES There is limited data regarding the demographics and clinical features of SARS-CoV-2 infection in children. This information is especially important as pneumonia is the single leading cause of death in children worldwide. This Systematic Review aims to elucidate a better understanding of the global impact of COVID-19 on the pediatric population. METHODS A systematic review of the literature was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to gain insight into pediatric COVID-19 epidemiology. Specifically, Pubmed and Google Scholar databases were searched to identify any relevant article with a focus on Pediatric Covid 19, Pediatric Covid-19, Pediatric SARS-COV-2, and Pediatric Coronavirus 19. References within the included articles were reviewed. All articles that met criteria where analyzed for demographics, clinical, laboratory, radiographic, treatment and outcomes data. RESULTS Ten studies including two case series and 8 retrospective chart reviews, altogether describing a total of 2914 pediatric patients with COVID-19 were included in this systematic review. Of the patients whose data was available, 56% were male, the age range was 1 day to 17 years, 79% were reported to have no comorbidities, and of the 21% with comorbidities, the most common were asthma, immunosupression, and cardiovascular disease. Of pediatric patients that were tested and positive for an infection with SARS-CoV-2, patients were asymptomatic, 14.9% of the time. Patients presented with cough (48%), fever (47%) and sore throat/pharyngitis (28.6%), more commonly than with upper respiratory symptoms/rhinorrhea/sneezing/nasal congestion (13.7%), vomiting/nausea (7.8%) and diarrhea (10.1%). Median lab values including those for WBC, lymphocyte count and CRP, were within the reference ranges with the exception of procalcitonin levels, which were slightly elevated in children with COVID-19 (median procalcitonin levels ranged from 0.07 to 0.5 ng/mL. Computed tomography (CT) results suggest that unilateral CT imaging findings are present 36% of cases while 64% of pediatric patients with COVID-19 had bilateral findings. Of the studies with age specific hospitalization data available, 27.0% of patients hospitalized were infants under 1 year of age. Various treatment regimens including interferon, antivirals, and hydroxychloroquine therapies have been trialed on the pediatric population but there are currently no studies showing efficacy of one regimen over the other. The mortality rate of children that were hospitalized with COVID-19 was 0.0018%. CONCLUSION In contrast to adults, most infected children appear to have a milder course and have better outcomes overall. Additional care may be needed for children with comorbidities and younger children. This review also suggests that unilateral CT chest imaging findings were seen in 36.4% pediatric COVID-19 patients. This is particularly concerning as the work-up of pediatric patients with cough may warrant a bronchoscopy to evaluate for airway foreign bodies. Extra precautions need to be taken with personal protective equipment for these cases, as aerosolizing procedures may be a method of viral transmission. LEVEL OF EVIDENCE 4 (Systematic Review).


title: Pulmonary Thermal Ablation Enables Long Chemotherapy-Free Survival in Metastatic Colorectal Cancer Patients.

text: BACKGROUND Chemotherapy (ct) is the preferred treatment option in metastatic colorectal cancer (mCRC). The objective of the study was to determine the overall survival (OS), disease-free survival (DFS) and ct-free survival (CFS) of pulmonary thermal ablation (TA) and its place in the treatment of mCRC. PATIENTS AND METHODS All consecutive patients treated (over 11 years) with percutaneous TA for lung metastasis of colorectal origin were reviewed. All sequences of treatments were considered. We determined the OS, DFS and CFS of pulmonary TA. RESULTS Two hundred and nine patients underwent 323 TA procedures for 630 lung metastases. Majority of the metastases (71.5%) were unilateral with a median diameter of 10 mm (2-46). A single metastasis was treated in 95 patients (45.5%), and 2-8 in 114 patients (54.5%). One hundred and thirty-two patients (63.2%) had only a single procedure, 77 patients (36.8%) had 2-5 procedures. Following the first TA (n = 209), 125 patients (59.8%) resumed ct. Sixty-four out of the 126 patients presenting lung progression were treated again with TA. The median CFS was 12.2 months (95% CI: 10.3-17.7). Patients with no extra-pulmonary metastases showed a statistically better CFS than those who had extra-pulmonary metastases with a median of 20.9 and 9.2 months, respectively (p < 0.001). Median follow-up and OS were 50 and 67.6 months, respectively. CONCLUSION This study demonstrates, for the first time, that TA enables a CFS of 12.2 months that extended to 20.9 months in patients who presented with lung-only metastases. TA is a viable option for a pause in the therapy of mCRCs.


title: Ecological dynamics of emerging bat virus spillover.

text: Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility.


title: Viral etiology of acute respiratory infections in children in Southern Iran.

text: INTRODUCTION Prevalence of influenza A virus (Flu-A), respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) was assessed in children with acute respiratory infections (ARIs). METHODS Nasopharyngeal aspirates and throat swabs were subjected to real-time polymerase chain reaction (PCR) to detect RSV and Flu-A and to conventional PCR to detect hMPV. RESULTS Of the 156 children assessed, 93 (59.6%) carried at least one virus, with 35.9% positive for RSV, 14.1% for hMPV, and 9.6% for Flu-A. The prevalence of co-infections was 2.6%. CONCLUSIONS The high detection rate may reflect increased sensitivity of real-time PCR compared to traditional PCR and viral culture.


title: Spontaneous pneumothorax: time to rethink management?

text: There are substantial differences in international guidelines for the management of pneumothorax and much geographical variation in clinical practice. These discrepancies have, in part, been driven by a paucity of high-quality evidence. Advances in diagnostic techniques have increasingly allowed the identification of lung abnormalities in patients previously labelled as having primary spontaneous pneumothorax, a group in whom recommended management differs from those with clinically apparent lung disease. Pathophysiological mechanisms underlying pneumothorax are now better understood and this may have implications for clinical management. Risk stratification of patients at baseline could help to identify subgroups at higher risk of recurrent pneumothorax who would benefit from early intervention to prevent recurrence. Further research into the roles of conservative management, Heimlich valves, digital air-leak monitoring, and pleurodesis at first presentation might lead to an increase in their use in the future.


title: Validation of robust tools to measure sialorrhea in amyotrophic lateral sclerosis: a study in a large French cohort.

text: There is an unmet need for validated tools to measure sialorrhea in amyotrophic lateral sclerosis, especially to evaluate treatments. We assessed the inter-/intra-rate reviewer reliability of two scales: the Oral Secretion Scale (OSS), specifically developed for ALS patients, and the Sialorrhea Scoring Scale (SSS), initially developed for Parkinson's disease patients. Sialorrhea was rated in 69 ALS consecutive patients by four evaluators: two neurologists, one nurse and one speech therapist. Inter-rater reliability was evaluated by the light kappa coefficient and intra-rater reliability by the weighted kappa coefficient. We also compared patients' and caregivers' answers. Results demonstrated that the two scales present a high inter-/intra-rater reliability: weighted kappas were 0.85 for both scales and light kappas 0.89 for the OSS and 0.88 for the SSS. Both scales also showed a good intra-profession reliability (OSS kappa = 0.84; SSS kappa = 0.79) and agreement between patients' and caregivers' answers. The SSS showed a higher responsiveness compared to OSS. In conclusion, both Oral Secretion Scale and Sialorrhea Scoring Scale are reliable tools to measure sialorrhea in ALS patients. Because of the wide range of salivation degrees, SSS may be more sensitive as a tool to evaluate treatments in patients with severe hypersialorrhea.


title: A Phosphatidylserine Source of Docosahexanoic Acid Improves Neurodevelopment and Survival of Preterm Pigs.

