title: Single-port access compared with three-port laparoscopic adnexal surgery in a randomized controlled trial.

text: OBJECTIVE Scar-related cosmetic outcomes were compared prospectively between conventional three-port and single-port access laparoscopic adnexal gynaecological surgery. METHODS Enrolled patients were randomly assigned to a single- or three-port surgery group. Scar-related outcomes were evaluated at 1 month, 6 months and 1 year. Scars were assessed by an independent observer using the modified Vancouver Scar Scale (mVSS). All patients were asked about pain related to the scar and scar satisfaction; results were recorded using a numerical rating scale. RESULTS Seventy-three patients were enrolled between June 2010 and June 2011. Demographic and surgical outcomes did not differ between the groups. mVSS results were similar in the two groups at each follow-up point. The scar satisfaction profile measured at 1 month showed no significant difference between the groups, but the single-port access group had better results than the conventional group at all other follow-up timepoints. CONCLUSION Cosmetic outcome was better for single-port than for three-port adnexal gynaecological surgery at 6-month and 1-year follow-up.


title: Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia.

text: RATIONALE Bronchopulmonary dysplasia (BPD) is an important complication of mechanical ventilation in preterm infants, and no definite therapy can eliminate this complication. Pulmonary inflammation plays a crucial role in its pathogenesis, and glucocorticoid is one potential therapy to prevent BPD. OBJECTIVES To compare the effect of intratracheal administration of surfactant/budesonide with that of surfactant alone on the incidence of death or BPD. METHODS A clinical trial was conducted in three tertiary neonatal centers in the United States and Taiwan, in which 265 very-low-birth-weight infants with severe respiratory distress syndrome who required mechanical ventilation and inspired oxygen (fraction of inspired oxygen, ≥50%) within 4 hours of birth were randomly assigned to one of two groups (131 intervention and 134 control). The intervention infants received surfactant (100 mg/kg) and budesonide (0.25 mg/kg), and the control infants received surfactant only (100 mg/kg), until each infant required inspired O2 at less than 30% or was extubated. MEASUREMENTS AND MAIN RESULTS The intervention group had a significantly lower incidence of BPD or death (55 of 131 [42.0%] vs. 89 of 134 [66%]; risk ratio, 0.58; 95% confidence interval, 0.44-0.77; P < 0.001; number needed to treat, 4.1; 95% confidence interval, 2.8-7.8). The intervention group required significantly fewer doses of surfactant than did the control group. The intervention group had significantly lower interleukin levels (IL-1, IL-6, IL-8) in tracheal aspirates at 12 hours and lower IL-8 at 3-5 and 7-8 days. CONCLUSIONS In very-low-birth-weight infants with severe respiratory distress syndrome, intratracheal administration of surfactant/budesonide compared with surfactant alone significantly decreased the incidence of BPD or death without immediate adverse effect. Clinical trial registered with www.clinicaltrials.gov (NCT-00883532).


title: Pyeloplasty in children: perioperative results and long-term outcomes of robotic-assisted laparoscopic surgery compared to open surgery.

text: BACKGROUND A few studies have compared robotic-assisted laparoscopic pyeloplasty (RALP) with open pyeloplasty (OP) in children, but no previous study includes a long-term follow-up of renal function and hydronephrosis in combination with a thorough prospective follow-up of the RALP patients of at least 2 years. OBJECTIVE To analyze perioperative results and long-term outcome of children with obstruction of the ureteropelvic junction, operated on with RALP compared to OP. PATIENTS AND METHODS Children ≤15 years operated on with RALP or OP from 2000 through 2013 were reviewed. Patient demographics, perioperative data, postoperative complications, and long-term outcome were evaluated. The outcome was based on pre- and postoperative examination of renal function, hydronephrosis and flank pain. RESULTS 129 pyeloplasties (84 OP, 39 RALP, 6 reoperations) on 123 patients were included. RALP had significantly longer operative time and shorter postoperative hospital stay, compared to OP. No difference was found in postoperative need of morphine or complication rates. Mean follow-up for RALP with ultrasound was 29 and 25 months with renal scan, compared to 34 and 28 months, respectively, for OP. The success rate for flank pain was 96 and 94 %, for hydronephrosis 93 and 95 %, and renal function 94 and 92 %, for RALP and OP, respectively. CONCLUSIONS RALP is a safe method, with advantages compared to OP, and with the same success rate. This study supports the use of RALP in children.


Catch-22: Carotid stenting is safe and effective (Food and Drug Administration) but is it reasonable and necessary (Centers for Medicare and Medicaid Services)?


title: Systemic responses during local viral infections: type I IFNs sound the alarm.

text: Type I IFNs are well known for their role in controlling virus replication and spread. Type I IFNs produced by the infected tissue also signal beyond the boundaries of the infection to regulate different elements of the anti-viral immune response. Recent reports show that type I IFNs directly condition naive monocytes residing in the distal bone marrow (BM) and induce the expression of effector molecules in memory T cells, before their recruitment to the infected site. In addition, hematopoietic stem cells (HSCs) were shown to enter the cell cycle in response to systemically distributed type I IFNs. These discoveries expand our understanding of the pleiotropic effects of type I IFNs during infection and highlight the critical role of systemic signals in the development of an effective response to a localized viral infection.


title: Effects of explicit cueing and ambiguity on the anticipation and experience of a painful thermal stimulus.

text: Many factors can influence the way in which we perceive painful events and noxious stimuli, but less is known about how pain perception is altered by explicit knowledge about the impending sensation. This study aimed to investigate the impact of explicit cueing on anxiety, arousal, and pain experience during the anticipation and delivery of noxious thermal heat stimulations. Fifty-two healthy volunteers were randomised to receive explicit instructions about visual cue-stimulus temperature pairings, or no explicit instructions about the cue-stimulus pairs. A pain anxiety task was used to investigate the effects of explicit cueing on anticipatory anxiety, pain experience and electrophysiological responses. Participants who received explicit instructions about the cue-stimulus pairs (i.e., the relationship between the colour of the cue and the temperature of the associated stimuli) reported significantly higher subjective anxiety prior to the delivery of the thermal heat stimuli (p = .025, partial eta squared = .10). There were no effects of explicit cueing on subsequent pain intensity, unpleasantness, or the electrophysiological response to stimulus delivery. The perceived intensity and unpleasantness of the stimuli decreased across the blocks of the paradigm. In both groups anticipating the ambiguous cue elicited the largest change in electrophysiological arousal, indicating that not knowing the impending stimulus temperature led to increased arousal, compared to being certain of receiving a high temperature thermal stimulus (both p < .001). Perceived stimulus intensity varied between ambiguous and non-ambiguous cues, depending on the temperature of the stimulus. Together these findings highlight the impact and importance of explicit cueing and uncertainty in experimental pain studies, and how these factors influence the way healthy individuals perceive and react to noxious and innocuous thermal stimuli.


title: Small bowel obstruction from barbed suture following laparoscopic myomectomy-A case report.

text: Myomectomy is commonly performed for symptomatic fibroids in women who wish to conserve fertility. Laparoscopic myomectomy provides advantages as a minimally invasive procedure. To facilitate the closure of the uterine wound after enucleation of the fibroid, barbed sutures have been introduced as they can shorten the operative time and reduce the amount of bleeding. However, the use of barbed suture is not without risk. There were a few reports on the risks of barbed sutures in the literature. We report herein a case of acute abdomen because of small bowel entrapment and obstruction following the use of barbed suture in laparoscopic myomectomy. Surgeons using barbed suture in myomectomy should be vigilant on the possibility of this bowel complication whenever adverse clinical situation arises as the outcome could be serious if the condition was left unchecked.


title: Evaluation of resorbable polydioxanone and polyglycolic acid meshes in a rat model of ventral hernia repair.

text: The objective of this study was to evaluate physical, mechanical, and biological properties of the polydioxanone (PDO) monofilament meshes and polyglycolide (PGA) polyfilament meshes in comparison with Permacol® implants. In rat experimental model, a 1.5 × 2.0 cm defect in abdominal wall was reconstructed by using the Permacol surgical implant or knitted meshes produced from either PDO monofilament, or PGA multifilament. The implant sites were assessed for the tensile strength and the extents of material resorption, host inflammatory response and host tissue replacement on days 3, 10, 30, or 60 after the surgery. The PDO and PGA meshes were rapidly pervaded by the host connective tissue with elements of skeletal muscle histogenesis. The degree of adhesions was significantly higher in the Permacol group. All of the prostheses underwent resorption, which correlated with gradual decreases in the overall tensile strength of the site and the Col1a1 gene expression level. Elevated expression of Fgf2 gene maintained longer in the PDO group, and the Mmp9 gene expression level in this group was higher than in the other groups. Gene expression levels of inflammatory cytokines were higher in the Permacol group. The foreign body giant cell numbers were lower in the PDO and Permacol groups than in the PGA group. Minimal macrophage infiltration with predominance of M2 cells was observed in the PDO group. Overall, the PDO prosthesis turned out to be significantly better than the PGA or Permacol prostheses by a number of indicators of biocompatibility and efficacy. © 2018 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000-000, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 652-663, 2019.


