title: [Feasibility of laparoendoscopic single-site surgery in gynecology with conventional laparoscopic instruments].

text: OBJECTIVES To describe the safety and efficacy of single-port access for laparoscopic surgery in gynecology with conventional laparoscopic instruments. PATIENTS AND METHODS In this prospective study, we report our experience with 90 patients who underwent Single Port Access (SPA) laparoscopic surgery for gynecologic pathology with the use of the SILS(®) Port Multiple Instrument Access Port (Covidien(®), Mansfield, MA). RESULTS We realised 15 ovarian cystectomies, 30 salpingo-oophrectomies with 14 one side, 9 lysis of adhesions, 7 distal tubal repairs, 6 salpingectomy, 8 other procedures. The mean surgical time is 47 min (25-120). One conversion to conventional laparoscopy and one in laparotomy were performed. The mean duration stay is 2 days [1-3]. DISCUSSION AND CONCLUSION SPA in gynecology is feasible with conventional laparoscopic instruments. SPA surgery represents the newest frontier in minimally invasive surgery.


title: Case report: a novel method for uterine-sparing hysteropexy.

text: OBJECTIVE The objective of this study was to describe a technique for uterine-sparing hysteropexy. CASE REPORT A 50-year-old multiparous woman with pelvic organ prolapse underwent laparoscopic sacrohysteropexy utilizing polypropylene mesh with good clinical result. CONCLUSIONS Placement of mesh arms medial to the uterine vessels during a laparoscopic sacrohysteropexy can be facilitated by using blunt needles to introduce the mesh arms.


title: Surgical technique: Muscle transfer restores extensor function after failed patella-patellar tendon allograft.

text: BACKGROUND Extensor mechanism allograft provides an effective remedy for severe quadriceps deficiency caused by loss of the patella, patellar tendon, and quadriceps tendon in TKA. Late failure is common, however, and major quadriceps deficiency occurs after removal of the allograft material. DESCRIPTION OF TECHNIQUE Six human cadaver specimens were dissected to evaluate the feasibility of transferring the vastus medialis, vastus lateralis, and medial head of the gastrocnemius muscle to fill the defect caused by loss of the patella and extensor tendon mechanism after failure and removal of allograft material. Transfer of the medial and lateral vastus muscles with their distal attachments into the tibia achieved closure of the defect but did not provide robust tendon material to fill the defect in the anterior knee. The medial gastrocnemius muscle reached easily to the muscular portion of the vastus medialis and lateralis flaps and provided secure closure of the anterior knee and strong attachment of viable muscle and tendon. METHODS Five knees (five patients) with failed patella-patellar tendon allograft between August 2008 and April 2010 were repaired using this technique. RESULTS Mean extensor lag was 47° (range, 35°-62°) before surgery and improved to 12° (range, 5°-15°) 1 year after surgery. CONCLUSIONS These preliminary results suggest that the described muscle transfer technique may provide an approach to salvage the failed extensor mechanism allograft after TKA.


title: TEP and Lichtenstein anatomy: does simulation accelerate acquisition among interns?

text: PURPOSE The anatomy of the inguinal region is notoriously challenging to master. We sought to teach open inguinal hernia (OIH) and totally extraperitoneal (TEP) anatomy with simulation models among general surgery (GS) interns. METHODS Low-fidelity OIH and TEP models were constructed out of cardboard, plastic bins, fabric, and yarn. GS interns (n = 30) participated in a 3-h hernia session including a pretest, anatomy lecture, simulated OIH and TEP hernia repair, and posttest. Pre- and posttest scores were based on a difficult 30-point exam which included didactic questions (10 points), drawing relevant TEP (10 points), and OIH (10 points) anatomy. Participants were surveyed following the session. RESULTS Median pretest scores were 13 % (range 0-60 %). Median posttest scores improved to 47 % (range 20-93 %, p < 0.001). Median number of structures drawn in the TEP image improved from 2 (range 0-14) to 11 (range 1-21, p < 0.001). Median number of structures drawn in the OIH image improved from 3 (range 0-15) to 7 (range 1-19, p < 0.001). 67 % (12/18) demonstrated improvement in knowledge of abdominal wall layers. 23 % (7/30) knew the triangles of pain/doom on the pretest vs. 77 % (23/30) on the posttest. Mean Likert scores favored session enjoyability (4.5), not a waste of training time (4.4), and improved understanding of OIH and TEP anatomy (4.4, 4.2). CONCLUSIONS Low-fidelity simulators can be used to teach and assess knowledge of TEP and OIH anatomy. While enjoyable and useful, one 3-h session does not create master hernia surgeons or expert anatomists out of novice trainees.


title: Balloon-assisted coil embolization and large stent delivery for cerebral aneurysms with a new generation of dual lumen balloons (Copernic 2L).

text: INTRODUCTION Dual coaxial lumen balloon microcatheters through which small stents can be delivered have recently been described. We report a series of a new type of dual lumen balloon catheter with a parallel lumen design enabling enhanced inflation and deflation properties through which larger stents may be deployed, including flow diverters (FD). METHODS All aneurysms that were treated with a Copernic 2L (COP2L) dual lumen balloon catheter at our institution between February 2014 and December 2016 were assessed. Patient demographics, aneurysm characteristics, clinical and angiographic follow-up, as well as adverse events were analyzed. RESULTS A total of 18 aneurysms in 16 patients (14 women) were treated with the COP2L. Mean maximal aneurysm diameter was 6.4 mm, mean neck size was 3.3 mm (min 1; max 6.3), and mean aneurysm height/width was 1.1 (min 0.5; max 2.1). The COP2L was used for balloon-remodeled coiling exclusively in 2 aneurysms; coiling and FD stenting in 8; coiling and braided stent delivery in 3; coiling, braided and FD stenting in 1; and FD stenting without coiling in 4 (stenting alone). The rate of Roy-Raymond 1 (complete occlusion) changed from 22% in the immediate postoperative period to 100% at 3 months (mean imaging follow-up 8.2 months). There were three technical complications (3/16, 18.7%), including a perforation and two thromboembolic asymptomatic events that were rapidly controlled with the COP2L. There was no immediate or delayed morbidity or mortality (modified Rankin Scale score 0-1 in 100% of patients). CONCLUSION The COP2L is a new type of dual lumen balloon catheter that may be useful for balloon and/or stent-assisted coiling of cerebral aneurysms. The same device can be used to deliver stents up to 4.5 mm and to optimize stent/wall apposition or serve as a life-saving tool in case of thromboembolic or hemorrhagic events. Long-term efficacy and safety need to be further assessed with larger case-controlled cohorts.


title: Cingulum-Callosal white-matter microstructure associated with emotional dysregulation in children: A diffusion tensor imaging study.

text: Emotional dysregulation symptoms in youth frequently predispose individuals to increased risk for mood disorders and other mental health difficulties. These symptoms are also known as a behavioral risk marker in predicting pediatric mood disorders. The underlying neural mechanism of emotional dysregulation, however, remains unclear. This study used the diffusion tensor imaging (DTI) technique to identify anatomically specific variation in white-matter microstructure that is associated with pediatric emotional dysregulation severity. Thirty-two children (mean age 9.53 years) with varying levels of emotional dysregulation symptoms were recruited by the Massachusetts General Hospital and underwent the DTI scans at Massachusetts Institute of Technology. Emotional dysregulation severity was measured by the empirically-derived Child Behavior Checklist Emotional Dysregulation Profile that includes the Attention, Aggression, and Anxiety/Depression subscales. Whole-brain voxel-wise regression tests revealed significantly increased radial diffusivity (RD) and decreased fractional anisotropy (FA) in the cingulum-callosal regions linked to greater emotional dysregulation in the children. The results suggest that microstructural differences in cingulum-callosal white-matter pathways may manifest as a neurodevelopmental vulnerability for pediatric mood disorders as implicated in the clinical phenotype of pediatric emotional dysregulation. These findings may offer clinically and biologically relevant neural targets for early identification and prevention efforts for pediatric mood disorders.


title: Advanced ultrasonography technologies to assess the effects of radiofrequency ablation on hepatocellular carcinoma.

text: BACKGROUND Radiofrequency ablation (RFA) is a curative therapy for hepatocellular carcinoma (HCC). In RFA, ultrasonography (US) is most commonly used to guide tumor puncture, while its effects are assessed using dynamic computed tomography or magnetic resonance. The differences in modalities used for RFA and assessment of its effects complicate RFA. We developed a method for assessing the effects of RFA on HCC by combining contrast-enhanced (CE) US and real-time virtual sonography with three-dimensional US data. PATIENTS AND METHODS Before RFA, we performed a sweep scan of the target HCC nodule and the surrounding hepatic parenchyma to generate three-dimensional US data. After RFA, we synchronized multi-planar reconstruction images derived from stored three-dimensional US data with real-time US images on the same US monitor and performed CEUS and real-time virtual sonography. Using a marking function, we drew a sphere marker along the target HCC nodule contour on pre-treatment US- multi-planar reconstruction images so that the automatically synchronized sphere marker represented the original HCC nodule contour on post-treatment real-time CEUS images. Ablation was considered sufficient when an avascular area with a margin of several millimeters in all directions surrounded the sphere marker on CEUS. RESULTS This method was feasible and useful for assessing therapeutic effects in 13 consecutive patients with HCC who underwent RFA. In 2 patients who underwent multiple sessions of RFA, HCC-nodule portions requiring additional RFA were easily identified on US images. CONCLUSIONS This method using advanced US technologies will facilitate assessment of the effects of RFA on HCC.


title: Pathogenesis and transmission of SARS-CoV-2 in golden hamsters.

text: SARS-CoV-2, a novel coronavirus with high nucleotide identity to SARS-CoV and SARS-related coronaviruses detected in horseshoe bats, has spread across the world and impacted global healthcare systems and economy1,2. A suitable small animal model is needed to support vaccine and therapy development. We report the pathogenesis and transmissibility of the SARS-CoV-2 in golden Syrian hamsters. Immunohistochemistry demonstrated viral antigens in nasal mucosa, bronchial epithelial cells, and in areas of lung consolidation on days 2 and 5 post-inoculation (dpi), followed by rapid viral clearance and pneumocyte hyperplasia on 7 dpi. Viral antigen was also found in the duodenum epithelial cells with viral RNA detected in feces. Notably, SARS-CoV-2 transmitted efficiently from inoculated hamsters to naïve hamsters by direct contact and via aerosols. Transmission via fomites in soiled cages was less efficient. Although viral RNA was continuously detected in the nasal washes of inoculated hamsters for 14 days, the communicable period was short and correlated with the detection of infectious virus but not viral RNA. Inoculated and naturally-infected hamsters showed apparent weight loss, and all animals recovered with the detection of neutralizing antibodies. Our results suggest that SARS-CoV-2 infection in golden Syrian hamsters resemble features found in humans with mild infections.


