title: EML4-ALK fusion variant V3 is a high-risk feature conferring accelerated metastatic spread, early treatment failure and worse overall survival in ALK+ non-small cell lung cancer.

text: In order to identify anaplastic lymphoma kinase-driven non-small cell lung cancer (ALK+ NSCLC) patients with a worse outcome, who might require alternative therapeutic approaches, we retrospectively analyzed all stage IV cases treated at our institutions with one of the main echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion variants V1, V2 and V3 as detected by next-generation sequencing or reverse transcription-polymerase chain reaction (n = 67). Progression under tyrosine kinase inhibitor (TKI) treatment was evaluated both according to Response Evaluation Criteria in Solid Tumors (RECIST) and by the need to change systemic therapy. EML4-ALK fusion variants V1, V2 and V3 were found in 39%, 10% and 51% of cases, respectively. Patients with V3-driven tumors had more metastatic sites at diagnosis than cases with the V1 and V2 variants (mean 3.3 vs. 1.9 and 1.6, p = 0.005), which suggests increased disease aggressiveness. Furthermore, V3-positive status was associated with earlier failure after treatment with first and second-generation ALK TKI (median progression-free survival [PFS] by RECIST in the first line 7.3 vs. 39.3 months, p = 0.01), platinum-based combination chemotherapy (median PFS 5.4 vs. 15.2 months for the first line, p = 0.008) and cerebral radiotherapy (median brain PFS 6.1 months vs. not reached for cerebral radiotherapy during first-line treatment, p = 0.028), and with inferior overall survival (39.8 vs. 59.6 months in median, p = 0.017). Thus, EML4-ALK fusion variant V3 is a high-risk feature for ALK+ NSCLC. Determination of V3 status should be considered as part of the initial workup for this entity in order to select patients for more aggressive surveillance and treatment strategies.


title: Coronavirus nsp10/nsp16 Methyltransferase Can Be Targeted by nsp10-Derived Peptide In Vitro and In Vivo To Reduce Replication and Pathogenesis.

text: UNLABELLED The 5' cap structures of eukaryotic mRNAs are important for RNA stability and protein translation. Many viruses that replicate in the cytoplasm of eukaryotes have evolved 2'-O-methyltransferases (2'-O-MTase) to autonomously modify their mRNAs and carry a cap-1 structure (m7GpppNm) at the 5' end, thereby facilitating viral replication and escaping innate immune recognition in host cells. Previous studies showed that the 2'-O-MTase activity of severe acute respiratory syndrome coronavirus (SARS-CoV) nonstructural protein 16 (nsp16) needs to be activated by nsp10, whereas nsp16 of feline coronavirus (FCoV) alone possesses 2'-O-MTase activity (E. Decroly et al., J Virol 82:8071-8084, 2008, http://dx.doi.org/10.1128/JVI.00407-08; M. Bouvet et al., PLoS Pathog 6:e1000863, 2010, http://dx.doi.org/10.1371/journal.ppat.1000863; E. Decroly et al., PLoS Pathog 7:e1002059, 2011, http://dx.doi.org/10.1371/journal.ppat.1002059; Y. Chen et al., PLoS Pathog 7:e1002294, 2011, http://dx.doi.org/10.1371/journal.ppat.1002294) . In this study, we demonstrate that stimulation of nsp16 2'-O-MTase activity by nsp10 is a universal and conserved mechanism in coronaviruses, including FCoV, and that nsp10 is functionally interchangeable in the stimulation of nsp16 of different coronaviruses. Based on our current and previous studies, we designed a peptide (TP29) from the sequence of the interaction interface of mouse hepatitis virus (MHV) nsp10 and demonstrated that the peptide inhibits the 2'-O-MTase activity of different coronaviruses in biochemical assays and the viral replication in MHV infection and SARS-CoV replicon models. Interestingly, the peptide TP29 exerted robust inhibitory effects in vivo in MHV-infected mice by impairing MHV virulence and pathogenesis through suppressing virus replication and enhancing type I interferon production at an early stage of infection. Therefore, as a proof of principle, the current results indicate that coronavirus 2'-O-MTase activity can be targeted in vitro and in vivo. IMPORTANCE Coronaviruses are important pathogens of animals and human with high zoonotic potential. SARS-CoV encodes the 2'-O-MTase that is composed of the catalytic subunit nsp16 and the stimulatory subunit nsp10 and plays an important role in virus genome replication and evasion from innate immunity. Our current results demonstrate that stimulation of nsp16 2'-O-MTase activity by nsp10 is a common mechanism for coronaviruses, and nsp10 is functionally interchangeable in the stimulation of nsp16 among different coronaviruses, which underlies the rationale for developing inhibitory peptides. We demonstrate that a peptide derived from the nsp16-interacting domain of MHV nsp10 could inhibit 2'-O-MTase activity of different coronaviruses in vitro and viral replication of MHV and SARS-CoV replicon in cell culture, and it could strongly inhibit virus replication and pathogenesis in MHV-infected mice. This work makes it possible to develop broad-spectrum peptide inhibitors by targeting the nsp16/nsp10 2'-O-MTase of coronaviruses.