Infection of severe acute respiratory syndrome coronavirus 2 in a patient with acquired immunodeficiency syndrome.


title: Non-galenic arteriovenous fistulas in adults: transarterial embolization and literature review.

text: BACKGROUND Non-galenic dural arteriovenous fistula (NGAVF) is a rare congenital vascular abnormality characterized by high flow connections between cerebral arteries and a dilated pial venous varix. These lesions have been reported mostly in the pediatric population. OBJECTIVES To examine the clinical features and treatment outcomes for adult (≥ 18 years) patients with NGAVFs. METHODS We retrospectively reviewed the records of patients with NGAVFs who underwent endovascular treatment between 2008 and 2013. A PubMed literature search was conducted to identify reports of adult patients with these lesions. RESULTS Two adults with NGAVFs were treated at our institution via transarterial embolization with a favorable outcome. The literature search revealed 24 adult NGAVF cases. Among these cases and ours, mean patient age was 33.4 ± 13.3 years, and 13 were women. Most patients experienced protracted neurological symptoms at the time of treatment whereas 5 (19.2%) patients presented with acute hemorrhage. 18 patients had single hole fistulas; 8 had multi-hole fistulas. 11 patients were treated by microsurgical ligation, 10 by embolization, 4 by combined therapy, and 1 with observation. Two patients died of reperfusion hemorrhage. Women were more likely to have a favorable outcome than men (100% vs 75.0%; p=0.07). No statistical difference was found in terms of clinical outcome for patients with single hole versus multi-hole fistulas or those treated by surgery versus embolization. CONCLUSIONS NGAVFs are extremely rare in the adult population and present a similar clinical course as in older children. In our experience, transarterial embolization can be safely and effectively utilized for the treatment of these lesions in adults.


title: Single-incision laparoscopic cholecystectomy learning curve experience seen in a single institution.

text: INTRODUCTION Single-incision laparoscopic surgery (SILS) is laparoscopic surgery done by one incision through the umbilicus. Cholecystectomy lends itself well to a SILS approach. As these procedures have become more widely adapted, it is important to determine the approximate learning curve to decrease two surgical endpoints: (1) time to completion of the procedure; and (2) decreased incidence of conversion. METHODS We prospectively reviewed our series of 50 cholecystectomies done using the SILS approach between May 2008 to September 2008. All cases were performed by two advanced laparoscopic surgeons at a single institution. Data was collected immediately after the case and entered into an Excel database. Cases were performed by insufflating the abdomen with a Veress needle through the umbilicus followed by placement of 5-mm ports at the umbilicus. RESULTS Patient ages ranged between 21 and 82 years with a median age of 45 years. Body mass index (BMI) range was 21 to 42 kg/m with a mean of 30 kg/m. Average length of time for cases was 1 hour 9 minutes with a range between 55 minutes and 120 minutes. The average length of time for the first 25 cases was 80 minutes. When compared with cases 26 to 50 the average length of time was 60 minutes (P<0.05). The conversion rate to conventional laparoscopic cholecystectomy was 10%. Conversion was accomplished through the addition of a 5-mm port elsewhere on the abdominal cavity. After the tenth case, the incidence of conversion went down to zero. When conversions were further stratified, they occurred within each individual surgeon's first ten cases. CONCLUSIONS The learning curve for successful consistent completion of SILS cholecystectomy cases appears to be after 25 cases. In addition, conversion rates drop dramatically after the first ten cases.


Comparing outcomes in ECMO between roller and centrifugal pumps in the face of evolving technology.


title: Supporting Social Distancing for COVID-19 Mitigation Through Community-Based Volunteer Networks.

text: Recent experiences during a variety of disease outbreaks, ranging from Ebola to influenza, have underscored the potential for epidemics to have an impact on daily life, even for those who are not themselves infected.1,2 In severe situations, epidemics or pandemics can even affect overall community functioning. For example, a rapidly expanding pandemic can result in shuttered schools, cancelled events, food insecurity, and social distrust in communities. (Am J Public Health. Published online ahead of print May 21, 2020: e1-e2. doi:10.2105/AJPH.2020.305740).


title: Anthropogenic factors affecting wildlife species status outcomes: why the fixation on pesticides?

text: Most Americans are at least three generations removed from the farm, thereby at least three generations removed from the reality of where their food comes from. Not surprisingly, there are many misconceptions about modern food production, including the potential collateral environmental damage attributed to agriculture, particularly the application of pesticides. However, the implication of conventional agriculture in the broader narrative of wildlife species status outcomes (SSOs) lacks context and relativity. Since the dawn of civilization, humans have had a profound impact on their environment. Originating as hunter-gatherer societies, our ancient ancestors initially exploited anything that could be consumed or brought to bear. With the advent of the "first proto-farmers," humans began manipulating their environments to maximize available resources. Urban centers propagated and flourished proximal to agricultural origins, where modern societies have been built primarily on an abundance of food. As societies "developed," and continue to develop, an inevitable economic transition occurs from agriculture to industry/service predominance, culminating in a corresponding shift in land use. Developed countries have typically experienced maximal expansion of the agricultural frontier, where farmland is now steadily eroding by a proverbial flood of urban development. In contrast, in developing countries, this shift in economic development has not yet fully manifested and the agricultural footprint continues to expand at the expense of native habitats. Thus, the relative influence of "agriculture" on SSOs, in terms of land use, is primarily dependent on economic developmental status, which can be, at least in part, ameliorated via technology by increasing yield from existing land. Moreover, in addition to the land use challenge, there are multiple other factors affecting wildlife SSOs, including a figurative plague of invasive species, a literal plague of disease, a barrage of buildings, bumpers, grilles, and windshields to collide with, light pollution to confuse cues with, poachers to contend with, and even more complicated factors such as climate change. Being an easy target does not mean pesticides are the right target, and this fixation can potentially detract from public awareness regarding the primary drivers affecting SSOs as well as the opportunity to proactively address them. So, relatively speaking, how do these other factors compare to "pesticides" in terms of driving SSOs? Moreover, why is the popular media so fixated on the pesticide narrative? Based on the available evidence, this manuscript attempts to address these questions from a holistic and relative perspective within the context of land use change, economic development, population growth, and associated implications of global connectivity and commerce.


title: Learning curve of single-port laparoscopic appendectomy for noncomplicated acute appendicitis: a preliminary analysis compared with conventional laparoscopic appendectomy.

text: BACKGROUND The aim of this study was to delineate the learning curve of single-port laparoscopic appendectomy for noncomplicated appendicitis. PATIENTS AND METHODS Thirty patients who underwent single-port laparoscopic appendectomy between July 2009 and June 2010 were compared retrospectively with 30 prior consecutive patients who underwent surgery in the three-port manner. Operative duration, number of conversions, time to resumption of oral intake, length of hospital stay, and complications were used as the indicators of the learning curve. RESULTS Demographics were similar between the single-port and three-port groups. A significant decrease in operative duration was noted after a surgical experience of 10 patients. An operative duration equivalent to that of the conventional three-port method could be achieved after 30 cases. CONCLUSIONS Single-port laparoscopic appendectomy is a safe and feasible procedure. The learning curve could be overcome safely without major complications. Our preliminary analysis showed that 30 cases are sufficient to achieve an equivalent operative duration compared with conventional three-port laparoscopic appendectomy.


title: Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43.

text: Human coronaviruses (HCoVs) are recognized respiratory pathogens for which accumulating evidence indicates that in vulnerable patients the infection can cause more severe pathologies. HCoVs are not always confined to the upper respiratory tract and can invade the central nervous system (CNS) under still unclear circumstances. HCoV-induced neuropathologies in humans are difficult to diagnose early enough to allow therapeutic interventions. Making use of our already described animal model of HCoV neuropathogenesis, we describe the route of neuropropagation from the nasal cavity to the olfactory bulb and piriform cortex and then the brain stem. We identified neuron-to-neuron propagation as one underlying mode of virus spreading in cell culture. Our data demonstrate that both passive diffusion of released viral particles and axonal transport are valid propagation strategies used by the virus. We describe for the first time the presence along axons of viral platforms whose static dynamism is reminiscent of viral assembly sites. We further reveal that HCoV OC43 modes of propagation can be modulated by selected HCoV OC43 proteins and axonal transport. Our work, therefore, identifies processes that may govern the severity and nature of HCoV OC43 neuropathogenesis and will make possible the development of therapeutic strategies to prevent occurrences.IMPORTANCE Coronaviruses may invade the CNS, disseminate, and participate in the induction of neurological diseases. Their neuropathogenicity is being increasingly recognized in humans, and the presence and persistence of human coronaviruses (HCoV) in human brains have been proposed to cause long-term sequelae. Using our mouse model relying on natural susceptibility to HCoV OC43 and neuronal cell cultures, we have defined the most relevant path taken by HCoV OC43 to access and spread to and within the CNS toward the brain stem and spinal cord and studied in cell culture the underlying modes of intercellular propagation to better understand its neuropathogenesis. Our data suggest that axonal transport governs HCoV OC43 egress in the CNS, leading to the exacerbation of neuropathogenesis. Exploiting knowledge on neuroinvasion and dissemination will enhance our ability to control viral infection within the CNS, as it will shed light on underlying mechanisms of neuropathogenesis and uncover potential druggable molecular virus-host interfaces.


title: Survival after long-term isoflurane sedation as opposed to intravenous sedation in critically ill surgical patients: Retrospective analysis.

text: BACKGROUND Isoflurane has shown better control of intensive care sedation than propofol or midazolam and seems to be a useful alternative. However, its effect on survival remains unclear. OBJECTIVE The objective of this study is to compare mortality after sedation with either isoflurane or propofol/midazolam. DESIGN A retrospective analysis of data in a hospital database for a cohort of consecutive patients. SETTING Sixteen-bed interdisciplinary surgical ICU of a German university hospital. PATIENTS Consecutive cohort of 369 critically ill surgical patients defined within the database of the hospital information system. All patients were continuously ventilated and sedated for more than 96 h between 1 January 2005 and 31 December 2010. After excluding 169 patients (93 >79 years old, 10 <40 years old, 46 mixed sedation, 20 lost to follow-up), 200 patients were studied, 72 after isoflurane and 128 after propofol/midazolam. INTERVENTIONS Sedation with isoflurane using the AnaConDa system compared with intravenous sedation with propofol or midazolam. MAIN OUTCOME MEASURES Hospital mortality (primary) and 365-day mortality (secondary) were compared with the Kaplan-Meier analysis and a log-rank test. Adjusted odds ratios (ORs) [with 95% confidence interval (95% CI)] were calculated by logistic regression analyses to determine the risk of death after isoflurane sedation. RESULTS After sedation with isoflurane, the in-hospital mortality and 365-day mortality were significantly lower than after propofol/midazolam sedation: 40 versus 63% (P = 0.005) and 50 versus 70% (P = 0.013), respectively. After adjustment for potential confounders (coronary heart disease, chronic obstructive pulmonary disease, acute renal failure, creatinine, age and Simplified Acute Physiology Score II), patients after isoflurane were at a lower risk of death during their hospital stay (OR 0.35; 95% CI 0.18 to 0.68, P = 0.002) and within the first 365 days (OR 0.41; 95% CI 0.21 to 0.81, P = 0.010). CONCLUSION Compared with propofol/midazolam sedation, long-term sedation with isoflurane seems to be well tolerated in this group of critically ill patients after surgery.


title: Potent In Vivo NK Cell-Mediated Elimination of HIV-1-Infected Cells Mobilized by a gp120-Bispecific and Hexavalent Broadly Neutralizing Fusion Protein.

