docid: pdwptphx

title: Seroprevalences to viral pathogens in free-ranging and captive cheetahs (Acinonyx jubatus) on Namibian Farmland.

text: Cheetah populations are diminishing rapidly in their natural habitat. One reason for their decline is thought to be a high susceptibility to (infectious) diseases because cheetahs in zoos suffer from high disease-induced mortality. Data on the health status of free-ranging cheetahs are scarce, and little is known about their exposure and susceptibility to infectious diseases. We determined seroprevalences to nine key viruses (feline herpesvirus 1, feline calicivirus, feline parvovirus, feline coronavirus, canine distemper virus, feline immunodeficiency virus [FIV], puma lentivirus, feline leukemia virus, and rabies virus) in 68 free-ranging cheetahs on east-central Namibian farmland, 24 nonvaccinated Namibian captive cheetahs, and several other wild carnivore species and conducted necropsies of cheetahs and other wild carnivores. Eight of 11 other wild carnivores were seropositive for at least one of the viruses, including the first record of an FIV-like infection in a wild felid west of the Kalahari, the caracal (Felis caracal). Seroprevalences of the free-ranging cheetahs were below 5% for all nine viruses, which is significantly lower than seroprevalences in nonvaccinated captive cheetahs and those for five of seven viruses in previously studied free-ranging cheetahs from north-central Namibia (L. Munson, L. Marker, E. Dubovi, J. A. Spencer, J. F. Evermann, and S. J. O'Brien, J. Wildl. Dis. 40:23-31, 2004). There was no clinical or pathological evidence of infectious diseases in living or dead cheetahs. The results suggest that while free-ranging wild carnivores may be a source of pathogens, the distribution of seroprevalences across studies mirrored local human population density and factors associated with human habitation, probably reflecting contact opportunities with (nonvaccinated) domestic and feral cats and dogs. They also suggest that Namibian cheetahs respond effectively to viral challenges, encouraging consistent and sustainable conservation efforts.


Covid-19: Confidentiality agreements allow antibody test manufacturers to withhold evaluation results.


title: COVID-19, Australia: Epidemiology Report 5 (Reporting week ending 19:00 AEDT 29 February 2020).

text: This is the fifth epidemiological report for coronavirus disease 2019 (COVID-19), reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 29 February 2020. It includes data on COVID-19 cases diagnosed in Australia, the international situation and a review of current evidence.


title: Technical innovation: Intragastric Single Port Sleeve Gastrectomy (IGSG). A feasibility survival study on porcine model.

text: PURPOSE To perform technically the laparoscopic sleeve gastrectomy (LSG) using a unique Intragastric Single Port (IGSG) in animal swine model, evidencing an effective and safe procedure, optimizing the conventional technique. METHODS IGSG was performed in 4 minipigs, using a percutaneous intragastric single port located in the pre-pyloric region. The gastric stapling of the greater curvature started from the pre-pyloric region towards the angle of His by Endo GIA™ system and the specimen was removed through the single port. In the postoperative day 30, the animals were sacrificed and submitted to autopsy. RESULTS All procedures were performed without conversion, and all survived 30 days. The mean operative time was 42 min. During the perioperative period no complications were observed during invagination and stapling. No postoperative complications occurred. Post-mortem examination showed no leaks or infectious complications. CONCLUSION Intragastric Single Port is a feasible procedure that may be a suitable alternative technique of sleeve gastrectomy for the treatment of morbid obesity.


title: Dietary Potassium Intake and Risk of Chronic Kidney Disease Progression in Predialysis Patients with Chronic Kidney Disease: A Systematic Review.

text: The prevalence of chronic kidney disease (CKD) is increasing and dietary interventions may be a strategy to reduce this burden. In the general population, higher potassium intake is considered protective for cardiovascular health. Due to the risk of hyperkalemia in CKD, limiting potassium intake is often recommended. However, given that poor cardiovascular function can cause kidney damage, following a low-potassium diet may be deleterious for patients with CKD. The aim of this systematic review was to summarize the evidence on dietary potassium intake and CKD progression. Multiple databases were searched on 7 June 2019 and data were managed with Covidence. No intervention trials met the inclusion criteria. Eleven observational studies met the inclusion criteria (10 post hoc analyses, 1 retrospective cohort), representing 49,573 stage 1-5 predialysis patients with CKD from 41 different countries. Of the 11 studies, 6 studies reported exclusively on early CKD (stage 1-2), 4 studies separately reported analyses on both early and late (stage 3-5) CKD, and 2 studies reported exclusively on late CKD. A total of 9 studies reported risk of disease progression in early CKD; in 4 studies high potassium intake was associated with lower risk, while in 2 studies the low intake showed a higher progression of risk, and 3 studies reported no relation. In late CKD, results are mixed: 2 studies suggested benefit of higher potassium intake and 1 suggested benefit of lower potassium intake, whereas 3 studies were neutral. These results should be interpreted with caution, as considerations preventing firm conclusions include 1) the overall low range of dietary potassium intake, with all studies reporting an average intake below the 2004 Kidney Disease Outcomes Quality Initiatives guidelines, and 2) the method used to assess potassium intake in most studies (i.e., urine) in late stages of CKD. Ideally, well-controlled intervention studies are needed to understand how dietary potassium intake is linked to CKD progression.


title: The permanent catheter.

text: An elderly woman receiving hemodialysis via a right brachiocephalic arteriovenous fistula presented to the clinic for elective removal of a tunneled hemodialysis catheter inserted 5 years ago. The catheter had not been removed earlier at the patient's request. Removal was now unsuccessful in the clinic. Exploration in the operating room revealed the innominate vein had fibrosed around the length of the catheter. The procedure was abandoned, catheter cut short and the remnant left in situ. This case serves as a reminder to exercise caution if there is difficulty in removing the catheter even after the cuff is dissected free, and to remove them once a working fistula or graft is available. Failing which, the patient bears an unnecessary risk of line infection, or as in this case, the catheter may unintentionally end up what its common misnomer "perm-cath" alludes to--becoming truly "permanent."


How the Lives of Neuroradiologists and Neurosurgeons Have Been Changed by COVID-19.


title: Infarct Topography and Detection of Atrial Fibrillation in Cryptogenic Stroke: Results from CRYSTAL AF.

text: BACKGROUND Insertable cardiac monitors (ICM) have been shown to detect atrial fibrillation (AF) at a higher rate than routine monitoring methods in patients with cryptogenic stroke (CS). However, it is unknown whether there are topographic patterns of brain infarction in patients with CS that are particularly associated with underlying AF. If such patterns exist, these could be used to help decide whether or not CS patients would benefit from long-term monitoring with an ICM. METHODS In this retrospective analysis, a neuro-radiologist blinded to clinical details reviewed brain images from 212 patients with CS who were enrolled in the ICM arm of the CRYptogenic STroke And underLying AF (CRYSTAL AF) trial. Kaplan-Meier estimates were used to describe rates of AF detection at 12 months in patients with and without pre-specified imaging characteristics. Hazard ratios (HRs), 95% confidence intervals (CIs), and p values were calculated using Cox regression. RESULTS We did not find any pattern of acute brain infarction that was significantly associated with AF detection after CS. However, the presence of chronic brain infarctions (15.8 vs. 7.0%, HR 2.84, 95% CI 1.13-7.15, p = 0.02) or leukoaraiosis (18.2 vs. 7.9%, HR 2.94, 95% CI 1.28-6.71, p < 0.01) was associated with AF detection. There was a borderline significant association of AF detection with the presence of chronic territorial (defined as within the territory of a first or second degree branch of the circle of Willis) infarcts (20.9 vs. 10.0%, HR 2.37, 95% CI 0.98-5.72, p = 0.05). CONCLUSIONS We found no evidence for an association between brain infarction pattern and AF detection using an ICM in patients with CS, although patients with coexisting chronic, as well as acute, brain infarcts had a higher rate of AF detection. Acute brain infarction topography does not reliably predict or exclude detection of underlying AF in patients with CS and should not be used to select patients for ICM after cryptogenic stroke.


title: Ocular signs, diagnosis and long-term treatment with allopurinol in a cat with leishmaniasis.

text: A case of leishmaniasis with predominantly ocular signs in a cat living in Switzerland and it's treatment is reported. The cat was imported from Spain 4 years earlier and was initially presented with chronic uveitis. Laboratory test results were negative for feline immunodeficiency virus (FIV), feline infectious peritonitis (FIP), feline leukaemia virus (FeLV) and Toxoplasma gondii, as well as for Bartonella haenselae and Leishmania spp. Twenty-one months later the cat was presented again because of development of keratitis and granulomatous blepharitis. Blood cell count revealed severe Pancytopenia; Cytology of fine needle aspirates of granulomatous lesions on both upper eyelids and of a corneal smear revealed intracytoplasmatic microorganisms. A preliminary diagnosis of leishmaniasis was supported by positive polymerase chain reaction from bone marrow and eyelid samples for Leishmania infantum DNA and by a high serum antibody titer for Leishmania spp. Treatment with Allopurinol (10 mg/kg, BID) orally led to rapid improvement of ocular signs, general condition and blood cell count with complete remission of lid and corneal lesions within 2 months of treatment.


title: Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma.

text: OBJECTIVE Oesophageal adenocarcinoma (OA) incidence has risen sharply in Western countries over recent decades. Local and systemic inflammation is considered an important contributor to OA pathogenesis. Established risk factors for OA and its precursor, Barrett's oesophagus (BE), include symptomatic reflux, obesity and smoking. The role of inherited genetic susceptibility remains an area of active investigation. Here, we explore whether germline variation related to inflammatory processes influences susceptibility to BE/OA. DESIGN We used data from a genomewide association study of 2515 OA cases, 3295 BE cases and 3207 controls. Our analysis included 7863 single-nucleotide polymorphisms (SNPs) in 449 genes assigned to five pathways: cyclooxygenase (COX), cytokine signalling, oxidative stress, human leucocyte antigen and nuclear factor-κB. A principal components-based analytic framework was employed to evaluate pathway-level and gene-level associations with disease risk. RESULTS We identified a significant signal for the COX pathway in relation to BE risk (p=0.0059, false discovery rate q=0.03), and in gene-level analyses found an association with microsomal glutathione-S-transferase 1 (MGST1); (p=0.0005, q=0.005). Assessment of 36 MGST1 SNPs identified 14 variants associated with elevated BE risk (q<0.05). Four of these were subsequently confirmed (p<5.5×10-5) in a meta-analysis encompassing an independent set of 1851 BE cases and 3496 controls, and are known strong expression quantitative trait loci for MGST1. Three such variants were associated with similar elevations in OA risk. CONCLUSIONS This study provides the most comprehensive evaluation of inflammation-related germline variation in relation to risk of BE/OA and suggests that variants in MGST1 influence disease susceptibility.