COVID-19 pandemic: palliative care for elderly and frail patients at home and in residential and nursing homes.


title: Treatment of experimental aneurysms with a new liquid embolic agent and a retrievable stent: proof of concept and feasibility study.

text: BACKGROUND Occlusion of canine bifurcation and sidewall aneurysms was undertaken with a new liquid embolic agent (PHIL 35) assisted by a high-density partially retrievable stent (FRED) with preservation of the carotid artery. METHODS Three dogs were used as acute preparations for development of the technique and two were used for chronic studies lasting 90 days. In one animal we intentionally did not completely fill the aneurysm to determine the long-term results of incomplete treatment. The degree of occlusion, carotid artery compromise, and dislodgement and/or migration of embolic material in treated aneurysms were assessed. RESULTS All aneurysms planned for complete obliteration were totally occluded successfully. By design, we partially occluded one aneurysm. In this aneurysm, angiography performed at 30 days revealed less filling, but at 90 days it had persistent small residual filling. We did not detect any distal embolization during the injection and no angiographic occlusions, change in configuration, or delayed migration of the embolic material were found. In the inspected stent, no foreign material was noted. In four animals we successfully removed the stent with preservation of the integrity of the carotid artery. In the fifth we intentionally left both stents deployed. CONCLUSIONS We have developed a new treatment for cerebral aneurysms using a combination of a retrievable stent and a new liquid embolic agent.


title: Appendectomy in Germany-an analysis of a nationwide survey 2011/2012.

text: INTRODUCTION Although appendectomies are frequently performed and new procedural techniques have emerged, no nationwide analysis exists after the cessation of the German quality control in 2004. METHODS One thousand eight hundred seventy surgical hospitals in Germany were asked to answer questions anonymously concerning the size of the department, applied procedural techniques, various technical details, as well as the approach to the intraoperative finding of an inconspicuous appendix. RESULTS We received 643 questionnaires (34.4 %) for evaluation. Almost all hospitals (95.5 %) offer laparoscopic appendectomy (LA), 15.4 % offer single-port (SPA), and 2.2 % (hybrid-) NOTES technique (NA). LA is the standard procedure in 85.2 % of male and in 89.1 % for female patients. In an open procedure (OA), the appendix and mesoappendix are mostly ligated (93.8 and 91.5 %). A Veress needle and open access are employed equally for LA. In 66.6 % of LA, the appendix is divided using an Endo-GIA, the mesoappendix in 45.5 % with bipolar coagulation. Almost half of the hospitals routinely flush the site in OA and LA. In open surgery with an inconspicuous appendix but a pathological finding elsewhere in the abdomen, it is resected "en principe" in 64.7 % and in the absence of any pathological finding in 91.2 %. For laparoscopic procedures, the numbers are 54.8 and 88.4 %. CONCLUSIONS Most German hospitals perform appendectomies laparoscopically regardless of patients' gender. Usage of an Endo-GIA is widely established. SPA has not gained much acceptance, nor is NA widely used yet. In the absence of any pathological findings in particular, the macroscopically inconspicuous appendix results in an appendectomy "en principe" in most German hospitals.


title: Prognostic value of perioperative near-infrared spectroscopy during neonatal and infant congenital heart surgery for adverse in-hospital clinical events.

text: BACKGROUND Perioperative monitoring with multisite near-infrared spectroscopy (NIRS) for congenital cardiac surgery with cardiopulmonary bypass may aid in predicting adverse clinical outcomes. METHODS Forty-one consecutive neonates and infants undergoing bypass were monitored with right + left cerebral and renal NIRS. Near-infrared spectroscopy and lactate were measured at 20 time points, from baseline 1 day preoperatively, during bypass and modified ultrafiltration (MUF; 10 minutes), until 24 hours postoperatively. Adverse events were extracorporeal membrane oxygenation (ECMO)/death, prolonged intensive care unit (ICU) or length of hospital stay. RESULTS Perioperative mean renal NIRS remained higher than baseline (n = 41) as did cerebral NIRS in all undergoing biventricular repair. During bypass (n = 41), mean right and left cerebral NIRS were equal. During MUF, cerebral and renal NIRS values increased (P < .001). Cerebral NIRS and lactate inversely correlated during the first six postoperative hours. Extracorporeal membrane oxygenation /death occurred in four patients, correlating with cerebral and renal NIRS below 45% (P = .030) and 40% (P = .019) at anytime, respectively, and with mean lactate levels >9.3 mmol/L in the first postoperative 24 hours (P < .001). Among survivors, renal NIRS below 30% at any time predicted a longer ICU stay. CONCLUSIONS At bypass conclusion, 10 minutes of MUF does not adversely affect cerebral or renal NIRS. Left and right cerebral NIRS are equal, so that biparietal cerebral NIRS monitoring is probably not warranted. Perioperative cerebral and renal NIRS readings, respectively, below 45% and 40% correlate with ECMO/death and renal NIRS below 30% with prolonged ICU stay. Cerebral NIRS and lactate levels showed a strong inverse correlation during the first six postoperative hours.


title: Season of birth and primary central nervous system tumors: a systematic review of the literature with critical appraisal of underlying mechanisms.

text: PURPOSE Season of birth has been considered a proxy of seasonally varying exposures around perinatal period, potentially implicated in the etiology of several health outcomes, including malignancies. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we have systematically reviewed published literature on the association of birth seasonality with risk of central nervous system tumors in children and adults. RESULTS Seventeen eligible studies using various methodologies were identified, encompassing 20,523 cases. Eight of 10 studies in children versus four of eight in adults showed some statistically significant associations between birth seasonality and central nervous system tumor or tumor subtype occurrence, pointing to a clustering of births mostly in fall and winter months, albeit no consistent pattern was identified by histologic subtype. A plethora of perinatal factors might underlie or confound the associations, such as variations in birth weight, maternal diet during pregnancy, perinatal vitamin D levels, pesticides, infectious agents, immune system maturity, and epigenetic modifications. CONCLUSIONS Inherent methodological weaknesses of to-date published individual investigations, including mainly underpowered size to explore the hypothesis by histological subtype, call for more elegant concerted actions using primary data of large datasets taking also into account the interplay between the potential underlying etiologic factors.


title: Genetic and Pathologic Characterization of a Novel Recombinant TC07-2-Type Avian Infectious Bronchitis Virus.

