title: Passive versus active intra-abdominal drainage following pancreatic resection: does a superior drainage system exist? A protocol for systematic review.

text: BACKGROUND Clinically relevant postoperative pancreatic fistula (CR-POPF) is the most common cause of major morbidity following pancreatic resection. Intra-abdominal drains are frequently positioned adjacent to the pancreatic anastomosis or transection margin at the time of surgery to aid in detection and management of CR-POPF. Drains can either evacuate fluid by passive gravity (PG) or be attached to a closed suction (CS) system using negative pressure. There is controversy as to whether one of these two systems is superior. The objective of this review is to identify and compare the incidence of adverse events (AEs) and resource utilisation associated with PG and CS drainage following pancreatic resections. METHODS AND ANALYSIS MEDLINE, EMBASE, CINAHL and Cochrane Central Registry of Controlled Trials will be searched from inception to April 2019, to identify interventional and observational studies comparing PG and CS drains following pancreatic resection. The primary outcome is POPF as defined by the International Study Group for Pancreatic Fistula in 2017. Secondary outcomes include postoperative AE, resource utilisation (length of stay, return to emergency department, readmission and reintervention), time to drain removal and quality of life. Study selection, data extraction and risk of bias assessment will be performed independently, by two reviewers. A meta-analysis will be conducted if deemed statistically appropriate. Subgroup analysis by study design will be performed. Study heterogeneity will be calculated with the χ2 test and reported as I2 statistics. Statistical analyses will be conducted and displayed using RevMan V.5.3 ETHICS AND DISSEMINATION: Ethics approval is not required. The results of this study will be submitted to relevant conferences for presentation and peer-reviewed journals for publication. PROSPERO REGISTRATION NUMBER CRD42019123647.


title: Postoperative Cervical Cord Compression Induced by Hydrogel Dural Sealant (DuraSeal®).

text: Cerebrospinal fluid (CSF) leakage is a potential complication of cranial and spinal surgery. Postoperative CSF leakage can induce delayed healing, wound infection and meningitis. DuraSeal® (Covidien, Waltham, MA, USA) is a synthetic product which has been increasingly used to facilitate watertight repair of dural defects after cranial and spinal surgery. Despite some advantages of Duraseal®, the authors report a patient who developed cord compression following the use of DuraSeal® in cervical spine surgery in which the expansion of the DuraSeal® was believed to be the causative factor.


title: Robotic-assisted thoracoscopic enucleation of esophageal leiomyoma.

text: Minimally invasive approaches to esophageal leiomyoma, including thoracoscopic and laparoscopic enucleation, have been shown to have better postoperative recovery compared with thoracotomy approach. We present a case of robotic-assisted thoracoscopic enucleation of esophageal leiomyoma using the da Vinci(®) S system.


title: Porcine Epidemic Diarrhea Virus and Porcine Deltacoronavirus not Detected in Waterfowl in the North American Mississippi Migratory Bird Flyway in 2013.

text: Cloacal swab samples collected from 538 migratory waterfowl along the Mississippi Migratory Bird Flyway in 2013 were tested for porcine epidemic diarrhea virus and porcine deltacoronavirus. Neither virus was detected in any of the samples, indicating that waterfowl likely did not contribute to the rapid spread of these viruses within central US.


title: Prediction of response to endoscopic therapy of Barrett's dysplasia by using genetic biomarkers.

text: BACKGROUND Endoscopic therapy for the treatment of high-grade dysplasia (HGD) and intramucosal cancer (IMC) in Barrett's esophagus (BE) may not always result in complete remission of dysplasia (CRD). OBJECTIVE To determine whether genetic alterations in the Barrett's mucosa can predict response to endoscopic therapy. DESIGN Retrospective cohort study. SETTING Tertiary-care institution. PATIENTS Selected patients who underwent endoscopic therapy for BE containing HGD/IMC between 2003 and 2010. INTERVENTIONS Endoscopic therapy combining mucosal resection and different ablation modalities was performed based on patient characteristics, endoscopic findings, and technique evolution. Fluorescence in situ hybridization was used to evaluate genetic alterations on baseline endoscopic cytology brushings by using probes directed to loci 8q24 (MYC), 9p21 (CDKN2A; alias P16), 17q12 (ERBB2; alias Her-2/neu), and 20q13.2 (ZNF217). MAIN OUTCOME MEASUREMENTS Genetic biomarkers predicting achievement of CRD after endoscopic therapy. RESULTS A total of 181 patients were included (145 men; 66 ± 10 years of age). There were 130 patients (72%) who responded to endoscopic therapy with CRD. Multiple gains detected by fluorescence in situ hybridization was found to be a negative predictor (hazard ratio 0.57; 95% confidence interval, 0.40-0.82) after adjusting for potential clinical confounders. Similar results were found when analyses were restricted to patients (n = 66) undergoing radiofrequency ablation (hazard ratio 0.58; 95% confidence interval, 0.31-1.09). LIMITATIONS Retrospective study, heterogeneity of treatment modalities. CONCLUSION Patients with multiple gains detected by brush cytology specimens may have a lower response rate to endoscopic therapy. The presence of multiple gains can be an adjunct to standard histology in prognosticating BE patients with HGD/IMC undergoing endoscopic therapy.


Covid-19: Health and care workers will be "highest priority" for vaccination, says JCVI.


title: The Role of Phosphodiesterase 12 (PDE12) as a Negative Regulator of the Innate Immune Response and the Discovery of Antiviral Inhibitors.

text: 2',5'-Oligoadenylate synthetase (OAS) enzymes and RNase-L constitute a major effector arm of interferon (IFN)-mediated antiviral defense. OAS produces a unique oligonucleotide second messenger, 2',5'-oligoadenylate (2-5A), that binds and activates RNase-L. This pathway is down-regulated by virus- and host-encoded enzymes that degrade 2-5A. Phosphodiesterase 12 (PDE12) was the first cellular 2-5A- degrading enzyme to be purified and described at a molecular level. Inhibition of PDE12 may up-regulate the OAS/RNase-L pathway in response to viral infection resulting in increased resistance to a variety of viral pathogens. We generated a PDE12-null cell line, HeLaΔPDE12, using transcription activator-like effector nuclease-mediated gene inactivation. This cell line has increased 2-5A levels in response to IFN and poly(I-C), a double-stranded RNA mimic compared with the parental cell line. Moreover, HeLaΔPDE12 cells were resistant to viral pathogens, including encephalomyocarditis virus, human rhinovirus, and respiratory syncytial virus. Based on these results, we used DNA-encoded chemical library screening to identify starting points for inhibitor lead optimization. Compounds derived from this effort raise 2-5A levels and exhibit antiviral activity comparable with the effects observed with PDE12 gene inactivation. The crystal structure of PDE12 complexed with an inhibitor was solved providing insights into the structure-activity relationships of inhibitor potency and selectivity.


title: A Custom-made Pupillometer System for Characterizing Pupillary Light Response.

text: Objectives This paper presents the design and construction of a viable pupillometer system and demonstrates its merits with extensive validation tests. Materials and Methods A web camera was modified by removing its infrared filter and mounted on a chin rest. Light emitting diodes (LEDs) operating at infrared and visible spectra were integrated to provide background and light stimulus, respectively. The LEDs were controlled by a microprocessor board. Stimulation was presented using a periodic paradigm with variable period and duty cycle. Videos of both pupils were recorded at 30 frames/second and processed offline using software developed in-house. The overall system was validated with data gathered from individuals with healthy vision under different stimulation paradigms. Temporal variations in pupil size were determined and analyzed statistically. Results The analysis revealed that the pupil sizes were accurately measured from the video frames provided that reflections from both infrared and visible lights remain outside the pupil. The system achieved moderate to excellent repeatability scores (87.8 and 86.8% for short 1 second and long 2 second pulses, respectively), which demonstrated its effectiveness and confirmed that it can be used reliably as a pupillometer. Conclusion The proposed pupillometer system produces useful, quantitative data characterizing pupillary light response. However, further development and implementation are needed to potentially turn it into a low-cost alternative for other studies involving the autonomic nervous system, cognitive function, drug metabolism, pain response, psychology, fatigue, and sleep disorders.


title: Cardiac manifestations in COVID-19 patients-A systematic review.

text: OBJECTIVES The coronavirus disease-2019 (COVID-19) pandemic has resulted in the worst global pandemic of our generation, affecting 215 countries with nearly 5.5 million cases. The association between COVID-19 and the cardiovascular system has been well described. We sought to systematically review the current published literature on the different cardiac manifestations and the use of cardiac-specific biomarkers in terms of their prognostic value in determining clinical outcomes and correlation to disease severity. METHODS A systematic literature review across PubMed, Cochrane database, Embase, Google Scholar, and Ovid was performed according to PRISMA guidelines to identify relevant articles that discussed risk factors for cardiovascular manifestations, cardiac manifestations in COVID-19 patients, and cardiac-specific biomarkers with their clinical implications on COVID-19. RESULTS Sixty-one relevant articles were identified which described risk factors for cardiovascular manifestations, cardiac manifestations (including heart failure, cardiogenic shock, arrhythmia, and myocarditis among others) and cardiac-specific biomarkers (including CK-MB, CK, myoglobin, troponin, and NT-proBNP). Cardiovascular risk factors can play a crucial role in identifying patients vulnerable to developing cardiovascular manifestations of COVID-19 and thus help to save lives. A wide array of cardiac manifestations is associated with the interaction between COVID-19 and the cardiovascular system. Cardiac-specific biomarkers provide a useful prognostic tool in helping identify patients with the severe disease early and allowing for escalation of treatment in a timely fashion. CONCLUSION COVID-19 is an evolving pandemic with predominate respiratory manifestations, however, due to the interaction with the cardiovascular system; cardiac manifestations/complications feature heavily in this disease, with cardiac biomarkers providing important prognostic information.


title: COVID-19, Australia: Epidemiology Report 12 (Reporting week to 23:59 AEST 19 April 2020).