title: Effect of COVID-19 on Urology Residency Training: A Nationwide Survey of Program Directors by the Society of Academic Urologists.

text: PURPOSE Coronavirus disease (COVID-19) has profoundly impacted residency training and education. To date, there has not been any broad assessment of urological surgery residency changes and concerns during the COVID-19 pandemic. MATERIALS AND METHODS The Society of Academic Urologists distributed a questionnaire to urology residency program directors on March 30, 2020 exploring residency programs changes related to the COVID-19 pandemic. Descriptive statistics are presented. A qualitative analysis of free response questions was undertaken. A post hoc analysis of differences related to local COVID-19 incidence is described. RESULTS The survey was distributed to 144 residency programs with 65 responses for a 45% response rate. Reserve staffing had started in 80% of programs. Patient-contact time had decreased significantly from 4.7 to 2.1 days per week (P<0.001). Redeployment was reported by 26% of programs. Sixty percent of programs reported concern that residents will not meet case minimums due to COVID-19. Wellness activities centered on increased communication. All programs had begun to use video-conferencing and the majority planned to continue using this. Programs in states with higher incidence of COVID-19 were more likely to report resident redeployment (48% vs 11%, P=0.002) and exposure to COVID-19-positive patients (70% vs 40%, P=0.03) and were less likely to report concerns regarding exposure (78% vs 97%, P=0.02) and personal protective equipment (PPE) availability (62% vs 89%, P=0.02). CONCLUSIONS As of April 1, 2020, the COVID-19 pandemic had resulted in significant changes in urology residency programs. These findings inform a rapidly changing landscape and aid in development of best practices.


title: Structure-modifying effects of chondroitin sulfate in knee osteoarthritis: an updated meta-analysis of randomized placebo-controlled trials of 2-year duration.

text: OBJECTIVE To update a published meta-analysis of double-blind placebo-controlled randomized clinical trials (RCTs) to assess the efficacy of chondroitin sulfate as a structure-modifying drug for knee osteoarthritis (OA). DESIGN A published meta-analysis of randomized controlled trials was updated to include data from one new trial and final data from a second trial both published recently in peer-reviewed literature. This meta-analysis was limited to three RCTs of 2-year duration. Data were pooled using a fixed effects model as there was no evidence of important heterogeneity. RESULTS Pooled results demonstrated a small significant effect of chondroitin sulfate on the reduction in rate of decline in minimum joint space width of 0.13 mm [95% confidence interval (CI) 0.06, 0.19] (P=0.0002) that corresponded to an effect size of 0.23 (95% CI 0.11, 0.35) (P=0.0001). CONCLUSION These results demonstrate that chondroitin sulfate is effective for reducing the rate of decline in minimum joint space width in patients with knee OA.


title: Identification of cardioviruses related to Theiler's murine encephalomyelitis virus in human infections.

text: Cardioviruses comprise a genus of picornaviruses that cause severe illnesses in rodents, but little is known about the prevalence, diversity, or spectrum of disease of such agents among humans. A single cardiovirus isolate, Saffold virus, was cultured in 1981 in stool from an infant with fever. Here, we describe the identification of a group of human cardioviruses that have been cloned directly from patient specimens, the first of which was detected using a pan-viral microarray in respiratory secretions from a child with influenza-like illness. Phylogenetic analysis of the nearly complete viral genome (7961 bp) revealed that this virus belongs to the Theiler's murine encephalomyelitis virus (TMEV) subgroup of cardioviruses and is most closely related to Saffold virus. Subsequent screening by RT-PCR of 719 additional respiratory specimens [637 (89%) from patients with acute respiratory illness] and 400 cerebrospinal fluid specimens from patients with neurological disease (aseptic meningitis, encephalitis, and multiple sclerosis) revealed no evidence of cardiovirus infection. However, screening of 751 stool specimens from 498 individuals in a gastroenteritis cohort resulted in the detection of 6 additional cardioviruses (1.2%). Although all 8 human cardioviruses (including Saffold virus) clustered together by phylogenetic analysis, significant sequence diversity was observed in the VP1 gene (66.9%-100% pairwise amino acid identities). These findings suggest that there exists a diverse group of novel human Theiler's murine encephalomyelitis virus-like cardioviruses that hitherto have gone largely undetected, are found primarily in the gastrointestinal tract, can be shed asymptomatically, and have potential links to enteric and extraintestinal disease.


Where do they go?


title: Economic interventions to ameliorate the impact of COVID-19 on the economy and health: an international comparison.

text: BACKGROUND The COVID-19 pandemic continues to challenge governments and policymakers worldwide. They have rightfully prioritised reducing the spread of the virus through social distancing interventions. However, shuttered business and widespread restrictions on travel and mobility have led to an economic collapse with increasing uncertainty of how quickly recovery will be achieved. METHODS The authors carried out a review of publicly available information on the economic intervention's countries have put in place to ameliorate the impact of COVID-19. RESULTS The strategies and scale of economic interventions have been broad, ranging from 2.5% to a reported 50% of Gross Domestic Product. CONCLUSIONS Numerous countries are beginning to ease lockdown restrictions and restart economies in different ways. There is therefore evolving, real-world data that should be used dynamically by governments and policymakers. The strategies on restarting the economy must be balanced against the uncertainty of a possible second wave of COVID-19. A nuanced approach to easing restrictions needs to take into account not only immediate risk to life but longer-term risks of widening inequalities and falling life expectancy.


title: Beliefs in Conspiracy Theories Following Ostracism.

text: Four studies (total valid N = 643) examined whether ostracism increases people's political conspiracy beliefs through heightened vulnerability and whether self-affirmation intervention counteracts the effect of ostracism on conspiracy beliefs. Compared with their nonostracized counterparts, ostracized participants were more likely to endorse conspiracy beliefs related to different political issues (Studies 1-3). Moreover, heightened vulnerability mediated the link between ostracism and conspiracy beliefs (Studies 1-3). Offering ostracized participants an opportunity to reaffirm values important to them could reduce their political conspiracy beliefs (Study 4). Taken together, our findings highlight the crucial role of vulnerability in understanding when and why ostracism increases conspiracy beliefs and how to ameliorate this relationship. Our findings also provide novel insights into how daily interpersonal interactions influence people's political beliefs and involvement.


title: The involvement of the central nervous system in patients with COVID-19.

text: Coronaviruses disease (COVID-19) has caused major outbreaks. A novel variant, SARS-CoV-2, is responsible for COVID-19 pandemic. Clinical presentations and pathological mechanisms of COVID-19 are broad. The respiratory aspect of the disease has been extensively researched. Emerging studies point out the possibility of the central nervous system (CNS) involvement by COVID-19. Here, we discuss the current evidence for CNS involvement in COVID-19 and highlight that the high pathogenicity of SARS-CoV-2 might be due to its neuroinvasive potential.


title: Salvage robotic transmesenteric off-clamp partial nephrectomy after multiple prior open kidney surgeries.

text: Repeat renal surgery is technically demanding with a high morbidity rate. We describe a novel surgical approach, a salvage robotic transmesenteric off-clamp partial nephrectomy for the management of a renal cell carcinoma in a patient with a history of VHL and multiple prior renal surgeries on the affected kidney. Upon pathological review, the specimen was diagnosed as clear cell RCC, Fuhrman Grade 3, with negative surgical margins. The patient suffered no post-operative complications and had a rapid convalescence. This approach is a feasible and safe alternative in select patients with a significant history of renal surgeries and favorable anatomy.


title: The Effect of Bioactive Glass-Enhanced Orthodontic Bonding Resins on Prevention of Demineralization: A Systematic Review.

text: At present, bioactive glasses (BAGs) are demonstrating promising results in the remineralization of hard tissues. Their bioactive properties can potentially overcome the demineralization effect accompanying orthodontic treatment. This review aimed to evaluate the effectiveness of bioactive glass enhanced orthodontic bonding resins on enamel remineralization, in addition to their antibacterial, ion release and acid neutralization effect. Four databases (PubMed, MEDLINE, Web of Science and Scopus) were searched. Two hundred and fifty-one full-text articles were screened independently, out of which seven studies satisfied the inclusion criteria. Quality appraisal was performed by two independent reviewers. Methodologies used to assess the anti-demineralization effect included Micro-Computed Tomography, Polarized Light Microscopy and Hardness Testing (Knoop and Berkovich). All seven articles confirmed the superior remineralization effect of BAG orthodontic bonding resins compared to their non-BAG counterparts. A proportional relationship was proved between BAG concentrations and increased anti-demineralization effect. The addition of antibacterial agents to BAG does not necessarily improve its anti-demineralization effect. Although studies have confirmed the effectiveness of BAG orthodontic bonding resins on enamel remineralization, there was a degree of heterogeneity across studies due to the lack of an in vitro studies standardized protocol.


title: Early results of the Axium MicroFX for Endovascular Repair of IntraCranial Aneurysm (AMERICA) study: a multicenter prospective observational registry.

text: BACKGROUND Axium MicroFX coils contain polymer (polyglycolic/polylactic acid, PGLA) microfilaments designed to significantly impact intra-aneurysmal flow and to encourage aneurysm thrombosis. To provide preliminary evaluation of the safety and suggested efficacy of the MicroFX design, we performed a multicenter prospective single-arm trial, Axium MicroFX for Endovascular Repair of IntraCranial Aneurysm study (AMERICA). METHODS AMERICA is a prospective multicenter 100 aneurysm observational study evaluating the safety and efficacy of Axium MicroFX PGLA coils. Enrollment was started in April 2010 and completed in October 2012. RESULTS 99 patients underwent treatment for 100 aneurysms at 13 centers. Mean age was 60.2 years, most were women (72%) and 18% of patients had previously undergone treatment for a separate aneurysm. 22% of patients underwent treatment after acute aneurysmal subarachnoid hemorrhage (SAH). Of these patients, all were Hunt and Hess grade 1-3. Pre-procedure modified Rankin score (mRS) was 0-2 in 92% of patients. The majority of aneurysms were anterior circulation (86%), with the most common aneurysm locations being the anterior communicating artery (23%) followed by the supraclinoid internal carotid artery and posterior communicating artery (18% each). The mean maximum diameter was 6.5 mm. Axium MicroFX coils could be placed in all but one treatment (99%). Raymond grade at conclusion of coiling was I (complete) in 52%, II (dog ear or residual neck) in 33% and III (residual aneurysm) in 15%. Discharge mRS was significantly worse in patients with SAH (62% mRS 0-2) compared with electively treated aneurysms (mRS 0-2 in 94%, p<001). Major events were uncommon (6% thromboembolic events, 3% intraoperative vessel or aneurysm rupture) and device-related adverse events (AE) were rare (2% of cases). CONCLUSIONS This prospective study of Axium MicroFX coils demonstrates excellent aneurysm occlusion rates. 52% of aneurysms were completely occluded post-procedure. Within the ruptured aneurysm group, post-procedure occlusion rates were 63.6%. Major AE rates were consistent with historical data.