text: Antibodies bound to human immunodeficiency virus type 1 (HIV-1) envelope protein expressed by infected cells mobilize antibody-dependent cellular cytotoxicity (ADCC) to eliminate the HIV-1-infected cells and thereby suppress HIV-1 infection and delay disease progression. Studies treating HIV-1-infected individuals with latency reactivation agents to reduce their latent HIV-1 reservoirs indicated that their HIV-1-specific immune responses were insufficient to effectively eliminate the reactivated latent HIV-1-infected T cells. Mobilization of ADCC may facilitate elimination of reactivated latent HIV-1-infected cells to deplete the HIV-1 reservoir and contribute to a functional HIV-1 cure. The most effective antibodies for controlling and eradicating HIV-1 infection would likely have the dual capacities of potently neutralizing a broad range of HIV-1 isolates and effectively mobilizing HIV-1-specific ADCC to eliminate HIV-1-infected cells. For this purpose, we constructed LSEVh-LS-F, a broadly neutralizing, defucosylated hexavalent fusion protein specific for both the CD4 and coreceptor gp120-binding sites. LSEVh-LS-F potently inhibited in vivo HIV-1 and simian-human immunodeficiency virus (SHIV) infection in humanized mouse and macaque models, respectively, including in vivo neutralization of HIV-1 strains resistant to the broadly neutralizing antibodies VRC01 and 3BNC117. We developed a novel humanized mouse model to evaluate in vivo human NK cell-mediated elimination of HIV-1-infected cells by ADCC and utilized it to demonstrate that LSEVh-LS-F rapidly mobilized NK cells to eliminate >80% of HIV-1-infected cells in vivo 1 day after its administration. The capacity of LSEVh-LS-F to eliminate HIV-1-infected cells via ADCC combined with its broad neutralization activity supports its potential use as an immunotherapeutic agent to eliminate reactivated latent cells and deplete the HIV-1 reservoir.IMPORTANCE Mobilization of antibody-dependent cellular cytotoxicity (ADCC) to eliminate reactivated latent HIV-1-infected cells is a strategy which may contribute to depleting the HIV-1 reservoir and achieving a functional HIV-1 cure. To more effectively mobilize ADCC, we designed and constructed LSEVh-LS-F, a broadly neutralizing, defucosylated hexavalent fusion protein specific for both the CD4 and coreceptor gp120-binding sites. LSEVh-LS-F potently inhibited in vivo HIV-1 and SHIV infection in humanized mouse and macaque models, respectively, including in vivo neutralization of an HIV-1 strain resistant to the broadly neutralizing antibodies VRC01 and 3BNC117. Using a novel humanized mouse model, we demonstrated that LSEVh-LS-F rapidly mobilized NK cells to eliminate >80% of HIV-1-infected cells in vivo 1 day after its administration. The capacity of LSEVh-LS-F to eliminate HIV-1-infected cells via ADCC combined with its broad neutralization activity supports its potential use as an immunotherapeutic agent to eliminate reactivated latent cells and deplete the HIV-1 reservoir.


title: Ebola Preparedness: Diagnosis Improvement Using Rapid Approaches for Proficiency Testing.

text: The unprecedented 2015 Ebolavirus (EBOV) outbreak in West Africa was declared a public health emergency, making diagnosis and quality of testing a global issue. The accuracy of laboratory diagnostic capacity for EBOV was assessed in 2014 to 2016 using a proficiency testing (PT) strategy developed by the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) in Biosecurity. Following a literature search, EBOV-specific gene targets were ranked according to the frequency of their use in published methods. The most commonly used gene regions (nucleoprotein [NP], glycoprotein [GP], and RNA-dependent RNA polymerase [L]) were selected for the design of in vitro RNA transcripts to be included in the simulated EBOV specimens used for EBOV detection with PCR-based assays. Specimens were tested for stability and found to be stable on long-term storage (1 year) at -80°C and on shorter-term storage in lyophilized form (1 week at ambient temperature and a subsequent week at -80°C). These specimens were used in three EBOV PTs offered from April 2014 to March 2016. In the first and third PTs, all laboratories (3/3 and 9/9, respectively) correctly identified specimens containing EBOV RNA transcripts, while in the second PT, all but one laboratory (5/6) correctly confirmed the presence of EBOV. The EBOV PT panel was useful for ensuring the competency of laboratories in detecting EBOV in the absence of readily available clinical samples. The simulated EBOV specimen was safe, stable, and reliable and can be used in lyophilized form for future EBOV PT programs, allowing simplicity of transport.


title: Mid-term and long-term follow-up of intracranial aneurysms treated by the p64 Flow Modulation Device: a multicenter experience.

text: BACKGROUND Experience with the endovascular treatment of cerebral aneurysms using the p64 Flow Modulation Device is still limited. This study discusses the results and complications of this new flow diverter device. METHODS 40 patients (30 women, 10 men) with 50 cerebral aneurysms treated in six Italian neurointerventional centers with the p64 Flow Modulation Device between April 2013 and September 2015 were retrospectively reviewed. RESULTS Complete occlusion was obtained in 44/50 aneurysms (88%) and partial occlusion in 3 (6%). In the other three aneurysms (6%), two cases of asymptomatic in-stent thrombosis and one intraprocedural occlusion of the parent vessel occurred. Technical complications were observed in eight procedures (16%). Permanent morbidity due to acute in-stent thrombosis and consequent ischemic stroke occurred in one patient (2.5%). No delayed aneurysm rupture, subarachnoid or intraparenchymal hemorrhage, or ischemic complications occurred and there were no deaths. CONCLUSIONS Endovascular treatment with the p64 Flow Modulation Device is a safe treatment for unruptured cerebral aneurysms, resulting in a high rate of occlusion. As with other flow diverter devices, we recommend this treatment mainly for large-necked aneurysms of the internal carotid artery siphon. However, endovascular treatment with the p64 device should also be encouraged in difficult cases such as aneurysms of the posterior circulation and beyond the circle of Willis.


title: Medicinal herbal extracts of Sophorae radix, Acanthopanacis cortex, Sanguisorbae radix and Torilis fructus inhibit coronavirus replication in vitro.

text: BACKGROUND Cimicifuga rhizome, Meliae cortex, Coptidis rhizome and Phellodendron cortex have been previously shown to exhibit anti-coronavirus activity. Here, an additional 19 traditional medicinal herbal extracts were evaluated for antiviral activities in vitro. METHODS A plaque assay was used to evaluate the effects of 19 extracts, and the concentration of extract required to inhibit 50% of the replication (EC(50)) of mouse hepatitis virus (MHV) A59 strain (MHV-A59) was determined. The 50% cytotoxic concentration (CC(50)) of each extract was also determined. Northern and western blot analyses were conducted to evaluate antiviral activity on viral entry, viral RNA and protein expression, and release in MHV-infected DBT cells. RESULTS Sophorae radix, Acanthopanacis cortex and Torilis fructus reduced intracellular viral RNA levels with comparable reductions in viral proteins and MHV-A59 production. The extracts also reduced the replication of the John Howard Mueller strain of MHV, porcine epidemic diarrhoea virus and vesicular stomatitis virus in vitro. Sanguisorbae radix reduced coronavirus production, partly as a result of decreased protein synthesis, but without a significant reduction in intracellular viral RNA levels. The EC(50) values of the four extracts ranged from 0.8 to 3.7 microg/ml, whereas the CC(50) values ranged from 156.5 to 556.8 microg/ml. Acanthopanacis cortex and Torilis fructus might exert their antiviral activities in MHV-A59-infected cells by inducing cyclooxygenase-2 expression via the activation of extracellular signal-related kinase (ERK) and p38 or ERK alone, respectively. CONCLUSIONS Sophorae radix, Acanthopanacis cortex, Sanguisorbae radix and Torilis fructus might be considered as promising novel anti-coronavirus drug candidates.


title: Thermal spread of vessel-sealing devices evaluated in a clinically relevant in vitro model.

text: INTRODUCTION Bipolar vessel-sealing devices (VSDs) have advantages in urological surgeries (less hemorrhage, shorter operating time). However, these instruments can cause thermal injuries, which can result in neural damage and necrosis. The objectives of this study were to establish a reproducible in vitro model for standardized assessment of electrosurgical devices and to evaluate whether optimized placement of surgical instruments can reduce the thermal spread. METHODS We evaluated thermal spread of two VSDs in vitro using thin bovine muscle strips. Thermal injury was measured using an infrared camera, temperature probes and histology. The recordings were made with the VSD alone and with a rectangular clamp next to the VSD. RESULTS Both instruments showed a significant temperature spread of 2.5 mm lateral to the VSD. The placement of a metal clamp next to the VSD significantly reduced the temperature spread. Histological examinations were able to underline these findings. CONCLUSIONS In this study we describe a straightforward clinically relevant in vitro model for the evaluation of future electrosurgical instruments. We demonstrated that the thermal spread of VSD could be further reduced by optimized placement of an additional surgical instrument. Our results could help surgeons protect sensitive structures like nerves in the vicinity of the VSD.


title: Innate immune responses in raccoons after raccoon rabies virus infection.

text: Zoonotic wildlife diseases pose significant health risks not only to their primary vectors but also to humans and domestic animals. Rabies is a lethal encephalitis caused by rabies virus (RV). This RNA virus can infect a range of terrestrial mammals but each viral variant persists in a particular reservoir host. Active management of these host vectors is needed to minimize the negative impacts of this disease, and an understanding of the immune response to RV infection aids strategies for host vaccination. Current knowledge of immune responses to RV infection comes primarily from rodent models in which an innate immune response triggers activation of several genes and signalling pathways. It is unclear, however, how well rodent models represent the immune response of natural hosts. This study investigates the innate immune response of a primary host, the raccoon, to a peripheral challenge using the raccoon rabies virus (RRV). The extent and temporal course of this response during RRV infection was analysed using genes predicted to be upregulated during infection (IFNs; IFN regulatory factors; IL-6; Toll like receptor-3; TNF receptor). We found that RRV activated components of the innate immune system, with changes in levels of transcripts correlated with presence of viral RNA. Our results suggest that natural reservoirs of rabies may not mimic the immune response triggered in rodent models, highlighting the need for further studies of infection in primary hosts.