text: Confirmed cases in Australia notified up to 19 April 2020: notifications = 6,606; deaths = 69. The reduction in international travel and domestic movement, social distancing measures and public health action have likely slowed the spread of the disease. Notifications in Australia remain predominantly among people with recent overseas travel, with some locally-acquired cases being detected. Most locally-acquired cases can be linked back to a confirmed case, with a small portion unable to be epidemiologically linked. The distribution of overseas-acquired cases to locally-acquired cases varies by jurisdiction. The crude case fatality rate (CFR) in Australia remains low (1.0%) compared to the World Health Organization's globally-reported rate (6.8%) and to other comparable high-income countries such as the United States of America (4.7%) and the United Kingdom (13.5%). The low CFR is likely reflective of high case ascertainment including detection of mild cases. High case ascertainment enables public health response and reduction of disease transmission. Internationally, cases continue to increase. The rates of increase have started to slow in several regions, although it is too soon to tell whether this trend will be sustained. Interpretation of international epidemiology should be conducted with caution as it differs from country to country depending not only on the disease dynamics, but also on differences in case detection, testing and implemented public health measures.


title: Limitations of the db/db mouse in translational wound healing research: Is the NONcNZO10 polygenic mouse model superior?

text: Murine models have provided valuable insights into the pathogenesis of both diabetes and chronic wounds. However, only a few published reports to date have investigated wound healing differences among the differing diabetic mouse models. The goal of the present study was to further define the wound healing deficiency phenotypes of streptozotocin-induced (STZ-induced), Akita, and db/db diabetic mice in comparison with a promising new polygenic strain of Type 2 diabetes (NONcNZO10) by using three specific wound models that targeted different critical processes in the pathogenesis of chronic wounds. Incisional, excisional, and ischemia/reperfusion wound models were established on mice of each strain. Wound healing parameters including tensile strength, epithelial gap, and wound necrosis were evaluated. In contrast to the other diabetic mice, the NONcNZO10 strain was found to have significant wound healing impairments in all wound healing models. Not only do the NONcNZO10 mice appear to better model human Type 2 diabetes, these provocative findings suggest that the mice may show more clinically relevant wound healing deficiencies than previous diabetic mouse models.


title: Current status of robot-assisted radical cystectomy for bladder cancer.

text: Radical cystectomy is associated with significant morbidity. However, the introduction of minimally invasive surgical approaches has attempted to improve perioperative outcomes and decrease surgical complications. Emerging data suggest that robot-assisted radical cystectomy (RARC) might have some advantages compared with open radical cystectomy (ORC). However, the oncologic performance of RARC in patients with locally advanced disease is currently unclear, making it crucial to select patients for the procedure very carefully. No long-term prospective studies comparing the robot-assisted and open techniques have been reported. Until long-term oncologic outcomes of RARC and the results of currently ongoing randomized trials comparing the two techniques become available, ORC remains the gold standard.


title: Fatal bilateral pneumothorax and generalized emphysema following contraindicated speaking-valve application.

text: We report a case of a contraindicated attachment of a speaking valve to a tracheal tube with an inflated cuff, which rapidly resulted in the patient's death. The attached one-way valve allowed unrestrained inspiration through the tracheal tube but prevented physiological expiration. The increased pulmonary pressure resulted in alveolar rupture and replaced expiration with a steady release of air into the peribronchial sheaths and the mediastinum, resulting in what is commonly known as the Macklin effect. From the mediastinum, air inflated both pleural cavities, the peritoneum, and the subcutaneous tissue of the entire body. No gas was found in the blood vessels, the brain, the bones, or in the inner organs. The entire air volume was estimated by radiological segmentation to be more than 25 l. This implies continuous inspiration, while expiration turned into an aberrant pulmonary decompression by whole-body gas-enclosure. Death ultimately resulted from asphyxia following bilateral (tension) pneumothorax.


title: Sucrose and warmth for analgesia in healthy newborns: an RCT.

text: BACKGROUND AND OBJECTIVE Increasing data suggest that neonatal pain has long-term consequences. Nonpharmacologic techniques (sucrose taste, pacifier suckling, breastfeeding) are effective and now widely used to combat minor neonatal pain. This study examined the analgesic effect of sucrose combined with radiant warmth compared with the taste of sucrose alone during a painful procedure in healthy full-term newborns. METHODS A randomized, controlled trial included 29 healthy, full-term newborns born at the University of Chicago Hospital. Both groups of infants were given 1.0 mL of 25% sucrose solution 2 minutes before the vaccination, and 1 group additionally was given radiant warmth from an infant warmer before the vaccination. We assessed pain by comparing differences in cry, grimace, heart rate variability (ie, respiratory sinus arrhythmia), and heart rate between the groups. RESULTS The sucrose plus warmer group cried and grimaced for 50% less time after the vaccination than the sucrose alone group (P < .05, respectively). The sucrose plus warmer group had lower heart rate and heart rate variability (ie, respiratory sinus arrhythmia) responses compared with the sucrose alone group (P < .01), reflecting a greater ability to physiologically regulate in response to the painful vaccination. CONCLUSIONS The combination of sucrose and radiant warmth is an effective analgesic in newborns and reduces pain better than sucrose alone. The ready availability of this practical nonpharmacologic technique has the potential to reduce the burden of newborn pain.


title: Safety and feasibility of laparoscopic gastrectomy accompanied by D1+ lymph node dissection for early gastric cancer in elderly patients.

text: INTRODUCTION The age of patients with gastric cancer has increased worldwide. The aim of this study was to investigate the safety and feasibility of laparoscopic gastrectomy (LG) for early gastric cancer in elderly patients. METHODS We retrospectively investigated 221 consecutive patients who underwent LG for early gastric cancer during a 5-year period (January 2010 to December 2014). We divided the patients into two groups: elderly patients (≥75 years old) and younger patients (<75 years old). We compared these two groups with respect to clinical characteristics, histopathological findings, intraoperative factors, and postoperative outcomes. RESULTS The preoperative characteristics were similar in both groups. Except for the number of harvested lymph nodes (42.0 vs 34.9; P = 0.0016), the short-term operative outcomes, including postoperative complications and histopathological findings, were comparable between the two groups. Although significantly fewer lymph nodes were harvested in the elderly group, the overall survival and relapse-free survival rates did not significantly differ between the groups. Postoperative complications, such as acute cholecystitis and internal hernia, occurred during the long-term postoperative period after LG, and these unexpected complications were more frequently observed in elderly patients. All elderly patients required additional emergent surgeries for delayed complications. CONCLUSION The outcomes of LG for early gastric cancer in elderly patients seem to be reasonable. Aggressive lymph node dissection may be omissible in elderly patients with acceptable results. LG can be a safe and feasible procedure in elderly patients. However, the higher rate of delayed but urgent complications during the long-term postoperative period must be considered.


title: Metagenomic study of bacterial microbiota in persistent endodontic infections using Next-generation sequencing.

text: AIM To determine the bacterial microbiota in root canals associated with persistent apical periodontitis and their relationship with the clinical characteristics of patients using next-generation sequencing (NGS). METHODOLOGY Bacterial samples from root canals associated with teeth having persistent apical periodontitis were taken from 24 patients undergoing root canal retreatment. Bacterial DNA was extracted, and V3-V4 variable regions of the 16S rRNA gene were amplified. The amplification was deep sequenced by Illumina technology to establish the metagenetic relationships among the bacterial species identified. The composition and diversity of microbial communities in the root canal and their relationships with clinical features were analysed. Parametric and nonparametric tests were used to analyse differences between patient characteristics and microbial data. RESULTS A total of 86 different operational taxonomic units (OTUs) were identified and Good's nonparametric coverage estimator method indicated that 99.9 ± 0.00001% diversity was recovered per sample. The largest number of bacteria belonged to the phylum Proteobacteria. According to the medical history from the American Society of Anesthesiologists (ASA) Classification System, ASA II-III had higher richness estimates and distinct phylogenetic relationships compared to ASA I individuals (P < 0.05). Periapical index (PAI) score 5 was associated with increased microbiota diversity in comparison to PAI score 4, and this index was reduced in symptomatic patients. CONCLUSIONS Based on the findings of this study, it is possible to suggest a close relationship between several clinical features and greater microbiota diversity with persistent endodontic infections. This work provides a better understanding on how microbial communities interact with their host and vice versa.


title: Nurses as substitutes for doctors in primary care.

text: BACKGROUND Current and expected problems such as ageing, increased prevalence of chronic conditions and multi-morbidity, increased emphasis on healthy lifestyle and prevention, and substitution for care from hospitals by care provided in the community encourage countries worldwide to develop new models of primary care delivery. Owing to the fact that many tasks do not necessarily require the knowledge and skills of a doctor, interest in using nurses to expand the capacity of the primary care workforce is increasing. Substitution of nurses for doctors is one strategy used to improve access, efficiency, and quality of care. This is the first update of the Cochrane review published in 2005. OBJECTIVES Our aim was to investigate the impact of nurses working as substitutes for primary care doctors on:• patient outcomes;• processes of care; and• utilisation, including volume and cost. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), part of the Cochrane Library (www.cochranelibrary.com), as well as MEDLINE, Ovid, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and EbscoHost (searched 20.01.2015). We searched for grey literature in the Grey Literature Report and OpenGrey (21.02.2017), and we searched the International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov trial registries (21.02.2017). We did a cited reference search for relevant studies (searched 27.01 2015) and checked reference lists of all included studies. We reran slightly revised strategies, limited to publication years between 2015 and 2017, for CENTRAL, MEDLINE, and CINAHL, in March 2017, and we have added one trial to 'Studies awaiting classification'. SELECTION CRITERIA Randomised trials evaluating the outcomes of nurses working as substitutes for doctors. The review is limited to primary healthcare services that provide first contact and ongoing care for patients with all types of health problems, excluding mental health problems. Studies which evaluated nurses supplementing the work of primary care doctors were excluded. DATA COLLECTION AND ANALYSIS Two review authors independently carried out data extraction and assessment of risk of bias of included studies. When feasible, we combined study results and determined an overall estimate of the effect. We evaluated other outcomes by completing a structured synthesis. MAIN RESULTS For this review, we identified 18 randomised trials evaluating the impact of nurses working as substitutes for doctors. One study was conducted in a middle-income country, and all other studies in high-income countries. The nursing level was often unclear or varied between and even within studies. The studies looked at nurses involved in first contact care (including urgent care), ongoing care for physical complaints, and follow-up of patients with a particular chronic conditions such as diabetes. In many of the studies, nurses could get additional support or advice from a doctor. Nurse-doctor substitution for preventive services and health education in primary care has been less well studied.Study findings suggest that care delivered by nurses, compared to care delivered by doctors, probably generates similar or better health outcomes for a broad range of patient conditions (low- or moderate-certainty evidence):• Nurse-led primary care may lead to slightly fewer deaths among certain groups of patients, compared to doctor-led care. However, the results vary and it is possible that nurse-led primary care makes little or no difference to the number of deaths (low-certainty evidence).• Blood pressure outcomes are probably slightly improved in nurse-led primary care. Other clinical or health status outcomes are probably similar (moderate-certainty evidence).• Patient satisfaction is probably slightly higher in nurse-led primary care (moderate-certainty evidence). Quality of life may be slightly higher (low-certainty evidence).We are uncertain of the effects of nurse-led care on process of care because the certainty of this evidence was assessed as very low.The effect of nurse-led care on utilisation of care is mixed and depends on the type of outcome. Consultations are probably longer in nurse-led primary care (moderate-certainty evidence), and numbers of attended return visits are slightly higher for nurses than for doctors (high-certainty evidence). We found little or no difference between nurses and doctors in the number of prescriptions and attendance at accident and emergency units (high-certainty evidence). There may be little or no difference in the number of tests and investigations, hospital referrals and hospital admissions between nurses and doctors (low-certainty evidence).We are uncertain of the effects of nurse-led care on the costs of care because the certainty of this evidence was assessed as very low. AUTHORS' CONCLUSIONS This review shows that for some ongoing and urgent physical complaints and for chronic conditions, trained nurses, such as nurse practitioners, practice nurses, and registered nurses, probably provide equal or possibly even better quality of care compared to primary care doctors, and probably achieve equal or better health outcomes for patients. Nurses probably achieve higher levels of patient satisfaction, compared to primary care doctors. Furthermore, consultation length is probably longer when nurses deliver care and the frequency of attended return visits is probably slightly higher for nurses, compared to doctors. Other utilisation outcomes are probably the same. The effects of nurse-led care on process of care and the costs of care are uncertain, and we also cannot ascertain what level of nursing education leads to the best outcomes when nurses are substituted for doctors.