Role of antimalarials in COVID-19: observational data from a cohort of rheumatic patients.


title: Nuclear medicine in the first year of life.

text: Nuclear medicine has an important role in the care of newborns and children less than 1 y old. Patients in this age group present with a spectrum of diseases different from those of older children or adults. These patients can benefit from the full range of nuclear medicine studies. In these young children, nuclear medicine studies are more likely to be used to evaluate a wide range of congenital conditions but also can be helpful for evaluating acquired conditions such as infection, cancer, and trauma. This review first will cover the general aspects of nuclear medicine practice with these patients, including the special considerations that can help achieve successful diagnostic imaging. These topics will include clinical indications, imaging technology, instrumentation, software, positioning and immobilization, sedation, local and general anesthesia, radiopharmaceutical doses, radiation risk, and dose reduction. The review then will discuss the specific nuclear medicine studies that typically are obtained in patients in this age group. With extra care and attention to the special needs of this population, nuclear medicine departments can successfully study patients less than 1 y old.


title: The international agreement study on the diagnosis of the septate uterus at office hysteroscopy in infertile patients.

text: OBJECTIVE To assess the international agreement on the hysteroscopic diagnosis of septate uterus. DESIGN Interobserver study. SETTING Eight hysteroscopy recordings were put online on the website of the European Society of Gynaecological Endoscopy. PATIENT(S) Asymptomatic, infertile women indicated for a first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment cycle. INTERVENTION(S) Office hysteroscopy. MAIN OUTCOME MEASURE(S) The interobserver agreement on the uterine shape and necessity to correct the abnormality found. RESULT(S) Seventy-eight observers from 24 different countries assessed 8 hysteroscopy recordings. The interobserver agreement on uterine shape variations septate and arcuate was fair (intraclass correlation coefficient = 0.27). Observers from the same country reached a significantly higher level of agreement. The agreement on the necessity of correction was poor (intraclass correlation coefficient = 0.17). The most distinct features for diagnosing a septate uterus judged to be the extent of endocavitary bulging and the angle of the bulging structure from the fundal area. CONCLUSION(S) The agreement among international experts on the hysteroscopic diagnosis of the septate uterus was found to be poor. This may have implications for the accuracy of screening hysteroscopy for diagnosing uterine cavity abnormalities in infertile patients. Development of consented definitions for the hysteroscopic diagnosis of septate and arcuate uterus is recommended.


Protecting the population with immune individuals.


title: Comparison of high-frequency oscillatory ventilation and conventional mechanical ventilation in pediatric respiratory failure.

text: IMPORTANCE Outcomes associated with use of high-frequency oscillatory ventilation (HFOV) in children with acute respiratory failure have not been established. OBJECTIVE To compare the outcomes of HFOV with those of conventional mechanical ventilation (CMV) in children with acute respiratory failure. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective, observational study using deidentified data obtained from all consecutive patients receiving mechanical ventilation aged 1 month to 18 years in the Virtual PICU System database from January 1, 2009, through December 31, 2011. The study population was divided into 2 groups: HFOV and CMV. The HFOV group was further divided into early and late HFOV. Propensity score matching was performed as a 1-to-1 match of HFOV and CMV patients. A similar matching process was performed for early HFOV and CMV patients. EXPOSURE High-frequency oscillatory ventilation. MAIN OUTCOMES AND MEASURES Length of mechanical ventilation, intensive care unit (ICU) length of stay, ICU mortality, and standardized mortality ratio (SMR). RESULTS A total of 9177 patients from 98 hospitals qualified for inclusion. Of these, 902 (9.8%) received HFOV, whereas 8275 (90.2%) received CMV. A total of 1764 patients were matched to compare HFOV and CMV, whereas 942 patients were matched to compare early HFOV and CMV. Length of mechanical ventilation (CMV vs HFOV: 14.6 vs 20.3 days, P < .001; CMV vs early HFOV: 14.6 vs 15.9 days, P < .001), ICU length of stay (19.1 vs 24.9 days, P < .001; 19.3 vs 19.5 days, P = .03), and mortality (8.4% vs 17.3%, P < .001; 8.3% vs 18.1%, P < .001) were significantly higher in HFOV and early HFOV patients compared with CMV patients. The SMR in the HFOV group was 2.00 (95% CI, 1.71-2.35) compared with an SMR in the CMV group of 0.85 (95% CI, 0.68-1.07). The SMR in the early HFOV group was 1.62 (95% CI, 1.31-2.01) compared with an SMR in the CMV group of 0.76 (95% CI, 0.62-1.16). CONCLUSIONS AND RELEVANCE Application of HFOV and early HFOV compared with CMV in children with acute respiratory failure is associated with worse outcomes. The results of our study are similar to recently published studies in adults comparing these 2 modalities of ventilation for acute respiratory distress syndrome.


title: Interleukin-15 is associated with disease severity in viral bronchiolitis.

text: Disease severity in viral bronchiolitis in infancy is difficult to predict and has been linked to host innate immunity. The study aimed to investigate the innate cytokine interleukin-15 (IL-15) as a marker of disease severity.A prospective single-centre observational study was conducted in a university-affiliated paediatric teaching hospital, comparing children (0-18 months) hospitalised for viral bronchiolitis, those admitted to the paediatric intensive care unit with severe disease and healthy age-matched controls. IL-15-related parameters were compared between groups. PCR and microRNA (miRNA) sequencing was undertaken on natural killer (NK) cells collected from study participants.Samples from 88 children with viral bronchiolitis and 43 controls enrolled between 2009 and 2012 were analysed. Peripheral blood mononuclear cell (PBMC) IL-15 mRNA expression was significantly higher in those with moderate severity bronchiolitis compared with controls and those with severe disease. Serum IL-15 levels correlated with disease severity. The relative frequency of NK cells in peripheral blood was significantly reduced in participants with bronchiolitis. The NK cell miRNA transcriptome in bronchiolitis was distinct. Targets of de-regulated miRNA were differentially expressed in bronchiolitis, including JAK3, STAT5A and NFKB1 on the IL-15 signalling pathway.IL-15 is associated with disease severity in children hospitalised with viral bronchiolitis.


title: Efficacy of a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in pigs naturally exposed to a heterologous European (Italian cluster) field strain: Clinical protection and cell-mediated immunity.

text: The purpose of this study was to assess clinical protection in pigs vaccinated with a commercially available attenuated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine (Porcilis) PRRS) and then naturally exposed under field conditions to a heterologous (Italian cluster) strain of virulent PRRSV. A total of 30, 4-week-old pigs seronegative for PRRSV were allocated to 1 of 3 groups (IM, ID, and C groups). At 5 weeks of age, pigs of groups IM (n=10 pigs) and ID (n=10 pigs) were vaccinated intramuscularly and intradermally, respectively, with modified live PRRSV-1 vaccine (Porcilis) PRRS). Pigs of group C (n=10 pigs) were kept as non-vaccinated controls. At post-vaccination (PV) days 0, 7, 14, 28, and 45, blood samples were collected for detection of vaccine virus (PCR) and antibody response (ELISA), identification of changes in lymphocyte subpopulations by cytometry, and IFN-gamma PRRSV-specific secreting cells (SC) by ELISpot. At PV day 45, pigs of A, B, and C groups were moved to a site 3 conventional finishing herd with a history of respiratory disease caused by PRRSV and the most common bacteria to be exposed to a natural challenge. The PRRSV field strain, belonging to the Italian cluster of the PRRSV-1, demonstrated a 84% identity with the vaccine virus (DV strain) at ORF5 sequencing. At 0 (exposure day=45 days PV), 4, 7, 11, 14, 19, 21, 28, and 34 days post-exposure (PE) blood samples were collected for detection and titration of PRRSV and antibody, as well as for lymphocyte and IFN-gamma measurement as described above. Throughout the post-exposure period, all pigs were observed daily for clinical signs. The overall clinical signs were reduced by 68 and 72%, respectively in the intramuscularly and intradermally vaccinated pigs compared to controls. Respiratory signs were reduced by 72 and 80%, respectively in the IM and ID groups. Clinical protection was associated with marked activation of cell-mediated immune response. The highest levels of specific IFN-gamma production at 21-34 days PE were concomitant and associated to changes in natural killer (NK) cells, gamma/delta T, and cytotoxic T lymphocytes in the blood. In our field study, evidences of EU attenuated vaccine-induced clinical protection against natural exposure to a genetically diverse (84% homology) PRRSV-1 isolate (Italian cluster) was demonstrated by the statistically significant reduction in clinical signs in terms of incidence, duration and severity and by a more efficient cell-mediated immune response in the vaccinated pigs as compared to the unvaccinated controls.


title: Live-interactive teledermatology program in Taiwan: One-year experience serving a district hospital in rural Taitung County.

text: BACKGROUND/PURPOSE Population aging and unequal accessibility of health care are increasingly important in developed countries. One strategy to overcome these issues is utilizing telemedicine, which is recently made possible technologically by the advancement of internet speed, high speed zooming cameras, and the information storages. In Taiwan, the telemedicine is granted legally by the amendment for Taiwan's Physician Act in 2018. METHODS Kaohsiung Chang Gung Memorial Hospital (Kaohsiung CGMH) is the first hospital in Taiwan to provide the telemedicine service connecting to Cheng Kung Branch of Taitung Hospital since Nov 2018. Consultation services from Dermatology, ENT, and Ophthalmology have been delivered in the live-interactive and face to face module every week. RESULTS Dermatology consultation comprises the majorities. In the first year, there were totally 426 dermatology consultation services. Eczema, fungal infections, and scabies infestation were the three most common diseases in the beginning. The disease diagnosis became more diverse after several months, including some ready-to-treat diseases pending correct diagnosis, such as pediculosis, psoriasis, and urticaria. Coupled with dermoscopic images, diseases such as hair loss, pediculosis capitis, skin tumor, and scabies, were diagnosed promptly. The subjective patient improvement rate was more than 75% year-round and the case closure rate was more than 85% year-round. CONCLUSION Teledermatology is a promising approach to serve the remote medical-underprivileged regions. The teledermatology is anticipated to help underserved regions, nursing homes, prisons, and in situations with severe pandemic infections, such as COVID-19.


title: Label-free, electrical detection of the SARS virus N-protein with nanowire biosensors utilizing antibody mimics as capture probes.

text: Antibody mimic proteins (AMPs) are polypeptides that bind to their target analytes with high affinity and specificity, just like conventional antibodies, but are much smaller in size (2-5 nm, less than 10 kDa). In this report, we describe the first application of AMP in the field of nanobiosensors. In(2)O(3) nanowire based biosensors have been configured with an AMP (Fibronectin, Fn) to detect nucleocapsid (N) protein, a biomarker for severe acute respiratory syndrome (SARS). Using these devices, N protein was detected at subnanomolar concentration in the presence of 44 microM bovine serum albumin as a background. Furthermore, the binding constant of the AMP to Fn was determined from the concentration dependence of the response of our biosensors.


title: Development of a novel real-time RT-PCR assay to detect Seneca Valley virus associated with emerging cases of vesicular disease in pigs.

text: Seneca Valley virus (SVV) can cause vesicular disease that is clinically indistinguishable from foot-and-mouth disease, vesicular stomatitis and swine vesicular disease. SVV-associated disease has been identified in pigs in several countries, namely USA, Canada, Brazil and China. Diagnostic tests are required to reliably detect this emerging virus, and this report describes the development and evaluation of a novel real-time reverse-transcription (RT) PCR assay (rRT-PCR), targeting the viral polymerase gene (3D) of SVV. This new assay detected all historical and contemporary SVV-1 isolates examined (n=8), while no cross-reactivity was observed with nucleic acid template prepared from other vesicular disease viruses or common swine pathogens. The analytical sensitivity of the rRT-PCR was 0.79 TCID50/ml and the limit of detect was equivalent using two different RT-PCR master-mixes. The performance of the test was further evaluated using pig nasal (n=25) and rectal swab samples (n=25), where concordant results compared to virus sequencing were generated for 43/50 samples. The availability of this assay, will enable laboratories to rapidly detect SVV in cases of vesicular disease in pigs, negated for notifiable diseases, and could enable existing knowledge gaps to be investigated surrounding the natural epidemiology of SVV.