text: Avian infectious bronchitis viruses (IBVs) with the TC07-2 genotype have spread rapidly in East Asia since they were first reported in China in 2007. In 2015, an IBV with the TC07-2 genotype (designated KrD1515) was isolated from layer chickens with severe respiratory symptoms in Korea. In the present study, the full-length open reading frames of the spike (S) and nucleocapsid (N) genes of the virus were sequenced and analyzed. S1 gene phylogenetic analysis revealed that the KrD1515 virus clustered with viruses with the TC07-2 genotype, whereas N gene phylogenetic analysis revealed that the KrD1515 virus clustered with Korean IBVs, but not with Chinese TC07-2 IBV. When 7-day-old specific-pathogen-free chickens were inoculated with the KrD1515 virus, they developed severe respiratory symptoms and tracheal lesions. However, there were no other clinical symptoms or pathologic lesions in other tissues. The virus was shed from the trachea for at least a week and from the cloaca for only a day. Our findings suggest that the KrD1515 virus is a recombinant virus between a Chinese TC07-2 IBV and a non-TC07-2 Korean IBV and engages in respiratory tropism in chickens.


title: Generation of cubic membranes by controlled homotypic interaction of membrane proteins in the endoplasmic reticulum.

text: Cell membranes predominantly consist of lamellar lipid bilayers. When studied in vitro, however, many membrane lipids can exhibit non-lamellar morphologies, often with cubic symmetries. An open issue is how lipid polymorphisms influence organelle and cell shape. Here, we used controlled dimerization of artificial membrane proteins in mammalian tissue culture cells to induce an expansion of the endoplasmic reticulum (ER) with cubic symmetry. Although this observation emphasizes ER architectural plasticity, we found that the changed ER membrane became sequestered into large autophagic vacuoles, positive for the autophagy protein LC3. Autophagy may be targeting irregular membrane shapes and/or aggregated protein. We suggest that membrane morphology can be controlled in cells.


Endovascular management of a giant symptomatic gluteal artery aneurysm with selective arterial embolization.


title: Development of a standardized laparoscopic caecum resection model to simulate laparoscopic appendectomy in rats.

text: BACKGROUND Laparoscopic appendectomy (LA) has become one of the most common surgical procedures to date. To improve and standardize this technique further, cost-effective and reliable animal models are needed. METHODS In a pilot study, 30 Wistar rats underwent laparoscopic caecum resection (as rats do not have an appendix vermiformis), to optimize the instrumental and surgical parameters. A subsequent test study was performed in another 30 rats to compare three different techniques for caecum resection and bowel closure. RESULTS Bipolar coagulation led to an insufficiency of caecal stump closure in all operated rats (Group 1, n = 10). Endoloop ligation followed by bipolar coagulation and resection (Group 2, n = 10) or resection with a LigaSure™ device (Group 3, n = 10) resulted in sufficient caecal stump closure. CONCLUSIONS We developed a LA model enabling us to compare three different caecum resection techniques in rats. In conclusion, only endoloop closure followed by bipolar coagulation proved to be a secure and cost-effective surgical approach.


The Ebola emergency--immediate action, ongoing strategy.


title: Clinical features, pathogenesis and immunobiology of severe acute respiratory syndrome.

text: PURPOSE OF REVIEW Severe acute respiratory syndrome coronavirus is a novel virus responsible for the major pandemic in 2003, and it re-emerged in China in late 2003 and 2004 following resumption of wild animal trading activities. Over the past few years, research work has looked into factors that may lead to super-spreading events, clinical/laboratory parameters that may differentiate severe acute respiratory syndrome from other causes of community-acquired pneumonia, the origin of severe acute respiratory syndrome, reservoir host distribution and transmission routes. A better understanding of these issues may help prevent and control future outbreaks of severe acute respiratory syndrome. RECENT FINDINGS Bats are natural reservoirs of severe acute respiratory syndrome like coronaviruses. The human and civet isolates of severe acute respiratory syndrome coronavirus nestle phylogenetically within the spectrum of severe acute respiratory syndrome like coronaviruses. Severe acute respiratory syndrome has the potential of being converted from droplet to airborne transmission. When evaluating epidemiologically high-risk patients with community-acquired pneumonia and no immediate alternative diagnosis, a low absolute neutrophil count on presentation, along with poor responses after 72 h of antibiotic treatment, may raise the index of suspicion for severe acute respiratory syndrome. SUMMARY The presence of severe acute respiratory syndrome like coronaviruses in horseshoe bats raises the possible role of bats in previous and potentially future severe acute respiratory syndrome outbreaks in human. Healthcare workers should take adequate respiratory protection in addition to strict contact and droplet precautions when managing patients with severe acute respiratory syndrome.


Home Care and Use of Telehealth Amidst the COVID-19 Pandemic.


title: A risk balancing act - tourism competition using health leverage in the COVID-19 era.

text: The world is currently in the throes of the COVID-19 pandemic which has halted the tourism sector and created an unprecedented global economic crisis. This paper will outline economics pertaining to COVID-19 lockdown, recovery and the inevitable competition that will occur between countries for tourists who will be scarcer and therefore more valuable. Countries are competing with a variety of incentives in order to lure visitors. However, persistent first waves that extend into July will put off tourists, further reducing tourism revenues and accelerate job losses and bankruptcies in affected countries. The example of Sweden's response to COVID-19 in this regard will be described. Countries that have COVID-19 relatively under control but experience second waves will also manifest negative tourism effects. Governments and public health must act in unison so as to exit lockdown as speedily and as safely as feasible, with COVID-19 rises that are as low and brief as possible in order to better compete in the tourism sector with other countries. Websites are already online comparing not only safety for travellers vis-à-vis COVID-19 but also the incentives offered by different countries in their attempts to woo tourists in this difficult market.