title: Intraperitoneal Local Anesthetic Instillation and Postoperative Infusion Improves Functional Recovery Following Colectomy: A Randomized Controlled Trial.

text: BACKGROUND Intraperitoneal local anesthetic is an analgesic technique for inclusion in the polypharmacy approach to postoperative pain management in enhanced recovery after surgery programs. Previously, augmentation of epidural analgesia with intraperitoneal local anesthetic was shown to improve functional postoperative recovery following colectomy. OBJECTIVE This study determines whether intraperitoneal local anesthetic improves postoperative recovery in patients undergoing colectomy, in the absence of epidural analgesia, with standardized enhanced recovery after surgery perioperative care. DESIGN This is a multisite, double-blinded, randomized, placebo-controlled trial (ClinicalTrials.gov Identifier NCT02449720). SETTINGS This study was conducted at 3 hospital sites in South Australia. PATIENTS Eighty-six adults undergoing colectomy were stratified by approach (35 open; 51 laparoscopic), then randomly assigned to intraperitoneal local anesthetic (n = 44) and control (n = 42) groups. INTERVENTIONS Patients in the intraperitoneal local anesthetic group received an intraoperative intraperitoneal ropivacaine 100-mg bolus both pre- and postdissection and 20 mg/h continuous postoperative infusion for 48 hours. Patients in the control group received a normal saline equivalent. MAIN OUTCOME MEASURES Functional postoperative recovery was assessed by using the surgical recovery scale for 45 days; postoperative pain was assessed by using a visual analog scale; and opioid consumption, use of rescue ketamine, recovery of bowel function, time to readiness for discharge, and perioperative complications were recorded. RESULTS The intraperitoneal local anesthetic group reported improved surgical recovery scale scores at day 1 and 7, lower pain scores, required less rescue ketamine, and passed flatus earlier than the control group (p < 0.05). The improvement in surgical recovery scale at day 7 and pain scores remained when laparoscopic colectomy was considered separately. Opioid consumption and time to readiness for discharge were equivalent. LIMITATIONS This study was powered to detect a difference in surgical recovery scale, but not the other domains of recovery, when the intraperitoneal local anesthetic group was compared with control. CONCLUSIONS We conclude that instillation and infusion of intraperitoneal ropivacaine for patients undergoing colectomy, including by the laparoscopic approach, decreases postoperative pain and improves functional postoperative recovery. We recommend routine inclusion of intraperitoneal local anesthetic into the multimodal analgesia component of enhanced recovery after surgery programs for laparoscopic colectomy. See Video Abstract at http://links.lww.com/DCR/A698.


title: Relationship between bispectral index values and volatile anesthetic concentrations during the maintenance phase of anesthesia in the B-Unaware trial.

text: BACKGROUND Hypnotic depth during anesthesia affects electroencephalography waveforms and electroencephalogram-derived indices, such as the bispectral index (BIS). Titrating anesthetic administration against the BIS assumes reliable relationships between BIS values, electroencephalogram waveforms, and effect site concentration, beyond loss of responsiveness. Associations among BIS, end-tidal anesthetic concentrations (ETAC), and patient characteristics were examined during anesthetic maintenance, using B-Unaware trial data. METHODS Pharmacokinetically stable ETAC epochs during intraoperative anesthetic maintenance were analyzed. A generalized estimating equation determined independent relationships among BIS, ETAC (in age-adjusted minimum alveolar concentration equivalents), patient characteristics, and 1-yr mortality. Further individual and population characteristics were explored graphically. RESULTS A total of 3,347,523 data points from 1,100 patients were analyzed over an ETAC range from 0.42 to 1.51 age-adjusted minimum alveolar concentration. A generalized estimating equation yielded a best predictive equation: BIS = 62.9-1.6 (if age younger than 60 yr) -1.6 (if female) -2.5 (if American Society of Anesthesiologists physical status more than 3) -2.6 (if deceased at 1 yr) -2.5 (if N2O was not used) -1.4 (if midazolam dose more than 2 mg) -1.3 (if opioid dose more than 50 morphine equivalents) -15.4 × age-adjusted minimum alveolar concentration. Although a population relationship between ETAC and BIS was apparent, interindividual variability in the strength and reliability of this relationship was large. Decreases in BIS with increasing ETAC were not reliably observed. Individual-patient linear regression yielded a median slope of -8 BIS/1 age-adjusted minimum alveolar concentration (interquartile range -30, 0) and a median correlation coefficient of -0.16 (interquartile range -0.031, -0.50). CONCLUSIONS Independent of pharmacokinetic confounding, BIS frequently correlates poorly with ETAC, is often insensitive to clinically significant changes in ETAC, and is vulnerable to interindividual variability. BIS is therefore incapable of finely guiding volatile anesthetic titration during anesthetic maintenance.


title: Globalisation and global health governance: implications for public health.

text: Globalisation is a defining economic and social trend of the past several decades. Globalisation affects health directly and indirectly and creates economic and health disparities within and across countries. The political response to address these disparities, exemplified by the Millennium Development Goals, has put pressure on the global community to redress massive inequities in health and other determinants of human capability across countries. This, in turn, has accelerated a transformation in the architecture of global health governance. The entrance of new actors, such as private foundations and multi-stakeholder initiatives, contributed to a doubling of funds for global health between 2000 and 2010. Today the governance of public health is in flux, with diminished leadership from multilateral institutions, such as the WHO, and poor coherence in policy and programming that undermines the potential for sustainable health gains. These trends pose new challenges and opportunities for global public health, which is centrally concerned with identifying and addressing threats to the health of vulnerable populations worldwide.


title: Extended series of cardiac compressions during CPR in a swine model of perinatal asphyxia.

text: BACKGROUND The rationale for a compression to ventilation ratio of 3:1 in neonates with primary hypoxic, hypercapnic cardiac arrest is to emphasize the importance of ventilation; however, there are no published studies testing this approach against alternative methods. An extended series of cardiac compressions offers the theoretical advantage of improving coronary perfusion pressures and hence, we aimed to explore the impact of compression cycles of two different durations. MATERIALS AND METHODS Newborn swine (n = 32, age 12-36 h, weight 2.0-2.7 kg) were progressively asphyxiated until asystole occurred. Animals were randomized to receive compressions:ventilations 3:1 (n=16) or 9:3 (n=16). Return of spontaneous circulation (ROSC) was defined as a heart rate ≥ 100 beats min⁻¹. RESULTS All animals except one in the 9:3 group achieved ROSC. One animal in the 3:1 group suffered bradycardia at baseline, and was excluded, leaving us with 15 animals in each group surviving to completion of protocol. Time to ROSC (median and interquartile range) was 150 s (115-180) vs. 148 s (116-195) for 3:1 and 9:3, respectively (P = 0.74). There were no differences in diastolic blood pressure during compression cycles or in markers of hypoxia and inflammation. The temporal changes in mean arterial blood pressure, heart rate, arterial blood gas parameters, and systemic and regional oxygen saturation were comparable between groups. CONCLUSION Neonatal pigs with asphyxia-induced cardiac arrest did not respond to a compression:ventilation ratio of 9:3 better than to 3:1. Future research should address if alternative compression:ventilation ratios offer advantages over the current gold standard of 3:1.


title: Evaluation of recombinant Onchocerca volvulus activation associated protein-1 (ASP-1) as a potent Th1-biased adjuvant with a panel of protein or peptide-based antigens and commercial inactivated vaccines.

text: Alum, the only adjuvant approved for clinical applications, can induce strong humoral (Th2) but weak cellular (Th1) immune responses. It is necessary to develop safe and effective adjuvants capable of inducing both humoral and cellular immune responses. We previously showed that activation-associated protein-1 (ASP-1) derived from Onchocerca volvulus has potent adjuvant activity. In this study, we have further evaluated the adjuvanticity of recombinant ASP-1 using a panel of recombinant proteins or synthetic peptide-based antigens, including ovalbumin (OVA), synthetic HIV peptide (HIV-p), recombinant HIV gp41 (rgp41) and HBV HBsAg, as well as three commercially available inactivated vaccines against haemorrhagic fever with renal syndrome (HFRS), Influenza and Rabies. Our results indicate that ASP-1 induced significantly higher IgG1 (Th2-associated) and IgG2a (Th1-associated) responses than alum adjuvant against OVA antigen, HIV-p, and rgp41. Consistently, it induced similar level of IgG1 responses as alum but higher level of IgG2a and IFN-gamma-producing T cell responses than alum adjuvant against HBsAg. Further, ASP-1 improved both IgG1 and IgG2a responses to three commercial inactivated vaccines when used separately or in combination. In conclusion, the recombinant ASP-1, unlike alum adjuvant, is able to induce both Th1 and Th2-associated humoral responses and Th1 cellular responses, suggesting that it can be further developed as a promising adjuvant for subunit-based and inactivated vaccines.


title: Current incidence and outcome of the acute respiratory distress syndrome.

text: PURPOSE OF REVIEW This article discusses recently published articles reporting the incidence and outcome of patients with the acute respiratory distress syndrome (ARDS). This is a difficult task since there is a marked variability regarding the methodology of the few, large epidemiological, and observational studies on ARDS. RECENT FINDINGS The review will mainly focus on publications from the past 18 months. We have reviewed new epidemiological studies reporting population-based incidence of ARDS. Also, we have reviewed the data on survival reported in observational and randomized controlled trials, discussed how the current ARDS definition modifies the true incidence of ARDS, and briefly mentioned recent approaches that appear to improve ARDS outcome. SUMMARY On the basis of current evidence, it seems that the incidence and overall hospital mortality of ARDS has not changed substantially in the last decade. Independent of the definition used for identification of ARDS patients, reported population-based incidence of ARDS is an order of magnitude lower in Europe than in the USA. Current hospital mortality of combined moderate and severe ARDS reported in observational studies is greater than 40%.