Endoscopic Abscess Septotomy for Management of Sleeve Gastrectomy Leak.


title: Necrobiotic xanthogranuloma as an unusual cause of refractive chronic bilateral leg ulceration.

text: Necrobiotic xanthogranuloma is a progressive histiocytic granulomatous disease with frequent extracutaneous involvement. We have documented an unusual case of necrobiotic xanthogranuloma in a 58-year-old man with a history of recalcitrant and chronic arm and leg ulcerations in the absence of characteristic periorbital involvement. Our patient demonstrates a therapeutic challenge and may display a new necrobiotic inflammatory disorder not previously characterized.


Program at a glance.


Mental Health and the Covid-19 Pandemic.


title: Short-term outcomes of laparoscopic total mesorectal excision following neoadjuvant chemoradiotherapy.

text: OBJECTIVE To investigate the feasibility of laparoscopic total mesorectal excision (TME) in mid and lower rectal cancers following neoadjuvant chemoradiation (nCRT). BACKGROUND The laparoscopic approach for colon cancer has been widely accepted. A few studies have shown that there are advantages of laparoscopic over open TME surgery for rectal cancer. However, the role of laparoscopy has not been clearly defined specifically in cases following nCRT. METHODS All patients with rectal cancer who underwent nCRT were identified; no operations for rectal carcinoma were performed laparoscopically between 1997 and 2005. The laparoscopic cases were matched to open cases based on gender, procedure, age, and body mass index (BMI). The medical records were reviewed and short-term outcome was compared between these two groups. Statistical analysis was performed using SPSS 15 software. RESULTS Between 2002 and 2008, 64 patients were identified, including 32 patients who underwent laparoscopic surgery and 32 who had a laparotomy. There was no difference between the two groups based on gender, procedure, age, BMI or American Society of Anesthesiologists (ASA) classification. The procedures performed within each group included 8 abdominoperineal resections and 24 anterior resections, which included 20 colonic J-pouch-anal anastomoses and 4 straight coloanal anastomoses. In the laparoscopic group, 12 patients underwent totally laparoscopic operations, 12 were either laparoscopic-assisted or hand-assisted procedures, and 8 were converted to laparotomy. The reasons for conversion included bleeding, splenic injury, and difficult anatomy. There were no differences in comorbidities, tumor location, tumor size, tumor stage or radiation dose between the two groups. Operative time was longer in the laparoscopic group (267 + or - 76 versus 205 + or - 49 min, p < 0.001). Operative blood loss, complication rate, and mortality rate were all similar between the two groups. However, the laparoscopic group benefited from shorter length of stay (6.1 + or - 2.4 versus 7.6 + or - 2.3 days, p = 0.012), earlier first bowel movement (1.9 + or - 1 versus 3.3 + or - 2.4 days, p = 0.006), and shorter time to regular diet (3.9 + or - 2.1 versus 5.8 + or - 2.5 days, p = 0.003). There was no difference in lymph node harvest (both positive node harvest and total lymph node harvest), distal margin or radial margin. CONCLUSIONS In our experience, laparoscopic TME for mid and lower rectal cancer is feasible and safe. Patients benefit from the short-term advantages of laparoscopy, including shorter length of hospital stay, time to tolerating a regular diet, and time to first bowel movement or stoma function. Although there were no short-term differences in oncologic parameters, the long-term oncologic outcome requires further investigation.


Endovascular therapy for stroke: getting to the "heart" of the matter.


title: Positron emission tomography/computed tomography and biomarkers for early treatment response evaluation in metastatic colon cancer.

text: BACKGROUND Treatment options for metastatic colon cancer (mCC) are widening. We prospectively evaluated serial 2-deoxy-2-[18F]fluoro-d-glucose positron-emission tomography/computed tomography (PET/CT) and measurements of tissue inhibitor of metalloproteinases-1 (TIMP-1), carcinoembryonic antigen (CEA), and liberated domain I of urokinase plasminogen activator receptor (uPAR(I)) for early assessment of treatment response in mCC patients. METHODS Thirty-three mCC patients scheduled for first-line chemotherapy with capecitabine and oxaliplatin (CAPOX) and bevacizumab participated; 27 were evaluated by PET/CT before treatment, after one and four treatment series. Morphological and metabolic response was independently assessed according to Response Evaluation Criteria in Solid Tumors and European Organization for Research and Treatment of Cancer PET criteria. Plasma TIMP-1, plasma uPAR(I), and serum CEA were determined. RESULTS Metabolic response after one treatment course predicted the ability of CAPOX and bevacizumab to induce morphological response after four treatment series with a sensitivity of 80%, specificity of 69%, and odds ratio of 13.9 (95% confidence interval [CI] 1.9; 182). Early metabolically stable or progressive disease was associated with shorter progression-free survival (hazard ratio [HR] = 3.2 [CI 1.3; 7.8]). Biomarker levels at early evaluation were associated with shorter OS (TIMP-1 per unit increase on a log-2-transformed ng/mL scale: HR = 2.6 [CI 1.4; 4.9]; uPAR(I) per 25 fmol/mL increase: HR = 1.5 [CI 1.1; 2.1]). CONCLUSION This monocentric study demonstrated predictive value of early metabolic PET response and prognostic value of TIMP-1 and uPAR(I) levels in mCC treated with CAPOX and bevacizumab. Results support investigation of PET/CT, TIMP-1, and uPAR(I) guided early treatment adaptation in mCC.


title: Comparison of performance achievement award recognition with primary stroke center certification for acute ischemic stroke care.

text: BACKGROUND Hospital certification and recognition programs represent 2 independent but commonly used systems to distinguish hospitals, yet they have not been directly compared. This study assessed acute ischemic stroke quality of care measure conformity by hospitals receiving Primary Stroke Center (PSC) certification and those receiving the American Heart Association's Get With The Guidelines-Stroke (GWTG-Stroke) Performance Achievement Award (PAA) recognition. METHODS AND RESULTS The patient and hospital characteristics as well as performance/quality measures for acute ischemic stroke from 1356 hospitals participating in the GWTG-Stroke Program 2010-2012 were compared. Hospitals were classified as PAA+/PSC+ (hospitals n = 410, patients n = 169,302), PAA+/PSC- (n = 415, n = 129,454), PAA-/PSC+ (n = 88, n = 26,386), and PAA-/PSC- (n = 443, n = 75,565). A comprehensive set of stroke measures were compared with adjustment for patient and hospital characteristics. Patient characteristics were similar by PAA and PSC status but PAA-/PSC- hospitals were more likely to be smaller and nonteaching. Measure conformity was highest for PAA+/PSC+ and PAA+/PSC- hospitals, intermediate for PAA-/PSC+ hospitals, and lowest for PAA-/PSC- hospitals (all-or-none care measure 91.2%, 91.2%, 84.3%, and 76.9%, respectively). After adjustment for patient and hospital characteristics, PAA+/PSC+, PAA+/PSC-, and PAA-/PSC+ hospitals had 3.15 (95% CIs 2.86 to 3.47); 3.23 (2.93 to 3.56) and 1.72 (1.47 to 2.00), higher odds for providing all indicated stroke performance measures to patients compared with PAA-/PSC- hospitals. CONCLUSIONS While both PSC certification and GWTG-Stroke PAA recognition identified hospitals providing higher conformity with care measures for patients hospitalized with acute ischemic stroke, PAA recognition was a more robust identifier of hospitals with better performance.


title: Pathophysiology and treatment options in trigeminal meningoceles.

text: Trigeminal meningoceles, lateral to the maxillary nerve (V2), have seldom been reported as underlying pathology for spontaneous rhinoliquorrhea. In contrast to sphenoid meningoceles arising from a persistent lateral craniopharyngeal canal (Sternberg-Cruveilhier, medial to V2), their occurrence seems to be generated by addition of erosive processes to the constitutively thin bony shell underneath the semilunar ganglion, lateral to the round foramen (and V2). The developmental and anatomical relationships of trigeminal meningoceles to the sphenoid bone are depicted, and in a review of the literature we present the different surgical approaches employed for sealing the dura leak. In view of these techniques we discuss an unusual case of therapy-resistant rhinoliquorrhea with left-sided trigeminal meningocele involving the Meckel cave at the lateral sphenoid and reaching the superior orbital fissure and the medial orbital space. In contrast to patients who have lateral sphenoidal meningoceles with a persistent lateral craniopharyngeal canal (Sternberg-Cruveilhier), who can be treated successfully using an endoscopic transsphenoidal approach (recurrence rate 13.7%), the recurrence rate of cerebrospinal fluid (CSF) efflux for trigeminal meningoceles lies much higher (endoscopically 66%, open craniotomy 33%). The surgical strategy thus has to be chosen individually, taking into account specific anatomical situations and eventually preceding operations.


title: SSTR-Mediated Imaging in Breast Cancer: Is There a Role for Radiolabeled Somatostatin Receptor Antagonists?