title: Esophageal epiphrenic diverticulum associated with diffuse esophageal spasm.

text: INTRODUCTION Esophageal diverticulum, a relatively rare condition, has been considered to be associated with motor abnormalities such as conditions that cause a lack of coordination between the distal esophagus and lower esophageal sphincter. PRESENTATION OF CASE We herein report a case of esophageal epiphrenic diverticulum associated with diffuse esophageal spasm. A 73-year-old woman presented with dysphagia and regurgitation. Imaging examinations revealed a right-sided esophageal diverticulum located about 10cm above the esophagogastric junction. High-resolution manometry revealed normal esophageal motility. However, 24-h pH monitoring revealed continuous acidity due to pooling of residue in the diverticulum. An esophageal epiphrenic diverticulum was diagnosed and resected thoracoscopically. Her dysphagia recurred 2 years later. High-resolution manometry revealed diffuse esophageal spasm. DISCUSSION The diverticulum in the present case was considered to have been associated with diffuse esophageal spasm. The motility disorder was likely not identified at the first evaluation. CONCLUSION In this case, the patient's symptoms spontaneously resolved without any treatment; however, longer-term follow-up is needed.


title: Colectomies in children with inflammatory bowel disease: a national referral centre experience.

text: OBJECTIVES Few studies have reported on the utility and efficacy of laparoscopic colectomy in the paediatric population. We aim to compare the characteristics and outcomes of children with inflammatory bowel disease (IBD) who underwent open vs laparoscopic treatment at our centre. METHODS A 10-year retrospective review was performed. Collected data included demographics, indication for surgery, operative characteristics, histopathology results, post-operative course and peri-operative complications. RESULTS A total of 58 patients underwent subtotal colectomy for IBD, with 38 laparoscopic procedures. The cohort included 33 males and 25 females with a mean age at surgery of 12.9 ± 3.3 years. The pre-operative diagnosis was ulcerative colitis in n = 41, Crohn's disease in n = 5 and indeterminate colitis in n = 11. There was an 84.2% concordance between the pre-operative and the post-operative histological diagnoses. Overall, 34 (58.6%) patients had complications, of which 19 (32.7%) patients required return to theatre. The complication rate was significantly smaller for laparoscopic compared to open procedures (42.1% vs 75%) as well as for elective compared with emergency colectomies (38.4% vs 75%). Four patients (10.5%) required conversion to open approach. CONCLUSIONS Laparoscopic approach is feasible and safe in most paediatric patients with IBD and has a lower complication rate and better recovery than open procedures, especially when performed in an elective setting.


title: Adaptive support ventilation: an appropriate mechanical ventilation strategy for acute respiratory distress syndrome?

text: BACKGROUND Adaptive support ventilation (ASV) allows the clinician to set a maximum plateau pressure (PP) and automatically adjusts tidal volume to keep PP below the set maximum. METHODS ASV was compared to a fixed tidal volume of 6 ml/kg. ASV determined the respiratory rate and tidal volume based on its algorithms. Maximum airway pressure limit was 28 cm H2O in ASV. Six sets of lung mechanics were simulated for two ideal body weights: 60 kg, Group I; 80 kg, Group II. Positive end expiratory pressure was 8, 12, and 16 cm H2O, and target minute volume 120%, 150%, and 200% of predicted minute volume. RESULTS ASV "sacrificed" tidal volume and minute ventilation to maintain PP in 9 (17%) of 54 scenarios in Group I and 20 (37%) of 54 scenarios in Group II. In Group I, the number of scenarios with PP of 28 cm H2O or more was 14 for ASV (26%) and 19 for 6 ml/kg (35%). In these scenarios, mean PP were ASV 28.8 +/- 0.86 cm H2O (min 28, max 30.3) and 6 ml/kg 33.01 +/- 3.48 cm H2O (min 28, max 37.8) (P = 0.000). In group II, the number of scenarios PP of 28 cm H2O or more was 10 for ASV (19%) and 21 for 6 ml/kg (39%). In these cases, mean PP values were ASV 28.78 +/- 0.54 cm H2O (min 28, max 29.6) and 6 ml/kg 32.66 +/- 3.37 cm H2O (min 28.2, max 38.2) (P = 0.000). CONCLUSION In a lung model with varying mechanics, ASV is better able to prevent the potential damaging effects of excessive PP (greater than 28 cm H2O) than a fixed tidal volume of 6 ml/kg by automatically adjusting airway pressure, resulting in a decreased tidal volume.


title: Circular economy and the matter of integrated resources.

text: A circular economy offers solutions for global sustainability challenges through the transition from the linear take-make-use-dispose economy to a better organisation of resources. However, realising a circular economy has ran into various biophysical constraints. Circular economy implementation is shaped by the Ellen MacArthur Foundation's butterfly diagram that depicts 'biological' and 'technical' flows as separate cycles, subsequently interpreted as organic materials circulating in open loop systems via the environment and inorganic materials circulating in closed loop systems within society. Conversely, in our view, resource flows often contain tightly bound combinations of organic and inorganic materials either due to their natural composition or due to their technical design. Building on this observation, a new diagram is proposed that broadens the scope of the circular economy to cover extractive sectors and the return of materials from anthropogenic use to natural reserves, thereby reshaping the conceptual space within which solutions such as effective zero-waste-residue technologies, business models, and policies can be developed for the optimal management of integrated resources from a whole-system perspective. The diagram offers a realistic outlook on the biophysical limitations of circularity and endeavours to inspire discussion that supports the transition towards a sustainable circular economy.


title: Impact of Human Disasters and COVID-19 Pandemic on Mental Health: Potential of Digital Psychiatry.