How to help the free market fight coronavirus.


title: High performance of F-fluorodeoxyglucose positron emission tomography and contrast-enhanced CT in a rapid outpatient diagnostic program for patients with suspected lung cancer.

text: BACKGROUND The diagnostic evaluation of patients presenting with possible lung cancer is often complex and time consuming. A rapid outpatient diagnostic program (RODP) including (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contrast-enhanced computed tomography (CT) as a routine diagnostic tool may improve timeliness, however the diagnostic performance of such a combined approach of RODP remains unclear. OBJECTIVES We evaluated timeliness of care and diagnostic performance of FDG-PET and contrast-enhanced CT (FDG-PET/CT) in an RODP for all patients referred with a chest X-ray suspicious of lung cancer. METHODS Charts of patients referred to the 2-day RODP of our tertiary care university clinic after an abnormal chest X-ray between 1999 and 2009 were reviewed. Between 1999 and 2005 co-registered FDG-PET and CT imaging took place; from September 2005 onwards, a hybrid system was used. We analyzed timeliness of care and diagnostic performance of FDG-PET/CT to differentiate malignant from benign lesions. RESULTS In 386 patients available for analysis, 260 were diagnosed with lung cancer and 23 had another type of malignancy; in 78 patients benign disease was confirmed, and in another 45 the diagnosis was not pathologically confirmed but a median 24.5-month follow-up confirmed a benign outcome. Sensitivity, specificity, negative and positive predictive values and accuracy of FDG-PET/CT to differentiate lung cancer from benign disease were 97.7, 60.2, 92.5, 84.0 and 85.8%, respectively. Lung cancer patients had a median referral, diagnostic and therapeutic delay of 7, 2 and 19 days, respectively. CONCLUSIONS FDG-PET/CT in an RODP setting for suspected lung cancer has high performance in detecting cancer and facilitates timely care.


title: Current antimicrobial management of community-acquired pneumonia in HIV-infected children.

text: INTRODUCTION Community-acquired pneumonia is a leading cause of morbidity and mortality amongst HIV-infected infants and children. Polymicrobial infection is common and, due to the difficulties in confirming the etiology of pneumonia, empiric broad-spectrum antimicrobial therapy is frequently used. Areas covered: The author based this article on literature identified from PubMed. The author's search terms included: pneumonia, community-acquired pneumonia, HIV, children. The articles reviewed included original studies, recent review articles and current guidelines on the management of pneumonia in HIV-infected children. The microbiological etiology and the empiric and pathogen-specific antimicrobial therapy of community-acquired pneumonia in HIV-infected and HIV-exposed infants and children are also discussed. Expert opinion: There are many changing epidemiological factors impacting antimicrobial management of community-acquired pneumonia in the context of HIV infection in infants and children. These include vaccination strategies, antimicrobial prophylaxis, emerging drug-resistant pathogens, and recognition of the importance of viruses and tuberculosis in the etiology of community-acquired pneumonia. Further research is needed on optimal amtimicrobial management strategies in HIV-exposed uninfected children, and HIV-infected children receiving antiretroviral therapy.


title: A novel purgative protocol for capsule endoscopy of the small bowel produces better quality of visibility than 2 l of PEG: Timing is of the essence.

text: INTRODUCTION The ideal way of preparing patients for small-bowel capsule endoscopy has been controversial. Previous studies have shown that ingestion of 2 l of polyethylenglycol (PEG) 12 hours prior to capsule ingestion leads to improved visibility in comparison to no preparation at all. We speculated that using a post-ingestion (PI), booster-based cleansing protocol might provide an alternative to the PEG cleansing protocol. METHODS This randomized, blinded, prospective study enrolled 45 individuals. Patients were allocated to either of two groups. The PEG group ingested 2 l PEG 12 hours prior to the exam (n = 22) and the PI group ingested one sachet of Picolax® dissolved in 250 ml of water one hour after swallowing the capsule with 500 ml of water (n = 18). Primary endpoints were overall small bowel and distal third of small bowel cleansing levels. Secondary endpoints were average gastric and small-bowel transit time. RESULTS Forty-five patients participated in this study. Five individuals were excluded because of incomplete study. Percentage of patients with adequate visibility in the distal third of the small bowel in the PEG group was 9% vs 72% in the PI group (p < 0.0001). Average gastric time and total transit time were shorter in the PI group vs the PEG group (p = 0.0065). CONCLUSION Timing of ingestion of the Picolax® purgative 60 minutes after swallowing the capsule endoscopy delivers better visibility in the distal third of the small bowel than the accepted cleansing protocol of ingesting 2 l PEG 12 hours prior to the capsule endoscopy procedure.


title: Early surgeon impressions and technical difficulty associated with laparoendoscopic single-site surgery: a Society of American Gastrointestinal and Endoscopic Surgeons Learning Center study.

text: BACKGROUND Interest in laparoendoscopic single-site surgery (LESS) is growing rapidly among surgeons. This study aimed to characterize current surgeon impressions about LESS and to determine the relative difficulty of performing a simulated LESS task using a multiport access device. METHODS This study was conducted at the 2009 Society of Gastrointestinal Endoscopic Surgeons (SAGES) Learning Center. The 56 study participants were asked to complete pre- and post-test questionnaires regarding their level of training, prior clinical experience, and opinions about LESS. Technical skill performance was evaluated using the standardized fundamentals of laparoscopic surgery Peg Transfer task scored according to time and error metrics. The participants completed three repetitions: conventional laparoscopy (LAP), LESS with nonarticulated instruments (LESS Straight), and LESS with articulated instruments (LESS Articulating). RESULTS Complete data were collected for 45 (80%) of the 56 participants, which included 27 practicing surgeons, nine minimally invasive surgery (MIS) fellows, seven residents, and two allied health professionals. Five surgeons (LESS experienced) had managed at least one LESS case in the preceding 6 months. Participants rated their comfort with LESS as 2.0 ± 1.2 (5-point scale, 1 = very uncomfortable). Compared with conventional laparoscopy, the participants indicated that LESS had 97% better cosmesis, 25% decreased postoperative pain, 18% faster recovery, 97% more demanding, 73% increased rate of complications, and 82% anticipated wide adoption. They all indicated a readiness to offer LESS to their patients if appropriately trained. Peg Transfer performance was significantly worse for LESS than for LAP (40-65% performance decline), and for LESS Articulating than for LESS Straight (44% performance decline). Construct validity for the LESS simulated tasks was supported because the LESS-experienced scores were significantly better than the LESS-nonexpert scores. CONCLUSION Despite the increased technical difficulty associated with the LESS approach, surgeons are enthusiastic about offering these techniques and seeking additional training. Robust simulation-based methods that foster skill acquisition through repetitive practice and verification of proficiency are needed such that safe adoption may be fostered.


title: Outcome of laparoscopic rectopexy versus perineal rectosigmoidectomy for full-thickness rectal prolapse in elderly patients.

text: BACKGROUND The balance between abdominal and perineal approaches for rectal prolapse is always the higher morbidity but better outcome in the former setting. Therefore, perineal approaches have been preferred for the treatment of full-thickness rectal prolapse (FTRP) in elderly patients. However, laparoscopic rectopexy with or without resection also may be used for elderly patients and may confer the same benefits. PURPOSE The objective of this study was to evaluate safety and efficacy of laparoscopic rectopexy compared with perineal rectosigmoidectomy for FTRP in elderly patients. METHODS Between July 2000 and June 2009, eight consecutive patients (8 women; mean age, 71 (range, 65-77) years) with FTRP underwent laparoscopic rectopexy (LAP group). During the same period, 143 patients underwent perineal rectosigmoidectomy (PRS group). A total of 123 patients were selected who underwent perineal rectosigmoidectomy (117 women; mean age, 80.7 (range, 66-98) years). RESULTS Three patients (37.5%) in the LAP group and 29 patients (23.6%) in the PRS group had undergone previous operations for rectal prolapse. The mean follow-up periods were 6.9 months and 12.8 months, respectively. In the LAP group, operative time was longer (166.5 vs. 73.5 minutes; p > 0.05) and bleeding loss was more (101.7 vs. 31.6; p < 0.05), whereas the length of hospitalization was same between the two groups (5.4 vs. 5.3 days; p > 0.05). Postoperative complications included an incisional hernia in the LAP group (12.5%) and urinary retention (4.8%), anastomotic disruption (2.4%), urinary tract infection (1.6%), and atelectasis (1.6%) in the PRS group (13.8%). Recurrences were 1 (12.5%) in the LAP group and 14 (11.4%) in the PRS group. CONCLUSIONS Laparoscopic rectopexy is a safe and feasible procedure in elderly patients with FTRP but results in increased operative time.


title: ALK Rearrangement Adenocarcinoma with Histological Transformation to Squamous Cell Carcinoma Resistant to Alectinib and Ceritinib.

text: Specific tyrosine-kinase inhibitors (TKIs) are widely used for the treatment of non-small-cell lung cancers with anaplastic lymphoma kinase (ALK) translocations. However, most treated patients eventually develop resistance to the TKIs. The histological transformation into small cell carcinoma is well known to be the underlying mechanism for acquired resistance; however, transformation to squamous cell carcinoma is extremely rare. We, herein, report a case of ALK rearrangement-positive adenocarcinoma that transformed to squamous cell carcinoma after administration of alectinib, and was found to be resistant to ceritinib.


title: A compact and hand-held infection-screening system for use in rapid medical inspection at airport quarantine stations: system design and preliminary validation.

text: To conduct mass screening and thereby reduce the spread of infection, a compact (13.5 cm × 8.5 cm × 2.5 cm), highly-mobile and hand-held infection-screening system was developed for rapid medical inspection in mass gathering places such as airports. The system is capable of non-contact vital-sign monitoring using two integrated sensors: a 24-GHz microwave radar for measuring heart and respiration rates and a thermopile array for capturing facial temperature. Subsequently, the system detects infected individuals using a linear discriminant function (LDA) from the derived vital-signs data. The system was tested on 10 subjects under two conditions (resting as normal and exercising as pseudo-infected, i.e. a 10-min bicycle ergometer at 100 W exercise); the normal and pseudo-infected conditions were classified successfully via LDA for all subjects (p < 0.01; classification error rate < 5%). The proposed non-contact system can be applied for preventing secondary exposure of medical doctors at the outbreak of highly pathogenic infectious diseases such as the Ebola virus.