text: Recent studies have shown enhanced tumor targeting by novel somatostatin receptor (SSTR) antagonists compared with clinically widely used agonists. However, these results have been obtained mostly in neuroendocrine tumors, and only limited data are available for cancer types with lower SSTR expression, including breast cancer (BC). To date, two studies have reported higher binding of the antagonist than the agonist in BC, but in both studies only a limited number of cases were evaluated. In this preclinical study, we further investigated whether the application of an SSTR antagonist can improve SSTR-mediated BC imaging in a large panel of BC specimens. We also generated an in vivo BC mouse model and performed SPECT/MRI and biodistribution studies. Methods: Binding of 111In-DOTA-Tyr3-octreotate (SSTR agonist) and 111In-DOTA-JR11 (SSTR antagonist) to 40 human BC specimens was compared using in vitro autoradiography. SSTR2 immunostaining was performed to confirm SSTR2 expression of the tumor cells. Furthermore, binding of the radiolabeled SSTR agonist and antagonist was analyzed in tissue material from 6 patient-derived xenografts. One patient-derived xenograft, the estrogen receptor-positive model T126, was chosen to generate in vivo mouse models containing orthotopic breast tumors for in vivo SPECT/MRI and biodistribution studies after injection with 177Lu-DOTA-Tyr3-octreotate or 177Lu-DOTA-JR11. Results:111In-DOTA-JR11 binding to human BC tissue was significantly higher than 111In-DOTA-Tyr3-octreotate binding (P < 0.001). The median ratio of antagonist binding versus agonist binding was 3.39 (interquartile range, 2-5). SSTR2 immunostaining confirmed SSTR2 expression on the tumor cells. SPECT/MRI of the mouse model found better tumor visualization with the antagonist. This result was in line with the significantly higher tumor uptake of the radiolabeled antagonist than of the agonist as measured in biodistribution studies 285 min after radiotracer injection (percentage injected dose per gram of tissue: 1.92 ± 0.43 vs. 0.90 ± 0.17; P = 0.002). Conclusion: SSTR antagonists are promising candidates for BC imaging.


title: Uptrend in distress and psychiatric symptomatology in pregnant women during the COVID-19 pandemic.

text: INTRODUCTION Prenatal maternal distress has a negative impact on the course of pregnancy, fetal development, offspring development and later psychopathologies. The study aimed to determine the extent to which the Coronavirus disease 2019 (COVID-19) pandemic may aggravate pregnant women prenatal distress and psychiatric symptomatology. MATERIAL AND METHODS Two cohorts of pregnant volunteer women were evaluated, one that was recruited before the COVID-19 pandemic (n=496) through advertisements in prenatal clinics in Quebec, Canada, from April 2018 to March 2020; the other (n=1258) was recruited online during the pandemic from April 2 to April 13 2020. Prenatal distress and psychiatric symptomatology were measured with the Kessler Distress Scale (K10), Post-traumatic Checklist for DSM-5 (PCL-5), Dissociative Experiences Scale (DES-II) and Positive and Negative Affect Schedule (PANAS). RESULTS The 1754 pregnant women (Mage =29.27, SD=4.23) were between 4 and 41 gestational weeks (M=24.80, SD=9.42), were generally educated (91.3% had post-high school training) and financially well-resourced (85.3% were above the low-income cut-off). A multivariate analysis of covariance controlling for age, gestational age, household income, education and lifetime psychiatric disorders showed a large effect size (ES) in the difference between the two cohorts on psychiatric symptoms (Wilks' λ=0.68, F6,1400 =108.50, p < 0.001, partial η2 = 0.32). According to post-hoc analyses of covariance, the COVID-19 women reported higher levels of depressive and anxiety symptoms (ES=0.57), dissociative symptoms (ES=0.22 and 0.25), symptoms of post-traumatic stress disorder (ES=0.19), negative affectivity (ES = 0.96) and less positive affectivity (ES=0.95) than the pre-COVID-19 cohort. Women from the COVID-19 cohort were more likely than pre-COVID-19 women to present clinically significant levels of depressive and anxiety symptoms [OR=1.94, χ2(1)=10.05, p=.002]. Multiple regression analyses indicated that COVID-19 pregnant women having a previous psychiatric diagnosis or low income would be more prone to elevated distress and psychiatric symptoms. CONCLUSIONS Pregnant women assessed during the COVID-19 pandemic reported more distress and psychiatric symptoms than pregnant women assessed before the pandemic, mainly in the form of depression and anxiety symptoms. Given the harmful consequences of prenatal distress on mothers and offspring, the presently observed upsurge of symptoms in pregnant women calls for special means of clinical surveillance.


title: Airborne exposure patterns from a passenger source in aircraft cabins.

text: Airflow is a critical factor that influences air quality, airborne contaminant distribution, and disease transmission in commercial airliner cabins. The general aircraft-cabin air-contaminant transport effect model seeks to build exposure-spatial relationships between contaminant sources and receptors, quantify the uncertainty, and provide a platform for incorporation of data from a variety of studies. Knowledge of infection risk to flight crews and passengers is needed to form a coherent response to an unfolding epidemic, and infection risk may have an airborne pathogen exposure component. The general aircraf-tcabin air-contaminant transport effect model was applied to datasets from the University of Illinois and Kansas State University and also to case study information from a flight with probable severe acute respiratory syndrome transmission. Data were fit to regression curves, where the dependent variable was contaminant concentration (normalized for source strength and ventilation rate), and the independent variable was distance between source and measurement locations. The data-driven model showed exposure to viable small droplets and post-evaporation nuclei at a source distance of several rows in a mock-up of a twin-aisle airliner with seven seats per row. Similar behavior was observed in tracer gas, particle experiments, and flight infection data for severe acute respiratory syndrome. The study supports the airborne pathway as part of the matrix of possible disease transmission modes in aircraft cabins.


Editorial comment on: complications of laparoscopic and percutaneous renal cryoablation in a single tertiary referral center.


title: Burn wound care.

text: The goals of burn wound care are removal of nonviable tissue, prevention of infection, and facilitation of wound healing, while controlling pain and maximizing outcome. This article reviews the basic pathophysiology of burn wounds; describes the evaluation of the depth, location, and extent of the wound; and discusses the myriad of wound care products on the market including their strengths and weaknesses. This article guides the reader through wound assessment and designing the appropriate treatment plan.


title: Meningioma embolization with the pressure cooker technique using Squid 12.

text: Background Preoperative meningioma embolization may be performed with microparticles or liquid embolic agents. The pressure cooker technique (PCT) has recently been described for the embolization of brain arteriovenous malformations (AVMs). Case We present the case of a 73-year-old woman with a large frontal interhemispheric meningioma that was successfully preoperatively embolized with the PCT using Squid 12, a new ethyl-vinyl alcohol copolymer embolic agent. The PCT presents considerable advantages relative to conventional embolization techniques such as deeper and faster tumor penetration and embolization of tumors with difficult vascular access, and retrograde feeling of pial afferents may be achieved. Conclusions The use of the PCT with Squid 12 may potentially increase the effectiveness of meningioma embolization, increase tumor devascularization and improve outcomes of surgical resection.


title: Thoughts on the alveolar phase of COVID-19.

text: COVID-19 can be divided into three clinical stages, and one can speculate that these stages correlate with where the infection resides. For the asymptomatic phase, the infection mostly resides in the nose where it elicits a minimal innate immune response. For the mildly symptomatic phase, the infection is mostly in the psuedostatified stratified epithelium of the larger airways and is accompanied by a more vigorous innate immune response. In the conducting airways, the epithelium can recover from the infection, because the keratin V basal cells are spared and they are the progenitor cells for the bronchial epithelium. There may be more severe disease in the respiratory bronchioles where the club cells are likely infected. The devastating third phase is in the gas exchange units of the lung, where ACE2 expressing alveolar type II cells and perhaps type I cells are infected. The loss of type II cells results in respiratory insufficiency due to the loss of pulmonary surfactant, alveolar flooding, and loss of normal repair, since type II cells are the progenitors of type I cells. The loss of type I and type II cells will also block normal active resorption of alveolar fluid. Subsequent endothelial damage leads to transudation of plasma proteins, formation of hyaline membranes, and an inflammatory exudate, characteristic of ARDS. Repair might be normal, but if the type II cells are severely damaged, alternative pathways for epithelial repair may be activated, which would result in some residual lung disease.


COVID-19 as a confounding factor in a child submitted to staged surgical palliation of hypoplastic left heart syndrome: One of the first reports of SARS-CoV-2 infection in patients with congenital heart disease.


title: The Effects of Vasoconstriction And Volume Expansion on Veno-Arterial ECMO Flow.

text: BACKGROUND Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is gaining widespread use in the treatment of severe cardiorespiratory failure. Blood volume expansion is commonly used to increase ECMO flow (QECMO), with risk of positive fluid balance and worsening prognosis. We studied the effects of vasoconstriction on recruitment of blood volume as an alternative for increasing QECMO, based on the concepts of venous return. METHODS In a closed chest, centrally cannulated porcine preparation (n = 9) in ventricular fibrillation and VA-ECMO with vented left atrium, mean systemic filling pressure (MSFP), and venous return driving pressure (VRdP) were determined in Euvolemia, during Vasoconstriction (norepinephrine 0.05, 0.125, and 0.2 μg/kg/min) and after Volume Expansion (3 boluses of 10 mL/kg Ringer's lactate). Maximum achievable QECMO was examined. RESULTS Vasoconstriction and Volume Expansion both increased maximum achievable QECMO, delivery of oxygen (DO2), and MSFP, but right atrial pressure increased in parallel. VRdP did not change. The vascular elastance curve was shifted to the left by Vasoconstriction, with recruitment of stressed volume. It was shifted to the right by Volume Expansion with direct expansion of stressed volume. Volume Expansion decreased resistance to venous return and pump afterload. CONCLUSIONS In a circulation completely dependent on ECMO support, maximum achievable flow directly depended on the vascular factors governing venous return-i.e., closing conditions, stressed vascular volume and the elastance and resistive properties of the vasculature. Both treatments increased maximum achievable ECMO flow at stable DO2, via increases in stressed volume by different mechanisms. Vascular resistance and pump afterload decreased with Volume Expansion.


title: Gadolinium enhancement on cranial MRI in multiple sclerosis is age dependent.

text: BACKGROUND Epidemiological, pathological and radiological studies suggest that inflammatory demyelination in MS is an age-dependent process, and that the formation of focal inflammatory demyelinating lesions decreases with age. Gadolinium-enhancing lesions are a biomarker of inflammatory disease activity in MS, but little is known about the relation of age and gadolinium enhancement on cranial MRI scans in people with MS. In this study, we investigated the association of age and other risk factors with gadolinium enhancement on cranial MRI in a retrospective cross-sectional clinical MS cohort. METHODS In a cohort including 1543 people with CIS and MS, we investigated the association of the risk factors age, sex, disease course, immunomodulatory drug (IMD) treatment, and disability with gadolinium enhancement on cranial MRI scans using a binary logistic regression model. RESULTS Age was the most important factor associated with gadolinium enhancement, with the odds of gadolinium enhancement decreasing with advancing age. Participants with CIS had lower odds of gadolinium enhancement (odds ratio of 0.42, 95% confidence interval of 0.24-0.72 compared to RRMS). Sex, disease course and IMD treatment were not significantly associated with gadolinium enhancement in our cohort. CONCLUSIONS Our investigation shows that gadolinium enhancement is strongly associated with age. Since gadolinium enhancement is a marker of inflammatory disease activity, our findings suggest that inflammatory disease activity declines with age, and that IMD treatment may be more beneficial in younger and less useful in older people with MS.