text: The amount, composition, and sources of nutrition support provided to preterm infants is critical for normal growth and development, and particularly for structural and functional neurodevelopment. Although omega-3 long chain polyunsaturated fatty acids (LC-PUFA), and particularly docosahexanoic acid (DHA), are considered of particular importance, results from clinical trials with preterm infants have been inconclusive because of ethical limitations and confounding variables. A translational large animal model is needed to understand the structural and functional responses to DHA. Neurodevelopment of preterm pigs was evaluated in response to feeding formulas to term-equivalent age supplemented with DHA attached to phosphatidylserine (PS-DHA) or sunflower oil as the placebo. Newborn term pigs were used as a control for normal in utero neurodevelopment. Supplementing formula with PS-DHA increased weight of the brain, and particularly the cerebellum, at term-equivalent age compared with placebo preterm pigs (P's < 0.10 and 0.05 respectively), with a higher degree of myelination in all regions of the brain examined (all p < 0.06). Brains of pigs provided PS-DHA were similar in weight to newborn term pigs. Event-related brain potentials and performance in a novel object recognition test indicated the PS-DHA supplement accelerated development of sensory pathways and recognition memory compared with placebo preterm pigs. The PS-DHA did not increase weight gain, but was associated with higher survival. The benefits of PS-DHA include improving neurodevelopment and possibly improvement of survival, and justify further studies to define dose-response relations, compare benefits associated with other sources of DHA, and understand the mechanisms underlying the benefits and influences on the development of other tissues and organ systems.


title: Initial use of supplementary oxygen for trauma patients: a systematic review.

text: OBJECTIVE This systematic review aimed to identify and describe the evidence for supplementary oxygen for spontaneously breathing trauma patients, and for high (0.60-0.90) versus low (0.30-0.50) inspiratory oxygen fraction (FiO2) for intubated trauma patients in the initial phase of treatment. METHODS Several databases were systematically searched in September 2017 for studies fulfilling the following criteria: trauma patients (Population); supplementary oxygen/high FiO2 (Intervention) versus no supplementary oxygen/low FiO2 (Control) for spontaneously breathing or intubated trauma patients, respectively, in the initial phase of treatment; mortality, complications, days on mechanical ventilation and/or length of stay (LOS) in hospital/intensive care unit (ICU) (Outcomes); prospective interventional trials (Study design). Two independent reviewers screened and identified studies and extracted data from included studies. RESULTS 6142 citations were screened with an inter-rater reliability (Cohen's kappa) of 0.88. One interventional trial of intubated trauma patients was included. 68 trauma patients were randomised to receive an FiO2 of 0.80 (intervention group) or 0.50 (control group) during mechanical ventilation (first 6 hours). There was no significant difference in hospital or ICU LOS between the groups. No patient died in either group. Another interventional trial, not strictly fulfilling the inclusion criteria, was presented for descriptive purposes. 21 trauma patients were alternately assigned to two types of mechanical ventilation (first 48 hours), both aiming at an FiO2 of 0.40, but resulted in estimated mean FiO2s of 0.45 (intervention group) and 0.60 (control group). No difference in days on mechanical ventilation was found. Two patients in the control group died, none in the intervention group. No prospective, interventional trials on spontaneously breathing trauma patients were identified. CONCLUSIONS Evidence for the use of supplementary oxygen for spontaneously breathing trauma patients is lacking, and the evidence for low versus high FiO2 for intubated trauma patients is limited. PROSPERO REGISTRATION NUMBER 42016050552.


title: Is ileostomy always necessary following rectal resection for deep infiltrating endometriosis?

text: OBJECTIVE To verify the hypothesis that in most patients bowel segmental resection to treat endometriosis can be safely performed without creation of a stoma and to discuss the limitations of this statement. DESIGN Retrospective study (Canadian Task Force classification III). SETTING Tertiary referral center. PATIENTS Forty-one women with sigmoid and rectal endometriotic lesions who underwent segmental resection. INTERVENTION Segmental resection procedures performed between 2004 and 2011. Patient demographic, operative, and postoperative data were compared. MEASUREMENTS AND MAIN RESULTS Sigmoid resection was performed in 6 patients (15%), and rectal anterior resection in 35 patients (high in 21 patients [51%], and low, i.e., <10 cm from the anal verge, in 14 [34%]). In 4 patients a temporary ileostomy was created. There was 1 anastomotic leak (2.4%), in a patient with an unprotected anastomosis, which was treated via laparoscopic surgery and creation of a temporary ileostomy. Other postoperative complications included hemoperitoneum, pelvic abscess, pelvic collection, and a ureteral vaginal fistula, in 1 patient each (all 2.4%). CONCLUSION A protective stoma may be averted in low anastomosis if it is >5 cm from the anal verge and there are no adverse intraoperative events.


title: Efficacy of Indigo Naturalis in a Multicenter Randomized Controlled Trial of Patients With Ulcerative Colitis.

text: BACKGROUND & AIMS Indigo naturalis (IN) is a traditional Chinese medicine that contains ligands for the aryl hydrocarbon receptor and promotes regeneration of the mucosa by inducing production of interleukin 22. IN might induce mucosal healing in patients with ulcerative colitis (UC). We performed a randomized controlled trial to investigate the safety and efficacy of IN in patients with UC. METHODS We performed a multicenter, double-blind trial evaluating the safety of 86 patients in Japan with active UC (Mayo scores of 6 or more), enrolled from March 30 through December 27, 2016. Patients were randomly assigned to groups and given a daily dose of 0.5, 1.0, or 2.0 g IN or placebo (1:1:1:1 ratio) for 8 weeks. The primary endpoint was the rate of clinical response at week 8, defined as a 3-point decrease in the Mayo score and a decrease of at least 30% from baseline, with a decrease of at least 1 point for the rectal bleeding subscore or absolute rectal bleeding score of 0-1. The main secondary endpoint was the rate of clinical remission at week 8, defined as a Mayo score or ≤2 and no subscores with a value >1. Mucosal healing was also assessed at week 8. RESULTS The trial was terminated because of an external reason: a report of pulmonary arterial hypertension in a patient who used self-purchased IN for 6 months. In the intent-to-treat analysis, we observed a significant, dose-dependent linear trend in proportions of patients with clinical responses (13.6% with a clinical response to placebo; 69.6% to 0.5 g IN; 75.0% to 1.0 g IN; and 81.0% to 2.0 g IN) (Cochran-Armitage trend test P < .0001 compared with placebo). Proportions of patients in clinical remission at week 8 were significantly higher in the 1.0 g IN group (55.0%, P = .0004) and the 2.0 g IN group (38.1%, (P = .0093) than in the placebo group (4.5%). Proportions of patients with mucosal healing were 13.6% in the placebo group, 56.5% in the 0.5 g IN group, 60.0% in the 1.0 g IN group, and 47.6% in the 2.0 g IN group (P = .0278 compared with placebo). Although mild liver dysfunction was observed in 10 patients who received IN, no serious adverse events were observed. CONCLUSIONS In a randomized, placebo-controlled trial, we found 8 weeks of IN (0.5-2.0 g per day) to be effective in inducing a clinical response in patients with UC. However, IN should not yet be used because of the potential for adverse effects, including pulmonary arterial hypertension. Clinical Trials Registry no: UMIN000021439 (http://www.umin.ac.jp/ctr/).


title: Stress hormones predict a host superspreader phenotype in the West Nile virus system.

text: Glucocorticoid stress hormones, such as corticosterone (CORT), have profound effects on the behaviour and physiology of organisms, and thus have the potential to alter host competence and the contributions of individuals to population- and community-level pathogen dynamics. For example, CORT could alter the rate of contacts among hosts, pathogens and vectors through its widespread effects on host metabolism and activity levels. CORT could also affect the intensity and duration of pathogen shedding and risk of host mortality during infection. We experimentally manipulated songbird CORT, asking how CORT affected behavioural and physiological responses to a standardized West Nile virus (WNV) challenge. Although all birds became infected after exposure to the virus, only birds with elevated CORT had viral loads at or above the infectious threshold. Moreover, though the rate of mortality was faster in birds with elevated CORT compared with controls, most hosts with elevated CORT survived past the day of peak infectiousness. CORT concentrations just prior to inoculation with WNV and anti-inflammatory cytokine concentrations following viral exposure were predictive of individual duration of infectiousness and the ability to maintain physical performance during infection (i.e. tolerance), revealing putative biomarkers of competence. Collectively, our results suggest that glucocorticoid stress hormones could directly and indirectly mediate the spread of pathogens.


title: Outcomes of high-volume bariatric surgery in the public system.