COVID-19 Cases and Deaths in Federal and State Prisons.


Acute oncology in small and rural hospitals.


Without food, there can be no exit from the pandemic.


title: On the selection of a tracer for PET imaging of HER2-expressing tumors: direct comparison of a 124I-labeled affibody molecule and trastuzumab in a murine xenograft model.

text: UNLABELLED Human epidermal growth factor receptor type 2 (HER2) is a tyrosine kinase, which is often overexpressed in many carcinomas. Imaging HER2 expression in malignant tumors can provide important prognostic and predictive diagnostic information. The use of anti-HER2 tracers labeled with positron-emitting radionuclides may increase the sensitivity of HER2 imaging. The goal of this study was to compare directly 2 approaches for developing anti-HER2 PET tracers: a (124)I-labeled monoclonal antibody and a small (7-kDa) scaffold protein, the Affibody molecule. METHODS The anti-HER2 Affibody Z(HER2:342) and humanized monoclonal antibody trastuzumab were labeled with (124/125)I using p-iodobenzoate (PIB) as a linker. Cellular processing of both tracers by HER2-expressing cells was investigated. The biodistributions of (124)I-PIB-Z(HER2:342) and (125)I-PIB-trastuzumab were compared in BALB/C nu/nu mice bearing HER2-expressing NCI-N87 xenografts using paired labels. Small-animal PET of (124)I-PIB-Z(HER2:342) and (124)I-PIB-trastuzumab in tumor-bearing mice was performed at 6, 24, and 72 h after injection. RESULTS Both radioiodinated Z(HER2:342) and trastuzumab bound specifically to HER2-expressing cells in vitro and specifically targeted HER2-expressing xenografts in vivo. Radioiodinated trastuzumab was more rapidly internalized and degraded, which resulted in better retention of radioactivity delivered by Z(HER2:342). Total uptake of trastuzumab in tumors was higher than that of (124)I-PIB-Z(HER2:342). However, tumor-to-organ ratios were appreciably higher for (124)I-PIB-Z(HER2:342) due to the more rapid clearance of radioactivity from blood and normal organs. The ex vivo results were confirmed by small-animal PET. CONCLUSION The use of the small scaffold targeting Affibody provides better contrast in HER2 imaging than does the monoclonal antibody.


title: Perioperative outcomes of three-port robotically assisted hysterectomy: a continuous series of 53 cases.

text: This study evaluated the feasibility and safety of 3-port robotically assisted laparoscopic hysterectomy (RALH), using a consecutive series of women who underwent 3-port RALH in a university hospital. From November 2010 until June 2013 we operated on 53 women, whose mean age was 48.4 ± 7.7 years (range 35-68 years), and mean body mass index was 27.1 ± 5.1 kg/m(2) (range 19.5-42.9 kg/m(2)). The indications for hysterectomy were myoma in 31 (58.5 %), adenomyosis in 10 (18.9 %), cervical dysplasia in 4 (7.5 %), neoplasia in 4 (7.5 %), and recurrent polyps or postmenopausal bleeding in the remaining 4 women (7.5 %). We performed total RALH in 50 cases (94.3 %) and subtotal in the others. The median duration of total intervention was 169 min (interquartile range 147.5-206.5 min). The mean weight of the uterus was 209.8 ± 166.6 g (range 36-790 g) and mean estimated blood loss was 72.3 ± 75.9 ml (range 0-300 ml). There were no perioperative complications, in particular no blood transfusions nor conversions to laparotomy. The median hospital stay was 4 days (interquartile range 3-4 days). One patient was reoperated 1 month later for vaginal vault hematoma and another was readmitted 3 weeks post-operatively due to vaginal vault dehiscence after premature intercourse, but did not require reoperation. Three-port RALH is feasible and safe for simple hysterectomy. We believe this experience using minimum ports to be useful to prepare for robotically assisted single-port hysterectomy.


title: Sex differences in remifentanil requirements for preventing cough during anesthetic emergence.

text: PURPOSE Target-controlled infusion (TCI) of remifentanil can suppress coughing during emergence from general anesthesia; nevertheless, previous studies under different clinical conditions recommend significantly different effective effect-site concentrations (effective Ce) of remifentanil for 50% of patients (EC₅₀). The differences among these studies include type of surgery and patient sex. In recent years, study of sex differences in regards to anesthetic pharmacology has drawn greater interest. Accordingly, we attempted to determine the effective Ce of remifentanil for preventing cough for each sex under the same clinical conditions. MATERIALS AND METHODS Twenty female and 25 male ASA physical status I-II grade patients between the ages of 20 and 46 years who were undergoing thyroidectomy were enrolled in this study. The effective Ce of remifentanil for preventing cough was determined for each sex using the isotonic regression method with a bootstrapping approach, following Dixon's up-and-down method. RESULTS Isotonic regression with a bootstrapping approach revealed that the estimated EC₅₀ of remifentanil for preventing coughing during emergence was significantly lower in females {1.30 ng/mL [83% confidence interval (CI), 1.20-1.47 ng/mL]} than in males [2.57 ng/mL (83% CI, 2.45-2.70 ng/mL)]. Mean EC₅₀ in females was also significantly lower than in males (1.23±0.21 ng/mL vs. 2.43±0.21 ng/mL, p<0.001). Mean arterial pressure, heart rate, and respiratory rate over time were not significantly different between the sexes. CONCLUSION When using remifentanil TCI for cough prevention during anesthetic emergence, patient sex should be a considered for appropriate dosing.


title: Impact of multimorbidity count on all-cause mortality and glycaemic outcomes in people with type 2 diabetes: a systematic review protocol.

text: INTRODUCTION Type 2 diabetes (T2D) is a leading health priority worldwide. Multimorbidity (MM) is a term describing the co-occurrence of two or more chronic diseases or conditions. The majority of people living with T2D have MM. The relationship between MM and mortality and glycaemia in people with T2D is not clear. METHODS AND ANALYSIS Medline, Embase, Cumulative Index of Nursing and Allied Health Complete, The Cochrane Library, and SCOPUS will be searched with a prespecified search strategy. The searches will be limited to quantitative empirical studies in English with no restriction on publication date. One reviewer will perform title screening and two review authors will independently screen the abstract and full texts using Covidence software, with disagreements adjudicated by a third reviewer. Data will be extracted using a using a Population, Exposure, Comparator and Outcomes framework. Two reviewers will independently extract data and undertake the risk of bias (quality) assessment. Disagreements will be resolved by consensus. A narrative synthesis of the results will be conducted and meta-analysis considered if appropriate. Quality appraisal will be undertaken using the Newcastle-Ottawa quality assessment scale and the quality of the cumulative evidence of the included studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. This protocol was prepared in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines to ensure the quality of our review. ETHICS AND DISSEMINATION This review will synthesise the existing evidence about the impact of MM on mortality and glycaemic outcomes in people living with T2D and increase our understanding of this subject and will inform future practice and policy. Findings will be disseminated via conference presentations, social media and peer-reviewed publication. PROSPERO REGISTRATION NUMBER CRD42017079500.


title: Flow Diversion versus Standard Endovascular Techniques for the Treatment of Unruptured Carotid-Ophthalmic Aneurysms.

text: BACKGROUND AND PURPOSE Over the past few years, flow diversion has been increasingly adopted for the treatment of intracranial aneurysms, especially in the paraclinoid and paraophthalmic carotid segment. We compared clinical and angiographic outcomes and complication rates in 2 groups of patients with unruptured carotid-ophthalmic aneurysms treated for 7 years by either standard coil-based techniques or flow diversion. MATERIALS AND METHODS From February 2006 to December 2013, 162 unruptured carotid-ophthalmic aneurysms were treated endovascularly in 138 patients. Sixty-seven aneurysms were treated by coil-based techniques in 61 patients. Flow diverters were deployed in 95 unruptured aneurysms (77 patients), with additional coiling in 27 patients. Complication rates, clinical outcome, and immediate and long-term angiographic results were retrospectively analyzed. RESULTS No procedure-related deaths occurred. Four procedure-related thromboembolic events (6.6%) leading to permanent morbidity in 1 case (1.6%) occurred in the coiling group. Neurologic complications were observed in 6 patients (7.8%) in the flow-diversion group, resulting in 3.9% permanent morbidity. No statistically significant difference was found between complication (P = .9) and morbidity rates (P = .6). In the coiling group (median follow-up, 31.5 ± 24.5 months), recanalization occurred at 1 year in 23/50 (54%) aneurysms and 27/55 aneurysms (50.9%) at the latest follow-up, leading to retreatment in 6 patients (9%). In the flow-diversion group (mean follow-up, 13.5 ± 10.8 months), 85.3% (35/41) of all aneurysms were occluded after 12 months, and 74.6% (50/67) on latest follow-up. The retreatment rate was 2.1%. Occlusion rates between the 2 groups differed significantly at 12 months (P < .001) and at the latest follow-up (P < .005). CONCLUSIONS Our retrospective analysis shows better long-term occlusion of carotid-ophthalmic aneurysms after use of flow diverters compared with standard coil-based techniques, without significant differences in permanent morbidity.


title: New vaccines needed for pathogens infecting animals and humans: One Health.

text: The field of "One Health" encourages researchers to collaborate across a wide range of disciplines to improve health at the animal-human-ecosystems interface. One Health recognizes the potential of emerging infectious diseases to impact public health and global food security, and the need for a multidisciplinary approach to counteract the effect of these diseases. Vaccinologists are also beginning to engage in research related to One Health, recognizing that preventing transmission of emerging infectious diseases at the animal-human interface is critically important for protecting the world population from epizootics and pandemics. In this synopsis of recent work in the One Health field, we describe some emerging One Health pathogens, discuss the importance of One Health to food safety and biodefense, propose strategies for improving One Health including the development of new vaccines and new vaccine design approaches, and close with a brief discussion of the opportunities and risks related to One Health vaccine research.