title: Jailed Artery Ostia Modifications After Flow-Diverting Stent Deployment at Arterial Bifurcations: A Scanning Electron Microscopy Translational Study.

text: BACKGROUND Even though flow-diverting stents are being increasingly used to treat intracranial aneurysms, the fate of jailed side branches remains controversial, with recent clinical data contradicting finding of earlier animal studies that reported patency. OBJECTIVE To quantify the surface area of the ostia after 3 months of jailing by flow-diverting stents as a more accurate means of patency evaluation. METHODS Ten large white swine were stented by flow-diverting stents placed at common carotid-ascending pharyngeal arterial bifurcation sites. A dual antiplatelet regimen was initiated 72 hours before stenting and maintained during follow-up. Optical coherence tomography was used to search for per-procedural thrombus formation. Selective control digital subtraction angiography was performed 12 weeks post-stenting. Subsequently, the stented arterial segments were harvested en bloc and observed under scanning electron microscopy, photographed, and quantified. RESULTS The absence of per-procedural thrombus formation was confirmed. All ostia were patent at 12 weeks (or 3 months) post stenting, with no angiographic or scanning electron microscopy-evident thrombus formation. The mean initial ostium surface was 2 048 617 ± 731 625 μm. At 3 months, the mean nonendothelialized ostium surface was 229 218 ± 140 172 μm, and mean endothelialized ostium surface was 1 819 399 ± 672 632 μm. A statistically significant difference (reduction) was observed between the initial and 12-week ostium surfaces (P < .001), with an significant statistical power (1.000). CONCLUSION Jailed side branches remained patent after stenting, but the surface quantifications showed significant endothelial coverage, with a significant reduction of patent ostium surfaces at 12 weeks post-stenting. ABBREVIATIONS APhA, ascending pharyngeal arteryCI, confidence interval3DRA, 3-dimensional rotational angiographyDSA, digital subtraction angiographyFDS, flow-diverting stentOCT, optical coherence tomographyOS, ostium surfaceSEM, scanning electron microscopy.


Letter: For Whom the Bell Tolls: Overcoming the Challenges of the COVID Pandemic as a Residency Program.


title: COVID-19 and pulmonary hypertension.

text: Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by pulmonary arterial remodeling and vasoconstriction leading to elevated pulmonary artery pressure and, ultimately, right heart failure. So far, few cases of COVID-19 disease in patients with PH have been reported. Caution is warranted in interpreting this observation as data are evolving and several factors may influence the number of reported cases of PH and COVID-19. Social distancing and quarantine could play a role, especially for patients with chronic diseases who might be more vigilant of their potential for respiratory infection. In addition, PH is a rare disease, and because testing is not universal, we could be underestimating the number of cases. Other hypothetical factors to consider are the underlying pathophysiology of PH and the medications used to treat PH and their implications in COVID-19.


title: Combination of Multicatheter Plus Stent or Balloon for Treatment of Complex Aneurysms.

text: BACKGROUND AND PURPOSE Coiling of complex aneurysms is still difficult even with current adjuvant techniques. This study sought to evaluate the safety and effectiveness of a combination of multicatheter plus stent or balloon for the treatment of complex aneurysms. MATERIALS AND METHODS All complex aneurysms that underwent coiling with the combination technique were identified from prospectively maintained neurointerventional data bases. "Complex aneurysm" was defined as a wide-neck aneurysm with branch incorporation into or a deep lobulation of the sac. The clinical and angiographic outcomes were retrospectively analyzed. RESULTS Sixty-two complex aneurysms (12 ruptured, 50 unruptured) in 62 patients (mean age, 57 years; male/female ratio, 12:50) were treated with a combination technique by using a multicatheter plus stent (n = 42, 3 ruptured) or balloon (n = 20, 9 ruptured). Treatment-related morbidity (grade 3 hemiparesis) occurred in 1 patient (1.6%). Except for 1 patient who had treatment-related morbidity, none of the other patients with unruptured aneurysms developed new neurologic symptoms at discharge. Nine of the 12 patients with ruptured aneurysms had good outcomes (Glasgow Outcome Score, 4 or 5) at the latest follow-up (mean, 32 months; range, 6-72 months), and 1 patient died from an initial SAH. Posttreatment control angiograms revealed complete occlusion in 27, neck remnant in 34, and incomplete occlusion in 1 aneurysm. At least 1 follow-up catheter or MR angiogram was available in 80.6% (n = 50) (mean, 21 months; range, 6-65 months). There were 4 minor and 3 major recurrences (14.0%). CONCLUSIONS In this case series, the combination technique by using multicatheter plus stent or balloon seemed safe and effective for the treatment of complex aneurysms.


Tackling the mental health burden of frontline healthcare staff in the COVID-19 pandemic: China's experiences.


title: Emerging microbiology diagnostics for transplant infections: On the cusp of a paradigm shift.

text: In light of the heightened risk for infection associated with solid organ and hematopoietic stem cell transplantation, rapid and accurate microbiology diagnostics are essential to the practice of transplant clinicians, including infectious diseases specialists. In the last decade, diagnostic microbiology has seen a shift towards culture-independent techniques including single-target and multiplexed molecular testing, mass-spectrometry, and magnetic resonance-based methods which have together greatly expanded the array of pathogens identified, increased processing speed and throughput, allowed for detection of resistance determinants, and ultimately improved the outcomes of infected transplant recipients. More recently, a newer generation of diagnostics with immense potential has emerged, including multiplexed molecular panels directly applicable to blood and blood culture specimens, next-generation metagenomics and gas chromatography mass spectrometry. Though these methods have some recognized drawbacks, many have already demonstrated improved diagnostic sensitivity and a positive impact on clinical outcomes in transplant and immunocompromised patients.


title: An N-terminal region of Lassa virus L protein plays a critical role in transcription but not replication of the virus genome.

text: The central domain of the 200-kDa Lassa virus L protein is a putative RNA-dependent RNA polymerase. N- and C-terminal domains may harbor enzymatic functions important for viral mRNA synthesis, including capping enzymes or cap-snatching endoribonucleases. In the present study, we have employed a large-scale mutagenesis approach to map functionally relevant residues in these regions. The main targets were acidic (Asp and Glu) and basic residues (Lys and Arg) known to form catalytic and binding sites of capping enzymes and endoribonucleases. A total of 149 different mutants were generated and tested in the Lassa virus replicon system. Nearly 25% of evolutionarily highly conserved acidic and basic side chains were dispensable for function of L protein in the replicon context. The vast majority of the remaining mutants had defects in both transcription and replication. Seven residues (Asp-89, Glu-102, Asp-119, Lys-122, Asp-129, Glu-180, and Arg-185) were selectively important for mRNA synthesis. The phenotype was particularly pronounced for Asp-89, Glu-102, and Asp-129, which were indispensable for transcription but could be replaced by a variety of amino acid residues without affecting genome replication. Bioinformatics disclosed the remote similarity of this region to type IIs endonucleases. The mutagenesis was complemented by experiments with the RNA polymerase II inhibitor alpha-amanitin, demonstrating dependence of viral transcription from the cellular mRNA pool. In conclusion, this paper describes an N-terminal region in L protein being important for mRNA, but not genome synthesis. Bioinformatics and cell biological experiments lend support to the hypothesis that this region could be part of a cap-snatching enzyme.


title: Use of cardiac biomarkers in neonatology.

text: Cardiac biomarkers are used to identify cardiac disease in term and preterm infants. This review discusses the roles of natriuretic peptides and cardiac troponins. Natriuretic peptide levels are elevated during atrial strain (atrial natriuretic peptide (ANP)) or ventricular strain (B-type natriuretic peptide (BNP)). These markers correspond well with cardiac function and can be used to identify cardiac disease. Cardiac troponins are used to assess cardiomyocyte compromise. Affected cardiomyocytes release troponin into the bloodstream, resulting in elevated levels of cardiac troponin. Cardiac biomarkers are being increasingly incorporated into clinical trials as indicators of myocardial strain. Furthermore, cardiac biomarkers can possibly be used to guide therapy and improve outcome. Natriuretic peptides and cardiac troponins are potential tools in the diagnosis and treatment of neonatal disease that is complicated by circulatory compromise. However, clear reference ranges need to be set and validation needs to be carried out in a population of interest.


title: Our technique of preceding diaphragm resection and partial mobilization of the hepatic right lobe using a vessel sealing device (LigaSure™) for huge hepatic tumors with diaphragm invasion.

text: We describe and assess our technique of preceding diaphragm resection and partial mobilization of the hepatic right lobe to treat a huge hepatic tumor with diaphragm invasion. The right hepatic artery and portal vein were divided at the hepatic hilum, and the mesenteries were then dissected with a vessel sealing device (LigaSure Impact™). The invaded diaphragm was dissected roundly using a vessel sealing device and the right lobe was partially mobilized. A soft catheter was then passed along the anterior aspect of the retrohepatic inferior vena cava and the liver parenchyma was dissected via a liver hanging maneuver. We performed eight hepatectomies using this technique. The median blood loss was 532.5 ml and the mean excised liver weight was 1859 g. Our results demonstrate the safety and efficiency of the preceding diaphragm resection and partial mobilization technique using a vessel sealing device for right hepatectomy to resect a very large tumor with diaphragm invasion.


title: Follow Up Data of MRI-Visible Synthetic Meshes for Reinforcement in Large Hiatal Hernia in Comparison to None-Mesh Repair-A Prospective Cohort Study.

text: Background: Mesh augmentation for large hiatal hernia is still controversial because of high alleged risk of chronic reaction or shrinkage of mesh orifice surrounding the esophagus. The aim of this cohort study was to develop and establish an image analysis scheme, including 3D reconstruction, for MRI-visible meshes (DynaMesh®) to measure postoperative mesh shrinkage in order to observe potential complications. Methods: Between 12/2012 and 10/2016, n = 33 patients underwent surgery to correct symptomatic hiatal hernia (implantation indicated: n = 18). Intraoperative measurement of the hiatal surface area (HSA) > 5 cm2 was indication for mesh implantation. Early postoperatively, and during long-term follow-up, MRI was performed and patients filled out the gastrointestinal quality of life index (GIQLI score). Results: Follow-up rate was 76% (n = 25/33). Overall recurrence rate was 4% (1/25). No other patient showed reflux or dysphagia symptoms. Mesh related complications were not observed during follow-up period. Median GIQLI score of patients with mesh was 123 (range: 67-144), and 93 (52-141) for patients without mesh. Comparison of early and mid-term postoperative MRI for patients with mesh showed changes in mesh orifice size of 3% (corresponding to a slight increase in size of about 6 mm2) without any significant correlations with BMI, HSA, or patient age. Conclusion: We established an image analysis and 3D reconstruction scheme for MRI visible meshes in hiatal hernia repair. MRI images of normal clinical quality are sufficient for this analysis. Mesh orifice size in MRI-visible meshes does not seem to change at a clinically relevant level in the small cohort observed here. Further studies of large cohorts are necessary to establish if HSA >5 cm2 could be a suitable measure for indication of mesh implantation.