title: Prospective randomized controlled trial of conventional laparoscopic versus laparoendoscopic single-site radical nephrectomy for localized renal cell carcinoma: a preliminary report regarding quality of life.

text: PURPOSE The safety and efficacy of laparoendoscopic single-site surgery (LESS) for renal cell carcinoma (RCC) have not been clearly demonstrated. We aimed to present preliminary data from a prospective randomized controlled trial of LESS versus conventional laparoscopic radical nephrectomy for localized RCC. METHODS Patients with cT1-2 RCC were randomized to LESS (n = 17) or conventional laparoscopy (n = 18) group. The short-term outcome measures assessed were perioperative morbidity, postoperative pain, and quality of recovery as determined using QoR-40. RESULTS No significant differences were observed between the LESS and conventional laparoscopy groups with respect to operative time (143.5 vs. 126.1 min, p = 0.218), blood loss (143.6 vs. 118.2 ml, p = 0.121), hospital stay (3.8 vs. 3.1 day s, p = 0.170), analgesic requirements (63.2 vs. 60.0 mg, p = 0.956), and complication rates (26.7 vs. 22.2 %, p = 0.767). However, postoperative quality of recovery was better in the LESS group (176.4 vs. 152.6, p = 0.005). Furthermore, quality of recovery, as measured using the QoR-40 dimensions of emotional state (39.9 vs. 34.0, p = 0.003), physical comfort (51.9 vs. 46.7, p = 0.034), psychological support (32.2 vs. 25.8, p = 0.003), and physical independence (20.7 vs. 17.5, p = 0.047), but not pain (31.8 vs. 29.6, p = 0.259), was significantly better in the LESS group. CONCLUSIONS The preliminary results from this prospective trial suggest that LESS could be a safe and effective treatment option for localized RCC with equivalent surgical outcomes and improved postoperative quality of recovery compared with conventional laparoscopic surgery.


Ramadan and COVID-19: A Challenge amongst Challenges.


title: Ingestible Sensors and Sensing Systems for Minimally Invasive Diagnosis and Monitoring: The Next Frontier in Minimally Invasive Screening.

text: Ingestible electronic systems that are capable of embedded sensing, particularly within the gastrointestinal (GI) tract and its accessory organs, have the potential to screen for diseases that are difficult, if not impossible to detect at an early stage using other means. Furthermore, these devices have the potential to (1) reduce labor and facility costs for a variety of procedures, (2) promote research for discovering new biomarker targets for associated pathologies, (3) promote the development of autonomous or semi-autonomous diagnostic aids for consumers, and (4) provide a foundation for topically targeted therapeutic interventions. These technological advances have the potential to make disease surveillance and treatment far more effective for a variety of conditions, allowing patients to lead longer and more productive lives. This review will examine the conventional techniques as well as ingestible sensors and sensing systems that are currently under development for use in disease screening and diagnosis for GI disorders. Design considerations, fabrication, and applications will be discussed.


Re: Delayed Radical Prostatectomy is not Associated with Adverse Oncological Outcomes: Implications for Men Experiencing Surgical Delay due to the COVID-19 Pandemic.


title: Comparison of perivascular and intramuscular applied botulinum toxin a pretreatment on muscle flap ischemia-reperfusion injury and chemical delay.

text: BACKGROUND AND PURPOSE Muscle flaps are known to be prone to local ischemia more than other flaps. The local and systemic injury that ensues after reperfusion of ischemic skeletal muscle is an important clinical problem in flap surgery. Flap delay may be applied chemically or sympathetically. Early use of botulinum toxin A (Btx-A) in muscle flap surgery relied on chemical denervation; however, in our study, we tried to emphasize a possible chemical delay mechanism of Btx-A, through the release of substance P and calcitonin gene-related peptide (CGRP) and vascular endothelial growth factor (VEGF). METHODS Pretreatment with perivascular or intramuscular Btx-A was applied 1 week before the flap elevation, 3.5 units in 2 experimental groups each containing 8 Sprague-Dawley rats. The control groups (2 groups, each containing 8 rats) received 0.07 mL saline perivascularly and intramuscularly. The right gastrocnemius muscle flap was used as the experimental model. Ischemia-reperfusion cycle was applied to all groups. On the seventh day, the gastrocnemius flap was elevated, and perivascular tissues were observed macroscopically. Comparisons between perivascular Btx-A and intramuscular Btx-A groups were made, and the animals were killed. Muscle biopsies were taken. Damaged myocytes were counted using McCormack technique, and chemical delay was shown as angiogenesis, lymphocyte counts, and edema formation with VEGF3-R, CGRP, and substance P markers as immunohistochemical staining. RESULTS The amount of muscle necrosis was the highest in intramuscular Btx-A admitted groups. The intramuscular and perivascular Btx-A groups showed significant angiogenesis scored blindly by the senior pathologist. CONCLUSIONS Potential role of Btx-A in ischemic preconditioning of muscle flaps achieved through the release of substance P, CGRP, and VEGF was investigated. Chemical delay was shown objectively by Btx-applied groups.


A review series on the management of burns injury.


title: Molecular detection of Histoplasma capsulatum in insectivorous and frugivorous bats in Southeastern Brazil.

text: Bats are considered to play a significant role in the epidemiology of histoplasmosis, worldwide. We investigated the occurrence of H. capsulatum in lung samples from 89 bats, from urban areas in Southeastern Brazil, using nested PCR based on ribosomal DNA. Fungal DNA was detected in 31/89 samples (34.8%), of which 13/31 were Molossids (41.9%), 4/31 Eumops spp. (12.9%), 2/31 Artibeus lituratus (6.5%), and 12/31 others (38.7%). This is the first report of natural infection by H. capsulatum in A. lituratus in Southeastern Brazil, which reinforces the importance of these synanthropic animals in the epidemiology of histoplasmosis in urban areas.


title: Atraumatic intubation: experience using a 5.0 endotracheal tube without a stylet for laryngeal surgery.

text: OBJECTIVES/HYPOTHESIS Vocal fold injury is a well-know complication of intubation, with rates reported as high as 69%. Laryngology textbooks recommend the use of a small endotracheal tube (ETT) to help avoid these complications and optimize visualization. Case reports have suggested that the rigid stylet can lead to laryngeal injury. Given the additional risks, intubation without the stylet is our preferred practice. There is limited documentation in the literature regarding this viewpoint. Our study investigated the feasibility of and potential barriers to intubation using 5.0 ETT without a stylet. STUDY DESIGN Prospective study. METHODS Consecutive adult patients undergoing laryngeal surgery were recruited for intubation with a 5.0 ETT without a stylet. Demographic data, specialty and training level of the intubator, and factors that would predict a difficult intubation were recorded. Descriptive statistical analysis was performed. RESULTS Findings of the participants (n = 67) included average American Society of Anesthesiologists (ASA) physical status classification (2.2), average Mallampati score (1.7), average Cormack-Lehane grade (1.5), and average body mass index (28.0). Five patients (7.4%) required intubation using a stylet, and one of these five participants was intubated initially with a stylet. Of these five participants, 80% required use of a GlideScope (P < .001), and they had significantly higher ASA classification (P = .047) and number of intubation attempts (P = .042). One patient sustained an oropharyngeal injury during intubation with a stylet. No participants had laryngeal injury. CONCLUSIONS Most patients can be intubated successfully using a 5.0 ETT without a stylet. There were no cases of laryngeal trauma with this technique. LEVEL OF EVIDENCE 2b.


title: Mind-Body Therapies for Opioid-Treated Pain: A Systematic Review and Meta-analysis.

text: Importance Mind-body therapies (MBTs) are emerging as potential tools for addressing the opioid crisis. Knowing whether mind-body therapies may benefit patients treated with opioids for acute, procedural, and chronic pain conditions may be useful for prescribers, payers, policy makers, and patients. Objective To evaluate the association of MBTs with pain and opioid dose reduction in a diverse adult population with clinical pain. Data Sources For this systematic review and meta-analysis, the MEDLINE, Embase, Emcare, CINAHL, PsycINFO, and Cochrane Library databases were searched for English-language randomized clinical trials and systematic reviews from date of inception to March 2018. Search logic included (pain OR analgesia OR opioids) AND mind-body therapies. The gray literature, ClinicalTrials.gov, and relevant bibliographies were also searched. Study Selection Randomized clinical trials that evaluated the use of MBTs for symptom management in adults also prescribed opioids for clinical pain. Data Extraction and Synthesis Independent reviewers screened citations, extracted data, and assessed risk of bias. Meta-analyses were conducted using standardized mean differences in pain and opioid dose to obtain aggregate estimates of effect size with 95% CIs. Main Outcomes and Measures The primary outcome was pain intensity. The secondary outcomes were opioid dose, opioid misuse, opioid craving, disability, or function. Results Of 4212 citations reviewed, 60 reports with 6404 participants were included in the meta-analysis. Overall, MBTs were associated with pain reduction (Cohen d = -0.51; 95% CI, -0.76 to -0.26) and reduced opioid dose (Cohen d = -0.26; 95% CI, -0.44 to -0.08). Studies tested meditation (n = 5), hypnosis (n = 25), relaxation (n = 14), guided imagery (n = 7), therapeutic suggestion (n = 6), and cognitive behavioral therapy (n = 7) interventions. Moderate to large effect size improvements in pain outcomes were found for meditation (Cohen d = -0.70), hypnosis (Cohen d = -0.54), suggestion (Cohen d = -0.68), and cognitive behavioral therapy (Cohen d = -0.43) but not for other MBTs. Although most meditation (n = 4 [80%]), cognitive-behavioral therapy (n = 4 [57%]), and hypnosis (n = 12 [63%]) studies found improved opioid-related outcomes, fewer studies of suggestion, guided imagery, and relaxation reported such improvements. Most MBT studies used active or placebo controls and were judged to be at low risk of bias. Conclusions and Relevance The findings suggest that MBTs are associated with moderate improvements in pain and small reductions in opioid dose and may be associated with therapeutic benefits for opioid-related problems, such as opioid craving and misuse. Future studies should carefully quantify opioid dosing variables to determine the association of mind-body therapies with opioid-related outcomes.


title: COVID-19, Australia: Epidemiology Report 8 (Reporting period from 19:00 AEDT 14 March to 23:59 AEDT 22 March 2020).

text: This is the eighth epidemiological report for coronavirus disease 2019 (COVID-19), reported in Australia as at 23:59 Australian Eastern Daylight Time [AEDT] 22 March 2020. It includes data on COVID-19 cases diagnosed in Australia, the international situation and a review of current evidence.


title: The Effect of Body Mass Index on Outcome after Endovascular Treatment in Acute Ischemic Stroke Patients: A Post Hoc Analysis of the MR CLEAN Trial.