Low dose radiation therapy for COVID-19 pneumonia: is there any supportive evidence?


title: Treatment of Intracranial Aneurysms with the Pipeline Embolization Device Only: a Single Center Experience.

text: Purpose The aim of this study was to evaluate the technical feasibility and rate of mid-term occlusion in aneurysms treated solely with the Pipeline Embolization Device (PED) in a German tertiary care university hospital. Materials and Methods Forty-nine non-consecutive intracranial aneurysms underwent endovascular treatment using the PED exclusively between March 2011 and May 2017 at our institution. Primary endpoint was a favorable aneurysm occlusion defined as OKM C1-3 and D (O'Kelly Marotta Scale). Secondary endpoints were retreatment rate and delayed complications. Median follow-up was 200 days. Results The mean aneurysm size was 7.1 ± 5.3 mm. Forty-four aneurysms were located in the anterior circulation (90%). Ten aneurysms were ruptured (20%). Branching vessels from the sac were observed in 11 aneurysms (22%). Favorable obliteration immediately after PED placement was seen in 13/49 aneurysms (27%), of those nine aneurysms were completely occluded (18%). Angiographic and clinical follow-up was available for 45 cases (92%); 36/45 aneurysms (80%) were occluded completely and 40/45 aneurysms (89%) showed a favorable occlusion result. A branching vessel arising from the aneurysm sac was associated with incomplete occlusion (P < .05). All electively treated patients had good outcome (mRS 0). Three aneurysms (6%) required additional treatment due to aneurysm recurrence. Conclusion In our series, treatment of intracranial aneurysms with the PED was associated with favorable occlusion rates and low complication rates at mid-term follow-up. The presence of branching vessels arising from the aneurysms sac was predictive for an incomplete occlusion.


The coronavirus outbreak could make it quicker and easier to trial drugs.


title: MALDI-TOF MS combined with magnetic beads for detecting serum protein biomarkers and establishment of boosting decision tree model for diagnosis of hepatocellular carcinoma.

text: No single biologic marker is used in the routine diagnosis of hepatocellular carcinoma (HCC). We screened for potential biomarkers in 142 samples, including samples from 60 patients with HCC, 36 patients with hepatic disease other than HCC, and 46 age- and sex-matched healthy volunteers. Pretreated samples were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with weak cationic exchange magnetic beads. The diagnostic pattern with a panel of 4 potential protein biomarkers of a mass-to-charge (m/z) ratio of 4,471, 8,936, 11,670, and 13,752 could accurately recognize 56 of 60 patients with HCC, 34 of 36 patients with hepatic disease, and 44 of 46 healthy people. The preliminary data suggest a potential application of MALDI-TOF MS combined with magnetic beads as an effective technology to profile serum proteome, and, with pattern analysis, a diagnostic model comprising 4 potential biomarkers was indicated to differentiate people with hepatic disease and healthy control subjects rapidly and precisely.


title: Correlation between cytokines and coagulation-related parameters in patients with coronavirus disease 2019 admitted to ICU.

text: BACKGROUND The novel SARS-CoV-2 caused a large number of infections and deaths worldwide. Thus, new ideas for an appropriated assessment of patients' condition and clinical treatment are of utmost importance. Therefore, in this study, the laboratory parameters of patients with coronavirus disease 2019 (COVID-19) were evaluated to identify the correlation between cytokine expression and other laboratory parameters. METHODS A retrospective and single-center study was performed in Wuhan, involving 83 severe or critical COVID-19 patients admitted to the intensive care unit (ICU). Laboratory parameters in ICU patients with laboratory-confirmed infection of SARS-CoV2 were collected. The association between parameters was assessed by Spearman's rank correlation. RESULTS Patients' median age was 66 years (IQR, 57-73), and 55 (66%) were men. Among the 83 patients, 61 (73%) had 1 or more coexisting medical condition. The median concentration of IL-2R, IL-6, IL8, IL10, and TNFα were above the normal range, without IL-1β. A significant negative correlation between IL-6 and platelet count was discovered (r2 = -0.448, P<0.001) as well as a significant correlation between IL-6 and other platelet parameters. Finally, a correlation between multiple cytokines and coagulation indicators was found, pro-inflammatory factors were found to be more associated to coagulation parameters, with the highest correlation between IL-6 and the International normalized ratio (INR) (r2=0.444, P<0.001). CONCLUSIONS Our results suggested that cytokines play an important role in the pathogenesis of COVID-19. In addition, IL-6 seems more relevant in the evaluation of the condition of COVID-19 patients.


title: Parallel stent grafts for the treatment of complex aortic aneurysms: A single center study.

text: Background "Chimney" techniques with parallel grafts used in order to extend the landing zones in endovascular aneurysm repair (ch-EVAR) are increasingly being reported. Conflicting data has been reported regarding the success and durability of the repair. We report a single center experience using ch-EVAR in treating complex aortic pathologies. Methods We performed a retrospective review of all patients treated with ch-EVAR in our institution between 2013 and 2017. Data collected included patients demographics, indications for surgery, configuration of parallel grafts, technical success, and perioperative morbidity and mortality. Follow-up data included aortic sac size, reintervention rate, and overall mortality. Results Thirty-five patients underwent treatment of their aneurysms with parallel grafts. Sixty parallel grafts were placed. Mean age was 75 years (range 59-93) and 30 (85%) were male. Technical success was achieved in 32 (91%) patients. Mean follow up was 12 months. Sac size decreased in diameter or remained unchanged in 26 of the 30 (86.6%) patients. Four patients were found to have enlarging aneurysms due to gutter endoleaks. All were treated successfully with endovascular methods. The estimated primary patency was 95% at 12 months. Probability of freedom from intervention was 75% at 12 months. No late aneurysm related mortality occurred. Conclusion The use of ch-EVAR in treating complex aortic aneurysms is technically feasible and safe. Gutter endoleaks are encountered only in a minority of the cases, and can be treated with minimally invasive techniques. Longer term follow up is required to evaluate the patency of these parallel grafts and the durability of the aneurysm exclusion.


title: Guidance for rebooting electrophysiology through the COVID-19 pandemic from the Heart Rhythm Society and the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology.

text: Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted health care delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for arrhythmia patients. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of outpatient and periprocedural care pathways.


title: Microbiological performance of a robotic system for aseptic compounding of cytostatic drugs.

text: BACKGROUND Compounding of cytostatic drugs requires strict aseptic procedures, while exposure to toxic drugs and repetitive manual movements should be minimized. Furthermore, reuse of vials is desirable to lower the costs. To assess if all this might be safely achieved with a robot, this study aimed at qualifying the aseptic preparation process with the robotic system APOTECAchemo. METHODS The aseptic compounding of patient-individual cytostatic solutions was simulated with media fill simulation tests to qualify the performance according to European GMP Annex 1. The contamination in the environment was measured in critical places using settle plates, contact plates, active air sampling and particle counting. Media-fill simulation tests were prepared in 3 production batches. The second part of the study evaluated the microbiological shelf-life of commercial drug vials after repeated puncturing. On six days, fifty syringes of 15 ml media were prepared from the same 50 vials with the robot. After each preparation, vials were covered with an IVA seal upon unloading from the robot to protect them from microbiological contamination. RESULTS No microbiological contamination was found in any of the 96 media fill preparations, nor in any of the 300 syringes that were prepared with repeated puncturing. The compounding area met class A limits, while class A criteria were not fulfilled by the contact plates and settle plates placed on the right side of the loading area. There, the average colony forming units (cfu) were 3 and 1.17, respectively, meeting class B criteria. CONCLUSIONS Robotical compounding of cytostatic drugs with APOTECAchemo meets the microbiological requirements of the European GMP. In addition, the robot can reuse vials repeatedly and safely, thereby enabling extended usage.


Kidney function and the risk of cardiovascular disease.


title: [Practical aspects of care for a critically ill COVID-19 infected patient in need of respiratory support].

text: In December 2019, an outbreak of a new type of pneumonia was reported from the Chinese city of Wuhan, caused by a new coronavirus. The disease, which initially spread from animal to human, later spread from person to person, causing a pandemic. Viral disease (COVID-19) can present in a variety of forms, from asymptomatic to mildly symptomatic with severe, respiratory failure, requiring intensive care. The care of the latter group of patients places a significant burden on health care. The purpose of this summary is to present the practical aspects of caring for patients requiring intensive care and respiratory support / mechanical ventilation. Orv Hetil. 2020; 161 (17): 678-684.


title: Ureteral Papilla Implantation as a Technique for Neoureterocystostomy in Cats Undergoing Renal Transplantation: 30 Cases.

text: OBJECTIVE To describe the clinical outcome of donor and recipient cats undergoing ureteral papilla harvest and implantation as a technique for neoureterocystostomy in clinical kidney transplant. STUDY DESIGN Retrospective case series. ANIMALS Donor (n=31) and recipient (n=30) cats that underwent kidney harvest and transplantation using ureteral papilla implantation technique for neoureterocystostomy. METHODS Medical records for donor and recipient cats presented to the University of Wisconsin Veterinary Teaching Hospital from January 2003 to December 2014 were reviewed. Data recorded included complete blood count, serum chemistry panel, surgical technique, diagnostic imaging results, short- and long-term complications, and anesthetic survival. RESULTS All 30 recipients recovered from anesthesia. Four died within 24 hours and 26 survived to hospital discharge. Serum creatinine was within the reference interval by 72 hours in 22/26 cats (85%). Complications related to the ureteral papilla implantation technique were seen in only 1 cat (3%). Uroabdomen diagnosed on day 3 ultimately resolved over the following 24 hours without surgical intervention. All 31 donor cats survived to discharge. Four donors (13%) experienced mild, transiently increased serum creatinine. CONCLUSION Ureteral papilla implantation is a viable technique for neoureterocystostomy in cats undergoing kidney transplantation. Proposed benefits for the recipient include a less technically challenging anastomosis, decreased risk of ureteral obstruction at the anastomosis site, and reduced risk of leakage compared to previous reports. Benefits for recipients should be weighed against risks to donors, including a more complex ureteral harvest, increased surgical time, and potential injury or obstruction of the contralateral ureteral papilla.