Covid-19: doctors' leaders warn that staff could quit and may die over lack of protective equipment.


title: Lung resection using transumbilical incision: an animal survival study.

text: INTRODUCTION Transumbilical single-port surgery is a potentially less invasive approach to many types of abdominal surgeries and offers better cosmetic outcomes than conventional 3-port laparoscopic surgery. It avoids the complication of intercostal neuralgia and may reduce the risk of pulmonary complications after video-assisted thoracic surgery. This study evaluated the feasibility of transumbilical lung wedge resection. METHODS Lung resection was performed in 11 beagle dogs weighing 5.9 to 8.5 kg. A 3-cm umbilical incision and one diaphragmatic incision were made, and an endoscopic stapler was used. The diaphragmatic incisions were repaired under video guidance using a V-Loc knotless suturing device (Covidien, Mansfield, Massachusetts). Animals were monitored daily for signs of postoperative infection. White blood cell count, C-reactive protein level, and IL-6 level were measured in all animals. Animals were euthanized 14 days after surgery and underwent necropsy evaluation. RESULTS Accurate lung resection was achieved in 10 of 11 animals during a median operative time of 98 minutes (range 60-165). In 1 animal, transumbilical lung resection was not possible and was converted to thoracotomy. All animals survived without major postoperative complications. At necropsy, evidence of uneventful healing of the stapled resection margin and diaphragmatic wound were found. There was no evidence of vital organ injury or intrathoracic infection. CONCLUSION A transumbilical approach to thoracic cavity exploration and stapled lung resection is technically feasible. Primary suturing of the diaphragmatic incision is a simple and effective means of diaphragmatic wound closure. This may be an alternative to video-assisted thoracic surgery for the management of simple thoracic disease.


title: Management of common cold symptoms with over-the-counter medications: clearing the confusion.

text: The common cold, an acute upper respiratory tract infection of viral origin, is among the most widespread ailments in the world. Although the general public usually relies on over-the-counter (OTC) medication(s) to treat cough/cold symptoms, reliable guidance is needed to help select the appropriate OTC medication for each individual. Consumers may be confused by the wide variety of products available, containing ≥ 1 active pharmaceutical ingredient. Health care professionals are in a position to help people identify the most bothersome symptom(s), evaluate underlying medical conditions and medications, and recommend the most appropriate OTC active ingredient(s) for treatment. Patients should be educated about available OTC medications to manage cough/cold symptoms and the importance of learning to read the package labeling for appropriate dosing and administration. In addition, potentially serious causes of cough/cold symptoms (eg, influenza, asthma, bronchitis) or underlying medical conditions that put the individual at increased risk for complications should be ruled out when symptoms do not resolve within a typical cold timeline. This review article discusses the active ingredients found in OTC medications and the clinical evidence supporting their use. The need to educate health care professionals and patients on the safe and effective use of OTC medications is addressed, and we offer a guide for the management of symptoms that appear during the timeline of a typical common cold.


title: Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19.

text: Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1β-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1β-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.


title: Re-treatment rates after treatment with the Pipeline Embolization Device alone versus Pipeline and coil embolization of cerebral aneurysms: a single-center experience.

text: OBJECT The optimal strategy for use of the Pipeline Embolization Device (PED, ev3 Neurovascular) has not been clearly defined. The authors examined re-treatment rates after treatment with PED alone versus PED and adjunctive coil embolization (PED/coil). METHODS The authors retrospectively examined cerebral aneurysms treated with the PED from May 2011 to March 2014. Overall, 133 patients (25 men, 108 women; mean age 60.4 years, range 23-85 years) were treated for 140 aneurysms (mean size 11.8 ± 8.3 mm) requiring 224 PEDs (mean 1.7 PEDs per patient). Sixty-eight patients (13 men, 55 women) were treated with PED alone for 73 aneurysms (mean size 10.6 ± 9.2 mm) and 65 patients (12 men, 53 women) were treated with PED/coil for 67 aneurysms (mean size 12.8 ± 7.4 mm). RESULTS Eight aneurysms in 8 patients were re-treated in the PED-alone cohort versus only 1 aneurysm in 1 patient in the PED/coil cohort for re-treatment rates of 11.8% (8/68) and 1.5% (1/65), respectively (p = 0.03). Two patients in the PED-alone cohort were re-treated due to PED contraction, while the other 6 were re-treated for persistent filling of the aneurysms. The PED/coil patient experienced continued filling of a vertebrobasilar artery aneurysm. No aneurysms in either group ruptured after treatment. CONCLUSIONS Adjunctive coil embolization during flow diversion with the PED resulted in a significantly lower re-treatment rate compared with PED alone, suggesting an added benefit with adjunctive coil embolization. This result may provide the basis for future evaluation with randomized, controlled trials.


title: Risk factors for postoperative complications following bilateral closed anal sacculectomy in the dog.

text: OBJECTIVES To report the complication rate for bilateral closed anal sacculectomy in the dog and to evaluate potential risk factors for the development of postoperative complications. To identify breed groups at risk of requiring anal sacculectomy. METHODS A retrospective review of medical records of dogs undergoing bilateral closed anal sacculectomy between 2003 and 2013. RESULTS Sixty-two dogs were included in the study of which 32·3% developed mild and self-limiting complications including 14·5% dogs that experienced postoperative defaecatory complications. No dog developed permanent faecal incontinence. Dogs less than 15 kg bodyweight were more likely to develop postoperative complications. Dogs that used gel to distend the anal sac were more likely to have postoperative complications than those that did not. Previous abscess formation, recurrent disease and pretreatment with antibiotics had no significant effect on postoperative complication rates. Cavalier King Charles spaniels and Labrador-type dogs were over-represented within this study population. CLINICAL SIGNIFICANCE Anal sacculectomy is a safe procedure with a relatively high rate of short-term but self-limiting, minor, postoperative complications. Smaller (<15 kg) dogs are more likely to experience postoperative complications but the risk of permanent faecal incontinence is low.


Successful use of i-gel™ in a patient with tracheal stenosis undergoing Montgomery t-tube insertion.


title: Screening for Middle East respiratory syndrome coronavirus among febrile Indonesian Hajj pilgrims: A study on 28,197 returning pilgrims.

text: There were 211,000 Indonesian Hajj pilgrims going to Mecca through 11 main airports in 2015 who were at risk of contracting the Middle East respiratory syndrome coronavirus (MERS-CoV). We aimed to find out whether there was any occurrence of MERS-CoV by performing screening on 28,197 returning pilgrims. Those with a body temperature of > 38 °C and respiratory symptoms were sent to the airport clinic to have an oropharyngeal swab and a bacterial culture. Fifteen pilgrims had fever (> 38 °C) accompanied by respiratory symptoms; of these, 12 patients were diagnosed with upper and lower respiratory tract infections and three patients with pneumonia. However, none of them were found to be infected with MERS-CoV. The bacterial cultures showed evidence of normal flora growth.


title: Novel Technique Using Cyanoacrylate and Local Hemostatic Agents in the Management of High-Risk Exodontia Bleeding in a Patient With a Large Facial Arteriovenous Malformation.

text: PURPOSE This report describes a case of a 32-year-old woman who had been diagnosed with a facial arteriovenous malformation during childhood. Because this patient possessed a major risk of perioperative hemorrhage, the use of several local hemostatic measures was thoroughly explored before routine exodontia. MATERIALS AND METHODS Selective embolization of the right superior thyroid artery was performed intraoperatively and a novel hemostatic technique using a combination of a packing of Gelfoam wrapped in Surgicel was placed within the extraction sites and sealed with SwiftSet. RESULTS Local hemostasis was achieved with a novel technique using a combination of cyanoacrylate and local hemostatic agents despite aggressive hemorrhaging after routine exodontia. CONCLUSION By exploiting the local properties of these agents, local hemostasis can be achieved with this novel technique even in the most challenging cases of vascular anomalies.


title: Preventing SARS-CoV-2 transmission in rehabilitation pools and therapeutic water environments.

text: SARS-CoV-2 is mainly transmitted by respiratory droplets and contact with contaminated surfaces. It can be retrieved in faeces but there is no evidence of faecal-oral transmission, which is the main route of contamination in recreational waters. Standard cleaning and disinfecting procedure, microbiologic control and health rules aim to prevent infectious risk regardless of the microorganisms. In the context of progressive lockdown exit and hospital activities recovery, we assessed the risk of SARS-CoV-2 transmission in rehabilitation pools and therapeutic water environments in order to provide specific recommendations to control the spread of SARS-CoV-2 while ensuring essential rehabilitation cares for patients.


Comment on: "Do We Have Enough Ophthalmologists to Manage Vision-Threatening Diabetic Retinopathy? A Global Perspective".


Global health for future ophthalmologists--time to address the gaps: a UK perspective.


Natural orifice imaging of the abdominal wall.


title: Endonasal instrumentation and aerosolization risk in the era of COVID-19: simulation, literature review, and proposed mitigation strategies.

text: INTRODUCTION International experience with COVID-19 suggests it poses a significant risk of infectious transmission to skull base surgeons, due to high nasal viral titers and the unknown potential for aerosol generation during endonasal instrumentation. The purpose of this study was to simulate aerosolization events over a range of endoscopic procedures to gain an evidence-based aerosol risk assessment. METHODS Aerosolization was simulated in a cadaver using fluorescein solution (0.2mg/10ml) and quantified using a blue-light filter and digital image processing. Outpatient sneezing during endoscopy was simulated using an intranasal atomizer in the presence or absence of intact and modified surgical mask barriers. Surgical aerosolization was simulated during non-powered instrumentation, suction microdebrider, and high-speed drilling following nasal fluorescein application. RESULTS Among the outpatient conditions, a simulated sneeze event generated maximal aerosol distribution at 30cm extending to 66cm. Both an intact surgical mask and a modified VENT mask (which enables endoscopy) eliminated all detectable aerosol spread. Among the surgical conditions, cold instrumentation and microdebrider use did not generate detectable aerosols. Conversely, use of a high-speed drill produced significant aerosol contamination in all tested conditions. CONCLUSION We confirm that aerosolization presents a risk to the endonasal skull base surgeon. In the outpatient setting, use of a barrier significantly reduces aerosol spread. Cold surgical instrumentation and microdebrider use pose significantly less aerosolization risk than a high-speed drill. Procedures requiring drill use should carry a special designation as an "Aerosol Generating Surgery" to convey this unique risk, and support the need for protective PPE. This article is protected by copyright. All rights reserved.


title: Transvaginal sacrospinous rectopexy: initial clinical experience.