text: BACKGROUND Bariatric surgery has not been widely used in the Australian public health system. As obesity is strongly associated with socio-economic status, excluding its use from the public system will deny many of the most in-need access to a potentially very effective treatment. Alternatively, with rigorous follow-up and behavioural change requirements, highly successful outcomes in the private system may not translate to the public system. METHODS The Alfred Hospital rapidly expanded bariatric surgery from 2007. A 6-year prospective follow-up study was conducted with annual review of weight, co-morbidities, retention in follow-up, serum HbA1c, quality of life and patient satisfaction. RESULTS There were 1453 patients. Procedures were predominantly laparoscopic-adjustable gastric bands (n = 861). Patient details were age 49 ± 11 years, body mass index 50.7 ± 11.2 kg/m(2) and weight 139.0 ± 30.2 kg. There was no mortality, and mean length of stay was 1.1 ± 1.2 days. Follow-up was 98% (1 year) and 85% (6 years). Weight loss was 22 ± 13.1 kg (32.8 ± 18% excess weight loss) at 1 and 30.1 ± 16.8 kg (60 ± 28%) at 6 years. The mean number of co-morbidities was 4.2 ± 1.1 with significant improvements observed. Patient satisfaction was 7.7 ± 2.3 out of 10. Mental and physical summary scores (SF-36) improved from 41.02 ± 13.17 to 45.50 ± 13.27 (P < 0.001) and 33.97 ± 10.53 to 44.79 ± 11.19 (P < 0.001). CONCLUSIONS Patients were older, heavier and suffered more co-morbid disease than previously reported cohorts. For the first time, excellent outcomes across a range of key quality domains in a large patient cohort have been reported in the public system. High-volume bariatric surgery in the public system is viable.


title: Retreatment strategies for recurrent and residual aneurysms after treatment with flow-diverter devices.

text: PURPOSE The management of residual or persistent intracranial aneurysms after flow-diversion therapy is not well defined in the literature. In this multicentric study, we report clinical and angiographic outcomes of 11 patients that underwent retreatment for 12 aneurysms initially treated with flow-diverter stents. METHODS The median patient age was 53 years. Aneurysms (median size, 7.3 mm) were located at the internal carotid artery in 9 cases, and at the posterior circulation in 3. Treatment strategies, complications, and angiographic outcome were retrospectively assessed. RESULTS Retreatment was feasible in all cases and performed by overlapping flow-diverter implantation. Overall, 12 side vessels were covered during retreatment, whereof 10 (83.3%) remained patent until mid-term follow-up. There were no further technical or symptomatic complications and no treatment-related morbidity. Angiographic follow-up (median, 17 months) showed improved aneurysm occlusion in all patients. Complete or near-complete aneurysm occlusion was achieved in 11 aneurysms (91.7%). CONCLUSION Required retreatment after failed flow-diversion therapy can be performed with adequate safety and efficacy by placement of additional flow-diverter stents.


title: Assessment of anxiety-depression levels and perceptions of quality of life in adolescents with dysmenorrhea.

text: BACKGROUND This study aimed to assess the anxiety-depression levels and the perceptions of quality of life, as well as the factors affecting these variables, in adolescents with dysmenorrhea. METHODS The participants included 60 adolescents with dysmenorrhea and 41 healthy adolescents between the ages of 12 and 18. This study used the Pediatric Quality of Life Inventory (PedsQL) for assessing the perceptions of quality of life, the State-Trait Anxiety Inventory (STAI) for measuring anxiety levels, and the Children's Depression Inventory (CDI) for measuring depression levels. RESULTS It was determined that compared to healthy controls, the depression and anxiety scores were higher and the quality of life was impaired in adolescents with dysmenorrhea. In addition, it was shown that the depression and anxiety levels increased and the psychosocial health subscale scores of quality of life decreased with increasing dysmenorrhea severity. However, the likelihood of dysmenorrhea was found to be higher with increasing depression scores, while the anxiety levels had no effect on dysmenorrhea. CONCLUSION In dysmenorrhea management, it is important to enhance awareness among pediatric clinicians and gynecologists regarding the associations between dysmenorrhea and mental problems.


Virtual Nation: Telemedicine's Breakout Moment.


title: Resection of Sentinel Lymph Nodes by an Extraperitoneal Minilaparoscopic Approach Using Indocyanine Green for Uterine Malignancies: A Preclinical Comparative Study.

text: Background The sentinel lymph node (SLN) concept might minimize surgical aggressiveness in cervical and endometrial malignancies. The aim of the study was to test the feasibility and reliability of minilaparoscopic extraperitoneal SLN excision after indocyanine green (ICG) cervical injection using a high-definition near infrared (NIR) imaging system in an in vivo porcine model. The same procedure was performed using conventional laparoscopic instruments and both outcomes were compared. Methods Twenty-four animals were equally and randomly divided into a minilaparoscopic group (group A) and a 5-mm conventional laparoscopic group (group B). A high-definition NIR imaging system and a 30° ICG endoscope were used. First, ICG (0.5 mL) was injected in the paracervical region. The SLN coloring time was recorded. An extraperitoneal approach to the SLN was executed with the same CO2 retropneumoperitoneum pressures (10 mm Hg). In both groups, the times for SLN localization and excision, as well as complications, were registered. Finally, a laparotomy was then done to evaluate whether any stained SLN still remained. The same surgical team performed all experiments. Results SLNs were identified and extraperitoneally excised in all animals without major complications. The SLN localization varied between animals from external iliac to preaortic regions. The surgical times were shorter with minilaparoscopy (39.3 ± 13 minutes) than with conventional 5-mm instruments (51.3 ± 14.17 minutes; P = .042). In group B, one stained SLN remained and was only detected by laparotomy. Conclusions We confirmed the feasibility and reliability of extraperitoneal minilaparoscopic approach for identification, dissection, and excision of SLN using an NIR imaging system and ICG.


title: NB protein does not affect influenza B virus replication in vitro and is not required for replication in or transmission between ferrets.

text: The influenza B virus encodes a unique protein, NB, a membrane protein whose function in the replication cycle is not, as yet, understood. We engineered a recombinant influenza B virus lacking NB expression, with no concomitant difference in expression or activity of viral neuraminidase (NA) protein, an important caveat since NA is encoded on the same segment and initiated from a start codon just 4 nt downstream of NB. Replication of the virus lacking NB was not different to wild-type virus with full-length NB in clonal immortalized or complex primary cell cultures. In the mouse model, virus lacking NB induced slightly lower IFN-α levels in infected lungs, but this did not affect virus titres or weight loss. In ferrets infected with a mixture of viruses that did or did not express NB, there was no fitness advantage for the virus that retained NB. Moreover, virus lacking NB protein was transmitted following respiratory droplet exposure of sentinel animals. These data suggest no role for NB in supporting replication or transmission in vivo in this animal model. The role of NB and the nature of selection to retain it in all natural influenza B viruses remain unclear.


title: Perspectives on Cardiopulmonary Critical Care for COVID-19 Patients: From Members of the American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation.

text: The coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), marks a global event that will permanently reshape implementation of intensive care medicine. As of June 4, 2020, there are 6,606,455 reported cases of COVID-19 including 388,556 fatalities spanning 215 countries and territories, although epidemiological data remain incomplete. Early autopsy reports emphasize proximal airway and distal airspace involvement, including alveolar epithelial inflammation and capillary thickening.


title: Hapivirins and diprovirins: novel θ-defensin analogs with potent activity against influenza A virus.