text: Deep emotional traumas in societies overwhelmed by large-scale human disasters, like, global pandemic diseases, natural disasters, man-made tragedies, war conflicts, social crises, etc., can cause massive stress-related disorders. Motivated by the ongoing global coronavirus pandemic, the article provides an overview of scientific evidence regarding adverse impact of diverse human disasters on mental health in afflicted groups and societies. Following this broader context, psychosocial impact of COVID-19 as a specific global human disaster is presented, with an emphasis on disturbing mental health aspects of the ongoing pandemic. Limited resources of mental health services in a number of countries around the world are illustrated, which will be further stretched by the forthcoming increase in demand for mental health services due to the global COVID-19 pandemic. Mental health challenges are particularly important for the Republic of Croatia in the current situation, due to disturbing stress of the 2020 Zagreb earthquake and the high pre-pandemic prevalence of chronic Homeland-War-related posttraumatic stress disorders. Comprehensive approach based on digital psychiatry is proposed to address the lack of access to psychiatric services, which includes artificial intelligence, telepsychiatry and an array of new technologies, like internet-based computer-aided mental health tools and services. These tools and means should be utilized as an important part of the whole package of measures to mitigate negative mental health effects of the global coronavirus pandemic. Our scientific and engineering experiences in the design and development of digital tools and means in mitigation of stress-related disorders and assessment of stress resilience are presented. Croatian initiative on enhancement of interdisciplinary research of psychiatrists, psychologists and computer scientists on the national and EU level is important in addressing pressing mental health concerns related to the ongoing pandemic and similar human disasters.


Dealing With the CARDS of COVID-19.


title: Biannual birth pulses allow filoviruses to persist in bat populations.

text: Filoviruses Ebolavirus (EBOV) and Marburgvirus (MARV) cause haemorrhagic fevers with high mortality rates, posing significant threats to public health. To understand transmission into human populations, filovirus dynamics within reservoir host populations must be understood. Studies have directly linked filoviruses to bats, but the mechanisms allowing viral persistence within bat populations are poorly understood. Theory suggests seasonal birthing may decrease the probability of pathogen persistence within populations, but data suggest MARV may persist within colonies of seasonally breeding Egyptian fruit bats, Rousettus aegyptiacus. I synthesize available filovirus and bat data in a stochastic compartmental model to explore fundamental questions relating to filovirus ecology: can filoviruses persist within isolated bat colonies; do critical community sizes exist; and how do host-pathogen relationships affect spillover transmission potential? Synchronous annual breeding and shorter incubation periods did not allow filovirus persistence, whereas bi-annual breeding and longer incubation periods, such as reported for Egyptian fruit bats and EBOV in experimental studies, allowed persistence in colony sizes often found in nature. Serological data support the findings, with bats from species with two annual birth pulses more likely to be seropositive (odds ratio (OR) 4.4, 95% confidence interval (CI) 2.5-8.7) than those with one, suggesting that biannual birthing is necessary for filovirus persistence.


title: Emerging indications of endoscopic radiofrequency ablation.

text: INTRODUCTION Radiofrequency ablation (RFA) is a well-validated treatment of dysplastic Barrett's esophagus. Other indications of endoscopic RFA are under evaluation. RESULTS Four prospective studies (total 69 patients) have shown that RFA achieved complete remission of early esophageal squamous intra-epithelial neoplasia at a rate of 80%, but with a substantial risk of stricture. In the setting of gastric antral vascular ectasia, two prospective monocenter studies, and a retrospective multicenter study, (total 51 patients), suggest that RFA is efficacious in terms of reducing transfusion dependency. In the setting of chronic hemorrhagic radiation proctopathy, a prospective monocenter study and a retrospective multicenter study (total 56 patients) suggest that RFA is an efficient treatment. A retrospective comparative study (64 patients) suggests that RFA improves stents patency in malignant biliary strictures. CONCLUSIONS Endoscopic RFA is an upcoming treatment modality in early esophageal squamous intra-epithelial neoplasia, as well as in gastric, rectal, and biliary diseases.


title: Antiviral Compounds Against Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus.

text: Porcine epidemic diarrhea (PED) is a severe diarrhea disease in swine that is caused by porcine epidemic diarrhea virus (PEDV). Nucleocapsid (N) protein is the RNA-binding protein of PEDV, which plays an important role for virus life cycle. The aim of this research was to screen and characterize the compounds that could inhibit the activity of PEDV N protein. The gene encoding PEDV N protein obtained from PEDV Thai isolate was cloned and expressed in E. coli. Its amino acid sequence was employed to generate the three dimensional structure by homology modeling. There were 1,286 compounds of FDA-approved drug database that could virtually bind to the RNA-binding region of N protein. Three compounds, trichlormethiazide, D-(+) biotin, and glutathione successfully bound to the N protein, in vitro, with the IC50 at 8.754 mg/mL, 0.925 mg/mL, and 2.722 mg/mL. Antiviral activity in PEDV-infected Vero cells demonstrated that the effective concentration of trichlormethiazide, D-(+) biotin, and glutathione in inhibiting PEDV replication were 0.094, 0.094 and 1.5 mg/mL. This study demonstrated a strategy applied for discovery of antiviral agents capable of inhibiting PEDV N protein and PEDV replication. The compounds identified here exhibited a potential use as therapeutic agents for controlling PEDV infection.


title: Intraoperative fluorescence-based enhanced reality laparoscopic real-time imaging to assess bowel perfusion at the anastomotic site in an experimental model.