text: BACKGROUND There is a wide range of surgical procedures available to treat rectal prolapse that differ in approach as well as in principle. The current perineal approaches available involve mucosal or full thickness resection. There are currently no accepted procedures combining rectal fixation without resection using the perineal approach. We present our initial report of transvaginal sacrospinous rectopexy for the treatment of rectal prolapse. METHODS A longitudinal incision was made in the posterior wall of the vagina. The rectum and sacrospinous ligament were identified. Two sutures were placed in the sacrospinous ligament and brought through a piece of Surgisis mesh previously anchored to the anterior surface of the rectum. This was performed bilaterally. These sutures were tied to complete the rectal suspension, and the posterior wall of the vagina was closed. RESULTS Transvaginal sacrospinous rectopexy was performed in all seven cases. In the first two cases, a Delorme procedure was performed concurrently. Two patients had rubber band ligation for symptomatic internal hemorrhoids, one patient had a sphincter plication, and one patient had an anal encirclement procedure with Surgisis. Six of the seven patients had concomitant urologic procedures. The average operative time was 163 min, and the average blood loss was 107 mL. None of the cases required conversion to an open procedure. There was one full thickness recurrence at 18 weeks. CONCLUSION Transvaginal sacrospinous rectopexy is a safe, minimally invasive, technically feasible technique for the treatment of rectal prolapse.


title: Tuberculosis, Cholera, Anthrax: Dreadful Culprits.

text: Dreadful culprits from the minuscule world, indeed, but … what about poverty, war, and terrorism in the macroscopic nowadays world?


title: Fundus-first transumbilical single-incision laparoscopic cholecystectomy with a cholangiogram: a feasibility study.

text: BACKGROUND An increasing number of techniques are emerging in the literature describing single-incision laparoscopic cholecystectomy (SILC). The advent of a new surgical approach is a reminder of the increase in bile duct injuries in the past when laparoscopic cholecystectomy was first introduced. With this in mind, the authors describe a safe and reproducible approach to SILC. METHODS Between August 2008 and August 2009, 20 patients with symptomatic gallbladder disease underwent SILC using a totally transumbilical fundus-first approach with an intraoperative cholangiogram. Data including pain scores were collected prospectively. RESULTS In this initial series, the median operative time was 103 min (range, 55-177 min), including the time for two patients undergoing additional procedures at the time of surgery. Intraoperative cholangiograms were completed for 18 of 19 patients. Additional ports were required in four patients for safe completion of the procedure. The mean pain score 12 h postoperatively was 2.5 on a visual analogue scale with a range of 0-10. There was no morbidity or mortality. CONCLUSION According to the findings, SILC with an intraoperative cholangiogram can be performed safely using a fundus-first approach. However, for SILC to become the operation of choice for the treatment of gallbladder disease, evidence is required to demonstrate its advantage over laparoscopic cholecystectomy.


title: Infection Control in Dental Practice During the COVID-19 Pandemic.

text: COVID-19 is the disease supported by SARS-CoV-2 infection, which causes a severe form of pneumonia. Due to the pathophysiological characteristics of the COVID-19 syndrome, the particular transmissibility of SARS-CoV-2, and the high globalization of our era, the epidemic emergency from China has spread rapidly all over the world. Human-to-human transmission seems to occur mainly through close contact with symptomatic people affected by COVID-19, and the main way of contagion is via the inhalation of respiratory droplets, for example when patients talk, sneeze or cough. The ability of the virus to survive outside living organisms, in aerosol or on fomites has also been recognized. The dental practitioners are particularly exposed to a high risk of SARS-CoV-2 infection because they cannot always respect the interpersonal distance of more than a meter and are exposed to saliva, blood, and other body fluids during surgical procedures. Moreover, many dental surgeries can generate aerosol, and the risk of airborne infection is to be considered higher. The aim of this paper is to provide practical advice for dentists based on the recent literature, which may be useful in reducing the risk of spreading COVID-19 during clinical practice.


title: Prevalence and risk factors related to haloperidol use for delirium in adult intensive care patients: the multinational AID-ICU inception cohort study.

text: PURPOSE We assessed the prevalence and variables associated with haloperidol use for delirium in ICU patients and explored any associations of haloperidol use with 90-day mortality. METHODS All acutely admitted, adult ICU patients were screened during a 2-week inception period. We followed the patient throughout their ICU stay and assessed 90-day mortality. We assessed patients and their variables in the first 24 and 72 h in ICU and studied their association together with that of ICU characteristics with haloperidol use. RESULTS We included 1260 patients from 99 ICUs in 13 countries. Delirium occurred in 314/1260 patients [25% (95% confidence interval 23-27)] of whom 145 received haloperidol [46% (41-52)]. Other interventions for delirium were benzodiazepines in 36% (31-42), dexmedetomidine in 21% (17-26), quetiapine in 19% (14-23) and olanzapine in 9% (6-12) of the patients with delirium. In the first 24 h in the ICU, all subtypes of delirium [hyperactive, adjusted odds ratio (aOR) 29.7 (12.9-74.5); mixed 10.0 (5.0-20.2); hypoactive 3.0 (1.2-6.7)] and circulatory support 2.7 (1.7-4.3) were associated with haloperidol use. At 72 h after ICU admission, circulatory support remained associated with subsequent use of haloperidol, aOR 2.6 (1.1-6.9). Haloperidol use within 0-24 h and within 0-72 h of ICU admission was not associated with 90-day mortality [aOR 1.2 (0.5-2.5); p = 0.66] and [aOR 1.9 (1.0-3.9); p = 0.07], respectively. CONCLUSIONS In our study, haloperidol was the main pharmacological agent used for delirium in adult patients regardless of delirium subtype. Benzodiazepines, other anti-psychotics and dexmedetomidine were other frequently used agents. Haloperidol use was not statistically significantly associated with increased 90-day mortality.


title: Identifying hotspots of viral haemorrhagic fevers in the Eastern Mediterranean Region: perspectives for the Emerging and Dangerous Pathogens Laboratory Network.

text: Background The emergence and re-emergence of viral haemorrhagic fevers (VHFs) is a growing concern worldwide. They are associated with major epidemics with an estimated 51-101 million cases each year, of which around 67 000 are fatal. In 2007, 13 countries in the Eastern Mediterranean Region reported VHF cases. Aims The main purpose of the study was to review the epidemiological situation in the Region vis-à-vis VHFs to obtain baseline epidemiological information for the establishment of the Emerging Dangerous Pathogen Laboratory Network (EDPLN). Methods A literature search was performed using PubMed, ProMED-Mail and GIDEON databases. Reported data included disease burden (reported cases and deaths), human prevalence (general population, high-risk groups), vectors and reservoirs. A scoring method was employed to divide countries into 4 groups (very highly, highly, medium and low affected countries). Results Very highly affected countries were Afghanistan, Egypt, Islamic Republic of Iran, Saudi Arabia and Sudan. Highly affected countries were Djibouti, Morocco, Oman, Pakistan, Tunisia and Yemen. Medium affected countries were Iraq, Somalia and United Arab Emirates. Low affected countries were Bahrain, Jordan, Lebanon, Libya, Palestine, Qatar and Syrian Arab Republic. Conclusions This study contributes in prioritizing countries to be part of EDPLN and in addressing specific needs related to outbreak investigations, surveillance and research.


title: Evolving techniques for gastrointestinal endoscopic hemostasis treatment.

text: With mortality due to gastrointestinal (GI) bleeding remaining stable, the focus on endoscopic hemostasis has been on improving other outcomes such as rebleeding rate, need for transfusions, and need for angiographic embolization or surgery. Over the past few years, a number of devices have emerged to help endoscopically assess and treat bleeding GI lesions. These include the Doppler endoscopic probe, hemostatic powder, and over-the-scope clip. Also, new applications have been described for radiofrequency ablation. In this article, we will discuss these evolving tools and techniques that have been developed, including an analysis of their efficacy and limitations.


title: Packed red blood cells transfusion in neonates: effect on FiO2 and PaO2/SaO2 ratio, and implications for neonatal saturation targeting.

text: OBJECTIVE To assess the effect of blood transfusions in neonates on partial pressure of oxygen in arterial blood (PaO2), arterial hemoglobin oxygen saturation (SaO2) and arterial hemoglobin oxygen saturation as measured by pulse oximetry (SpO2). STUDY DESIGN Retrospective study of neonates that received a first blood transfusion while having an indwelling arterial line. We compared PaO2, SaO2, SpO2, SaO2/PaO2 ratio and fraction of inspired oxygen (FiO2) 12 h before and after blood transfusion. RESULTS Post-transfusion neonates had higher PaO2 and SaO2, had lower SaO2/PaO2 ratio, and received higher FiO2 with no change in SpO2. CONCLUSIONS Post-transfusion, neonates had lower hemoglobin oxygen affinity. They received higher FiO2 and had higher PaO2 at the same SpO2. We speculate that FiO2 was increased in order to maintain SpO2. Larger prospective trials are needed to confirm our findings.


title: Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study.

text: RATIONALE A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown. OBJECTIVES To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza. METHODS We quantified influenza A(H3N2) virus-specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases. MEASUREMENTS AND MAIN RESULTS A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11-0.68; P = 0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact. CONCLUSIONS Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity.