title: Respiratory Care year in review 2012: invasive mechanical ventilation, noninvasive ventilation, and cystic fibrosis.

text: For the busy clinician, educator, or manager, it is becoming an increasing challenge to filter the literature to what is relevant to one's practice and then update one's practice based on the current evidence. The purpose of this paper is to review the recent literature related to invasive mechanical ventilation, noninvasive ventilation, and cystic fibrosis. These topics were chosen and reviewed in a manner that is most likely to have interest to the readers of Respiratory Care.


title: Outcomes of aortic arch repair with extended (≥ 90 minutes) antegrade cerebral perfusion.

text: OBJECTIVES To analyze outcomes with extended duration of antegrade cerebral perfusion (ACP) during hypothermic circulatory arrest (HCA) for total arch repair (TAR). DESIGN Retrospective study of consecutive patients undergoing TAR with HCA and ACP. Patients were divided into group A (ACP ≥ 90 min, n = 12) and group B (ACP < 90 min, n = 17) and compared regarding in-hospital mortality and neurological complications (primary outcome measures) and major complications, biochemical markers of organ damage, and blood product use (secondary outcome measures). Complications were analyzed according to standards of the International Aortic Arch Surgery Study Group. RESULTS Overall in-hospital mortality was 4/29 (14%); 1/12 (8.3%) in group A versus 3/17 (18%) in group B, p = 0.62. No grade-V (lethal) neurological complication occurred, but five patients (all in group B) had grade-IV neurological complications: one general and two each focal and spinal neurological deficit (p = 0.047, overall). Prevalence of grade-II (temporary) general neurological deficit was 17% (group A) versus 27% (group B), p = 0.66. None of the patients suffered ≥ grade-IV respiratory or renal complications. Other complications, biochemical markers, and blood product usage were not significantly different. CONCLUSION Outcomes in TAR with HCA and extended (≥ 90 min) three-vessel ACP were encouraging and could be contemplated with anticipated time-consuming TAR.


title: Coronavirus causes lower respiratory tract infections less frequently than RSV in hospitalized Norwegian children.

text: BACKGROUND We have described occurrence and clinical manifestations of human coronaviruses (HCoV) in hospitalized Norwegian children with respiratory tract infection (RTI) and compared them with a group of respiratory syncytial virus (RSV)-infected children. METHODS AND POPULATION We used in-house TaqMan multiplex real-time polymerase chain reaction to test nasopharyngeal samples from 536 RTI episodes in 452 children who were admitted during the 2006-2007 winter. Twenty-one viruses, including HCoV-OC43, HCoV-NL63, HCoV-229E, HCoV-HKU1, and RSV were tested. The amount of viral nucleic acid was recorded semiquantitatively based on the cycle threshold value. RESULTS A total of 665 positive polymerase chain reaction tests were recorded in 536 nasopharyngeal specimens. Coronavirus was found in 68 (12.7%): HCoV-OC43, n = 44 (8.2%), and HCoV-NL63, n = 24 (4.5%). Only RSV and rhinovirus were detected more frequently. Neither HCoV-229E nor HCoV-HKU1 was detected. Among children with HCoV-OC43, 73.0% tested positive for at least one other virus, compared with 41.2% with HCoV-NL63 and 40.3% with RSV (P = 0.03 and P < 0.01, respectively). Children with HCoV-OC43 and HCoV-NL63 were older than children with RSV (median age, 19 vs. 10 months, P = 0.01). Lower respiratory tract infection (LRTI) was half as common in children with HCoV-OC43 (48.6%) and HCoV-NL63 (47.1%) as in children with RSV (82.3%) (both P < 0.01). After adjusting for age, chronic disease, LRTI, and co-detection of other viruses in a multiple logistic regression analysis, HCoV was associated with a shorter fever period and shorter hospitalization time than RSV. CONCLUSIONS HCoV-OC43 and HCoV-NL63 are common among hospitalized Norwegian children with RTI. Children with HCoV-OC43 and HCoV-NL63 have LRTI less frequently and may need a shorter hospital stay than children with RSV.


The potential Ebola-infected patient in the ambulatory care setting: preparing for the worst without compromising care.


title: Pulmonary Nodules in Patients With Nonpulmonary Cancer: Not Always Metastases.

text: INTRODUCTION The differential diagnosis of pulmonary nodules (PNs) includes metastases, lung cancers, infectious diseases, and scar tissue, among others. Because data regarding whether and when to perform a PN biopsy in patients with cancer are scarce, clinicians tend to assume that PNs are metastatic disease based solely on imaging. The current study evaluated the findings of PN biopsies in a population of patients with cancer and sought to determine the variables that correlated with higher odds of metastatic disease. PATIENTS AND METHODS We conducted a retrospective, single-institution study that included consecutive patients with nonpulmonary solid malignancies who underwent PN biopsy from January 2011 to December 2013. Imaging and clinical variables were analyzed by logistic regression to determine the correlation between such variables and the odds of metastatic disease. Patients with previously known metastatic disease or primary hematologic malignancies were excluded. RESULTS Two hundred twenty-eight patients were included in the study. Metastatic disease was found in 146 patients (64%), 60 patients (26.3%) were diagnosed with a second primary lung tumor, and 22 patients (9.6%) had no cancer on biopsy. On multivariate analysis, the presence of multiple PNs (> 5 mm) and cavitation/necrosis were the only variables associated with higher odds (P < .05) of metastatic disease. We registered six (2.6%) procedure complications demanding active interventions, and no procedure-related death occurred. CONCLUSION Multiple PNs (> 5 mm) and cavitation were the two characteristics associated with the highest chances of metastatic disease. Our findings demonstrate that PNs should not be assumed to be metastases without performing a biopsy. This assumption may lead to high rates of misdiagnosis. Tissue sampling is fundamental for accurately diagnosing patients with cancer.


title: COVID-19 and lung transplant patients.

text: COVID-19 is a novel respiratory disease leading to high rates of acute respiratory failure requiring hospital admission. It is unclear if specific patient populations such as lung transplant patients are at higher risk for COVID-19. Some reports suggest that transplant patients may not be at higher risk if proper social distancing and preventive measures are employed. Efforts to ensure the safety of wait-listed patients, transplant recipients, and healthcare workers are underway. Recommendations for the care of lung transplant patients during the COVID-19 pandemic are discussed and will likely change as the pandemic evolves.


title: A population mental health perspective on the impact of COVID-19.

text: The global pandemic of coronavirus disease 2019 (COVID-19) has resulted in massive societal, economic, and environmental impacts that have both short- and long-term mental health influences. This commentary serves to tie existing literature on mental health and COVID-19 to the clinical experiences of a psychologist working in the Canadian hospital sector. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Headaches Associated with Personal Protective Equipment - A Cross-sectional Study Amongst Frontline Healthcare Workers During COVID-19 (HAPPE Study).

text: BACKGROUND COVID-19 is an emerging infectious disease of pandemic proportions. Healthcare workers in Singapore working in high-risk areas were mandated to wear personal protective equipment (PPE) such as N95 face-mask and protective eyewear while attending to patients. OBJECTIVES We sought to determine the risk factors associated with the development of de novo PPE-associated headaches as well as the perceived impact of these headaches on their personal health and work performance. The impact of COVID-19 on pre-existing headache disorders was also investigated. METHODS This is a cross-sectional study amongst healthcare workers at our tertiary institution who were working in high-risk hospital areas during COVID-19. All respondents completed a self-administered questionnaire. RESULTS A total of 158 healthcare workers participated in the study. Majority [126/158 (77.8%)] were aged 21-35 years. Participants included nurses [102/158 (64.6%)], doctors [51/158 (32.3%)] and paramedical staff [5/158 (3.2%)]. Pre-existing primary headache diagnosis was present in about a third [46/158 (29.1%)] of respondents. Those based at the emergency department had higher average daily duration of combined PPE exposure compared to those working in isolation wards [7.0 (SD 2.2) vs 5.2 (SD 2.4) hours, p<0.0001] or medical ICU [7.0 (SD 2.2) vs 2.2 (SD 0.41) hours, p<0.0001]. Out of 158 respondents, 128 (81.0%) respondents developed de novo PPE-associated headaches. A pre-existing primary headache diagnosis (OR=4.20, 95% CI 1.48-15.40; p=0.030) and combined PPE usage for >4 hours per day (OR 3.91, 95% CI 1.35-11.31; p=0.012) were independently associated with de novo PPE-associated headaches. Since COVID-19 outbreak, 42/46 (91.3%) of respondents with pre-existing headache diagnosis either 'agreed' or 'strongly agreed' that the increased PPE usage had affected the control of their background headaches, which affected their level of work performance. CONCLUSION Most healthcare workers develop de novo PPE-associated headaches or exacerbation of their pre-existing headache disorders.


title: Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry.

text: The type II transmembrane protease TMPRSS2 activates the spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) on the cell surface following receptor binding during viral entry into cells. In the absence of TMPRSS2, SARS-CoV achieves cell entry via an endosomal pathway in which cathepsin L may play an important role, i.e., the activation of spike protein fusogenicity. This study shows that a commercial serine protease inhibitor (camostat) partially blocked infection by SARS-CoV and human coronavirus NL63 (HCoV-NL63) in HeLa cells expressing the receptor angiotensin-converting enzyme 2 (ACE2) and TMPRSS2. Simultaneous treatment of the cells with camostat and EST [(23,25)trans-epoxysuccinyl-L-leucylamindo-3-methylbutane ethyl ester], a cathepsin inhibitor, efficiently prevented both cell entry and the multistep growth of SARS-CoV in human Calu-3 airway epithelial cells. This efficient inhibition could be attributed to the dual blockade of entry from the cell surface and through the endosomal pathway. These observations suggest camostat as a candidate antiviral drug to prevent or depress TMPRSS2-dependent infection by SARS-CoV.


title: The significance of microthrombosis and fgl2 in no-reflow phenomenon of rats with acute myocardial ischemia/reperfusion.

text: No-reflow phenomenon due to cardiac microvascular dysfunction or disturbance aggravates clinic outcomes of a portion of patients with acute myocardial infarction undergoing percutaneous coronary intervention or thrombolytic therapy. Our working hypothesis was that cardiac microthrombosis would play an important role in the pathogenesis. We investigated that cardiac microthrombi were observed by Martius, Scarlet, Blue methocl (MSB) and Masson trichrome staining. Furthermore, we investigated the expression of fibrinogen-like protein 2 (fgl2) in rats with acute myocardial ischemia/reperfusion (MI/R) and its possible pathological and clinical significance. The fgl2 was highly expressed in myocardium of rats with acute MI/R and located at cardiac microvascular walls. We found that the expression of fgl2 in peripheral mononuclear cells of rats with acute MI/R significantly increased correspondingly with its cardiac expression. Expression of cardiac fgl2 was correlated with no-reflow size of rats with acute MI/R, which was detected and calculated by thioflavin S staining. No-reflow size was in line with cardiac diastolic dysfunction of rats with acute MI/R monitored by hemodynamics. Thus, microthrombosis is involved in cardiac microvascular dysfunction or disturbance of rats with acute MI/R as one cause, and fgl2 may emerge as a predictor of the occurrence of no-reflow phenomenon.