title: Regeneration of severely damaged lungs using an interventional cross-circulation platform.

text: The number of available donor organs limits lung transplantation, the only lifesaving therapy for the increasing population of patients with end-stage lung disease. A prevalent etiology of injury that renders lungs unacceptable for transplantation is gastric aspiration, a deleterious insult to the pulmonary epithelium. Currently, severely damaged donor lungs cannot be salvaged with existing devices or methods. Here we report the regeneration of severely damaged lungs repaired to meet transplantation criteria by utilizing an interventional cross-circulation platform in a clinically relevant swine model of gastric aspiration injury. Enabled by cross-circulation with a living swine, prolonged extracorporeal support of damaged lungs results in significant improvements in lung function, cellular regeneration, and the development of diagnostic tools for non-invasive organ evaluation and repair. We therefore propose that the use of an interventional cross-circulation platform could enable recovery of otherwise unsalvageable lungs and thus expand the donor organ pool.


title: Laparoscopic gastric plication for the treatment of morbid obesity: a review.

text: Introduction. Laparoscopic greater curvature plication is an operation that is gaining ground in the treatment of morbid obesity, as it appears to replicate the results of laparoscopic sleeve gastrectomy with fewer complications. Aim. Review of current literature, especially results on weight loss and complications. Method. 11 (eleven) published articles on laparoscopic gastric plication, of which 1 preclinical study, 8 prospective studies for a total of 521 patients and 2 case reports of unusual complications. Results. Reported Paracentage of EWL in all studies is comparable to Laparoscopic Sleeve Gastrectomy (around 50% in 6 months, 60-65% in 12 months, 60-65% in 24 months) and total complication rate is at 15,1% with minor complications in 10,7%, major complications in 4,4%. Reoperation rate was 3%, conversion rate was 0,2%, and mortality was zero. Conclusion. Current literature on gastric plication and its modifications is limited and sketchy at times. Low cost, short hospital stay, absence of prosthetic material, and reversibility make it an attractive option. Initial data show that LGCP is effective for short- and medium-term weight loss, complication and reoperation rates are low, and GERD symptoms are unaffected. More data is required, and randomized control trials must be completed in order to reach safe conclusions.


title: Web Exclusive. Annals On Call - Clinical Reasoning and Testing for COVID-19.

text: [Figure: see text].


title: Reference values, intertest correlations, and test-retest repeatability of selected tear film tests in healthy cats.

text: OBJECTIVE To determine reference values, intertest correlations, and test-retest repeatability of Schirmer tear test 1 (STT-1), phenol red thread test (PRTT), tear film breakup time (TFBUT), tear osmolarity, and meibometry in healthy cats. DESIGN Evaluation study. ANIMALS 135 healthy domestic cats aged 0.5 to 12.8 years. PROCEDURES Each test was performed once in 120 cats and repeated in 40. Pearson correlation was used to assess correlation among tests. Intraclass correlation coefficients (ICCs) and 95% limits of agreement (LOA) were used to evaluate test-retest repeatability. RESULTS Median (95% central range) values were 18 mm/min (9 to 34 mm/min) for STT-1, 29 mm/15 s (15 to 37 mm/15 s) for PRTT, 12.4 seconds (9.1 to 17.7 seconds) for TFBUT, 322 mOsm/L (297 to 364 mOsm/L) for osmolarity, and 32 meibometry units (MU; 11 to 114 MU) for peak meibometry value. The STT-1 and PRTT values were positively correlated. Age was weakly associated with TFBUT and osmolarity. Meibometry measurements were higher for strips that contacted the tear film (285 MU) than for those that touched the eyelid margin only (32 MU). All ICCs were < 0.75, and 95% LOA were wide. CONCLUSIONS AND CLINICAL RELEVANCE Tear deficiency should be suspected in cats with STT-1 < 9 mm/min, PRTT < 15 mm/15 s, or TFBUT < 9 to 10 seconds. Generally poor correlation among tests suggested that thorough tear film analysis requires performance of multiple tests in concert. Relatively poor test-retest repeatability should be considered when repeated tests are used to monitor tear film dysfunction and response to treatment.


title: Interaction of Sindbis virus non-structural protein 3 with poly(ADP-ribose) polymerase 1 in neuronal cells.

text: The alphavirus non-structural protein 3 (nsP3) has a conserved N-terminal macro domain and a variable highly phosphorylated C-terminal domain. nsP3 forms complexes with cellular proteins, but its role in virus replication is poorly understood and protein interaction domains have not been defined. As the N-terminal macro domain can bind poly(ADP-ribose) (PAR), and PAR polymerase-1 (PARP-1) is activated and autoribosylated during Sindbis virus (SINV) infection, it was hypothesized that PARP-1 and nsP3 may interact. Co-immunoprecipitation studies showed that PARP-1 interacted with nsP3 during SINV infection of NSC34 neuronal cells and was most abundantly present in replication complexes that contained plus- and minus-strand SINV RNAs 10-14 h after infection, prior to PARP-1 activation or automodification with PAR. Treatment with an inhibitor of PARP enzymic activity did not affect the interaction between nsP3 and PARP-1 or SINV replication. Co-expression of individual domains of nsP3 with PARP-1 showed that nsP3 interacted with PARP-1 through the C-terminal domain, not the N-terminal macro domain, and that phosphorylation was not required. It was concluded that PARP-1 interacts with the C-terminal domain of nsP3, is present in replication complexes during virus amplification and may play a role in regulating virus RNA synthesis in neuronal cells.


title: Lest we forget.

text: The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic has caused shockwaves throughout the US healthcare system. Nowhere has coronavirus 19 (COVID-19) caused more infections than in New York, where there have been over 26,500 infections. Resources have been appropriately allocated towards combating this outbreak, but where does this leave patients with severe non-COVID-19 diseases? Herein we provide the views of a liver transplant surgeon and transplant hepatologist in New York.


title: Minimally Invasive Surgery in Pregnancy.

text: If it is medically necessary to perform nonobstetrical abdominal surgery in pregnancy, a minimally invasive approach should be considered. The benefits of laparoscopy are well known and current studies promote the safety of laparoscopy in pregnancy, when certain guidelines are followed. This article will review the safety of surgery in pregnancy, maternal physiology, fetal considerations, maternal obesity, laparoscopic cerclage, large adnexal mass, and complications. Guidelines for surgery will be reviewed as well.


Covid-19: Highest risk patients are asked to stay at home for 12 weeks.


title: Presentation and management of keloid scarring following median sternotomy: a case study.

text: INTRODUCTION Keloid scars following median sternotomy are rare and occur more frequently in pigmented skin. Different management strategies have been described with variable success. We present a case of keloid scar formation following cardiac surgery including our management and the final aesthetic result. CASE DESCRIPTION A 64 year old female of fair complexion underwent mitral valve replacement. The procedure and postoperative recovery were uncomplicated, however, during the following year, thick keloid scars formed over the incision sites. Initial non surgical measures failed to relieve pain and did not offer any tangible aesthetic benefit. Eventually surgical excision was attempted. She presented to our clinic for nine months follow up with significant improvement in pain and aesthetic result. DISCUSSION AND EVALUATION Several theories have attempted to explore the pathophysiology of keloid scar formation. A number of predisposing factors have been documented however none existed in this case. A variety of invasive and non invasive approaches have been described but significant differences in success rates and methodology of investigations still precludes a standardized management protocol. CONCLUSIONS In this case study a rare presentation of keloid scar has been presented. The variety of methods used to improve pain and aesthetic result demonstrates the propensity of keloid scars to recur and the therapeutic challenges that surgeons have to face in their quest for a satisfactory patient outcome.


title: COVID-19 and the Ocular Surface: A Review of Transmission and Manifestations.

text: PURPOSE The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached pandemic proportions within an unprecedented span of time. It is controversial whether the virus can be transmitted via tears and its ocular implications have not been widely studied. In this article, the current evidence related to ocular transmission and ocular manifestations is reviewed. RESULTS Several mechanisms for the ocular transmission of the virus are proposed with highlight on the nasolacrimal system as a conduit between the eye and the respiratory tract, and the role of the lacrimal gland in hematogenous spread. Ocular surface manifestations such as conjunctivitis are more commonly reported. CONCLUSION The exact pathophysiology of ocular transmission of the virus remains incompletely understood, although there is preliminary evidence of SARS-CoV-2 being detected in ocular secretions. The ocular tropism of the virus and its potential to cause localized ocular disease are worth considering.


title: COVID-19 Science Policy, Experts, and Publics: Why Epistemic Democracy Matters in Ecological Crises.

text: In times of planetary health crises such as the COVID-19 pandemic, a critically informed science and technology policy is crucial. In this overarching context, governments are faced with making rapid and high-stake decisions dictated by emergency that in a state of normalcy they would not, or could not pursue. Governments tend to gather, therefore, an incredible amount of unchecked power in times of fast-moving ecological crises that raises concerns about where the legitimacy of such excessive power comes from. Moreover, the elected politicians rely on the expert advice in a pandemic. This takes away democratic political authority from the sovereign people and instead places it on allegedly objective unelected experts. In contrast, experts have (1) a dubious reputation in predicting the future and (2) varying degrees of biases and self-interests, which make them susceptible, for instance, to "framing problems" in relation to the urgent public issues at stake. This article suggests new ways of thinking about COVID-19 technology policy, drawing from the field of political science and democratic theory. It examines the power-laden tensions between the political authority and the expert authority. Going forward, I highlight the brief history of epistemic democracy, taking into consideration that in advanced modern democracies, political decision making has to draw, in part, from expert knowledge, but without resulting in democratic deficits. The COVID-19 science and technology policy can usefully build on epistemic democracy while strengthening the science, society, and democracy nexus.