text: BACKGROUND Though obesity is a well-known risk factor for vascular disease, the impact of obesity on stroke outcome has been disputed. Several studies have shown that obesity is associated with better functional outcome after stroke. Whether obesity influences the benefit of endovascular treatment (EVT) in stroke patients is unknown. We evaluated the association between body mass index (BMI) and outcome in acute ischemic stroke patients with large vessel -occlusion (LVO), and assessed whether BMI affects the -benefit of EVT. METHODS This is a post hoc analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands trial (-ISRCTN10888758). BMI was used as a continuous and categorical variable, distinguishing underweight and normal weight (BMI <25), overweight (BMI 25-30), and obesity (BMI ≥30). We used multivariable ordinal logistic regression analysis to estimate the association of BMI with functional outcome (shift analysis), assessed with modified Rankin Scale (mRs) at 90 days. The impact of BMI on EVT effect was tested by the use of a multiplicative interaction term. RESULTS Of 366 patients, 160 (44%) were underweight or normal weight, 145 (40%) overweight, and 61 (17%) were obese. In multivariable analysis with BMI as a continuous variable, we found a shift toward better functional outcome with higher BMI (mRS adjusted common OR 1.04; 95% CI 1.0-1.09), and mortality was inversely related to BMI (aOR 0.92; 95% CI 0.85-0.99). Safety analysis showed that higher BMI was associated with lower risk of stroke progression (aOR 0.92, 95% CI 0.87-0.99). Additional analysis showed no interaction between BMI and EVT effect on functional outcome, mortality, and other safety outcomes. CONCLUSION Our study confirms the effect of obesity on outcome in acute ischemic stroke patients with LVO, meaning better functional outcome, lower mortality, and lower risk of stroke progression for patients with higher BMI. As we found no interaction between BMI and EVT effect, all BMI classes may expect the same benefit from EVT.


title: Disposition to home or acute rehabilitation is associated with a favorable clinical outcome in the SENTIS trial.

text: OBJECTIVE To explore the impact of stroke severity and discharge disposition on 90-day outcomes in US patients enrolled in the SENTIS trial. METHODS SENTIS is a previously published prospective randomized controlled trial. We analyzed the demographic information, National Institutes of Health Stroke Scores (NIHSS) on day 4, discharge disposition and 90-day modified Rankin Score (mRS). Univariate models were constructed to determine the impact of discharge disposition on 90-day outcomes as well as the association of the day 4 NIHSS with outcomes. RESULTS A total of 292 patients with a mean age of 65 ± 14 years were analyzed. Discharge disposition was distributed as follows: 153 (52.1%) to an inpatient rehabilitation facility (IRF), 111 (38.0%) to home and 28 (9.6%) to a skilled nursing facility (SNF). Only 2 out of 28 patients (7.1%) discharged to a SNF achieved a 90-day mRS ≤ 2 compared with 60/153 (39.2%) in the IRF group (OR 8.39 (95% CI 1.92 to 36.64), p = 0.0047). This association persisted after adjusting for age and admission NIHSS. Only 3 of 50 patients (6%) with a NIHSS of ≥ 14 at day 4 achieved a mRS 0-2 at day 90. CONCLUSIONS This analysis shows that discharge to an IRF is associated with better neurological outcomes than discharge to a SNF. Additionally, patients with a NIHSS of ≥ 14 at day 4 are unlikely to achieve independent function.


title: Spinal anaesthesia in neonates and infants: what about the cerebral oxygen saturation?

text: Background Spinal Anaesthesia (SA) has been firmly established as an efficient and safe technique, with minimal cardio-respiratory disturbance when administered in the neonatal period. Our objective was to assess the haemodynamic consequences of SA in infants, particularly its impact on cerebral perfusion using near-infrared spectroscopy (NIRS)-based cerebral oximetry (rSco2). Methods All infants up to 60 weeks' postmenstrual age, whether formerly preterm or not, and undergoing spinal anaesthesia, were enrolled. Haemodynamic data records, rSco2 and mean arterial blood pressure (MAP), were prospectively collected before SA (T0) and every five min for 30 min (T30) after the puncture. Compared with baseline measures, any changes of > 10% in rSco2 and of > 20% in MAP were considered clinically significant. Relative variations of data between T0 and T30 were analysed. Results Data of 103 infants were analysed. The mean relative changes in rSco2 were -2.25% (97.5% CI [-3.97; -0.5]) at T15, and 0.11% (97.5% CI [-1.67; 1.90]) at T30. No significant variation of rSco2 was recorded. The mean changes in MAP were respectively -13.94% (97.5% CI [-17.74; -10.14]) at T15 and -20.27% (97.5% CI [-24,25; -16.29]) at T30. MAP decrease was statistically and clinically significant 30 min after SA. No correlation between changes in MAP and rSco2 was found. The subgroup analysis did not reveal any effect of added intrathecal clonidine or preterm birth history on these results. Conclusions In neonate and infants, SA did not cause clinically significant variation in cerebral oxygen saturation. Despite a significant decrease in MAP, cerebral auto-regulation seems to remain effective in neonates and not altered by spinal anaesthesia.


A Simple Three-Tier Classification System for Triage, Communication, and Resource Utilization by Patients Afflicted with COVID-19 Disease.


title: Protocol for the development of guidance for stakeholder engagement in health and healthcare guideline development and implementation.

text: BACKGROUND Stakeholder engagement has become widely accepted as a necessary component of guideline development and implementation. While frameworks for developing guidelines express the need for those potentially affected by guideline recommendations to be involved in their development, there is a lack of consensus on how this should be done in practice. Further, there is a lack of guidance on how to equitably and meaningfully engage multiple stakeholders. We aim to develop guidance for the meaningful and equitable engagement of multiple stakeholders in guideline development and implementation. METHODS This will be a multi-stage project. The first stage is to conduct a series of four systematic reviews. These will (1) describe existing guidance and methods for stakeholder engagement in guideline development and implementation, (2) characterize barriers and facilitators to stakeholder engagement in guideline development and implementation, (3) explore the impact of stakeholder engagement on guideline development and implementation, and (4) identify issues related to conflicts of interest when engaging multiple stakeholders in guideline development and implementation. DISCUSSION We will collaborate with our multiple and diverse stakeholders to develop guidance for multi-stakeholder engagement in guideline development and implementation. We will use the results of the systematic reviews to develop a candidate list of draft guidance recommendations and will seek broad feedback on the draft guidance via an online survey of guideline developers and external stakeholders. An invited group of representatives from all stakeholder groups will discuss the results of the survey at a consensus meeting which will inform the development of the final guidance papers. Our overall goal is to improve the development of guidelines through meaningful and equitable multi-stakeholder engagement, and subsequently to improve health outcomes and reduce inequities in health.


title: Anxiety and Depression Scores in Maternity Healthcare Workers during the Covid-19 Pandemic.

text: While Severe-Acute-Respiratory-Syndrome-CoronaVirus-2 (SARSCoV-2/Covid-19) causes physical morbidity for healthcare workers (HCWs), Covid-19 also carries psychological morbidity for HCWs. This morbidity translates to anxiety and depressive symptomatology. To this end, we assessed anxiety and depression among HCWs during Covid-19 pandemic.


title: Preliminary Estimate of Excess Mortality During the COVID-19 Outbreak - New York City, March 11-May 2, 2020.

text: SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was first identified in December 2019 in Wuhan, China, and has since spread worldwide. On March 11, 2020, the World Health Organization declared COVID-19 a pandemic (1). That same day, the first confirmed COVID-19-associated fatality occurred in New York City (NYC). To identify confirmed COVID-19-associated deaths, defined as those occurring in persons with laboratory-confirmed SARS-CoV-2 infection, on March 13, 2020, the New York City Department of Health and Mental Hygiene (DOHMH) initiated a daily match between all deaths reported to the DOHMH electronic vital registry system (eVital) (2) and laboratory-confirmed cases of COVID-19. Deaths for which COVID-19, SARS-CoV-2, or an equivalent term is listed on the death certificate as an immediate, underlying, or contributing cause of death, but that do not have laboratory-confirmation of COVID-19 are classified as probable COVID-19-associated deaths. As of May 2, a total of 13,831 laboratory-confirmed COVID-19-associated deaths, and 5,048 probable COVID-19-associated deaths were recorded in NYC (3). Counting only confirmed or probable COVID-19-associated deaths, however, likely underestimates the number of deaths attributable to the pandemic. The counting of confirmed and probable COVID-19-associated deaths might not include deaths among persons with SARS-CoV-2 infection who did not access diagnostic testing, tested falsely negative, or became infected after testing negative, died outside of a health care setting, or for whom COVID-19 was not suspected by a health care provider as a cause of death. The counting of confirmed and probable COVID-19-associated deaths also does not include deaths that are not directly associated with SARS-CoV-2 infection. The objective of this report is to provide an estimate of all-cause excess deaths that have occurred in NYC in the setting of widespread community transmission of SARS-CoV-2. Excess deaths refer to the number of deaths above expected seasonal baseline levels, regardless of the reported cause of death. Estimation of all-cause excess deaths is used as a nonspecific measure of the severity or impact of pandemics (4) and public health emergencies (5). Reporting of excess deaths might provide a more accurate measure of the impact of the pandemic.


Pulmonary Embolism or Pulmonary Thrombosis in COVID-19? Is the Recommendation to Use High-Dose Heparin for Thromboprophylaxis Justified?


title: Identification of imaging selection patterns in acute ischemic stroke patients and the influence on treatment and clinical trial enrollment decision making.

text: BACKGROUND AND PURPOSE For the STroke Imaging Research (STIR) and VISTA-Imaging Investigators The purpose of this study was to collect precise information on the typical imaging decisions given specific clinical acute stroke scenarios. Stroke centers worldwide were surveyed regarding typical imaging used to work up representative acute stroke patients, make treatment decisions, and willingness to enroll in clinical trials. METHODS STroke Imaging Research and Virtual International Stroke Trials Archive-Imaging circulated an online survey of clinical case vignettes through its website, the websites of national professional societies from multiple countries as well as through email distribution lists from STroke Imaging Research and participating societies. Survey responders were asked to select the typical imaging work-up for each clinical vignette presented. Actual images were not presented to the survey responders. Instead, the survey then displayed several types of imaging findings offered by the imaging strategy, and the responders selected the appropriate therapy and whether to enroll into a clinical trial considering time from onset, clinical presentation, and imaging findings. A follow-up survey focusing on 6 h from onset was conducted after the release of the positive endovascular trials. RESULTS We received 548 responses from 35 countries including 282 individual centers; 78% of the centers originating from Australia, Brazil, France, Germany, Spain, United Kingdom, and United States. The specific onset windows presented influenced the type of imaging work-up selected more than the clinical scenario. Magnetic Resonance Imaging usage (27-28%) was substantial, in particular for wake-up stroke. Following the release of the positive trials, selection of perfusion imaging significantly increased for imaging strategy. CONCLUSIONS Usage of vascular or perfusion imaging by Computed Tomography or Magnetic Resonance Imaging beyond just parenchymal imaging was the primary work-up (62-87%) across all clinical vignettes and time windows. Perfusion imaging with Computed Tomography or Magnetic Resonance Imaging was associated with increased probability of enrollment into clinical trials for 0-3 h. Following the release of the positive endovascular trials, selection of endovascular only treatment for 6 h increased across all clinical vignettes.