text: θ-Defensins are cyclic octadecapeptides found in nonhuman primates whose broad antiviral spectrum includes HIV-1, HSV-1, severe acute respiratory syndrome coronavirus, and influenza A virus (IAV). We previously reported that synthetic θ-defensins called retrocyclins can neutralize and aggregate various strains of IAV and increase IAV uptake by neutrophils. This study describes two families of peptides, hapivirins and diprovirins, whose design was inspired by retrocyclins. The goal was to develop smaller partially cyclic peptides that retain the antiviral activity of retrocyclins, while being easier to synthesize. The novel peptides also allowed for systemic substitution of key residues to evaluate the role of charge or hydrophobicity on antiviral activity. Seventy-two hapivirin or diprovirin peptides are described in this work, including several whose anti-IAV activity equals or exceeds that of normal α- or θ-defensins. Some of these also had strong antibacterial and antifungal activity. These new peptides were active against H3N2 and H1N1 strains of IAV. Structural features imparting strong antiviral activity were identified through iterative cycles of synthesis and testing. Our findings show the importance of hydrophobic residues for antiviral activity and show that pegylation, which often increases a peptide's serum t(1/2) in vivo, can increase the antiviral activity of DpVs. The new peptides acted at an early phase of viral infection, and, when combined with pulmonary surfactant protein D, their antiviral effects were additive. The peptides strongly increased neutrophil and macrophage uptake of IAV, while inhibiting monocyte cytokine generation. Development of modified θ-defensin analogs provides an approach for creating novel antiviral agents for IAV infections.


title: A model to measure lymphatic drainage from the eye.

text: Intraocular pressure (IOP) is the most important risk factor for glaucoma development and progression. Most anti-glaucoma treatments aim to lower IOP by enhancing aqueous humor drainage from the eye. Aqueous humor drainage occurs via well-characterized trabecular meshwork (TM) and uveoscleral (UVS) pathways, and recently described ciliary body lymphatics. The relative contribution of the lymphatic pathway to aqueous drainage is not known. We developed a sheep model to quantitatively assess lymphatic drainage along with TM and UVS outflows. This study describes that model and presents our initial findings. Following intracameral injection of (125)I-bovine serum albumin (BSA), lymph was continuously collected via cannulated cervical lymphatic vessels and the thoracic lymphatic duct over either a 3-h or 5-h time period. In the same animals, blood samples were collected from the right jugular vein every 15 min. Lymphatic and TM drainage were quantitatively assessed by measuring (125)I-BSA in lymph and plasma, respectively. Radioactive tracer levels were also measured in UVS and "other" ocular tissue, as well as periocular tissue harvested 3 and 5 h post-injection. Tracer recovered from UVS tissue was used to estimate UVS drainage. The amount of (125)I-BSA recovered from different fluid and tissue compartments was expressed as a percentage of total recovered tracer. Three hours after tracer injection, percentage of tracer recovered in lymph and plasma was 1.64% ± 0.89% and 68.86% ± 9.27%, respectively (n = 8). The percentage of tracer in UVS, other ocular and periocular tissues was 19.87% ± 5.59%, 4.30% ± 3.31% and 5.32% ± 2.46%, respectively. At 5 h (n = 2), lymphatic drainage was increased (6.40% and 4.96% vs. 1.64%). On the other hand, the percentage of tracer recovered from UVS and other ocular tissue had decreased, and the percentage from periocular tissue showed no change. Lymphatic drainage increased steadily over the 3 h post-injection period, while TM drainage increased rapidly - reaching a plateau at 30 min. This quantitative sheep model enables assessment of relative contributions of lymphatic drainage, TM and UVS outflows, and may help to better understand the effects of glaucoma agents on outflow pathways.


Underutilization of Healthcare for strokes during the COVID-19 outbreak.


title: Is there a dysbiosis in individuals with a neurodevelopmental disorder compared to controls over the course of development? A systematic review.

text: Many scientific papers reported that an unbalanced gut microbiota could lead to or worsen neurodevelopmental disorders (NDD). A dysbiosis may then be observed in the course of development and mark a dysfunction within what is called the gut-brain axis. The aim of this systematic review is to investigate potential evidence of dysbiosis in children and young adults with NDD compared to controls. Using the PRISMA guidelines we systematically reviewed studies that compared the gut microbiota in NDD participants (with an age inferior to thirty) to the gut microbiota of controls, regardless of the data analysis methods used. The MEDLINE, Scopus and PsycINFO databases were searched up to September 2018. 31 studies with a total sample size of 3002 ASD (Autism Spectrum Disorder) and 84 ADHD (Attention Deficit Hyperactivity Disorder) participants were included in this systematic review. Independent data extraction and quality assessment were conducted. The quality of the studies was rated from low to high. Population characterization and experimental methods were highly heterogeneous in terms of the data available, selection of criteria, and dysbiosis measurement. A dysbiosis was reported in 28 studies in terms of either diversity, bacterial composition or metabolome dysfunction. Due to heterogeneity, a quantitative synthesis was not applicable. In this paper, we discuss the different biases to understand the complexity of microbiota and neurodevelopmental disorders to provide leads for future cohort studies looking to answer the questions raised by the trillions of microorganisms that inhabit key body niches.


title: Hybrid laparo-endoscopic single port transperitoneal right adrenalectomy.

text: Laparoscopic surgery is a preferable technique for adrenalectomy. Laparo-endoscopic single port surgery (LESS) is one of the newest areas in minimally invasive surgery. The development of the technology has made many surgical procedures less invasive. In this paper, we report hybrid laparo-endoscopic single port transperitoneal right adrenalectomy for a non-functional adrenal mass.


title: Effects of virtual reality simulator training method and observational learning on surgical performance.

text: BACKGROUND Virtual reality (VR) simulators and Web-based instructional videos are valuable supplemental training resources in surgical programs, but it is unclear how to optimally integrate them into minimally invasive surgical training. METHODS Medical students were randomized to proficiency-based training on VR laparoscopy and endoscopy simulators by two different methods: proctored training (automated simulator feedback plus human expert feedback) or independent training (simulator feedback alone). After achieving simulator proficiency, trainees performed a series of laparoscopic and endoscopic tasks in a live porcine model. Prior to their entry into the animal lab, all trainees watched an instructional video of the procedure and were randomly assigned to either observe or not observe the actual procedure before performing it themselves. The joint effects of VR training method and procedure observation on time to successful task completion were evaluated with Cox regression models. RESULTS Thirty-two students (16 proctored, 16 independent) completed VR training. Cox regression modeling with adjustment for relevant covariates demonstrated no significant difference in the likelihood of successful task completion for independent versus proctored training [Hazard Ratio (HR) 1.28; 95% Confidence Interval (CI) 0.96-1.72; p=0.09]. Trainees who observed the actual procedure were more likely to be successful than those who watched the instructional video alone (HR 1.47; 95% CI 1.09-1.98; p=0.01). CONCLUSIONS Proctored VR training is no more effective than independent training with respect to surgical performance. Therefore, time-consuming human expert feedback during VR training may be unnecessary. Instructional videos, while useful, may not be adequate substitutes for actual observation when trainees are learning minimally invasive surgical procedures.


title: Seasonality of respiratory viral identification varies with age and Aboriginality in metropolitan Western Australia.

text: BACKGROUND Viral respiratory infections are a major cause of pediatric illness. It is not known whether seasonality of viruses differs between Aboriginal and non-Aboriginal children of varying ages. METHODS We extracted data on respiratory syncytial virus (RSV), influenza viruses A and B, parainfluenza virus types 1, 2, and 3 and adenovirus identified through cell culture or direct immunofluorescence between 1997 and 2005 from nasopharyngeal or throat specimens at Western Australia's only pediatric hospital. We used harmonic analysis in generalized linear models to examine the variations in seasonality of these viruses with Aboriginality and age. RESULTS A respiratory virus was identified in 32% of 32 741 specimens. RSV (18.6%), influenza virus A (5.1%), and parainfluenza virus 3 (4.0%) were most common. The median age at time of identification was lower in Aboriginal children than non-Aboriginal for all viruses except RSV. Seasonality differed between all viruses and varied with age for RSV, influenza viruses and adenovirus. Influenza viruses A and B activity peaked earlier in Aboriginal than non-Aboriginal children during 1997, 1998, and 2002. CONCLUSIONS All viruses showed distinct seasonality. Variability with age and different seasonal patterns for influenza viruses in Aboriginal children compared with non-Aboriginal children has to be taken into account when identifying target groups and timing for vaccination and other interventions.


title: Single-stage endovascular treatment in patients with severe extracranial large vessel stenosis and concomitant ipsilateral unruptured intracranial aneurysm.