Diagnostic performance of a SARS-CoV-2 IgG/IgM lateral flow immunochromatography assay in symptomatic patients presenting to the emergency department.


title: Intravesical electromotive drug administration for non-muscle invasive bladder cancer.

text: BACKGROUND Electromotive drug administration (EMDA) is the use of electrical current to improve the delivery of intravesical agents to reduce the risk of recurrence in people with non-muscle invasive bladder cancer (NMIBC). It is unclear how effective this is in comparison to other forms of intravesical therapy. OBJECTIVES To assess the effects of intravesical EMDA for the treatment of NMIBC. SEARCH METHODS We performed a comprehensive search using multiple databases (CENTRAL, MEDLINE, EMBASE), two clinical trial registries and a grey literature repository. We searched reference lists of relevant publications and abstract proceedings. We applied no language restrictions. The last search was February 2017. SELECTION CRITERIA We searched for randomised studies comparing EMDA of any intravesical agent used to reduce bladder cancer recurrence in conjunction with transurethral resection of bladder tumour (TURBT). DATA COLLECTION AND ANALYSIS Two review authors independently screened the literature, extracted data, assessed risk of bias and rated quality of evidence (QoE) according to GRADE on a per outcome basis. MAIN RESULTS We included three trials with 672 participants that described five distinct comparisons. The same principal investigator conducted all three trials. All studies used mitomycin C (MMC) as the chemotherapeutic agent for EMDA. 1. Postoperative MMC-EMDA induction versus postoperative Bacillus Calmette-Guérin (BCG) induction: based on one study with 72 participants with carcinoma in situ (CIS) and concurrent pT1 urothelial carcinoma, we are uncertain (very low QoE) about the effect of MMC-EMDA on time to recurrence (risk ratio (RR) 1.06, 95% confidence interval (CI) 0.64 to 1.76; corresponding to 30 more per 1000 participants, 95% CI 180 fewer to 380 more). There was no disease progression in either treatment arm at three months' follow-up. We are uncertain (very low QoE) about serious adverse events (RR 0.75, 95% CI 0.18 to 3.11). 2. Postoperative MMC-EMDA induction versus MMC-passive diffusion (PD) induction: based on one study with 72 participants with CIS and concurrent pT1 urothelial carcinoma, postoperative MMC-EMDA may (low QoE) reduce disease recurrence (RR 0.65, 95% CI 0.44 to 0.98; corresponding to 147 fewer per 1000 participants, 95% CI 235 fewer to 8 fewer). There was no disease progression in either treatment arm at three months' follow-up. We are uncertain (very low QoE) about the effect of MMC-EMDA on serious adverse events (RR 1.50, 95% CI 0.27 to 8.45). 3. Postoperative MMC-EMDA with sequential BCG induction and maintenance versus postoperative BCG induction and maintenance: based on one study with 212 participants with pT1 urothelial carcinoma of the bladder with or without CIS, postoperative MMC-EMDA with sequential BCG may result (low QoE) in a longer time to recurrence (hazard ratio (HR) 0.51, 95% CI 0.34 to 0.77; corresponding to 181 fewer per 1000 participants, 95% CI 256 fewer to 79 fewer) and time to progression (HR 0.36, 95% CI 0.17 to 0.75; corresponding to 63 fewer per 1000 participants, 95% CI 82 fewer to 24 fewer). We are uncertain (very low QoE) about the effect of MMC-EMDA on serious adverse events (RR 1.02, 95% CI 0.21 to 4.94). 4. Single-dose, preoperative MMC-EMDA versus single-dose, postoperative MMC-PD: based on one study with 236 participants with primary pTa and pT1 urothelial carcinoma, preoperative MMC-EMDA likely (moderate QoE) results in a longer time to recurrence (HR 0.47, 95% CI 0.32 to 0.69; corresponding to 247 fewer per 1000 participants, 95% CI 341 fewer to 130 fewer) for a median follow-up of 86 months. We are uncertain (very low QoE) about the effect of MMC-EMDA on time to progression (HR 0.81, 95% CI 0.00 to 259.93; corresponding to 34 fewer per 1000 participants, 95% CI 193 fewer to 807 more) and serious adverse events (RR 0.79, 95% CI 0.30 to 2.05). 5. Single-dose, preoperative MMC-EMDA versus TURBT alone: based on one study with 233 participants with primary pTa and pT1 urothelial carcinoma, preoperative MMC-EMDA likely (moderate QoE) results in a longer time to recurrence (HR 0.40, 95% CI 0.28 to 0.57; corresponding to 304 fewer per 1000 participants, 95% CI 390 fewer to 198 fewer) for a median follow-up of 86 months. We are uncertain (very low QoE) about the effect of MMC-EMDA on time to progression (HR 0.74, 95% CI 0.00 to 247.93; corresponding to 49 fewer per 1000 participants, 95% CI 207 fewer to 793 more) or serious adverse events (HR 1.74, 95% CI 0.52 to 5.77). AUTHORS' CONCLUSIONS While the use of EMDA to administer intravesical MMC may result in a delay in time to recurrence in select patient populations, we are uncertain about its impact on serious adverse events in all settings. Common reasons for downgrading the QoE were study limitations and imprecision. A potential role for EMDA-based administration of MMC may lie in settings where more established agents (such as BCG) are not available. In the setting of low or very low QoE for most comparisons, our confidence in the effect estimates is limited and the true effect sizes may be substantially different from those reported here.


title: A human neutralizing antibody targets the receptor binding site of SARS-CoV-2.

text: An outbreak of the coronavirus disease 2019 (COVID-19)1-3, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)4 spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. In this study, we report the isolation of 2 specific human monoclonal antibodies (MAbs) from a convalescent COVID-19 patient. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro against SARS-CoV-2. In addition, CB6 inhibited SARS-CoV-2 infection in rhesus monkeys at both prophylactic and treatment settings. Further structural studies revealed that CB6 recognizes an epitope that overlaps with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 receptor binding domain (RBD), thereby interfering with the virus/receptor interactions by both steric hindrance and direct interface-residue competition. Our results suggest CB6 deserves further clinical translation.


title: New Approaches to Prevent Healthcare-Associated Infection.

text: Healthcare-associated infection (HCAI) in hospitals mainly results from unsolved but well-identified causes such as hand hygiene, overuse of catheters, and to a lesser extent, the airborne transmission of infectious agents caused by the misuse of respiratory precautions. The aims of the Institut Hospitalo-Universitaire Méditerranée Infection are to develop new approaches to fight HCAIs. Among them, new technologies that allow for the traceability of care and good practices reminders have been developed concomitantly to an anthropological approach, facilitating acceptability by healthcare workers. While the automated continuous monitoring system is validated and commercially available, some other technologies are still under clinical evaluation or in the early development phase. Quorum sensing-based biotechnologies are developed with the aims to fight against wound colonization.


title: Stent technology in ischemic stroke.

text: Atherosclerotic disease of the cerebral vasculature is a major cause of stroke worldwide. Atherosclerosis that is refractory to best medical management may require revascularization. In these instances, endovascular treatment provides a popular and safe alternative to open surgical techniques. The authors provide an overview of stent technology in the treatment of ischemic stroke, discussing the major studies evaluating stenting for extracranial carotid artery, vertebral artery, and intracranial atherosclerotic disease. The authors describe the commonly used stents with respect to their individual characteristics and technical limitations. Current and future developments in stent technology are also discussed, with areas for further innovation and clinical research.


title: Fibrin sealants and topical agents in hepatobiliary and pancreatic surgery: a critical appraisal.

text: INTRODUCTION Fibrin sealants and topical hemostatic agents have been used extensively in hepatobiliary and pancreatic (HPB) surgery to promote coagulation and clot formation decreasing the need for allogeneic blood transfusion and to act as tissue sealants, ideally preventing biliary, enteric, and pancreatic leaks. RESULTS Current literature has demonstrated some favorable outcomes using many different products for application in the field of HPB surgery. However, critical findings exist demonstrating lack of reproducible efficacy or benefit. In all, many clinical trials have demonstrated effectiveness of fibrin sealants and other agents at reducing the need for intraoperative and postoperative blood transfusion. Ability to effectively seal tissues providing biliostatic effect or preventing postoperative fistula formation remains debated as definitive evidence is lacking. CONCLUSIONS In the following invited review, we discuss current literature describing the use of topical agents and fibrin sealants in liver and pancreas surgery. We summarize major contemporary clinical trials and their findings regarding the use of these agents in HPB surgery and provide evidence from the preclinical literature as to the translation of these products into the clinical arena.


title: Vesicourethral anastomosis using V-Loc™ barbed suture during robot-assisted radical prostatectomy.

text: In Europe, localized prostate cancer (PCa) is increasingly treated by robot-assisted radical prostatectomy. This minimally invasive procedure is technically evolving, with benefits to both the patient and surgeon. One of the final steps of the operation is the formation of a watertight vesicourethral anastomosis (VUA). A suboptimal anastomosis can lead to serious consequences, including acute urinary leak, ileus, prolonged hospitalization and catheterization, urethral stricture, and urinary incontinence. It is therefore highly desirable to develop a simple, reproducible and dependable technique for VUA formation. We report a VUA formation technique using a unidirectional barbed suture (3-0 V-LocTM 180 absorbable suture, Covidien, Dublin, Ireland).


Fair Allocation of Scarce Medical Resources in the Time of Covid-19.


title: Advanced Monitoring Is Associated with Fewer Alarm Events During Planned Moderate Procedure-Related Sedation: A 2-Part Pilot Trial.

text: BACKGROUND Diagnostic and interventional procedures are often facilitated by moderate procedure-related sedation. Many studies support the overall safety of this sedation; however, adverse cardiovascular and respiratory events are reported in up to 70% of these procedures, more frequently in very young, very old, or sicker patients. Monitoring with pulse oximetry may underreport hypoventilation during sedation, particularly if supplemental oxygen is provided. Capnometry may result in false alarms during sedation when patients mouth breathe or displace sampling devices. Advanced monitor use during sedation may allow event detection before complications develop. This 2-part pilot study used advanced monitors during planned moderate sedation to (1) determine incidences of desaturation, low respiratory rate, and deeper than intended sedation alarm events; and (2) determine whether advanced monitor use is associated with fewer alarm events. METHODS Adult patients undergoing scheduled gastroenterology or interventional radiology procedures with planned moderate sedation given by dedicated sedation nurses under the direction of procedural physicians (procedural sedation team) were monitored per standard protocols (electrocardiography blood pressure, pulse oximetry, and capnometry) and advanced monitors (acoustic respiratory monitoring and processed electroencephalograpy). Data were collected to computers for analysis. Advanced monitor parameters were not visible to teams in part 1 (standard) but were visible to teams in part 2 (advanced). Alarm events were defined as desaturation-SpO2 ≤92%; respiratory depression, acoustic respiratory rate ≤8 breaths per minute, and deeper than intended sedation, indicated by processed electroencephalograpy. The number of alarm events was compared. RESULTS Of 100 patients enrolled, 10 were excluded for data collection computer malfunction or consent withdrawal. Data were analyzed from 90 patients (44 standard and 46 advanced). Advanced had fewer total alarms than standard (Wilcoxon-Mann-Whitney = 2.073, P = 0.038; Wilcoxon-Mann-Whitney odds, 1.67; 95% confidence interval [CI], 1.04-2.88). Similar numbers of standard and advanced had ≥1 alarm event (Wald difference, -10.2%; 95% CI, -26.4% to 7.0%; P = 0.237). Fewer advanced patients had ≥1 respiratory depression event (Wald difference, -22.1%; 95% CI, -40.9% to -2.4%; P = 0.036) or ≥1 desaturation event (Wald difference, -24.2%; 95% CI, -42.8% to -3.6%; P = 0.021); but there was no significant difference in deeper than intended sedation events (Wald difference, -1.38%; 95% CI, -20.21% to 17.49%; P = 0.887). CONCLUSIONS Use of advanced monitoring parameters during planned moderate sedation was associated with fewer alarm events, patients experiencing desaturation, and patients experiencing respiratory depression alarm events. This pilot study suggests that further study into the safety and outcome impacts of advanced monitoring during procedure-related sedation is warranted.