title: Renal colic caused by mycotic iliac artery aneurysm.

text: A 33-year-old female presented with acute colicky left loin-to-groin pain and microscopic haematuria, with a background of 6 months of muscle and joint pains and diplopia. A CT kidneys/ureters/bladder demonstrated fat stranding surrounding the left ureter, as it passed over the left common iliac vessels. Arterial and delayed phase imaging revealed an obstructed ureter secondary to a left common iliac artery aneurysm, later found to be mycotic. No previous descriptions of a mycotic aneurysm presenting as renal colic have been found in the literature. The diagnosis and management of infective endocarditis and mycotic aneurysm are discussed, with a review of the literature. This serves as a good example of a common presenting complaint occurring secondary to a rare and serious pathology.


title: The impact of warmed and humidified CO2 insufflation during robotic radical prostatectomy: Results of a randomized controlled trial.

text: BACKGROUND: Cool and dry gas insufflation during laparoscopy induces hypothermia and cytokine increase, with significant perioperative morbidity. Our aim was to assess if warmed and humidified CO2 insufflation with HumiGard™ device can achieve significant benefits over standard insufflation in terms of risk of hypothermia, cytokine response, blood gases, and intra- and postoperative parameters, in the setting of robot-assisted radical prostatectomy (RARP). METHODS: This was a prospective, randomized controlled clinical trial. Sixty-four patients with prostate cancer undergoing RARP were randomized to receive warmed and humidified CO2 insufflation with HumiGard device, plus hot air warming blanket (treatment group, H + WB), or standard CO2 insufflation, plus hot air warming blanket (control group, WB). Body core temperature (BCT), plasma levels of IL-6 and TNF-α, pain scores, and intraoperative parameters were recorded. The data were analyzed according to the Bayesian paradigm. RESULTS: Intraoperative BCT increased in both groups during surgery, with a statistically significant difference favoring group H + WB, ending at 0.2°C higher on average than group WB. No difference across groups was shown for cytokine levels. Blood gas parameters were not affected by warmed CO2 insufflation. No statistical differences were noted for pain scores and the other intra- and postoperative parameters. CONCLUSIONS: During RARP, warm and humidified CO2 insufflation with the HumiGard device was more effective than the standard CO2 insufflation in maintaining the patient's heat homeostasis, even if the difference was minimal. No imbalances were detected on blood gas analyses. No benefit could be shown in terms of cytokine levels and pain scores.


title: Comparison of laparoscopic sleeve gastrectomy leak rates in five staple-line reinforcement options: a systematic review.

text: BACKGROUND Staple-line leaks following laparoscopic sleeve gastrectomy (LSG) remain a concerning complication. Staple-line buttressing is largely adopted as an acceptable reinforcement but data regarding leaks have been equivocal. This study compared staple-line leaks in five reinforcement options during LSG: no reinforcement (NO-SLR), oversewing (suture), nonabsorbable bovine pericardial strips (BPS), tissue sealant or fibrin glue (Seal), or absorbable polymer membrane (APM). METHODS This systematic review study of articles published between 2012 and 2016 regarding LSG leak rates aligned with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Variables of interest included leak rates, bleeding, and complications in addition to surgical and population parameters. An independent Fisher's exact test was used to compare the number of patients with and without leaks for the different reinforcement options. RESULTS Of the 1633 articles identified, 148 met inclusion criteria and represented 40,653 patients. Differences in age (older in APM; p = 0.001), starting body mass index (lower in Suture; p = 0.008), and distance from pylorus (closer in BPS; p = 0.04) were observed between groups, but mean bougie size was equivalent. The overall leak rate of 1.5% (607 leaks) ranged from 0.7% for APM (significantly lower than all groups; p ≤ 0.007 for next lowest leak rate) to 2.7% (BPS). CONCLUSIONS This systematic review of staple-line leaks following LSG demonstrated a significantly lower rate using APM staple-line reinforcement as compared to oversewing, use of sealants, BPS reinforcement, or no reinforcement. Variation in surgical technique may also contribute to leak rates.


Highlights of the May issue.


title: Evaluating the economic impact of casino liberalization in Macao.

text: This paper aims to evaluate the economic impact after Macao decided to liberalize its gaming industry. By analysing both objective data of official statistics and subjective data of the perceptions of quality of life, we painted a picture of mixed blessings. Although objective indicators showed strong economic growth in terms of a rise in per capita GDP and public revenue as well as a decline in unemployment rate, subjective indicators revealed that local residents were less than optimistic about their own employment outlook and did not perceive any improvement in their overall economic situation. While casino liberalization brought forth tremendous economic gain, the general population did not subjectively feel the benefits. An integrative analysis of both objective and subjective indicators would therefore allow us to look closer how residents' lives in the micro-level could have been adversely affected by the prosperous economic outlook at the macro-level.


title: Comparing Observation, Axillary Radiotherapy, and Completion Axillary Lymph Node Dissection for Management of Axilla in Breast Cancer in Patients with Positive Sentinel Nodes: A Systematic Review.

text: PURPOSE Several randomized controlled trials (RCTs) have investigated observation or axillary radiotherapy (ART) in place of completion axillary lymph node dissection (cALND) for management of positive sentinel nodes (SNs) in clinically node-negative women with breast cancer. The optimal treatment strategy for this population is not known. METHODS MEDLINE, Embase, and EBM Reviews-NHS Economic Evaluation Database were searched from inception until July 2019. A systematic review and narrative summary was performed of RCTs comparing observation or ART versus cALND in clinically node-negative female breast cancer patients with positive SNs. The Cochrane risk of bias tool for RCTs was used to assess risk of bias. Outcomes of interest included overall survival (OS), disease-free survival (DFS), axillary recurrence, and axillary surgery-related morbidity. RESULTS Three trials compared observation with cALND, and two trials compared ART with cALND. No studies blinded participants or personnel, and there was heterogeneity in inclusion criteria, study design, and follow-up. Neither observation nor ART resulted in statistically inferior 5- or 8-year OS or DFS compared with cALND. There was also no statistically significant increase in axillary recurrences associated with either approach. Four trials reported morbidity outcomes, and all showed cALND was associated with significantly more lymphedema, paresthesia, and shoulder dysfunction compared with observation or ART. CONCLUSIONS Women with clinically node-negative breast cancer and positive SNs can safely be managed without cALND.


Ready, set, go for physical activity.


title: 68 Ga-PSMA PET/CT for the detection of bone metastases in prostate cancer: a systematic review of the published literature.

text: BACKGROUND 68 Ga-labelled prostate-specific membrane antigen (PSMA) is a promising PET ligand for the detection of prostate cancer. Little attention has been given to the ability of 68 Ga-PSMA PET/CT to detect malignant bone lesions and whether this approach is superior to existing bone imaging modalities. AIM To review the existing data of 68 Ga-PSMA PET/CT for the diagnosis of bone metastases in prostate cancer. METHODS Systematic review of the peer-reviewed literature. RESULTS Among 1858 papers in the original search, 37 papers were included in the analysis (six case reports and 31 case series). The vast majority of the studies were low-level evidence studies. Most studies presented data on detection rates without a reference standard. All but two studies were of a retrospective nature. Several cohort studies showed bone metastasis in 5-60% of patients with prostate cancer, including in patients with very low-PSA values. For primary staging, 68 Ga-PSMA PET/CT outperformed bone scans, while the superiority of 68 Ga-PSMA PET/CT compared with bone scans with respect to biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC) remains to be demonstrated. CONCLUSION 68 Ga-PSMA PET/CT has shown to be a promising technique for use in prostate cancer. 68 Ga-PSMA PET/CT shows more lesions than bone scans, but data on diagnostic performance are very limited and indicate improved diagnostic performance in primary staging but not in mCRPC. Properly designed studies are needed to clarify the diagnostic performance of 68 Ga-PSMA PET/CT as well as its superiority over existing methods before 68 Ga-PSMA PET/CT can be routinely used for bone imaging.


Tracheal cuff management as part of a lung-protective strategy.


title: In vivo porcine training model for laparoscopic Roux-en-Y choledochojejunostomy.

text: PURPOSE The purpose of this study was to develop a porcine training model for laparoscopic choledochojejunostomy (CJ) that can act as a bridge between simulation models and actual surgery for novice surgeons. The feasibility of this model was evaluated. METHODS Laparoscopic CJ using intracorporeal sutures was performed on ten animals by a surgical fellow with no experience in human laparoscopic CJ. A single layer of running sutures was placed in the posterior and anterior layers. Jejunojejunostomy was performed using a linear stapler, and the jejunal opening was closed using absorbable unidirectional sutures (V-Loc 180). RESULTS The average operation time was 131.3 ± 36.4 minutes, and the CJ time was 57.5 ± 18.4 minutes. Both the operation time and CJ time showed a steady decrease with an increasing number of cases. The average diameter of the CBD was 6.4 ± 0.8 mm. Of a total of ten animals, eight were sacrificed after the procedure. In two animals, a survival model was evaluated. Both pigs recovered completely and survived for two weeks, after which both animals were sacrificed. None of the animals exhibited any signs of bile leakage or anastomosis site stricture. CONCLUSION The porcine training model introduced in this paper is an adequate model for practicing laparoscopic CJ. Human tissue simulation is excellent.


Northern Ireland disease surveillance report, January to March 2015.


title: Usefulness of near-infrared spectroscopy in thrombectomy monitoring.

text: Monitoring recanalization and reperfusion during acute ischemic stroke is a challenge for therapeutic assessment. Near-infrared spectroscopy (NIRS) allows continuous monitoring of the brain regional saturation of oxygen (rSO2). We sought to evaluated rSO2 variation during mechanical thrombectomy during acute ischemic stroke. Three patients admitted for middle cerebral artery occlusion were continuously monitored during mechanical thrombectomy (rSO2 in the infarcted and non-infarcted side and interhemispheric difference). The procedure was a success in two of them and failed in the third. At the beginning, rSO2 was lower in the infarcted side and interhemispheric difference was more than 5%. When the procedure succeeded, rSO2 in the infarcted side rise (about 10%) and interhemisperic difference decrease (about 7%). When the procedure failed, rSO2 was the same at the beginning and at the end. NIRS may be useful to monitor recanalization during management of acute ischemic stroke.


Sex matters - a preliminary analysis of Middle East respiratory syndrome in the Republic of Korea, 2015.