text: PURPOSE We aimed to evaluate the safety and effectiveness of single-stage endovascular treatment in patients with severe extracranial large vessel stenosis and concomitant ipsilateral unruptured intracranial aneurysm. METHODS Hospital database was screened for patients who underwent single-stage endovascular treatment between February 2008 and June 2013 and seven patients were identified. The procedures included unilateral carotid artery stenting (CAS) (n=4), bilateral CAS (n=2), and proximal left subclavian artery stenting (n=1) along with ipsilateral intracranial aneurysm treatment (n=7). The mean internal carotid artery stenosis was 81.6% (range, 70%-95%), and the subclavian artery stenosis was 90%. All aneurysms were unruptured. The mean aneurysm diameter was 7.7 mm (range, 5-13 mm). The aneurysms were ipsilateral to the internal carotid artery stenosis (internal carotid artery aneurysm) in five patients, and in the anterior communicating artery in one patient. The patient with subclavian artery stenosis had a fenestration aneurysm in the proximal basilar artery. Stenting of the extracranial large vessel stenosis was performed before aneurysm treatment in all patients. In two patients who underwent bilateral CAS, the contralateral carotid artery stenosis, which had no aneurysm distally, was treated initially. RESULTS There were no procedure-related complications or technical failure. The mean clinical follow-up period was 18 months (range, 9-34 months). One patient who underwent unilateral CAS experienced contralateral transient ischemic attack during the clinical follow-up. There was no restenosis on six-month follow-up angiograms, and all aneurysms were adequately occluded. CONCLUSION A single-stage procedure appears to be feasible for treatment of patients with severe extracranial large vessel stenosis and concomitant ipsilateral intracranial aneurysm.


title: Different Solutions for Damaged Nasotracheal Tube during Maxillofacial Surgery: A Case Series.

text: Difficult airway management and intraoperative tube damage are important problems during maxillofacial surgery. Damage occurs frequently during the surgery, and the anesthesiologist must be ready to find a quick and safe solution. Replacing the damaged endotracheal tube involves additional difficulties, and various factors must be evaluated. We present two cases of nasotracheal tube (NTT) damage suffered during maxillofacial surgery. The different intraoperative conditions led us to decide for the replacement of NTT in one case and for conservative action in the other. The purpose of this article is to highlight the difficulties that the anesthesiologist may have in deciding quickly what is the best approach in case the endotracheal tube is damaged during maxillofacial surgery and possibly try to provide a rapid and safe solution for the situation.


title: Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects.

text: MicroRNAs (miRNAs) are being developed to enhance tissue regeneration. Here we show that a hyperbranched polymer with high miRNA-binding affinity and negligible cytotoxicity can self-assemble into nano-sized polyplexes with a 'double-shell' miRNA distribution and high transfection efficiency. These polyplexes are encapsulated in biodegradable microspheres to enable controllable two-stage (polyplexes and miRNA) delivery. The microspheres are attached to cell-free nanofibrous polymer scaffolds that spatially control the release of miR-26a. This technology is used to regenerate critical-sized bone defects in osteoporotic mice by targeting Gsk-3β to activate the osteoblastic activity of endogenous stem cells, thus addressing a critical challenge in regenerative medicine of achieving cell-free scaffold-based miRNA therapy for tissue engineering.


title: Minimally invasive preperitoneal balloon tamponade and abdominal aortic junctional tourniquet versus open packing for pelvic fracture-associated hemorrhage: Not all extrinsic compression is equal.

text: BACKGROUND Minimally invasive preperitoneal balloon tamponade (PPB) and abdominal aortic junctional tourniquets (AAJT) have been proposed as alternatives to open preperitoneal packing (OP) for the management of pelvic fracture-associated hemorrhage. We hypothesized that the PPB (SpaceMaker Pro) and AAJT would result in similar rates of survival and blood loss versus OP. METHODS Thirty-two swine underwent creation of a combined open-book pelvic fracture and major iliac vascular injuries. Animals were randomized to no intervention (n = 7), OP (n = 10), PPB (n = 9), or AAJT (n = 6) at a mean arterial pressure <40 mm Hg following initiation of uncontrolled hemorrhage. Survival (up to 60 minutes + 10 minutes after intervention reversal), hemodynamics, extraperitoneal pressures, blood loss, and associated complications were compared between groups. RESULTS Prior to injury, no difference was measured between groups for weight, hemodynamics, lactate, and hematocrit (all p > 0.05). The injury was uniformly lethal without intervention, with survival time (mean) of 5 minutes, peak preperitoneal pressure (PP) of 14 mm Hg, blood loss of 960 g, and peak lactate of 2.6 mmol/L. Survival time was 44 minutes with OP versus 60 minutes with PPB and AAJT (p < 0.01). Peak PP (mm Hg) was 19 with OP, 23 with PPB, and 23 with AAJT (p > 0.05). Blood loss (g) was 850 with OP, 930 with PPB, and 600 with AAJT (p > 0.05). Peak lactate (mmol/L) was 3.3 with OP, 4.3 with PPB, and 6.3 with AAJT (p < 0.01). Only 33% of AAJT animals survived intervention reversal versus 60% for OP and 67% for PPB (p < 0.01). Necropsy revealed bowel/bladder injury in 50% of AAJT subjects versus 0% in all other arms (p < 0.01). CONCLUSION Preperitoneal balloon tamponade is a safe and potentially effective alternative to OP for the management of lethal pelvic fracture-associated hemorrhage. Abdominal aortic junctional tourniquet offers a similar survival benefit to PPB but has concerning rates of ischemia-reperfusion and compressive abdominal organ injury.


title: Third trimester-equivalent ethanol exposure causes micro-hemorrhages in the rat brain.

text: Exposure to ethanol during fetal development produces long-lasting neurobehavioral deficits caused by functional alterations in neuronal circuits across multiple brain regions. Therapeutic interventions currently used to treat these deficits are only partially efficacious, which is a consequence of limited understanding of the mechanism of action of ethanol. Here, we describe a novel effect of ethanol in the developing brain. Specifically, we show that exposure of rats to ethanol in vapor chambers during the equivalent to the third trimester of human pregnancy causes brain micro-hemorrhages. This effect was observed both at low and high doses of ethanol vapor exposure, and was not specific to this exposure paradigm as it was also observed when ethanol was administered via intra-esophageal gavage. The vast majority of the micro-hemorrhages were located in the cerebral cortex but were also observed in the hypothalamus, midbrain, olfactory tubercle, and striatum. The auditory, cingulate, insular, motor, orbital, retrosplenial, somatosensory, and visual cortices were primarily affected. Immunohistochemical experiments showed that the micro-hemorrhages caused neuronal loss, as well as reactive astrogliosis and microglial activation. Analysis with the Catwalk test revealed subtle deficits in motor function during adolescence/young adulthood. In conclusion, our study provides additional evidence linking developmental ethanol exposure with alterations in the fetal cerebral vasculature. Given that this effect was observed at moderate levels of ethanol exposure, our findings lend additional support to the recommendation that women abstain from consuming alcoholic beverages during pregnancy.


title: Outcomes for Pressure Ulcer Trials (OUTPUTs): protocol for the development of a core domain set for trials evaluating the clinical efficacy or effectiveness of pressure ulcer prevention interventions.

text: BACKGROUND Core outcome sets (COS) are being developed in many clinical areas to increase the quality and comparability of clinical trial results as well as to ensure their relevance for patients. A COS represents an agreed standardized set of outcomes that describes the minimum that should be consistently reported in all clinical trials of a defined area. It comprises a core domain set (defining what core outcomes should be measured) and a core measurement set (defining measurement/assessment instruments for each core domain). For pressure ulcer prevention trials a COS is lacking. The great heterogeneity of reported outcomes in this field indicates the need for a COS. METHODS/DESIGN The first part of this project aims to develop a core domain set by following established methods, which incorporates four steps: (1) definition of the scope, (2) conducting a scoping review, (3) organizing facilitated workshops with service users, (4) performing Delphi surveys and establishing consensus in a face-to-face meeting with different stakeholders. DISCUSSION After achieving consensus on the core domain set, further work will be undertaken to determine a corresponding core measurement set. This will lead to better pressure ulcer prevention research in the future. There are a number of methodological challenges in the field of COS development. To meet these challenges and to ensure a high-quality COS, the OUTPUTS project affiliates to current standards and works in close collaboration with international experts and with existing international service user groups. TRIAL REGISTRATION The OUTPUTs project is registered in the COMET database: ( http://www.comet-initiative.org/studies/details/283 ). Registered on 2015.