title: A two-year prospective study of small poultry flocks in Ontario, Canada, part 1: prevalence of viral and bacterial pathogens.

text: In Ontario, within the past few years, there has been a marked increase in the number of non-commercial poultry flocks (referred to as "small flocks"). Small poultry flocks may act as a reservoir of avian and zoonotic pathogens, given the flocks' limited access to veterinary services, inadequate biosecurity practices, and increased risk of contact with wild birds. Despite these potential risks, there is a scarcity of data concerning the prevalence of poultry and zoonotic pathogens among these flocks. To assess the baseline prevalence of bacterial and viral infectious pathogens, prospective surveillance of small flock postmortem submissions to the Animal Health Laboratory was conducted over a 2-y period. With the owner's consent, a postmortem examination and pre-set tests for infectious agents were conducted. A total of 160 submissions, mainly chickens (84%), were received. Among bacterial pathogens, Brachyspira spp., Mycoplasma synoviae, Campylobacter spp., Mycoplasma gallisepticum, and Salmonella spp. were detected in 37%, 36%, 35%, 23%, and 3% of tested submissions, respectively. Among viral pathogens, infectious bronchitis virus, fowl adenovirus, infectious laryngotracheitis virus, avian reovirus, and infectious bursal disease virus were detected in 39%, 35%, 15%, 4%, and 1% of submissions, respectively. We detected non-virulent avian avulavirus 1 from two chickens in a single submission, and low-pathogenic H10N8 influenza A virus from a single turkey submission. Our study provides baseline prevalence of viral and bacterial pathogens circulating in Ontario small flocks and may help animal and human health professionals to educate small flock owners about disease prevention.


title: Regulation of tryptophan 2,3-dioxygenase by HOXA10 enhances embryo viability through serotonin signaling.

text: Tryptophan 2,3-dioxygenase (TDO) is expressed in endometrium and catabolizes tryptophan, a precursor in the biosynthesis of serotonin. Tryptophan metabolism is an important mechanism for regulation of serotonin levels. Preimplantation mouse embryos are known to express serotonin receptors, specifically the 5-HT1D and 5-HT7 serotonin receptor subtypes. Here we demonstrate that Hoxa10 regulates endometrial TDO expression and improves embryo viability through increased serotonin production. Transfection of pcDNA-Hoxa10 to the murine uterus increased total TDO expression. In vitro, epithelial cell TDO expression was decreased after transfection with Hoxa10. Decreased glandular TDO in response to HOXA10 may augment serotonin production by increasing tryptophan availability. Conversely, stromal TDO expression increased with constitutive Hoxa10 expression. In mice, epithelial serotonin was increased in response to constitutive expression of Hoxa10. Embryo quality was impaired after treatment with Hoxa10 antisense. Blockade of serotonin receptors 1D and 7 also resulted in impaired embryo development, indicating an essential role for Hoxa10 induction of TDO and subsequent serotonin production in embryo development. Transfection of pcDNA-TDO also decreased the number of T cells in the endometrial stroma. We have shown a novel mechanism by which HOXA10 regulates endometrial TDO expression. In the endometrial stroma, HOXA10 increases TDO mRNA, which may increase tryptophan catabolism, allowing for immune tolerance at the time of embryo implantation. In endometrial glands, HOXA10 decreases TDO mRNA leading to increased serotonin that in turn acts to promote normal embryo development.


title: [COVID-19: Variable symptoms in mild course: olfactory loss and increased resting heart rate].

text: HISTORY A 56-year-old, previously healthy male and long distance runner noticed short episodes of parosmia, followed by anosmia. Few days later, he monitored an increase in his resting heart rate. This was followed by a dry cough, fatigue, and myalgia. At the same time, symptoms occurred in all four family members. CLINICAL FINDINGS The patient had a dry cough. The medical examination was normal. Heart rate was 60/min, sinus rhythm, body temperature 36.6 °C. Complete anosmia was present. The RT-PCR for SARS-CoV-2 from a deep pharyngeal swab was positive in all five family members. THERAPY AND COURSE Symptoms were present for almost two weeks. All family members had anosmia, that started earlier and lasted longer than the other symptoms, and myalgia. Reduced taste sensation, fatigue, dry cough and sore throat were present in four of five persons. Shortness of breath at rest or gastrointestinal symptoms were absent. Four affected persons had sleep disturbances in the later course of the disease. None of the affected persons had raised temperature at any time during the disease. Specific medical or drug treatment was not necessary. All patients made full recoveries without signs of organ dysfunction, and with full restitution of physical strength. DISCUSSION We describe a family of 5 previously healthy persons with a mild course of COVID-19 disease. The symptoms and course are described in detail. Anosmia can precede other symptoms by several days and can indicate an early phase of infection. An increase in resting heart rate can occur in the absence of raised temperature or fever. The symptoms and course are discussed in the context of the ongoing pandemic, and efforts to control infection chains.


Shortcomings in India's first national attempt at universal healthcare through publicly funded health insurance.


title: Clinical Characteristics and Outcomes of 74 Patients With Severe or Critical COVID-19.

text: BACKGROUND The outbreak of the coronavirus disease (COVID-19) has led to a major concern and caused a pandemic globally. The goal of this study was to clarify the clinical characteristics of recovery and death in patients with severe or critical COVID-19. MATERIALS AND METHODS In this retrospective single-center study, clinical data were collected from 74 severe or critical COVID-19 patients in Wuhan Fourth Hospital between Jan. 25th and Feb. 26th, 2020. All patients were divided into a recovery group or a death group according to clinical outcomes, and the differences between the groups were compared. RESULTS Of the 74 patients enrolled in the study, 48 (64.9%) were severe cases and 26 (35.1%) were critical cases. Sixty (81.1%) patients were recovered and 14 (18.9%) died. Compared with recovery patients, patients in the death group were older, and had higher incidences of hypertension, coronary disease and dyspnea at admission. Laboratory tests for lactate dehydrogenase, creatine kinase, myoglobin, brain natriuretic peptide and D-dimer indicated higher levels in the death group. The PaO2:FiO2 ratio and minimum SpO2 were lower in the death group, and a higher proportion of these patients received noninvasive mechanical ventilation, invasive mechanical ventilation and extracorporeal membrane oxygenation treatment. CONCLUSIONS Elderly patients with comorbidities are at higher risk of severe COVID-19 or death. Patients with a low blood gas index and poor coagulation function at admission had a high mortality rate. For such patients, comprehensive treatment should be performed as soon as possible to improve the prognosis and reduce mortality.


title: Respiratory viral detection in the paranasal sinuses of patients with cystic fibrosis.

text: BACKGROUND Pulmonary colonization with antibiotic-resistant organisms in patients with cystic fibrosis (CF) is often preceded by upper-airway infections. Although there is a well-described relationship between pulmonary respiratory viral infections and overall disease progression of CF, the pathogenicity of respiratory viral infections in the paranasal sinuses of patients with CF remains unknown. With recent advances in respiratory virus detection techniques, this study sought to detect the presence of respiratory viruses in the paranasal sinuses of patients with CF in comparison with healthy controls and to correlate the viral presence with clinical measures of sinonasal disease. METHODS This prospective individual cohort study compared 24 patients with CF with 14 healthy controls. Basic demographics, clinical measures of disease and respiratory viral screens (commercial multiplex) obtained directly from the paranasal sinuses were compared between the two groups. RESULTS Respiratory viruses were detected in 33% of patients with CF (8/24) compared with 0% of the healthy controls (0/14) (p = 0.017). Respiratory viruses were only detected during the winter months, and the most commonly identified were influenza A and human rhinovirus strains. There was no statistical difference in the 22-Item Sino-Nasal Outcome Test (SNOT-22) scores (p = 0.93) or modified Lund-Kennedy scores (p = 0.74) between patients with CF with a positive viral test and those without a positive result. CONCLUSIONS Respiratory viral detection is more commonly detected in the paranasal sinuses of patients with CF compared with healthy controls. Although respiratory viral presence did not correlate with a worse clinical severity of sinonasal disease, these findings may provide insight into the pathophysiology of CF and open new avenues for potential targeted therapy.


title: High-volume bariatric surgery in a single center: safety, quality, cost-efficacy and teaching aspects in 2,000 consecutive cases.

text: BACKGROUND Obesity surgery is the most effective treatment for morbid obesity and the fastest growing area in surgery. Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the gold standard procedure in many countries. Optimization of the treatment process is important in order to keep the morbidity rate down and cost of treatment as low as possible. METHODS In September 2005, we established a bariatric surgery program. Until December 2010, 2,000 patients underwent LRYGB. Clinical pathways were established, with focus on safety, fast-track methodology and training of surgeons. Time recordings from all parts of the treatment, as well as clinical outcome, were prospectively registered. RESULTS Time consumption for the total procedure in the operating theater was reduced from 102 to 54 min (P < 0.001). With only 11 min turnover between patients, the total time for one patient has been reduced to 65 min, enabling us to perform six operations in a single operating theater during ordinary daytime. Early complication rate was 2.8%, and mean hospital stay was 2.3 days. We were able to double the patients treated in 2010 compared to 2007 with only 10% increase in staff. Three surgeons were trained during the period into fully qualified senior bariatric surgeons. CONCLUSIONS Multimodal evidence-based care within the fast-track methodology and routine time recordings was successful in order to increase the production volumes and reduce costs, without compromising the safety or quality for the patients. This kind of approach may be transferred to other types of standardized surgery.


title: Inactivation of hantaviruses by N-ethylmaleimide preserves virion integrity.

text: Thiol groups of cysteine residues are crucial for the infectivity of various enveloped viruses, but their role in the infectivity of viruses of the family Bunyaviridae has thus far not been studied. This report shows that thiol groups are essential to the infectivity of hantaviruses. Alkylation of the thiol functional groups using the membrane-permeable compound N-ethylmaleimide (NEM) and membrane-impermeable compound 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) showed NEM to be a highly effective inactivator of Puumala and Tula hantaviruses. The NEM-inactivated hantavirus maintained the buoyant density of the wild-type virus. Furthermore, the antigenicity of glycoproteins and the cell attachment capacity of virions were retained at NEM concentrations that totally abolished virus infectivity. These results signified preservation of virion integrity following inactivation with NEM, making chemically inactivated virions valuable research antigens. It was demonstrated with biotin-conjugated maleimide, a mechanistic analogue of NEM, that all the structural proteins of hantavirus were sensitive towards thiol alkylation. In contrast to hantaviruses, NEM did not abolish Uukuniemi phlebovirus infectivity to the same extent. This indicates differences in the use of free thiols in virus entry among members of the family Bunyaviridae.