Thousands of people will help scientists to track the long-term health effects of the coronavirus crisis.


title: Minilaparoendoscopic Single-site Pyeloplasty: The Best Compromise Between Surgeon's Ergonomy and Patient's Cosmesis (IDEAL Phase 2a).

text: BACKGROUND Laparoendoscopic single-site (LESS) surgery and minilaparoscopy (ML) represent the evolution of laparoscopy for the treatment of urologic diseases. OBJECTIVE To describe the technique and report the surgical outcomes of minilaparoendoscopic single-site dismembered pyeloplasty (MILESS-DP), a new technique overcoming the technical limitations of LESS and ML, and equally combining the advantages of both these surgical procedures. DESIGN, SETTING, AND PARTICIPANTS Twenty consecutive patients underwent MILESS-DP for ureteropelvic junction obstruction. SURGICAL PROCEDURE The SILS port was inserted through a transumbilical incision and two 3-mm trocars were inserted in the ipsilateral midclavicular line. The sequence of steps of MILESS-DP is comparable to standard laparoscopic dismembered pyeloplasty. MEASUREMENTS The end points of this study were: (1) feasibility; (2) safety; (3) efficacy; and (4) cosmesis, evaluated using a body image questionnaire. RESULTS AND LIMITATIONS All patients were symptomatic (100%) and three (15%) had concomitant kidney stones. (1) Feasibility: a conversion to either standard laparoscopic technique or open technique did not occur in any case. Median operative time was 147.3min (interquartile range [IQR]: 110-195min); (2) safety: no intraoperative complications were reported. Only in two patients (10%), a urinoma was postoperatively identified and conservatively treated with an ureteral stent. The median difference in post- and preoperative creatinine and haemoglobin was +0.55mg/dl and -0.76mg/dl (IQR: -0.20/-1.20mg/dl); (3) efficacy: the median postoperative hospital stay was 4.4 d (IQR: 4-9 d). The overall success rate was 95% at the follow-up; (4) cosmesis: all patients were enthusiastic with the appearance of the scars; the median body image score and the median cosmesis score were 19.95 (IQR 19-20) and 23.95 (IQR 23-24), respectively. The limitations of this study are the limited series and short follow-up. CONCLUSIONS Our phase 2a studies demonstrate that MILESS-DP is a safe and reproducible procedure with excellent cosmetic outcomes and short-term clinical outcomes in the hands of a surgical team with experience in laparoscopy. PATIENT SUMMARY Minilaparoscopy using 3-mm instruments and laparoendoscopic single-site using a single abdominal incision, still present several technical drawbacks which limit their reproducibility in urology. In order to overcome these technical limitations and equally combining the advantages of both these surgical procedures, we ideated a hybrid technique which we defined minilaparoendoscopic single-site. This study aims to demonstrate that minilaparoendoscopic single-site pyeloplasty is a safe and reproducible procedure with excellent cosmetic outcomes and short-term clinical outcomes in the hands of a surgical team with experience in mini-invasive surgery.


title: Guidelines and Recommendations for Patient Management, Surgical Activities, and Safety in the Maxillofacial Unit and Head and Neck Department During COVID-19 Pandemic.

text: The recent pandemic has led to an unprecedented overload of sanitary systems around the world. Despite that a maxillofacial department is not a frontline specialty in the treatment of coronavirus disease 2019 infections, our department has found itself faced with numerous problems in keeping the care system active and efficient while ensuring safety for patients and healthcare professionals. Massive redistribution of health personnel was needed to improve prevention and personal safety measures. The education and training system has been kept active, giving residents a decisive role in managing the state of emergency response. This article outlines new guidelines for infection prevention: from clinical control, treatment processes, clinical management, protection, and disinfection of healthcare professionals.


title: Regulation of de novo translation of host cells by manipulation of PERK/PKR and GADD34-PP1 activity during Newcastle disease virus infection.

text: Viral infections result in cellular stress responses, which can trigger protein translation shutoff via phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α). Newcastle disease virus (NDV) causes severe disease in poultry and selectively kills human tumour cells. In this report, we determined that infection of HeLa human cervical cancer cells and DF-1 chicken fibroblast cells with NDV maintained protein at early infection times, 0-12 h post-infection (p.i.), and gradually inhibited global protein translation at late infection times, 12-24 h p.i. Mechanistic studies showed that translation inhibition at late infection times was accompanied by phosphorylation of eIF2α, a checkpoint of translation initiation. Meanwhile, the eIF2α kinase, PKR, was upregulated and activated by phosphorylation and another eIF2α kinase, PERK, was phosphorylated and cleaved into two fragments. Pharmacological inhibition experiments revealed that only PKR activity was required for eIF2α phosphorylation, suggesting that recognition of viral dsRNA by PKR was responsible for translation shutoff. High levels of phospho-eIF2α led to preferential translation of the transcription factor ATF4 and an increase in GADD34 expression. Functionally, GADD34, in conjunction with PP1, dephosphorylated eIF2a and restored protein translation, benefiting virus protein synthesis. However, PP1 was degraded at late infection times, functionally counteracting the upregulation of GADD34. Taken together, our data support that NDV-induced translation shutoff at late infection times was attributed to sustaining phosphorylation of eIF2α, which is mediated by continual activation of PKR and degradation of PP1.


COVID-19 Health Technology Governance, Epistemic Competence, and the Future of Knowledge in an Uncertain World.


title: COVID-19 and pregnancy - where are we now? A review.

text: The new acute respiratory disease severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is highly contagious. It has caused many deaths, despite a relatively low general case fatality rate (CFR). The most common early manifestations of infection are fever, cough, fatigue and myalgia. The diagnosis is based on the exposure history, clinical manifestation, laboratory test results, chest computed tomography (CT) findings and a positive reverse transcription-polymerase chain reaction (RT-PCR) result for coronavirus disease 2019 (COVID-19). The effect of SARS-CoV-2 on pregnancy is not already clear. There is no evidence that pregnant women are more susceptible than the general population. In the third trimester, COVID-19 can cause premature rupture of membranes, premature labour and fetal distress. There are no data on complications of SARS-CoV-2 infection before the third trimester. COVID-19 infection is an indication for delivery if necessary to improve maternal oxygenation. Decision on delivery mode should be individualised. Vertical transmission of coronavirus from the pregnant woman to the fetus has not been proven. As the virus is absent in breast milk, the experts encourage breastfeeding for neonatal acquisition of protective antibodies.


Covid-19: Delays in attending emergency departments may have contributed to deaths of nine children.


First report of natural BoHV-1 infection in water buffalo.


docid: zjtgcckd

title: A step-up approach to managing acute pancreatitis-associated fluid collections.


title: Neurothrombectomy trial results: stroke systems, not just devices, make the difference.

text: The overwhelming benefit demonstrated in the four recent randomized trials comparing intra-arterial therapies to medical management alone will have a transformative effect on the emergent management of strokes throughout the world. New generation neurothrombectomy devices were critical to trial success, but not the sole driver of patient outcomes in these trials. Patients in the positive trials were treated at hospitals with complex, efficient, resource-rich, team-based stroke systems in place. To ensure attainment of trial results in actual practice, patients should receive treatment at facilities certified as having the resources, personnel, organization, and continuous quality improvement processes characteristic of trial centers. It is our hope that, through greater education initiatives, robust resource investment, and developing quality-based certification processes, the results demonstrated by these trials may be extrapolated to greater numbers of centers - in turn allowing greater access for patients to high-quality, advanced stroke care.


Mass intake of hydroxychloroquine or chloroquine in the present context of the Covid-19 outbreak: Possible consequences in endemic malaria settings.


title: Cardiac sympathetic dysfunction in genotyped patients with arrhythmogenic right ventricular cardiomyopathy and risk of recurrent ventricular tachyarrhythmias.

text: UNLABELLED Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) typically present with ventricular tachyarrhythmias preferentially triggered by an elevated sympathetic tone. Previous studies demonstrated an impairment of the presynaptic catecholamine reuptake as assessed by (123)I-labeled norepinephrine analog on metaiodobenzylguanidine ((123)I-MIBG) SPECT. Mutations in the gene encoding for plakophilin-2 (PKP-2) are the most common cause of autosomal dominant ARVC (ARVC-9). In this study, we investigated the potential role of adrenergic dysfunction on the arrhythmia profile in patients with ARVC and correlated these findings with the causative genotype. METHODS (123)I-MIBG SPECT was performed for 42 patients with definite ARVC (10 women, 32 men; mean age ± SD, 43 ± 14 y). Images were acquired at 4 h after injection and analyzed for regional (123)I-MIBG uptake in a standardized 33-segment polar map. Results were compared with those obtained from 10 control subjects (5 women, 5 men; mean age ± SD, 43 ± 12 y). RESULTS An abnormal tracer uptake was detected in 25 patients with ARVC (59%). The extents of right ventricular dilation and regional wall motion abnormalities as well as electrocardiographic markers of de- or repolarization were not significantly different between patients with normal and abnormal (123)I-MIBG SPECT findings. However, during long-term follow-up of 11.9 ± 4.1 y, patients with abnormal (123)I-MIBG SPECT findings experienced life-threatening ventricular tachyarrhythmias significantly more often (22/25 patients [88%]) and independent of the extent of right ventricular dysfunction than those with a normal sympathetic innervation (6/17 patients [35%]; P < 0.0005). Mutations in PKP-2 were identified in 17 patients (40%) but were not correlated with the degree of adrenergic dysfunction. CONCLUSION In patients with ARVC, an impairment of adrenergic innervation independent of the underlying genotype is associated with a higher incidence for future recurrences of ventricular tachyarrhythmias. This finding may suggest a potential role of (123)I-MIBG SPECT for individualized risk stratification in ARVC patients and asymptomatic PKP-2 mutation carriers alike.