Safety of dupilumab in atopic patients during COVID-19 outbreak.


title: Dying individuals and suffering populations: applying a population-level bioethics lens to palliative care in humanitarian contexts: before, during and after the COVID-19 pandemic.

text: BACKGROUND Humanitarian crises and emergencies, events often marked by high mortality, have until recently excluded palliative care-a specialty focusing on supporting people with serious or terminal illness or those nearing death. In the COVID-19 pandemic, palliative care has received unprecedented levels of societal attention. Unfortunately, this has not been enough to prevent patients dying alone, relatives not being able to say goodbye and palliative care being used instead of intensive care due to resource limitations. Yet global guidance was available. In 2018, the WHO released a guide on 'Integrating palliative care and symptom relief into the response to humanitarian emergencies and crises'-the first guidance on the topic by an international body. AIMS This paper argues that while a landmark document, the WHO guide took a narrowly clinical bioethics perspective and missed crucial moral dilemmas. We argue for adding a population-level bioethics lens, which draws forth complex moral dilemmas arising from the fact that groups having differential innate and acquired resources in the context of social and historical determinants of health. We discuss dilemmas concerning: limitations of material and human resources; patient prioritisation; euthanasia; and legacy inequalities, discrimination and power imbalances. IMPLICATIONS In parts of the world where opportunity for preparation still exists, and as countries emerge from COVID-19, planners must consider care for the dying. Immediate steps to support better resolutions to ethical dilemmas of the provision of palliative care in humanitarian and emergency contexts will require honest debate; concerted research effort; and international, national and local ethical guidance.


title: Mathematical models of the epidemiology and control of drug-resistant TB.

text: Recent reports of extensively drug-resistant TB in South Africa have renewed concerns that antibiotic resistance may undermine progress in TB control. We review three major questions for which mathematical models elucidate the epidemiology and control of drug-resistant TB. How is multiple drug-resistant Mycobacterium tuberculosis selected for in individuals exposed to combination chemotherapy? What factors determine the prevalence of drug-resistant TB? Which interventions to prevent the spread of drug-resistant TB are effective and feasible? Models offer insight into the acquisition and amplification of drug resistance, reveal the importance of distinguishing the intrinsic and extrinsic determinants of the reproductive capacity of drug-resistant M. tuberculosis, and demonstrate the cost effectiveness of interventions for drug-resistant TB. These models also highlight knowledge gaps for which new research will improve our ability to project trends of drug resistance and develop more effective policies for its control.


Betting on Pandemic.


title: Application of a liquid chromatography-tandem mass spectrometry method to the pharmacokinetics, tissue distribution and excretion in the study of anemoside B4, a novel antiviral agent candidate, in rats.

text: A simple, sensitive and reliable LC-MS/MS method was developed and validated for the quantification of anemoside B4, a potential antiviral constituent isolated from Pulsatilla chinensis in rat plasma, tissue, bile, urine and feces. All biological samples were prepared by protein precipitation method, and ginsenoside-Rg1 was chosen as the internal standard (IS). The analyte and IS were separated using a C18 column (2.1 × 50 mm, 1.8 μm) and a mobile phase consisting of 0.1% formic acid in water (v/v) and acetonitrile running at a flow rate of 0.2 mL/min for 5 min. The multiple reaction monitoring transitions were monitored at m/z 1219.5-749.5 for anemoside B4 and 845.4-637.4 for ginsenoside-Rg1 in electrospray ionization negative mode. The calibration curve was linear in the range of 10-2000 ng/mL for all biological matrices with a lower limit of quantification of 10 ng/mL. The validated method was successfully applied to a pharmacokinetics, tissue distribution and excretion study. These preclinical data will be beneficial for further development of anemoside B4 in future studies.


title: Evaluation of short-term outcome after lung lobectomy for resection of primary lung tumors via video-assisted thoracoscopic surgery or open thoracotomy in medium- to large-breed dogs.

text: OBJECTIVE To describe clinicopathologic features of dogs that underwent lung lobectomy for resection of primary lung tumors via video-assisted thoracoscopic surgery (VATS) or open thoracotomy (OT) and to compare short-term outcomes for dogs following these procedures. DESIGN Retrospective cohort study. ANIMALS 46 medium- to large-breed dogs with primary lung tumors. PROCEDURES Medical records of dogs that underwent a lung lobectomy via VATS (n = 22) or OT (24) for resection of primary lung tumors between 2004 and 2012 were reviewed. Dogs were included if they weighed > 10 kg (22 lb) and resection of a primary lung tumor was confirmed histologically. Tumor volumes were calculated from preoperative CT scans where available. Surgical time, completeness of excision, time in the ICU, indwelling thoracic drain time, postoperative and total hospitalization time, incidence of major complications, and short-term survival rate were evaluated. RESULTS VATS was performed with a 3-port (n = 12) or 4-port (10) technique and 1-lung ventilation (22). In 2 of 22 (9%) dogs, VATS was converted to OT. All dogs survived to discharge from the hospital. There were no significant differences between the VATS and OT groups with regard to most variables. Surgery time was significantly longer for VATS than for OT (median, 120 vs 95 minutes, respectively). CONCLUSIONS AND CLINICAL RELEVANCE In medium- to large-breed dogs, short-term outcomes for dogs that underwent VATS for lung lobectomy were comparable to those of dogs that underwent OT. Further studies are required to evaluate the effects of surgical approach on indices of postoperative pain and long-term outcomes.


title: Paramyxovirus infections in hematopoietic cell transplant recipients.

text: PURPOSE OF REVIEW In hematopoietic cell transplant (HCT) recipients, paramyxovirus infections are major viral respiratory tract infections that, if they progress to lower respiratory tract infections, are associated with reduced survival rates in this population. There are important knowledge gaps regarding treatment decisions for HCT recipients with these infections and in the identification of risk factors that predict infection severity. Here, we review recent data on paramyxovirus infections in HCT recipients focusing on risk factors, new diagnostic and prognostic tools, and management including new drugs and vaccines under development. RECENT FINDINGS Multiplexed molecular assays associated with immunodeficiency scoring index for respiratory syncytial virus (RSV) have improved our understanding of the epidemiology of RSV and other paramyxovirus infections and the risk factors for worse outcomes. Novel antiviral drugs, monoclonal antibodies, and vaccines are under evaluation with mixed preliminary results. SUMMARY Advances in our knowledge of paramyxovirus infections in HCT recipients in the last two decades contributed to better strategies for management and prevention of these infections. A widespread understanding of how to stratify HCT recipients with paramyxovirus infections who would benefit most from antiviral therapy remains to be ascertained. Vaccines and new drugs under development may mitigate the burden of paramyxovirus infections.


title: Intramural Hematoma as Unexpected Complication of COVID-19 Infection.

text: Novel coronavirus disease-2019 (COVID-19) is an ominous infectious disease that seems capable to attack any organ system, leading in the most severe cases to patient death. COVID-19 has been associated with multiple cardiovascular complications of inflammatory and immune origin, leading to a wide spectrum of vascular damage, myocardial injury, stroke, and pulmonary obstruction. We report the case of a patient with COVID-19 infection who developed an acute aortic syndrome with the characteristics of aortic intramural hematoma.


title: Role of thermal ablation in the management of colorectal liver metastasis.