title: Evidence of (anti)metamorphic properties of modified graphitic surfaces obtained in real time at a single-molecule level.

text: Understanding protein unfolding on a surface is of vital importance in nanoscience, nanobiotechnology, and medicine. Surfaces that retain the native conformation of adsorbed proteins (antimetamorphic surfaces) represent one of the main strategies for creating biocompatible materials, which are in great demand in biotechnology. Though the influence of surfaces on protein conformation has been studied for decades, real-time investigations of protein conformational behavior on a surface obtained at the single-molecule or sub-molecular level are still lacking and remain a challenge. In this work, we apply time-lapse atomic force microscopy (AFM) in aqueous solution to visualize the conformational dynamics of individual model protein molecules (E.coli RNA polymerase, RNAP) adsorbed on modified highly oriented pyrolytic graphite (HOPG) surfaces. We quantitatively characterize the evolution of height and shape of individual RNAP molecules adsorbed on a HOPG surface modified with an oligoglycine-hydrocarbon graphite modifier (GM) during the unfolding process and determine the characteristic unfolding time as ∼7 min. Furthermore, we make a HOPG surface antimetamorphic by modifying it with a denatured RNAP protein layer. Our results provide direct evidence of GM-HOPG-induced RNAP unfolding at the single-molecule level and open new strategies for the development and investigation of antimetamorphic graphitic surfaces.


Innovations in Education in Response to COVID-19: Online Medication Commercials.


title: Pharmacokinetic bias analysis of an association between clinical thyroid disease and two perfluoroalkyl substances.

text: Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) has been associated with the occurrence of thyroid disease in some epidemiologic studies. We hypothesized that in a specific epidemiologic study based on the National Health and Nutrition Examination Survey, the association of clinical thyroid disease with serum concentration of PFOA and PFOS was due to reverse causality. Thyroid hormone affects glomerular filtration, which in turn affects excretion of PFOA and PFOS. We evaluated this by linking a model of thyroid disease status over the lifetime to a physiologically based pharmacokinetic model of PFOA and PFOS. Using Monte Carlo methods, we simulated the target study population and analyzed the data using multivariable logistic regression. The target and simulated populations were similar with respect to age, estimated glomerular filtration rate, serum concentrations of PFOA and PFOS, and prevalence of clinical thyroid disease. The analysis showed little or no evidence of bias from the hypothesized mechanism. The largest bias was for the fourth quartile of PFOA in females, with an odds ratio of 0.93 (95% CI, 0.90, 0.97). The reported odds ratio of clinical thyroid disease for this group was 1.63 (1.07, 2.47), and if it were corrected for the bias would have been 1.74 (1.14, 2.65). Our results suggest that little of the reported association in the target study was due to reverse causality.


title: Impact of mobile health applications on self-management in patients with type 2 diabetes mellitus: protocol of a systematic review.

text: INTRODUCTION The emergence of mobile health (mHealth) solutions, particularly mHealth applications (apps), has shown promise in self-management of chronic diseases including type 2 diabetes mellitus (T2DM). While majority of the previous systematic reviews have focused on the effectiveness of mHealth apps in improving treatment outcomes in patients with T2DM, there is a need to also understand how mHealth apps influence self-management of T2DM. This is crucial to ensure improvement in the design and use of mHealth apps for T2DM. This protocol describes how a systematic review will be conducted to determine in which way(s) mHealth apps might impact on self-management of T2DM. METHODS The following electronic databases will be searched from inception to April 2019: PubMed, MEDLINE, EMBASE, Global Health, PsycINFO, CINAHL, The Cochrane Central Register of Controlled Trials, Scopus, Web of Science, ProQuest Dissertations & Theses Global, Health Management Information Consortium database, Google Scholar and ClinicalTrials.gov. The Cochrane risk of bias tool will be used to assess methodological quality. The primary outcome measures to be assessed will be 'change in blood glucose'. The secondary outcomes measures will be 'changes in cardiovascular risk markers' (including blood pressure, body mass index and blood lipids), and self-management practices. Others will include: health-related quality of life, economic data, social support, harms (eg, death or complications leading to hospital admissions or emergency unit attendances), death from any cause, anxiety or depression and adverse events (eg, hypoglycaemic episodes). ETHICS AND DISSEMINATION This study will not involve the collection of primary data and will not require ethical approval. The review will be published in a peer-reviewed journal and a one-page summary of the findings will be shared with relevant organisations. Presentation of findings will be made at appropriate conferences. TRIAL REGISTRATION NUMBER CRD42017071106.


title: Learning brain aneurysm microsurgical skills in a human placenta model: predictive validity.

text: OBJECTIVE Surgery for brain aneurysms is technically demanding. In recent years, the process to learn the technical skills necessary for these challenging procedures has been affected by a decrease in the number of surgical cases available and progressive restrictions on resident training hours. To overcome these limitations, surgical simulators such as cadaver heads and human placenta models have been developed. However, the effectiveness of these models in improving technical skills is unknown. This study assessed concurrent and predictive validity of brain aneurysm surgery simulation in a human placenta model compared with a "live" human brain cadaveric model. METHODS Two human cadaver heads and 30 human placentas were used. Twelve neurosurgeons participated in the concurrent validity part of this study, each operating on 1 human cadaver head aneurysm model and 1 human placenta model. Simulators were evaluated regarding their ability to simulate different surgical steps encountered during real surgery. The time to complete the entire aneurysm task in each simulator was analyzed. The predictive validity component of the study involved 9 neurosurgical residents divided into 3 groups to perform simulation exercises, each lasting 6 weeks. The training for the 3 groups consisted of educational video only (3 residents), human cadaver only (3 residents), and human placenta only (3 residents). All residents had equivalent microsurgical experience with superficial brain tumor surgery. After completing their practice training, residents in each of the 3 simulation groups performed surgery for an unruptured middle cerebral artery (MCA) aneurysm, and their performance was assessed by an experienced vascular neurosurgeon who watched the operative videos. RESULTS All human cadaver heads and human placentas were suitable to simulate brain aneurysm surgery. In the concurrent validity portion of the experiment, the placenta model required a longer time (p < 0.001) than cadavers to complete the task. The placenta model was considered more effective than the cadaver model in simulating sylvian fissure splitting, bipolar coagulation of oozing microvessels, and aneurysm neck and dome dissection. Both models were equally effective in simulating neck aneurysm clipping, while the cadaver model was considered superior for simulation of intraoperative rupture and for reproduction of real anatomy during simulation. In the predictive validity portion of the experiment, residents were evaluated for 4 tasks: sylvian fissure dissection, microvessel bipolar coagulation, aneurysm dissection, and aneurysm clipping. Residents trained in the human placenta simulator consistently had the highest overall performance scores when compared with those who had trained in the cadaver model and those who had simply watched operative videos (p < 0.001). CONCLUSIONS The human placenta biological simulator provides excellent simulation for some critical tasks of aneurysm surgery such as splitting of the sylvian fissure, dissection of the aneurysm neck and dome, and bipolar coagulation of surrounding microvessels. When performing surgery for an unruptured MCA aneurysm, residents who had trained in the human placenta model performed better than residents trained with other simulation scenarios/models. In this age of reduced exposure to aneurysm surgery and restrictions on resident working hours, the placenta model is a valid simulation for microneurosurgery with striking similarities with real surgery.


title: Early warning score predicts acute mortality in stroke patients.

text: OBJECTIVES Clinical deterioration and death among patients with acute stroke are often preceded by detrimental changes in physiological parameters. Systematic and effective tools to identify patients at risk of deterioration early enough to intervene are therefore needed. The aim of the study was to investigate whether the aggregate weighted track and trigger system early warning score (EWS) can be used as a simple observational tool to identify patients at risk and predict mortality in a population of patients with acute stroke. MATERIALS AND METHODS Patients admitted with acute stroke at the Copenhagen University Hospital, Nordsjaellands Hospital, Denmark, from May to September 2012 were enrolled in a retrospective cohort study (n = 274). Vital signs were measured immediately after admission and consistently during the hospitalization period. Based on the vital signs, a single composite EWS was calculated. Death within 30 days was used as outcome. Area under the receiver operating characteristics curve (AUROC) and a Kaplan-Meier curve were computed to examine the prognostic validity of EWS. RESULTS A total of 24 patients (8.8%) died within 30 days. The prognostic performance was high for both the EWS at admission (AUROC 0.856; 95% CI 0.760-0.951; P-value < 0.001) and the maximal EWS measured (AUROC 0.949; 95% CI 0.919-0.980; P-value < 0.001). Mortality rates were lowest for admission EWS 0-1 (2%) and highest for admission EWS ≥ 5 (63%). CONCLUSIONS Early warning score is a simple and valid tool for identifying patients at risk of dying after acute stroke. Readily available physiological parameters are converted to a single score, which can guide both nurses and physicians in clinical decision making and resource allocation.


title: Selection of phage-displayed human antibody fragments specific for CD1b presenting the Mycobacterium tuberculosis glycolipid Ac2SGL.

text: OBJECTIVE/BACKGROUND The development of new tools capable of targeting Mycobacterium tuberculosis (Mtb)-infected cells have potential applications in diagnosis, treatment, and prevention of tuberculosis. In Mtb-infected cells, CD1b molecules present Mtb lipids to the immune system (Mtb lipid-CD1b complexes). Because of the lack of CD1b polymorphism, specific Mtb lipid-CD1b complexes could be considered as universal Mtb infection markers. 2-Stearoyl-3-hydroxyphthioceranoyl-2'-sulfate-α-α'-d-trehalose (Ac2SGL) is specific for Mtb, and is not present in other mycobacterial species. The CD1b-Ac2SGL complexes are expressed on the surface of human cells infected with Mtb. The aim of this study was to generate ligands capable of binding these CD1b-Ac2SGL complexes. METHODS A synthetic human scFv phage antibody library was used to select phage-displayed antibody fragments that recognized CD1b-Ac2SGL using CD1b-transfected THP-1 cells loaded with Ac2SGL. RESULTS One clone, D11-a single, light-variable domain (kappa) antibody (dAbκ11)-showed high relative binding to the Ac2SGL-CD1b complex. CONCLUSION A ligand recognizing the Ac2SGL-CD1b complex was obtained, which is a potential candidate to be further tested for diagnostic and therapeutic applications.


NAFLD - sounding the alarm on a silent epidemic.


Mounting clues suggest the coronavirus might trigger diabetes.