Chinese guidelines for diagnosis and treatment of influenza (2011).


title: Integrating silicon nanowire field effect transistor, microfluidics and air sampling techniques for real-time monitoring biological aerosols.

text: Numerous threats from biological aerosol exposures, such as those from H1N1 influenza, SARS, bird flu, and bioterrorism activities necessitate the development of a real-time bioaerosol sensing system, which however is a long-standing challenge in the field. Here, we developed a real-time monitoring system for airborne influenza H3N2 viruses by integrating electronically addressable silicon nanowire (SiNW) sensor devices, microfluidics and bioaerosol-to-hydrosol air sampling techniques. When airborne influenza H3N2 virus samples were collected and delivered to antibody-modified SiNW devices, discrete nanowire conductance changes were observed within seconds. In contrast, the conductance levels remained relatively unchanged when indoor air or clean air samples were delivered. A 10-fold increase in virus concentration was found to give rise to about 20-30% increase in the sensor response. The selectivity of the sensing device was successfully demonstrated using H1N1 viruses and house dust allergens. From the simulated aerosol release to the detection, we observed a time scale of 1-2 min. Quantitative polymerase chain reaction (qPCR) tests revealed that higher virus concentrations in the air samples generally corresponded to higher conductance levels in the SiNW devices. In addition, the display of detection data on remote platforms such as cell phone and computer was also successfully demonstrated with a wireless module. The work here is expected to lead to innovative methods for biological aerosol monitoring, and further improvements in each of the integrated elements could extend the system to real world applications.


title: Mesenchymal Stem Cells Overexpressing Angiotensin-Converting Enzyme 2 Rescue Lipopolysaccharide-Induced Lung Injury.

text: Bone marrow-derived mesenchymal stem cells (MSCs), which have beneficial effects in acute lung injury (ALI), can serve as a vehicle for gene therapy. Angiotensin-converting enzyme 2 (ACE2), a counterregulatory enzyme of ACE that degrades angiotensin (Ang) II into Ang 1-7, has a protective role against ALI. Because ACE2 expression is severely reduced in the injured lung, a therapy targeted to improve ACE2 expression in lung might attenuate ALI. We hypothesized that MSCs overexpressing ACE2 would have further benefits in lipopolysaccharide (LPS)-induced ALI mice, when compared with MSCs alone. MSCs were transduced with ACE2 gene (MSC-ACE2) by a lentiviral vector and then infused into wild-type (WT) and ACE2 knockout (ACE2(-/y)) mice following an LPS-induced intratracheal lung injury. The results demonstrated that the lung injury of ALI mice was alleviated at 24 and 72 h after MSC-ACE2 transplantation. MSC-ACE2 improved the lung histopathology and had additional anti-inflammatory effects when compared with MSCs alone in both WT and ACE2(-/y) ALI mice. MSC-ACE2 administration also reduced pulmonary vascular permeability, improved endothelial barrier integrity, and normalized lung eNOS expression relative to the MSC group. The beneficial effects of MSC-ACE2 could be attributed to its recruitment into the injured lung and enhanced local expression of ACE2 protein without changing the serum ACE2 levels after MSC-ACE2 transplantation. The biological activity of the increased ACE2 protein decreased the Ang II amount and increased the Ang 1-7 level in the lung when compared with the ALI and MSC-only groups, thereby inhibiting the detrimental effects of accumulating Ang II. Therefore, compared to MSCs alone, the administration of MSCs overexpressing ACE2 resulted in a further improvement in the inflammatory response and pulmonary endothelial function of LPS-induced ALI mice. These additional benefits could be due to the degradation of Ang II that accompanies the targeted overexpression of ACE2 in the lung.


title: Percutaneous radiofrequency ablation of hepatocellular carcinoma in cirrhosis: analysis of complications in a single centre over 20 years.

text: OBJECTIVE To report on our 20 years' experience on complications after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) in patients with cirrhosis. METHODS From 1994 to 2014, 1787 RFA procedures were performed percutaneously in 1162 patients with cirrhosis (852 Child A and 310 Child B) with HCC nodules (1.2-7 cm), prothrombin time >50%, platelet count of 50.000 mm3 and total bilirubin ranging from 0.80 to 4.5 mg dl-1. In 67 patients, RFA was performed on both intraparenchymal HCC nodule and tumour thrombus extended in the main portal vein and/or its branches. RESULTS Four patients (0.3%) died after RFA. 39 patients (3.2%) changed in Child's class: 26 out of 28 Child A patients with cirrhosis changed to Child B and 2 changed to Child C class; 11 Child B patients changed to Child C class. On multivariate analysis, the total bilirubin pre-RFA was the only independent risk factor for impairment of liver function and death. Complications were hemoperitoneum, abscess and intrahepatic haematoma. CONCLUSION RFA of HCC in patients with cirrhosis is safe, even in case of invasion of the portal venous system. Functional liver reserve should be strictly monitored, mainly when pre-RFA total bilirubin value is >2.5 mg dl-1. The study was approved by our institutional review board. Advances in knowledge: The total bilirubin value >2.5 mg dl-1 represents the main marker of functional liver reserve that predicts decompensation of liver cirrhosis in patients undergoing RFA for HCC.


Acute Respiratory Failure in COVID-19 Pneumoniae: The Best Interface for an Optimal Management. A South Italian Experience.


title: Insulin resistance is associated with impaired cardiac sympathetic innervation in patients with heart failure.

text: AIMS Insulin resistance (IR) represents, at the same time, cause and consequence of heart failure (HF) and affects prognosis in HF patients, but pathophysiological mechanisms remain unclear. Hyperinsulinemia, which characterizes IR, enhances sympathetic drive, and it can be hypothesized that IR is associated with impaired cardiac sympathetic innervation in HF. Yet, this hypothesis has never been investigated. Aim of the present observational study was to assess the relationship between IR and cardiac sympathetic innervation in non-diabetic HF patients. METHODS AND RESULTS One hundred and fifteen patients (87% males; 65 ± 11.3 years) with severe-to-moderate HF (ejection fraction 32.5 ± 9.1%) underwent iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy to assess sympathetic innervation and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) evaluation to determine the presence of IR. From (123)I-MIBG imaging, early and late heart to mediastinum (H/M) ratios and washout rate were calculated. Seventy-two (63%) patients showed IR and 43 (37%) were non-IR. Early [1.68 (IQR 1.53-1.85) vs. 1.79 (IQR 1.66-1.95); P = 0.05] and late H/M ratio [1.50 (IQR 1.35-1.69) vs. 1.65 (IQR 1.40-1.85); P = 0.020] were significantly reduced in IR compared with non-IR patients. Early and late H/M ratio showed significant inverse correlation with fasting insulinemia and HOMA-IR. CONCLUSION Cardiac sympathetic innervation is more impaired in patients with IR and HF compared with matched non-IR patients. These findings shed light on the relationship among IR, HF, and cardiac sympathetic nervous system. Additional studies are needed to clarify the pathogenetic relationship between IR and HF.


title: A case-controlled comparison of single-site access versus conventional three-port laparoscopic appendectomy.

text: BACKGROUND The aim of this study was to compare patients who underwent single-site access laparoscopic appendectomy (SSALA) to those who underwent conventional three-port laparoscopic appendectomy (TPLA) in a case-controlled manner. METHODS Consecutive patients who underwent SSALA for suspected acute appendicitis between April and September 2009 were retrospectively compared to those who underwent TPLA between January and December 2008 in a case-controlled manner. The patients were matched for age, gender, and pathological findings. The main outcome measurements included postoperative recovery, morbidities, and mortalities. RESULTS During the study period, a total of 30 patients underwent SSALA and these were matched with 60 TPLA patients. There were no significant differences in the mean operative time, hospital stay, and 30-day morbidity rate between the two groups. None of the patients required conversion. Two patients with significant contamination and abscess collection noted during SSALA required a relaparotomy for peritoneal lavage and adhesiolysis due to prolonged ileus. CONCLUSIONS SSALA is feasible and the perioperative outcome was comparable to that of TPLA. However, future prospective studies will need to evaluate whether SSALA can adequately tackle patients with significant peritoneal contamination.


title: Implications of myocardial reperfusion on survival in women versus men with acute myocardial infarction undergoing primary coronary intervention.

text: We evaluated the effects of myocardial perfusion after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) on gender-based mortality rates. Research has demonstrated a gender-specific response of cardiomyocytes to ischemia and a potential increase in myocardial salvage in women compared with men. Myocardial blush grade (MBG), an angiographic surrogate of myocardial perfusion, is an independent predictor of early and late survival after AMI. Whether the incidence and prognosis of myocardial perfusion differs according to gender among patients with AMI undergoing PCI is unknown. MBG and short- and long-term mortality were evaluated in 1,301 patients (male = 935; female = 366) with AMI randomized to primary angioplasty ± abciximab versus stent ± abciximab. Following PCI, >96% of patients achieved final Thrombolysis In Myocardial Infarction 3 flow, of which MBG 2/3 was present in 58.3% of women versus 51.1% of men (p = 0.02). Worse MBG was an independent predictor of mortality in women at 30 days (7.4% for MBG 0/1 vs 2.4% for MBG 2/3, p = 0.04) and at 1-year (11.0% for MBG 0/1 vs 3.4% for MBG 2/3, p = 0.01); however, MBG was not associated with differences in mortality for men. In conclusion, impaired myocardial perfusion following PCI for AMI, indicated by worse MBG, is an independent predictor of early and late mortality in women but not in men. These findings imply an enhanced survival benefit from restoring myocardial perfusion for women compared with men during primary angioplasty and may have clinical implications for interventional strategies in women.


Single-Institution Experience in Clinical Trials During the COVID-19 Pandemic in Spain: Not So Bad After All?


docid: gvtjpxcz

title: Fluorescent imaging of superficial head and neck squamous cell carcinoma using a γ-glutamyltranspeptidase-activated targeting agent: a pilot study.

text: BACKGROUND Detecting superficial head and neck squamous cell carcinoma (HNSCC) by endoscopy is challenging because of limited morphological hallmarks, and iodine cannot be applied to head and neck lesions due to severe mucosal irritation. γ-glutamyltranspeptidase (GGT), a cell surface enzyme, is overexpressed in several cancers, and it has been reported that γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a fluorescent targeting agent which can be enzymatically activated and becomes fluorescent after cleavage of a GGT-specific sequence, can be activated within a few minutes after application to animal models. We investigated whether early HNSCC can be detected by applying gGlu-HMRG to clinical samples. METHODS gGlu-HMRG was applied to four HNSCC cell lines, and fluorescence was observed by fluorescence microscopy and flow cytometry. Immunohistological examination was performed in three recent cases of endoscopic submucosal dissection (ESD) to investigate GGT expression. Fluorescence imaging with gGlu-HMRG in eight clinical samples resected by ESD or surgery was performed, and fluorescence intensity of tumor and normal mucosa regions of interest (ROI) was prospectively measured. RESULTS All four gGlu-HMRG-applied cell lines emitted green fluorescence. Immunohistological examination demonstrated that GGT was highly expressed in HNSCC of the recent three ESD cases but barely in the normal mucosa. Fluorescence imaging showed that iodine-voiding lesions became fluorescent within a few minutes after application of gGlu-HMRG in all eight resected tumors. Tumor ROI fluorescence intensity was significantly higher than in the normal mucosa five minutes after gGlu-HMRG application. CONCLUSIONS Fluorescence imaging with gGlu-HMRG would be useful for early detection of HNSCC.