text: With a recent randomized prospective trial revealing that thermal ablative therapy as local tumor control improved overall survival (OS) in patients with unresectable colorectal cancer liver metastases (CRLM), thermal ablation continues to remain as an important treatment option in this patient population. Our aim of this article is to review the current role of the ablative therapy in the management of CRLM patients. Main indications for thermal ablation include (I) unresectable liver lesions; (II) in combination with hepatectomy; (III) in patients with significant medical comorbidities or poor performance status (PS); (IV) a small (<3 cm) solitary lesion, which would otherwise necessitate a major liver resection; and (V) patient preference. There are several approaches and modalities for ablative therapy, including open, percutaneous, and laparoscopic approaches, as well as radiofrequency ablation (RFA) and microwave ablation (MWA). Each approach and ablation modality have its own pros and cons. Percutaneous and laparoscopic approaches are preferred due to minimally invasive nature, yet laparoscopic approach has more benefits from thorough intraoperative ultrasound (US) exam as well as complete peritoneal staging with laparoscopy. Similarly, whereas high local tumor failure rate has been a major concern with RFA, MWA or microwave thermosphere ablation (MTA) have demonstrated significantly improved local tumor control due to homogenous tissue heating, ability to reach higher tissue temperatures, and less susceptible to the "heat-sink" effect. Although liver resection is the standard of care for CRLM, there have been some retrospective studies demonstrating similar oncological outcome between ablative therapy and surgical resection in very selected populations with small (<3 cm) solitary CRLM. Lastly, ablative therapy and liver resection should not be mutually exclusive, especially in the management of bilobar liver metastases. Concomitant ablative therapy with hepatectomy may spare the patients from having two-stage hepatectomy with less morbidity. The role of the thermal ablation will continue to evolve in patients with resectable and ablatable lesions owing to newly emerging technology, in addition to new systemic treatment options, including immunotherapy for metastatic colorectal cancer (CRC).


title: Peritoneal dialysis catheter function and survival are not adversely affected by obesity regardless of the operative technique used.

text: BACKGROUND Obesity has been considered a relative contraindication to peritoneal dialysis (PD). Surprisingly, PD catheter dysfunction rates and longevity have not been studied in the growing obese ESRD population. The aim of this study was to determine the effect of patient weight on PD catheter survival in the three insertion technique categories of advanced laparoscopy (AL), basic laparoscopy (BL), and open. METHODS We examine retrospectively collected data on 231 consecutive PD catheter insertions at the NorthShore University HealthSystem between 2004 and 2014. Three cohorts were created based on the catheter insertion technique: open, BL using selective adhesiolysis, and AL using rectus sheath tunnel, selective omentopexy, and adhesiolysis. Primary outcomes included catheter dysfunction and catheter dysfunction-free survival for each cohort by BMI: normal weight (18.5-24.9), overweight (25-29.9), obese (≥30). Nominal variables were compared using Chi-square test, continuous variables using ANOVA or Kruskal-Wallis tests, and catheter survival was assessed using the Kaplan-Meier method with log-rank test. Statistical significance was established at 0.05. RESULTS For the three BMI categories, there were no statistically significant differences in patient demographics. There were no statistically significant differences in catheter dysfunction or peri-operative complications by BMI category among all patients. This was also true in the AL cohort. Among all patients, similar 2-year dysfunction-free catheter survival was noted for normal weight, overweight, and obese patients (log-rank p = 0.79). This was also true across all insertion techniques: open (log-rank p = 0.87), BL (log-rank p = 0.41), AL (log-rank p = 0.43). In the obese cohort, the 2-year dysfunction-free catheter survival was 91.1% in AL, 83.5% in BL, and 65.7% in open (log-rank p = 0.58). CONCLUSION Obesity does not increase complications or shorten dysfunction-free PD catheter survival regardless of the operative technique used. Obesity should not be considered as a relative contraindication to PD catheter placement as it confers similar technique success to normal- and overweight individuals.


title: Toward the identification of ZDHHC enzymes required for palmitoylation of viral protein as potential drug targets.

text: Introduction: S-acylation is the attachment of fatty acids not only to cysteines of cellular, but also of viral proteins. The modification is often crucial for the protein´s function and hence for virus replication. Transfer of fatty acids is mediated by one or several of the 23 members of the ZDHHC family of proteins. Since their genes are linked to various human diseases, they represent drug targets.Areas covered: The authors explore whether targeting acylation of viral proteins might be a strategy to combat viral diseases. Many human pathogens contain S-acylated proteins; the ZDHHCs involved in their acylation are currently identified. Based on the 3D structure of two ZDHHCs, the regulation and the biochemistry of the palmitolyation reaction and the lipid and protein substrate specificities are discussed. The authors then speculate how ZDHHCs might recognize S-acylated membrane proteins of Influenza virus.Expert opinion: Although many viral diseases can now be treated, the available drugs bind to viral proteins that rapidly mutate and become resistant. To develop inhibitors for the genetically more stable cellular ZDHHCs, their binding sites for viral substrates need to be identified. If only a few cellular proteins are recognized by the same binding site, development of specific inhibitors may have therapeutic potential.


title: Periprocedural Intravenous Heparin During Endovascular Treatment for Ischemic Stroke: Results From the MR CLEAN Registry.

text: Background and Purpose- Intravenous administration of heparin during endovascular treatment for ischemic stroke may improve outcomes. However, risks and benefits of this adjunctive therapy remain uncertain. We aimed to evaluate periprocedural intravenous heparin use in Dutch stroke intervention centers and to assess its efficacy and safety. Methods- Patients registered between March 2014 and June 2016 in the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke), including all patients treated with endovascular treatment in the Netherlands, were analyzed. The primary outcome was functional outcome (modified Rankin Scale) at 90 days. Secondary outcomes were successful recanalization (extended Thrombolysis in Cerebral Infarction ≥2B), symptomatic intracranial hemorrhage, and mortality at 90 days. We used multilevel regression analysis to evaluate the association of periprocedural intravenous heparin on outcomes, adjusted for center effects and prognostic factors. To account for possible unobserved confounding by indication, we analyzed the effect of center preference to administer intravenous heparin, defined as percentage of patients treated with intravenous heparin in a center, on functional outcome. Results- One thousand four hundred eighty-eight patients from 16 centers were analyzed, of whom 398 (27%) received intravenous heparin (median dose 5000 international units). There was substantial between-center variability in the proportion of patients treated with intravenous heparin (range, 0%-94%). There was no significant difference in functional outcome between patients treated with intravenous heparin and those without (adjusted common odds ratio, 1.17; 95% CI, 0.87-1.56), successful recanalization (adjusted odds ratio, 1.24; 95% CI, 0.89-1.71), symptomatic intracranial hemorrhage (adjusted odds ratio, 1.13; 95% CI, 0.65-1.99), or mortality (adjusted odds ratio, 0.95; 95% CI, 0.66-1.38). Analysis at center level showed that functional outcomes were better in centers with higher percentages of heparin administration (adjusted common odds ratio, 1.07 per 10% more heparin, 95% CI, 1.01-1.13). Conclusions- Substantial between-center variability exists in periprocedural intravenous heparin use during endovascular treatment, but the treatment is safe. Centers using heparin more often had better outcomes. A randomized trial is needed to further study these effects.


title: Association Between Time From Stroke Onset and Fluid-Attenuated Inversion Recovery Lesion Intensity Is Modified by Status of Collateral Circulation.

text: BACKGROUND AND PURPOSE In patients with acute stroke, the intensity of a fluid-attenuated inversion recovery (FLAIR) lesion in the region of diffusion restriction is associated with time from symptom onset. We hypothesized that collateral status as assessed by the hypoperfusion intensity ratio could modify the association between time from stroke onset and FLAIR lesion intensity. METHODS From the AX200 for ischemic stroke trial, 141 patients had appropriate FLAIR, diffusion-weighted imaging, and perfusion-weighted imaging. In the region of nonreperfused core, we calculated voxel-based relative FLAIR (rFLAIR) signal intensity. The hypoperfusion intensity ratio was defined as the ratio of the Tmax >10 s lesion over the Tmax >6 s lesion volume. A hypoperfusion intensity ratio threshold of ≤0.4 was used to dichotomize good versus poor collaterals. We studied the interaction between collateral status on the association between time from symptom onset and FLAIR intensity. RESULTS Time from symptom onset was associated with the rFLAIR intensity in the region of nonreperfused core (B=1.05; 95% confidence interval, 1.0-1.1). We identified an interaction between this association and collateral status; an association was present between time and rFLAIR intensity in patients with poor collaterals (r=0.53), but absent in patients with good collaterals (r=0.17; P=0.04). CONCLUSIONS Our findings show that the relationship between time from symptom onset and rFLAIR lesion intensity depends on collateral status. In patients with good collaterals, the development of an rFLAIR-positive lesion is less dependent on time from symptom onset compared with patients with poor collaterals.


title: Successful treatment of a giant pediatric fusiform basilar trunk aneurysm with surpass flow diverter.

text: Fusiform aneurysms present a unique challenge to traditional microsurgical and endovascular treatment because of the lack of a discernible neck and the involvement of parent vessel. Flow diversion has increasingly become the treatment of choice for fusiform aneurysms in the anterior circulation, but its results in the posterior circulation are variable. We report successful treatment of a giant fusiform upper basilar trunk aneurysm with the Surpass flow diverter in an adolescent, and discuss the potential advantages of this emerging technology in the treatment of fusiform posterior circulation aneurysms.