text: BACKGROUND Fluorescence videography is a promising technique for assessing bowel perfusion. Fluorescence-based enhanced reality (FLER) is a novel concept, in which a dynamic perfusion cartogram, generated by computer analysis, is superimposed on to real-time laparoscopic images. The aim of this experimental study was to assess the accuracy of FLER in detecting differences in perfusion in a small bowel resection-anastomosis model. METHODS A small bowel ischaemic segment was created laparoscopically in 13 pigs. Animals were allocated to having anastomoses performed at either low perfusion (25 per cent; n = 7) or high perfusion (75 per cent; n = 6), as determined by FLER analysis. Capillary lactate levels were measured in blood samples obtained by serosal puncturing in the ischaemic area, resection lines and vascularized areas. Pathological inflammation scoring of the anastomosis was carried out. RESULTS Lactate levels in the ischaemic area (mean(s.d.) 5·6(2·8) mmol/l) were higher than those in resection lines at 25 per cent perfusion (3·7(1·7) mmol/l; P = 0·010) and 75 per cent perfusion (2·9(1·3) mmol/l; P < 0·001), and higher than levels in vascular zones (2·5(1·0) mmol/l; P < 0·001). Lactate levels in resection lines with 75 per cent perfusion were lower than those in lines with 25 per cent perfusion (P < 0·001), and similar to those in vascular zones (P = 0·188). Levels at resection lines with 25 per cent perfusion were higher than those in vascular zones (P = 0·001). Mean(s.d.) global inflammation scores were higher in the 25 per cent perfusion group compared with the 75 per cent perfusion group for mucosa/submucosa (2·1(0·4) versus 1·2(0·4); P = 0·003) and serosa (1·8(0·4) versus 0·8(0·8); P = 0·014). A ratio of preanastomotic lactate levels in the ischaemic area relative to the resection lines of 2 or less was predictive of a more severe inflammation score. CONCLUSION In an experimental model, FLER appeared accurate in discriminating bowel perfusion levels. Surgical relevance Clinical assessment has limited accuracy in evaluating bowel perfusion before anastomosis. Fluorescence videography estimates intestinal perfusion based on the fluorescence intensity of injected fluorophores, which is proportional to bowel vascularization. However, evaluation of fluorescence intensity remains a static and subjective measure. Fluorescence-based enhanced reality (FLER) is a dynamic fluorescence videography technique integrating near-infrared endoscopy and specific software. The software generates a virtual perfusion cartogram based on time to peak fluorescence, which can be superimposed on to real-time laparoscopic images. This experimental study demonstrates the accuracy of FLER in detecting differences in bowel perfusion in a survival model of laparoscopic small bowel resection-anastomosis, based on biochemical and histopathological data. It is concluded that real-time imaging of bowel perfusion is easy to use and accurate, and should be translated into clinical use.


title: The short-term outcomes of robotic sphincter-preserving surgery for rectal cancer: comparison with open and laparoscopic surgery using a propensity score analysis.

text: PURPOSE The aim of this study is to clarify the short-term outcomes of robotic sphincter-preserving surgery for rectal cancer in a retrospective study. METHODS The short-term outcomes of robotic sphincter-preserving surgery (n = 130) were retrospectively compared to open (n = 234) and laparoscopic surgery (n = 318) by a propensity score analysis. RESULTS Robotic surgery was performed more frequently for patients with lower rectal cancer (55%) than open (30%, p < 0.0001) or laparoscopic surgery (36%, p < 0.0001). None of the robotic surgery cases were converted to open surgery. After propensity score matching, robotic surgery was found to be associated with a longer operation time (342 vs. 230 min, p < 0.0001) and less blood loss (7 vs. 420 mL, p < 0.0001) than open surgery. The overall complication rate of robotic surgery was lower than that of open surgery (13 vs. 28%, p = 0.032). Robotic surgery was associated with a lower incidence of surgical site infections (SSIs) than laparoscopic surgery (0 vs. 7%, p = 0.028). There were no cases of anastomotic leakage after robotic surgery. The circumferential resection margin was involved in 0.8% of the patients who underwent robotic surgery; the incidence did not differ among the treatment groups. CONCLUSIONS Although robotic surgery for rectal cancer was associated with a longer operation time, it was associated with a very low incidence of SSIs. The degree of safety was comparable to both open and laparoscopic surgery.


title: Automatic inference model construction for computer-aided diagnosis of lung nodule: Explanation adequacy, inference accuracy, and experts' knowledge.

text: We aimed to describe the development of an inference model for computer-aided diagnosis of lung nodules that could provide valid reasoning for any inferences, thereby improving the interpretability and performance of the system. An automatic construction method was used that considered explanation adequacy and inference accuracy. In addition, we evaluated the usefulness of prior experts' (radiologists') knowledge while constructing the models. In total, 179 patients with lung nodules were included and divided into 79 and 100 cases for training and test data, respectively. F-measure and accuracy were used to assess explanation adequacy and inference accuracy, respectively. For F-measure, reasons were defined as proper subsets of Evidence that had a strong influence on the inference result. The inference models were automatically constructed using the Bayesian network and Markov chain Monte Carlo methods, selecting only those models that met the predefined criteria. During model constructions, we examined the effect of including radiologist's knowledge in the initial Bayesian network models. Performance of the best models in terms of F-measure, accuracy, and evaluation metric were as follows: 0.411, 72.0%, and 0.566, respectively, with prior knowledge, and 0.274, 65.0%, and 0.462, respectively, without prior knowledge. The best models with prior knowledge were then subjectively and independently evaluated by two radiologists using a 5-point scale, with 5, 3, and 1 representing beneficial, appropriate, and detrimental, respectively. The average scores by the two radiologists were 3.97 and 3.76 for the test data, indicating that the proposed computer-aided diagnosis system was acceptable to them. In conclusion, the proposed method incorporating radiologists' knowledge could help in eliminating radiologists' distrust of computer-aided diagnosis and improving its performance.


title: Is Low Alveolar Type II Cell SOD3 in the Lungs of Elderly Linked to the Observed Severity of COVID-19?