Response to "Does bariatric surgery influence diabetic retinopathy".


title: Rapid implementation of virtual neurology in response to the COVID-19 pandemic.

text: The COVID-19 pandemic is causing world-wide social dislocation, operational and economic dysfunction, and high rates of morbidity and mortality. Medical practices are responding by developing, disseminating and implementing unprecedented changes in health care delivery. Telemedicine has rapidly moved to the frontline of clinical practice due to the need for prevention and mitigation strategies; these have been encouraged, facilitated, and enabled by changes in government rules and regulations and payer-driven reimbursement policies.We describe our neurology department's situational transformation from in-person outpatient visits to a largely virtual neurology practice in response to the COVID-19 pandemic. Two key factors enabled our rapid deployment of virtual encounters in neurology and its subspecialties. The first was a well-established robust information technology infrastructure supporting virtual urgent care services at our institution; this connected physicians directly to patients using both the physician's and the patient's own mobile devices. The second is the concept of one patient, one chart, facilitated by a suite of interconnected electronic medical record (EMR) applications on several different device types.We present our experience with conducting general teleneurology encounters using secure synchronous audio and video connections integrated with an EMR. This report also details how we perform virtual neurological examinations that are clinically meaningful, and how we document, code and bill for these virtual services. Many of these processes can be used by other neurology providers, regardless of their specific practice model. We then discuss potential roles for teleneurology after the COVID-19 global pandemic has been contained.


title: In vitro antiviral activity of Brazilian plants (Maytenus ilicifolia and Aniba rosaeodora) against bovine herpesvirus type 5 and avian metapneumovirus.

text: CONTEXT Medicinal plants are well known for their use in traditional folk medicine as treatments for many diseases including infectious diseases. OBJECTIVE Six Brazilian medicinal plant species were subjected to an antiviral screening bioassay to investigate and evaluate their biological activities against five viruses: bovine herpesvirus type 5 (BHV-5), avian metapneumovirus (aMPV), murine hepatitis virus type 3, porcine parvovirus and bovine respiratory syncytial virus. MATERIALS AND METHODS The antiviral activity was determined by a titration technique that depends on the ability of plant extract dilutions (25 or 2.5 µg/mL) to inhibit the viral induced cytopathic effect and the extracts' inhibition percentage (IP). RESULTS Two medicinal plant species showed potential antiviral activity. The Aniba rosaeodora Ducke (Lauraceae) extract had the best results, with 90% inhibition of viral growth at 2.5 µg/mL when the extract was added during the replication period of the aMPV infection cycle. The Maytenus ilicifolia (Schrad.) Planch. (Celastraceae) extracts at a concentration of 2.5 µg/mL exhibited antiviral activity during the attachment phase of BHV-5 (IP = 100%). DISCUSSION AND CONCLUSION The biomonitored fractionation of the active extracts from M. ilicifolia and A. rosaeodora could be a potential tool for identifying their active compounds and determining the exact mechanism of action.


title: Decreased Mortality of COVID-19 with Renin-Angiotensin-Aldosterone System Inhibitors Therapy in Patients with Hypertension: A Meta-Analysis.

text: The coronavirus disease 2019 (COVID-19) is caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), having gradually developed into a pandemic and endangered global health. The continued use of angiotensin converting enzyme inhibitor (ACEIs) and angiotensin II receptor blockers (ARBs) which are part of renin-angiotensin-aldosterone system (RAAS) inhibitors in COVID-19 patients with hypertension has become controversial. We conducted a meta-analysis by searching Pubmed, Web of Science, Scopus and Embase up to 13 May 2020. Data analyses were performed by the Cochrane Collaboration's Review Manager 5.3 software. Finally, we included 9 studies comprising 3936 patients with hypertension and COVID-19 infection. Compared with non-ACEI/ARB treatment, ACEI/ARB treatment was not associated with disease severity (OR 0.71, 95 % CI 0.46-1.08, P 0.11, I2 59%) but was related to lower mortality of COVID-19 in patients with hypertension (OR 0.57, 95 % CI 0.38-0.84, P 0.004, I2 0). In summary, ACEI/ARB therapy did not aggravate disease severity of COVID-19. Besides, ACEI/ARB therapy can decrease the mortality of COVID-19. Current evidence suggested that RAAS inhibitors should be continued in COVID-19 patients with hypertension. Future well-designed randomized controlled trials are needed to confirm these findings.


David Oliver: Covid-19 highlights the need for effective government communications.


docid: iiziltun

title: Perspectives From COPD Subjects on Portable Long-Term Oxygen Therapy Devices.

text: BACKGROUND Oxygen therapy for patients with COPD and severe hypoxemia requires the use of oxygen delivery devices that allow mobility as needed. However, the characteristics of some devices may limit the freedom of individuals to be as physically active as they desire. Limited mobility may negatively affect the perceived quality of life of individuals with COPD. The aim of this study was to understand perceived limitations that patients with COPD experience in using long-term oxygen therapy (LTOT) devices. METHODS We performed a qualitative analysis of 311 responses to an open-ended question from a previously deployed electronic survey designed to investigate how LTOT devices affect oxygen-dependent patients with COPD. Our thematic analysis was facilitated by NVivo, a qualitative data analysis software package. This involved identifying patterns and themes within the robust, text-rich data from the open-ended survey question regarding the survey subjects' experiences with their LTOT devices. Cluster analysis was also performed to highlight relationships between various concepts. RESULTS Themes generated revealed that subjects experienced decreased mobility, which resulted in feelings of decreased autonomy and isolation. We also found that subjects perceived a decrease in quality of life due to their described experience of portable oxygen cylinders being heavy and cumbersome. Subjects described feelings of fear and anxiety due to insufficient support for breathing provided by pulse-dose portable oxygen concentrators, as well as portable oxygen cylinders that run out before they are able to complete errands and other activities of daily living. Some subjects also reported that they willingly pay for liquid oxygen systems out-of-pocket because of the mobility it affords, which in their perception improves their quality of life. CONCULSIONS Oxygen-dependent individuals with COPD may be at risk of adverse outcomes associated with decreased mobility encouraged by unsatisfactory physical and technical characteristics of portable oxygen cylinders and concentrators.


title: Frequency, Risk Factors, and Outcome of Coexistent Small Vessel Disease and Intracranial Arterial Stenosis: Results From the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial.

text: IMPORTANCE Intracranial arterial stenosis (ICAS) and small vessel disease (SVD) may coexist. There are limited data on the frequency and risk factors for coexistent SVD and the effect of SVD on stroke recurrence in patients receiving medical treatment for ICAS. OBJECTIVE To investigate the frequency and risk factors for SVD and the effect of SVD on stroke recurrence in patients with ICAS. DESIGN, SETTING, AND PARTICIPANTS A post hoc analysis of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study, a prospective, multicenter clinical trial. Among 451 participants, 313 (69.4%) had baseline brain magnetic resonance imaging scans read centrally for SVD that was defined by any of the following: old lacunar infarction, grade 2 to 3 on the Fazekas scale (for high-grade white matter hyperintensities), or microbleeds. Patient enrollment in SAMMPRIS began November 25, 2008, and follow-up ended on April 30, 2013. Data analysis for the present study was performed from May 13, 2014, to July 29, 2015. MAIN OUTCOMES AND MEASURES Risk factors in patients with vs without SVD and the association between SVD and other baseline risk factors with any ischemic stroke and ischemic stroke in the territory of the stenotic artery determined using proportional hazards regression. RESULTS Of 313 patients, 155 individuals (49.5%) had SVD noted on baseline magnetic resonance imaging. Variables that were significantly higher in patients with SVD, reported as mean (SD), included age, 63.5 (10.5) years (P < .001), systolic blood pressure, 149 (22) mm Hg (P < .001), glucose level, 130 (50) mg/dL (P = .03), and lower Montreal Cognitive Assessment scores (median, ≥24 [interquartile range, 20-26]; P = .02).Other significant variables were the number of patients with diabetes mellitus (88 of 155 [56.8%]; P = .003), coronary artery disease (46 [29.7%]; P = .004), stroke before the qualifying event (59 [38.1%]; P < .001), old infarct in the territory of the stenotic intracranial artery (88 [56.8%]; P < .001), and receiving antithrombotic therapy at the time of the qualifying event (109 [70.3%]; P = .005). The association between SVD and any ischemic stroke was nearly significant in the direction of a higher risk (18 [23.7%]); P = .07) for patients with SVD. On bivariate analysis, SVD was not associated with an increased risk on multivariable analyses (hazard ratio, 1.7 [95% CI, 0.8-3.8]; P = .20). In addition, SVD was not associated with an increased risk of stroke in the territory on either bivariate or multivariable analyses. CONCLUSIONS AND RELEVANCE Although SVD is common in patients with ICAS, the presence of SVD on baseline magnetic resonance imaging is not independently associated with an increased risk of stroke in patients with ICAS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00576693.


title: MHC class II proteins mediate cross-species entry of bat influenza viruses.

text: Zoonotic influenza A viruses of avian origin can cause severe disease in individuals, or even global pandemics, and thus pose a threat to human populations. Waterfowl and shorebirds are believed to be the reservoir for all influenza A viruses, but this has recently been challenged by the identification of novel influenza A viruses in bats1,2. The major bat influenza A virus envelope glycoprotein, haemagglutinin, does not bind the canonical influenza A virus receptor, sialic acid or any other glycan1,3,4, despite its high sequence and structural homology with conventional haemagglutinins. This functionally uncharacterized plasticity of the bat influenza A virus haemagglutinin means the tropism and zoonotic potential of these viruses has not been fully determined. Here we show, using transcriptomic profiling of susceptible versus non-susceptible cells in combination with genome-wide CRISPR-Cas9 screening, that the major histocompatibility complex class II (MHC-II) human leukocyte antigen DR isotype (HLA-DR) is an essential entry determinant for bat influenza A viruses. Genetic ablation of the HLA-DR α-chain rendered cells resistant to infection by bat influenza A virus, whereas ectopic expression of the HLA-DR complex in non-susceptible cells conferred susceptibility. Expression of MHC-II from different bat species, pigs, mice or chickens also conferred susceptibility to infection. Notably, the infection of mice with bat influenza A virus resulted in robust virus replication in the upper respiratory tract, whereas mice deficient for MHC-II were resistant. Collectively, our data identify MHC-II as a crucial entry mediator for bat influenza A viruses in multiple species, which permits a broad vertebrate tropism.


title: Frequency, determinants, and effects of early seizures after thrombolysis for acute ischemic stroke: The ENCHANTED trial.