Investigation of primary cilia in the pathogenesis of biliary atresia.


title: Measuring protein-protein interactions by equilibrium sedimentation.

text: This unit describes basic principles and practice of sedimentation equilibrium analytical ultracentrifugation for the study of reversible protein interactions, such as the characterization of self-association, heterogeneous association, and binding stoichiometry, as well as the determination of association constants. Advanced tools such as mass conservation analysis, multiwavelength analysis, and global analysis are introduced and discussed in the context of the experimental design. A detailed protocol guiding the investigator through the experimental steps and the data analysis is available as an internet resource.


Data sharing: Make outbreak research open access.


title: Leadership qualities.

text: If you are interested in examining your leadership qualities in depth, have a look at The Campaign for Leadership website, at www.theworkfoundation.com/solutions/leader/index2.jsp , writes Ruth Williams.


title: Ischaemic stroke and ST-segment elevation myocardial infarction: fast-track single-stop approach.

text: Current management of patients with AIS relies primarily on conservative approach. Suggested streamlined fast-track single-stop approach should expedite the workflow and improve clinical outcomes. Given the broadly available interventional cardiology expertise cardiologist should play an active and sensible role in the development of new interventional concepts of care of patients with acute ischaemic stroke.


title: Prions: Roles in Development and Adaptive Evolution.

text: Prions are often considered as anomalous proteins associated primarily with disease rather than as a fundamental source of diversity within biological proteomes. Whereas this longstanding viewpoint has its genesis in the discovery of the original namesake prions as causative agents of several complex diseases, the underlying assumption of a strict disease basis for prions could not be further from the truth. Prions and the spectrum of functions they comprise, likely represent one of the largest paradigm shifts concerning molecular-encoded phenotypic diversity since identification of DNA as the principle molecule of heredity. The ability of prions to recruit similar proteins to alternate conformations may engender a reservoir of diversity supplementing the genetic diversity resulting from stochastic mutations of DNA and subsequent natural selection. Here we present several currently known prions and how many of their functions as well as modes of transmission are intricately linked to adaptation from an evolutionary perspective. Further, the stability of some prion conformations across generations indicates that heritable prion-based adaptation is a reality.


title: Collection and motif-based prediction of phosphorylation sites in human viruses.

text: Although various databases have been established that are designed to compile an ever-growing list of protein phosphorylation sites in plants and animals, no such repository exists for viruses. Here, we developed the viral posttranslational modification (virPTM) database, which contains a comprehensive list of 329 accurately localized phosphorylation sites in proteins from 52 human viruses published between 1986 and the present. Additionally, to aid in the detection of new viral phosphorylation sites, we used the scan-x tool to make thousands of high-specificity serine, threonine, and tyrosine phosphorylation predictions in 229 viruses that replicate in human cells. By cross-validating our prediction results with the literature-based entries in the virPTM database, we highlight the effectiveness of the scan-x tool with viral data and extrapolate the existence of at least 4000 as yet unidentified phosphorylation sites on hundreds of viral proteins. Together, these results imply a substantial role for human kinases in mediating viral protein functions and suggest, more generally, that viral primary structure may provide important clues to aid in the rational design of therapeutic agents.


title: Epidemiologic and clinical features of non-polio enteroviral infections in northern Taiwan in 2008.

text: BACKGROUND Non-polio enteroviruses may cause different diseases, including herpangina, hand-foot-mouth disease (HFMD), meningitis, and nonspecific febrile illness; and cause epidemic outbreak annually. This study delineates the diversity of clinical presentations based on different serotypes and different groups [human enterovirus (HEV)-A and HEV-B] of enteroviruses (EVs) during the 2008 epidemic in National Taiwan University Hospital (NTUH). METHODS We retrospectively identified patients younger than 18 years who had positive isolates of non-polio EV in throat swabs, rectal swabs, or cerebrospinal fluid, in NTUH from January 1 to December 31, 2008. For serotyping, immunofluorescence assay and polymerase chain reaction followed by viral structure protein-1 sequencing were applied. We analyzed and compared their clinical features among different serotypes and different groups of EVs. RESULTS Among 172 patients who were enrolled, 16 serotypes were identified. The major serotype in NTUH was EV71 (25.6%) followed by coxsackievirus A (CA)16 and coxsackievirus B (CB)4. EV71 manifested mostly as HFMD (89%) and was complicated with encephalomyelitis in three patients. Serotypes of HFMD included EV71 (70%), CA16 (27%), CA4, and CA6. Serotypes of herpangina were heterogeneous, and the major serotype was CA2 (35.7%) followed by CB4 (23.8%). Aseptic meningitis was entirely caused by HEV-B and mostly infected by echovirus 30 (50%). Among children with EV-related respiratory tract infection, CB4 (32%) was dominant in upper respiratory tract infection, whereas echovirus 4 (71%) was the major cause of lower respiratory tract infection. Cases of HEV-A were significantly younger than the cases of HEV-B (p = 0.04). Multivariate analysis revealed that the most significant factor associated with hospitalization is HEV-B (odds ratio, 2.2; 95% confidence interval, 1.1-4.2; p = 0.02). CONCLUSIONS At least 16 serotypes circulated in northern Taiwan in 2008. EV71 is the predominant strain in this outbreak. All patients with HFMD were infected by HEV-A, but HEV-B was associated with a higher rate of hospitalization and aseptic meningitis, which should be a cause of alert regarding public health.


title: Randomized controlled trial of EndoWrist-enabled robotic versus human laparoendoscopic single-site access surgery (LESS) in the porcine model.

text: INTRODUCTION A robotic laparoendoscopic single-site access surgery (R-LESS) platform that incorporates the EndoWrist function of robotic instruments may provide better triangulation and retraction during LESS. The aim of the study is to assess if R-LESS is feasible with standard robotic instruments via a single incision and whether the approach could reduce the difficulty of the procedure and confer additional benefits over conventional LESS. METHODS This was a prospective randomized controlled study investigating the workload performance, efficacy, and risks of performing R-LESS when compared with human LESS (H-LESS) in a survival porcine model for cholecystectomy and gastrojejunostomy. The primary outcome is the NASA task load index. Secondary outcomes included the difficulty of the procedures, procedural time, morbidities, and mortalities. RESULTS Twenty-four cholecystectomies and gastrojejunostomies using the R-LESS or H-LESS approach (12:12) were performed. None of the swine suffered from procedural adverse events and none of the procedures required conversion. In both the cholecystectomy and gastrojejunostomy groups, R-LESS was associated with significantly lower NASA task load index (P < 0.001) and reduced difficulties in various steps of the procedures. No differences in the overall procedure times of the two procedures were observed (P = 0.315). CONCLUSION The R-LESS approach significantly reduced the workload and difficulties of LESS cholecystectomies and gastrojejunostomies. A dedicated single-site platform that could reduce instrument clashing while retaining the EndoWrist function is eagerly awaited.


Covid-19: Government must change course or risk further wave of infections, scientists warn.