text: Human lungs single cell RNA sequencing data from healthy donors (elderly and young; GEO accession number GSE122960) were analyzed to isolate and specifically study gene expression in alveolar type II cells. Co-localization of ACE2 and TMPRSS2 enables SARS-CoV 2 to enter the cells. Expression of these genes in the alveolar type II cells of elderly and young patients were comparable and therefore do not seem to be responsible for worse outcomes observed in COVID-19 affected elderly. In cells from the elderly, 263 genes were downregulated and 95 upregulated. SOD3 was identified as the top-ranked gene that was most down-regulated in the elderly. Other redox-active genes that were also downregulated in cells from the elderly included ATF4 and M2TA. ATF4, an ER stress sensor that defends lungs via induction of heme oxygenase 1. The study of downstream factors known to be induced by ATF4, according to Ingenuity Pathway AnalysisTM, identified 24 candidates. Twenty-one of these were significantly downregulated in the cells from the elderly. These downregulated candidates were subjected to enrichment using the Reactome Database identifying that in the elderly, the ability to respond to heme deficiency and the ATF4-dependent ability to respond to endoplasmic reticulum stress is significantly compromised. SOD3-based therapeutic strategies have provided beneficial results in treating lung disorders including fibrosis. The findings of this work propose the hypotheses that lung-specific delivery of SOD3/ATF4 related antioxidants may work in synergy with promising anti-viral drugs such as remdesivir to further improve COVID-19 outcomes in the elderly.


title: Short-term outcomes of endoscopic submucosal dissection versus laparoscopic surgery for colorectal neoplasms: An observational study.

text: OBJECTIVES With endoscopic submucosal dissection and laparoscopic surgery, treatment for colorectal neoplasms has become minimally invasive. However, few studies have compared endoscopic submucosal dissection with laparoscopic surgery for colorectal neoplasms, excluding deeply invasive cancer on preoperative diagnosis. METHODS We retrospectively reviewed the files of patients who had undergone endoscopic submucosal dissection or laparoscopic surgery for colorectal neoplasms between November 2005 and December 2015. We limited patients who were not suspected preoperatively to have aggressive submucosal invasion >1,000 μm. RESULTS Ninety-five patients underwent endoscopic submucosal dissection and 37 underwent laparoscopic surgery. Cases of endoscopic submucosal dissection tended to involve rectal neoplasms more often than colonic neoplasms, shorter operative times, and shorter lengths of hospital stay compared with laparoscopic surgery. The perforation rate during colonic endoscopic submucosal dissection in the early period (November 2005 to December 2010) and late period (January 2011 to December 2015) was 14.8% and 2.9%, respectively. In all cases of perforation during colonic endoscopic submucosal dissection, the ability to maneuver the endoscope was compromised. Though tumors were larger in patients who underwent rectal endoscopic submucosal dissection compared with colonic endoscopic submucosal dissection, the perforation and postoperative bleeding rates with rectal endoscopic submucosal dissection were both 3.2%. The most common indication for laparoscopic surgery was difficulty performing endoscopic submucosal dissection. Serious complications were rare. CONCLUSIONS For colonic neoplasms, laparoscopic surgery should be considered when endoscopic submucosal dissection is technically difficult in the early period. For rectal neoplasms, endoscopic submucosal dissection is desirable even for those of large size.


title: Transanal NOTES total mesorectal excision (TME) in patients with rectal cancer: Is anatomy better preserved?

text: BACKGROUND Natural orifice transluminal endoscopic surgery (NOTES) and single-incision laparoscopy are spreading worldwide. Total mesorectal excision (TME), the standard treatment for patients with distal rectal tumors, is usually performed in an "up-to-down" approach, either laparoscopically (LAPTME) or as an open procedure. We have already reported a NOTES-inspired, transanal, "down-to-up" variant of TME (NOTESTME). The main aim of this study was to assess the quality of the resected specimen in patients who had undergone either NOTESTME or LAPTME. METHODS All patients with distal rectal neoplasia presenting between January 2011 and December 2014 were considered for the study. Additional inclusion criteria comprised American Society of Anesthesiologists score ≤ III and the absence of previous open surgery. Assignment to either group was sequential and based on the rank of inclusion in the study. The primary endpoint was the macroscopic quality of the specimen. Secondary endpoints included nerve visualization, tumor perforation, operating time, status of margins, and number of retrieved nodes. RESULTS Eighteen patients (6 men, 12 women) were in the NOTESTME group and 15 (7 men, 8 women) in the LAPTME group, respectively. The TME specimen was considered complete or mainly regular in 16 patients who had undergone NOTESTME (88.9 %) and in 11 patients who had undergone LAPTME (73.3 %), (p > 0.05). During the procedure, we visually identified the neurovascular bundles of Walsh in 14 patients in the NOTESTME group (77.8 %) and in only 5 patients in the LAPTME group (33.3 %), (p < 0.05). Mean operative time was 245 min (range 155-440 min) in the NOTESTME group and 275 min (range 180-400 min) in the LAPTME group (p > 0.05). A median of 11 nodes per specimen (range 8-22 nodes) was retrieved in the NOTESTME group and 12 nodes (range 6-41 nodes) in the LAPTME group, respectively (p > 0.05). Distal and radial margins were comparable in both groups. CONCLUSIONS Compared to the LAPTME, the NOTESTME seems to be associated with a more frequent intraoperative identification of the sacral nerves. However, the difference in overall quality of the retrieved specimen, although favoring NOTESTME, did not reach statistical significance in this small series.


title: Nonoperating room anaesthesia: safety, monitoring, cognitive aids and severe acute respiratory syndrome coronavirus 2.