How should data on airborne transmission of SARS-CoV-2 change occupational health guidelines?


title: COVID-19 emergency in the cruise's ship: a case report of conjunctivitis.

text: Little is known about the Covid-19 transmission through ocular tissue, and more research needs to be carried out in order to confirm its ability to infect ocular tissue and its pathogenic mechanisms. Covid-19 may be detected in the tears and conjunctival secretions in novel coronavirus pneumonia patients with conjunctivitis. This case report shows a severe viral conjunctivitis in a patient diagnosed with Covid-19 on the Diamond Princess ship, characterized by both red, irritated and swollen eyes, with transparent serous secretions, conjunctival chemosis, pseudomembranes of fibrin and inflammatory cells on the tarsal conjunctiva accompanied by preauricular lymph nodes and enlarged submaxillaries.


title: Acute Ischemic Stroke with Very Early Clinical Improvement: A National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Trials Exploratory Analysis.

text: BACKGROUND A high proportion of patients excluded from recombinant tissue plasminogen activator (rt-PA) treatment because of rapid improvement occurring before treatment decision had incomplete recovery. The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trials dataset allows for systematic analyses of very early postrandomization improvement (VEPRIM) in stroke severity as a National Institutes of Health Stroke Scale (NIHSS) score was available for all subjects enrolled in the study at baseline (NIHSSB) and at 2 hours after randomization (NIHSS2H). We explored various definitions of VEPRIM to characterize predictive values for clinical outcomes. METHODS Post hoc analyses of the NINDS rt-PA Stroke Trials were conducted. VEPRIM was defined as the difference between the NIHSSB and the NIHSS2H scores using 3 approaches: raw, percent, and normalized change. We assessed the association between VEPRIM and 3-month favorable outcome (mRS score of 0-1), symptomatic intracerebral hemorrhage (sICH), and death. RESULTS In the 624 subjects, every VEPRIM definition was independently associated with an increased probability of favorable outcome: for each unit of change within the VEPRIM definitions, there were 2%-24% (all P < .05) relative increased probability of favorable outcome, 2%-15% (all P < .05) decreased likelihood of death, and 2%-13% (all P < .05) decreased likelihood of sICH. Adjusting for NIHSSB and prestroke mRS scores, there was a significant rt-PA treatment effect for improvement seen for all 3 VEPRIM definitions. CONCLUSIONS VEPRIM predicted favorable outcomes independent of definition and treatment arm. Patients with VEPRIM by any definition, while doing better than patients without VEPRIM, also derived increased clinical benefit when treated with rt-PA compared to placebo. Even with VEPRIM, a substantial percentage of patients had unfavorable outcomes.


title: Solidarity in response to COVID-19 outbreak in the Eastern Mediterranean Region.

text: The coronavirus disease 2019 (COVID-19) outbreak that began in Wuhan, Hubei Province, China in late 2019 has spread globally within a few months. The Director General of the World Health Organization (WHO) declared the COVID-19 outbreak to be a public health emergency of international concern (PHEIC) after the second meeting of the IHR (2005) Emergency Committee on 30 January 2020. On 12 March 2020, the outbreak of COVID-19 was characterized as a pandemic.


Re: "a novel cautery instrument for on-site fenestration of aortic stent-grafts: a feasibility study of 18 patients".


title: Dietary recommendations during the COVID-19 pandemic.

text: Optimal nutrition can improve well-being and might mitigate the risk and morbidity associated with coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review summarizes nutritional guidelines to support dietary counseling provided by dietitians and health-related professionals. The majority of documents encouraged the consumption of fruits, vegetables, and whole grain foods. Thirty-one percent of the guidelines highlighted the importance of minerals and vitamins such as zinc and vitamins C, A, and D to maintain a well-functioning immune system. Dietary supplementation has not been linked to COVID-19 prevention. However, supplementation with vitamins C and D, as well as with zinc and selenium, was highlighted as potentially beneficial for individuals with, or at risk of, respiratory viral infections or for those in whom nutrient deficiency is detected. There was no convincing evidence that food or food packaging is associated with the transmission of COVID-19, but good hygiene practices for handling and preparing foods were recommended. No changes to breastfeeding recommendations have been made, even in women diagnosed with COVID-19.


title: Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke.

text: BACKGROUND Emergence of the novel corona virus (severe acute respiratory syndrome (SARS)-CoV-2) in December 2019 has led to the covid-19 pandemic. The extent of covid-19 involvement in the central nervous system is not well established, and the presence or the absence of SARS-CoV-2 particles in the cerebrospinal fluid (CSF) is a topic of debate. CASE DESCRIPTION We present two patients with covid-19 and concurrent neurological symptoms. Our first patient is a 31-year-old man who had flu-like symptoms due to covid-19 and later developed an acute-onset severe headache and loss of consciousness and was diagnosed with a Hunt and Hess grade 3 subarachnoid haemorrhage from a ruptured aneurysm. Our second patient is a 62-year-old woman who had an ischaemic stroke with massive haemorrhagic conversion requiring a decompressive hemicraniectomy. Both patients' CSF was repeatedly negative on real-time PCR analysis despite concurrent neurological disease. CONCLUSION Our report shows that patients' CSF may be devoid of viral particles even when they test positive for covid-19 on a nasal swab. Whether SARS-CoV-2 is present in CSF may depend on the systemic disease severity and the degree of the virus' nervous tissue tropism and should be examined in future studies.


title: Resuming elective surgical activity after the COVID-19 wave: what the patients need to know.

text: As COVID-19 outbreak enters its second phase of lockdown ease, healthcare plans involve elective surgery re-establishment to provide essential life-saving care. Patients are increasingly requesting information about their facility's readiness for safely performing surgery. This information should be open and transparent including patient's education with objective data regarding the state of the pandemic in the country and the control measures undertaken by the facility.


title: A comparison of substrate oxidation during prolonged exercise in men at terrestrial altitude and normobaric normoxia following the coingestion of 13C glucose and 13C fructose.

text: This study compared the effects of coingesting glucose and fructose on exogenous and endogenous substrate oxidation during prolonged exercise at altitude and sea level, in men. Seven male British military personnel completed two bouts of cycling at the same relative workload (55% Wmax) for 120 min on acute exposure to altitude (3375 m) and at sea level (~113 m). In each trial, participants ingested 1.2 g·min-1 of glucose (enriched with 13C glucose) and 0.6 g·min-1 of fructose (enriched with 13C fructose) directly before and every 15 min during exercise. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate fat oxidation, total and exogenous carbohydrate oxidation, plasma glucose oxidation, and endogenous glucose oxidation derived from liver and muscle glycogen. Total carbohydrate oxidation during the exercise period was lower at altitude (157.7 ± 56.3 g) than sea level (286.5 ± 56.2 g, P = 0.006, ES = 2.28), whereas fat oxidation was higher at altitude (75.5 ± 26.8 g) than sea level (42.5 ± 21.3 g, P = 0.024, ES = 1.23). Peak exogenous carbohydrate oxidation was lower at altitude (1.13 ± 0.2 g·min-1) than sea level (1.42 ± 0.16 g·min-1, P = 0.034, ES = 1.33). There were no differences in rates, or absolute and relative contributions of plasma or liver glucose oxidation between conditions during the second hour of exercise. However, absolute and relative contributions of muscle glycogen during the second hour were lower at altitude (29.3 ± 28.9 g, 16.6 ± 15.2%) than sea level (78.7 ± 5.2 g (P = 0.008, ES = 1.71), 37.7 ± 13.0% (P = 0.016, ES = 1.45). Acute exposure to altitude reduces the reliance on muscle glycogen and increases fat oxidation during prolonged cycling in men compared with sea level.


Letter by Weir Regarding Article, "Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2".


title: Comparing Angiographic Devascularization with Histologic Penetration after Preoperative Tumor Embolization with Onyx: What Indicates an Effective Procedure?

text: BACKGROUND AND PURPOSE To assess Onyx (Covidien, Irvine, California, United States) efficacy as a preoperative embolic agent for neoplasms of the head, neck, and spine, and to compare angiographic and histologic evidence of tumor penetration as predictors of intraoperative blood loss. MATERIALS AND METHODS Retrospective analysis of preoperative Onyx embolization procedures for treatment of head, neck, and spine tumors from 2009 to 2011. Patient demographics and information relating to the embolization procedure and operation were recorded. Measures of Onyx efficacy included intraoperative blood loss and length of surgery. Angiographic and histologic penetration, in addition to percentage of tumor devascularization, were assessed as predictors of efficacy. RESULTS A total of 22 patients with 17 head or neck and 5 spinal lesions underwent trans-arterial preoperative Onyx embolization. Good angiographic penetration was reported in 41% of tumors and central histologic penetration in 59%, with mean tumor devascularization of 85.3% (standard deviation [SD]: 12.6%). There was no relationship between angiographic and histologic Onyx penetrance. Mean surgical blood loss was 1342 mL (SD: 1327 mL), and length of surgery was 289 minutes (SD: 162 minutes). Neither angiographic, nor histologic Onyx penetration predicted intraoperative blood loss (p = 0.38 and p = 0.32, respectively) or surgical length (p = 0.62 and 0.90, respectively). Devascularization was not associated with blood loss (p = 0.62), but it was a negative predictor of surgical length (p = 0.013). CONCLUSIONS Preoperative Onyx embolization of head, neck, and spine tumors is capable of deep histologic tumor penetration, even when not visualized on angiography. The lack of association between measures of procedural adequacy suggests that using angiographic devascularization as a measure of procedural efficacy may be of limited utility.