title: Cerebral aneurysm pulsation: do iterative reconstruction methods improve measurement accuracy in vivo?

text: BACKGROUND AND PURPOSE Electrocardiogram-gated 4D-CTA is a promising technique allowing new insight into aneurysm pathophysiology and possibly improving risk prediction of cerebral aneurysms. Due to the extremely small pulsational excursions (<0.1 mm in diameter), exact segmentation of the aneurysms is of critical importance. In vitro examinations have shown improvement of the accuracy of vessel delineation by iterative reconstruction methods. We hypothesized that this improvement shows a measurable effect on aneurysm pulsations in vivo. MATERIALS AND METHODS Ten patients with cerebral aneurysms underwent 4D-CTA. Images were reconstructed with filtered back-projection and iterative reconstruction. The following parameters were compared between both groups: image noise, absolute aneurysm volumes, pulsatility, and sharpness of aneurysm edges. RESULTS In iterative reconstruction images, noise was significantly reduced (mean, 9.8 ± 4.0 Hounsfield units versus 8.0 ± 2.5 Hounsfield units; P = .04), but the sharpness of aneurysm edges just missed statistical significance (mean, 3.50 ± 0.49 mm versus 3.42 ± 0.49 mm; P = .06). Absolute volumes (mean, 456.1 ± 775.2 mm(3) versus 461.7 ± 789.9 mm(3); P = .31) and pulsatility (mean, 1.099 ± 0.088 mm(3) versus 1.095 ± 0.082 mm(3); P = .62) did not show a significant difference between iterative reconstruction and filtered back-projection images. CONCLUSIONS CT images reconstructed with iterative reconstruction methods show a tendency toward shorter vessel edges but do not affect absolute aneurysm volumes or pulsatility measurements in vivo.


title: Comparison of high-performance liquid chromatography and supercritical fluid chromatography using evaporative light scattering detection for the determination of plasticizers in medical devices.

text: Recently, interest in supercritical fluid chromatography (SFC) has increased due to its high throughput and the development of new system improving chromatographic performances. However, most papers dealt with fundamental studies and chiral applications and only few works described validation process of SFC method. Likewise, evaporative light scattering detection (ELSD) has been widely employed in liquid chromatography but only a few recent works presented its quantitative performances hyphenated with SFC apparatus. The present paper discusses about the quantitative performances of SFC-ELSD compared to HPLC-ELSD, for the determination of plasticizers (ATBC, DEHA, DEHT and TOTM) in PVC tubing used as medical devices. After the development of HPLC-ELSD, both methods were evaluated based on the total error approach using accuracy profile. The results show that HPLC-ELSD was more precise than SFC-ELSD but lower limits of quantitation were obtained by SFC. Hence, HPLC was validated in the ± 10% acceptance limits whereas SFC lacks of accuracy to quantify plasticizers. Finally, both methods were used to determine the composition of plasticized-PVC medical devices. Results demonstrated that SFC and HPLC both hyphenated with ELSD provided similar results.


title: Altered activation of the diaphragm in late-onset Pompe disease.

text: Pompe disease is an inherited neuromuscular disorder that affects respiratory function and leads to dependence on external ventilatory support. We studied the activation of the diaphragm using bilateral phrenic magnetic stimulation and hypothesized that diaphragm compound muscle action potential (CMAP) amplitude and evoked transdiaphragmatic pressure (Twitch PDI) would correlate to disease severity. Eight patients with late onset Pompe disease (LOPD, aged 14-48 years) and four healthy control subjects completed the tests. Maximal Twitch PDI responses were progressively reduced in patients with LOPD compared to control subjects (1.4-17.1cm H2O, p<0.001) and correlated to voluntary functional tests (p<0.05). Additionally, CMAP amplitude (mA) was lower in the patients who used nighttime or fulltime ventilatory support, when compared to controls and patients who used no ventilatory support (p<0.005). However, the normalized (%peak) Twitch PDI and CMAP responses were similar between patients and controls. This suggests a loss of functional phrenic motor units in patients, with normal recruitment of remaining motor units.


title: Should We Screen for Coronary Heart Disease in Asymptomatic Persons?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

text: In March 2015, the American College of Physicians (ACP) released a clinical guideline on the value of screening for coronary heart disease (CHD) in asymptomatic persons. The guideline authors found that results of screening studies are unlikely to change patient management or the intensity of risk factor reduction strategies. Most events occur in patients who are at low to intermediate risk for CHD; and in low-risk asymptomatic patients, percutaneous coronary intervention in "screen-positive" patients does not improve outcomes and creates unnecessary risks. As a result, the ACP recommended against screening for asymptomatic patients who are at low risk for CHD. Instead, it recommended a focus on proven strategies, such as treatment of hypertension and hypercholesterolemia, to reduce risk in appropriately selected asymptomatic persons. Two discussants weigh the evidence for and against screening for CHD in asymptomatic patients with varying degrees of risk and provide recommendations for a specific patient who is uncertain whether to proceed to screening.


The lockdowns worked-but what comes next?


Vascular injury and COVID-19-related mortality: What lies below the tip of the iceberg?


title: Microbubble-enhanced ultrasound for the antivascular treatment and monitoring of hepatocellular carcinoma.

text: Background and Objective: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, and its current management relies heavily on locoregional therapy for curative therapy, bridge to transplant, and palliative therapy. Locoregional therapies include ablation and hepatic artery therapies such as embolization and radioembolization. In this study we evaluate the feasibility of using novel antivascular ultrasound (AVUS) as a noninvasive locoregional therapy to reduce perfusion in HCC lesions in a rat model and, monitor the effect with contrast-enhanced ultrasound imaging. Methods: HCC was induced in 36 Wistar rats by the ingestion of 0.01% diethylnitrosamine (DEN) for 12 weeks. Two therapy regimens of AVUS were evaluated. A primary regimen (n = 19) utilized 2-W/cm2, 3-MHz ultrasound (US) for 6 minutes insonation with 0.7 ml of microbubbles administered as an intravenous bolus. An alternate dose at half the primary intensity, sonication time, and contrast concentration was evaluated in 11 rats to assess the efficacy of a reduced dose. A control group (n = 6) received a sham therapy. Tumor perfusion was measured before and after AVUS with nonlinear contrast ultrasound (NLC) and power Doppler (PD). The quantitative perfusion measures included perfusion index (PI), peak enhancement (PE), time to peak (TTP), and perfusion area from NLC and PD scans. Total tumor area perfused during the scan was measured by a postprocessing algorithm called delta projection. Tumor histology was evaluated for signs of tissue injury and for vascular changes using CD31 immunohistochemistry. Results: DEN exposure induced autochthonous hepatocellular carcinoma lesions in all rats. Across all groups prior to therapy, there were no significant differences in the nonlinear contrast observations of peak enhancement and perfusion index. In the control group, there were no significant differences in any of the parameters after sham treatment. After the primary AVUS regimen, there were significant changes in all parameters (p ≤ 0.05) indicating substantial decreases in tumor perfusion. Peak enhancement in nonlinear contrast scans showed a 37.9% ± 10.1% decrease in tumor perfusion. Following reduced-dose AVUS, there were no significant changes in perfusion parameters, although there was a trend for the nonlinear contrast observations of peak enhancement and perfusion index to increase. Conclusion: This study translated low-intensity AVUS therapy into a realistic in vivo model of HCC and evaluated its effects on the tumor vasculature. The primary dose of AVUS tested resulted in significant vascular disruption and a corresponding reduction in tumor perfusion. A reduced dose of AVUS, on the other hand, was ineffective at disrupting perfusion but demonstrated the potential for enhancing tumor blood flow. Theranostic ultrasound, where acoustic energy and microbubbles are used to monitor the tumor neovasculature as well as disrupt the vasculature and treat lesions, could serve as a potent tool for delivering noninvasive, locoregional therapy for hepatocellular carcinoma.


title: Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients: a position paper endorsed by ESMINT and ESNR : part I: Current situation and major research questions.

text: A new era of stroke treatment may have begun with mechanical thrombectomy (MT) by fully deployed closed-cell self-expanding stents (stent-triever). Multiple case series and the first randomised controlled trials (RCTs) have now been published. More studies are under way involving large numbers of patients, which in turn has resulted in less strict "pragmatic" study protocols. Problems with current trials include a lack of standardisation in the conduct of the recanalisation procedure, the definition of primary endpoints such as the grade of arterial recanalisation and tissue reperfusion, and the post-surgical care provided. In Part 1 of this two part series, we outline the current situation and the major research questions.


title: Negative Transmission of SARS-CoV-2 to Hand-Expressed Colostrum from SARS-CoV-2-Positive Mothers.

text: Aim: The objective of our study was to determine whether the SARS-CoV-2-positive mothers transmit the virus to their hand-expressed colostrum. Methods: This is an observational prospective study that included pregnant women who tested positive for SARS-CoV-2 by PCR test on a nasopharyngeal swab at the moment of childbirth and who wanted to breastfeed their newborns. A colostrum sample was obtained from the mothers by manual self-extraction. To collect the samples, the mothers wore surgical masks, washed their hands with an 85% alcohol-based gel, and washed their breast with gauze that was saturated with soap and water. Results: We obtained seven colostrum samples from different mothers in the first hours postdelivery. SARS-CoV-2 was not detected in any of the colostrum samples obtained in our study. Conclusion: In our study, breast milk was not a source of SARS-CoV-2 transmission. Hand expression (assuring that a mask is used and that appropriate hygienic measures are used for the hands and the breast), when direct breastfeeding is not possible, appears to be a safe way of feeding newborns of mothers with COVID-19.


Safety first - assisted human reproduction second.


title: How to Conduct an Outpatient Telemedicine Rehabilitation or Prehabilitation Visit.

text: The novel coronavirus pandemic is resulting in an accelerated conversion of in-person physician visits to virtual visits. As barriers to adoption of telemedicine are rapidly decreasing, it is important to recognize the need for practical and immediately deployable information that can improve doctor-patient interactions, facilitate accurate documentation, and increase confidence in the transition to virtual visits. In this article we aim to outline the components of an outpatient telemedicine visit for physiatrists with a particular focus on an adapted virtual physical examination. Uses of telemedicine may include future largescale concerns such as natural disasters or climate change. We describe a general approach to the visit, review definitions of terms commonly used in telemedicine, and offer tips for optimizing the encounter. This article is protected by copyright. All rights reserved.