text: Background Seizures after ischemic stroke have not been well-studied. We aim to determine the frequency, determinants, and significance of early seizures after thrombolysis for acute ischemic stroke. Methods Data are from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, multicenter, randomized controlled trial where patients with acute ischemic stroke were randomized to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) IV alteplase. The protocol prespecified prospective data collection on in-hospital seizures over 7 days postrandomization. Logistic regression models were used to determine variables associated with seizures and their significance on poor outcomes of death or disability (modified Rankin scale scores 3-6), symptomatic intracerebral hemorrhage (sICH), and European Quality of Life 5-Dimensions questionnaire [EQ-5D] over 90 days. Results Data were available for 3,139 acute ischemic stroke participants, of whom 42 (1.3%) had seizures at a median 22.7 hours after the onset of symptoms. Baseline variables associated with seizures were male sex (odds ratio [OR] 2.19, 95% confidence interval [CI] 1.07-4.50), severe neurologic impairment (NIH Stroke Scale score ≥10; OR 2.16, 95% CI 1.06-4.40), and fever (OR 4.55, 95% CI 2.37-8.71). Seizures independently predicted poor recovery: death or major disability (OR 2.88, 95% CI 1.28-6.47), unfavorable ordinal shift of mRS scores (OR 1.94, 95% CI 1.10-3.39), and lower than median EQ-5D health utility index score (OR 3.50, 95% CI 1.37-8.91). There was no association of seizures with sICH in adjusted analysis. Conclusions In thrombolysis-treated patients with acute ischemic stroke, seizures are uncommon, occur early, and predict poor recovery. Clinicaltrialsgov identifier NCT01422616.


docid: hjtxkivh

title: A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm.

text: Neither the disease mechanism nor treatments for COVID-19 are currently known. Here we present a novel molecular mechanism for COVID-19 that provides therapeutic intervention points that can be addressed with existing FDA-approved pharmaceuticals. The entry point for the virus is ACE2, which is a component of the counteracting hypotensive axis of RAS, that produces the nonapeptide angiotensin1-9 from angiotensin I. Bradykinin is a potent, but often forgotten, part of the vasopressor system that induces hypotension and vasodilation 1, and is regulated by ACE and enhanced by angiotensin1-9 2. Here we perform a completely new analysis on gene expression data from cells of bronchoalveolar lavage samples from COVID-19 patients that were used to sequence the virus, but the host information was discarded 3. Comparison with lavage samples from controls identify a critical imbalance in RAS represented by decreased expression of ACE in combination with increases in ACE2, renin (REN) , angiotensin (AGT), key RAS receptors (AGTR2, AGTR1), kinogen (KNG) and the kallikrein enzymes (KLKB1, many of KLK-1-15) that activate it, and both bradykinin receptors (BDKRB1, BDKRB2). This very atypical pattern of the RAS is predicted to elevate bradykinin levels in multiple tissues and systems that will likely cause increases in vascular dilation, vascular permeability and hypotension. These bradykinin-driven outcomes explain many of the symptoms being observed in COVID-19.


title: ORCHIEPIDIDYMITIS IN A BOY WITH COVID-19.

text: Coronavirus disease 2019 (COVID-19) symptoms in children are incompletely described. We present the first case of orchiepididymitis associated with COVID-19 in a boy and discuss pathways of testicular involvement by SARS-CoV2 virus. This case underlines the need for further study of the clinical presentation of pediatric COVID-19 and the potential association with nonrespiratory symptoms.


title: Diagnostic laparoscopy in the cat: 2. Common procedures.

text: PRACTICAL RELEVANCE Minimally invasive techniques are becoming increasingly available in both first opinion and referral veterinary surgeries. Clients may be reluctant to pursue open surgery for the collection of biopsy samples in a sick cat but may be more open to a laparoscopic approach. Furthermore, a laparoscopic approach provides excellent visualization of the abdominal organs and enables high quality biopsies to be taken that are invariably more diagnostic than percutaneous needle biopsies. Although the feline patient is small in size, its distensible abdomen allows more room for surgical manipulation than afforded by a similar sized canine patient. CLINICAL CHALLENGES Clinical challenges for the most part relate to mastering laparoscopic technique. Familiarity with the use of long instrumentation viewed on a two-dimensional screen is essential. Hemostasis is an important consideration and suitable instrumentation for achieving hemostasis should be available at all times. Insufflation of the abdomen carries its own challenges with regard to anesthesia and this is covered in an accompanying article in this Special Issue series. AIM This article introduces the feline practitioner to basic techniques required to effectively utilize diagnostic laparoscopy within feline medical investigations. It focuses on the common procedures of liver biopsy, cholecystocentesis, pancreatic biopsy, kidney biopsy and laparoscopic-assisted intestinal biopsy. EVIDENCE BASE Information provided in this article is drawn from the published literature and the authors' own clinical experience.


title: Oxidative stress enhances toll-like receptor 3 response to double-stranded RNA in airway epithelial cells.

text: Virus infections are a major cause of chronic obstructive pulmonary disease (COPD) exacerbations. Recently, Toll-like receptor 3 (TLR3) has been demonstrated to react to double-stranded RNA (dsRNA) and to be involved in the immune responses after viral infections. In the present study, we examined whether oxidative stress, which is involved in the pathogenesis of COPD, enhances the responses of TLR3 in airway epithelial cells. The effect of hydrogen peroxide (H(2)O(2)) on the release of IL-8 from BEAS-2B cells and primary human bronchial epithelial cells after stimulation with polyinosine-polycytidylic acid [poly(I:C)], a synthetic analog of viral dsRNA and a ligand for TLR3, and the signal transduction were examined. One hundred to 150 muM H(2)O(2) significantly potentiated the release of IL-8 from the epithelial cells after stimulation with 10 microg/ml poly(I:C). The H(2)O(2)-augmented IL-8 release was inhibited by treatment with N-acetylcysteine. One hundred micromoles of H(2)O(2) enhanced the translocation of nuclear factor (NF)-kappaB p65, but not that of interferon regulatory factor-3 (IRF-3), into the nucleus and the NF-kappaB DNA binding activity after poly(I:C) stimulation, which effect was inhibited not by the silencing of IRF-3 but by MG132, a proteasome inhibitor, or dexamethasone. One hundred micromoles of H(2)O(2) potentiated the TLR3 expression on the airway epithelial cells treated with poly(I:C). These data suggest that oxidative stress augments the response of TLR3 in airway epithelial cells via NF-kappaB and that this effect might be partly mediated by the enhancement of TLR3 expression. Modulation of this pathway may be a therapeutic target for viral-induced exacerbations of COPD.


title: Functionalized N,N-Diphenylamines as Potent and Selective EPAC2 Inhibitors.

text: N,N-Diphenylamines were discovered as potent and selective EPAC2 inhibitors. A study was conducted to determine the structure-activity relationships in a series of inhibitors of which several compounds displayed submicromolar potencies. Selectivity over the related EPAC1 protein was also demonstrated. Computational modeling reveals an allosteric site that is distinct from the cAMP binding domain shared by both EPAC isoforms, providing a theory with regards to subtype selectivity.


Prolific research on a barren rock.


title: Prospective observational study of the effectiveness of prewarming on perioperative hypothermia in surgical patients submitted to spinal anesthesia.

text: Prewarming has been shown to prevent intraoperative inadvertent hypothermia. Nevertheless, data about optimal prewarming-time from published clinical trials report contradictory results. We conducted this pilot study to evaluate routine clinical practice regarding prewarming and its effect on the prevalence of perioperative hypothermia in patients undergoing transurethral resection (TUR) under spinal anesthesia. This was a prospective, observational, pilot study to examine clinical practice in a tertiary hospital regarding prewarming in 140 consecutive patients. When prewarming (pw) was performed, forced-air warming was provided in the pre-anesthesia room for 15 (pw15), 30 (pw30), or 45 (pw45) min. Tympanic temperature was recorded upon entering the pre-anesthesia room, at the time of initiating surgery, and every 15 min intra-operatively. We also recorded duration of the surgical procedure and length of stay in the Post-Anesthesia Care Unit (PACU). Pw15 was performed in 34 patients, pw30 in 29 patients, and pw45 in 21 patients. Fifty-six patients did not receive pw and 96% of them developed hypothermia at the end of the surgical procedure, compared to 73% of patients in pw15 (p = 0.002), 75% in pw30 (p = 0.006) and 90% in pw45 (p = 0.3). Length of stay in the PACU was markedly shorter in pw15 (131 ± 69 min) and pw30 (123 ± 60 min) than in the non-pw group (197 ± 105 min) (p = 0.015 and p = 0.011, respectively). This difference was not significant in pw45 (129 ± 56 min) compared to non-pw patients. In conclusion, prewarming for 15 or 30 min before TUR under spinal anesthesia prevents development of hypothermia at the end of the surgical procedure.


title: Clinical Predictors of Influenza in Young Children: The Limitations of "Influenza-Like Illness".

text: BACKGROUND Influenza-like illness (ILI) definitions have been infrequently studied in young children. Despite this, clinical definitions of ILI play an important role in influenza surveillance. This study aims to identify clinical predictors of influenza infection in children ≤5 years old from which age-specific ILI definitions are then constructed. METHODS Children aged 6-59 months with a history of fever and acute respiratory symptoms were recruited in the Western Australia Influenza Vaccine Effectiveness (WAIVE) Study. Clinical data and per-nasal specimens were obtained from all children. Logistic regression identified significant predictors of influenza infection. Different ILI definitions were compared for diagnostic accuracy. RESULTS Children were recruited from 2 winter influenza seasons (2008-2009; n = 944). Of 919 eligible children, 179 (19.5%) had laboratory-confirmed influenza infection. Predictors of infection included increasing age, lack of influenza vaccination, lower birth weight, fever, cough, and absence of wheeze. An ILI definition comprising fever ≥38°C, cough, and no wheeze had 58% sensitivity (95% confidence interval [CI], 50-66), 60% specificity (95% CI, 56-64), 26% positive predictive value (95% CI, 21-31), and 86% negative predictive value (95% CI, 82-89). The addition of other symptoms or higher fever thresholds to ILI definition had little impact. The Centers for Disease Control and Prevention definition of ILI (presence of fever [≥37.8°C] and cough and/or sore throat) was sensitive (92%; 95% CI, 86-95), yet lacked specificity (10%; 95% CI, 8-13) in this population. CONCLUSIONS Influenza-like illness is a poor predictor of laboratory-confirmed influenza infection in young children but can be improved using age-specific data. Incorporating age-specific ILI definitions and/or diagnostic testing into influenza surveillance systems will improve the accuracy of epidemiological data.


title: Differences in perceptions of coronary disease among Hong Kong Chinese: implications for the societal readiness in disease prevention.

text: Perceptions of coronary heart disease (CHD) influence individual health behavior, which is central to preventing the disease. Not enough is known about the demographic differences in perceptions of CHD among Chinese communities. This study examined these differences in the perceived seriousness and risk of CHD among Hong Kong Chinese. A self-developed questionnaire was administered to a convenient sample (n = 236). Significant differences were identified in the perceived seriousness and risk of CHD between younger and older age groups (p < 0.001) and groups with lower and higher education levels (p < 0.001), but not between genders (p > 0.05). Over 50% of participants expressed greater concern about infectious disease than about CHD, while two-thirds to over half of female, older, and less educated participants were more concerned about stroke. This study highlighted populations with lower levels of CHD perception that need increased public education. The findings have implications for the societal readiness to establishing ongoing public healthcare strategies to increase awareness of CHD.