text: PURPOSE OF REVIEW With an ageing population, mounting pressure on the healthcare dollar, significant advances in medical technology, and now in the context of coronavirus disease 2019, the traditional paradigm in which operative procedures are undertaken is changing. Increasingly, procedures are performed in more distant, isolated and less familiar locations, challenging anaesthesiologists and requiring well developed situational awareness. This review looks at implications for the practitioner and patient safety, outlining considerations and steps involved in translation of systems and processes well established in the operating room to more unfamiliar environments. RECENT FINDINGS Despite limited nonoperating room anaesthesia outcome data, analysis of malpractice claims, anaesthesia-related medical disputes and clinical outcome registries have suggested higher morbidity and mortality. Complications were often associated with suboptimal monitoring, nonadherence to recommended guidelines and sedationist or nonanaesthesiologist caregivers. More recently, clear monitoring guidelines, global patient safety initiatives and widespread implementation of cognitive aids may have contributed to nonoperating room anaesthesia (NORA) outcomes approaching that of traditional operating rooms. SUMMARY As NORA caseloads increase, understanding structural and anaesthetic requirements is essential to patient safety. The severe acute respiratory syndrome coronavirus 2 pandemic has provided an opportunity for anaesthesiologists to implement lessons learned from previous analyses, share expertise as patient safety leaders and provide valuable input into protecting patients and caregivers.


title: The effectiveness of bivalving, cast spreading, and webril cutting to reduce cast pressure in a fiberglass short arm cast.

text: BACKGROUND A fiberglass short arm cast can be used to treat a distal radial fracture, but posttraumatic edema may lead to excessive cast tightness and resultant soft-tissue injury. We sought to quantify a simulated edema-induced pressure within a fiberglass short arm cast and to determine the effectiveness of different cast-cutting methods for pressure reduction. We hypothesized that cast cutting could eliminate all clinically relevant pressure and Ace wrap would insignificantly increase pressure. METHODS Skin surface pressure under fiberglass short arm casts was measured on ninety wrists from forty-five volunteers randomly assigned to one cast-cutting method: single-cut (cast bivalve and Ace wrap), double-cut (cast bivalve, spread, and Ace wrap), or triple-cut (cast bivalve, spread, Webril cut, and Ace wrap). Each wrist was immobilized in a cast in the neutral position with one roll of 2-inch (5.1-cm) cotton Webril and one roll of 2-inch (5.1-cm) fiberglass. Each fiberglass short arm cast contained an empty intravenous fluid bag in which we infused air. This simulated edema, which generated a skin surface pressure, which was measured by a pressure transducer. RESULTS Each cast-cutting method significantly reduced (p < 0.0001) the skin surface pressure from the average maximum of 92.5 mm Hg in a non-fracture setting. Prior to Ace wrapping, there was a reduction in skin surface pressure of 70.8% for the single-cut method, 85.1% for the double-cut method, and 99.9% for the triple-cut method. Ace wrap significantly increased skin surface pressure (p < 0.0001), lessening the effectiveness of cast cutting. There was an overall reduction in skin surface pressure of 55.9% for the single-cut method, 64.3% for the double-cut method, and 77.2% for the triple-cut method. Throughout our study, women had significantly higher skin surface pressure than men (p < 0.0001); the average maximum was 104.4 mm Hg for women and 81.1 mm Hg for men. CONCLUSIONS The single-cut method provides the greatest pressure reduction, but only the triple-cut method eliminated all relevant skin surface pressure. Ace wrapping a cut cast noticeably increased skin surface pressure. CLINICAL RELEVANCE In volunteers without a fracture, only the triple-cut method is effective enough to eliminate clinically relevant skin surface pressure. Ace wrap should be applied with caution after the cast is cut. The specific effect on pressure reduction in a patient who requires some soft-tissue pressure to maintain fracture reduction was not studied.


title: Antithrombotic Treatment after Transcatheter Heart Valves Implant.

text: Transcatheter heart valve replacement technology was introduced as alternative to surgery for the growing high-risk profile population. Developed first, aortic valve replacement (TAVR) became a standard of care for patients with severe aortic stenosis at high operative risk, with a potential future use also for low-risk subjects. In the last decade, a multitude of transcatheter mitral valve replacement (TMVR) devices have been developed for the treatment of severe mitral regurgitation, with encouraging results coming from first-in-man and feasibility studies. As for biological surgical-type valves, transcatheter implanted valves still preserve the risk of thrombosis and embolic events and anticoagulation- or antiplatelet-based strategies are the most widely used options. Unfortunately, these last remain recommended on the basis of empirical or not widely validated evidence. Therefore, given the exponential rise of TAVR and TMVR procedures, it is important to identify the optimal antithrombotic strategies that best fit the risk of thromboembolic and bleeding events. Hereafter, this review evaluates the current guidelines, trials, and observational data discussing antithrombotic strategy after transcatheter aortic or mitral valve replacement.


title: Patients with interstitial lung disease and pulmonary sarcoidosis are at high risk for severe illness related to COVID-19.

text: Analyses of COVID-19 patients with preexisting interstitial lung disease (ILD) or pulmonary sarcoidosis is lacking but registries are ongoing. Treatment of COVID-19 for patients with underlying ILD or sarcoidosis may include hospital admission, possible drug treatment, caution with steroids, and avoidance of mechanical ventilation in acute exacerbation of ILD. Patients with COVID-19 respiratory illness are at risk for developing ILD.


title: A multiplex liquid-chip assay based on Luminex xMAP technology for simultaneous detection of six common respiratory viruses

text: We utilized one-step multiplex reverse transcription-PCR (RT-PCR) and Luminex xMAP technology to develop a respiratory multiplex liquid-chip assay (rMLA) for simultaneous detection of 6 common respiratory viruses, including influenza virus type A (FluA) and type B (FluB), para-influenza virus type 3 (PIV-3), respiratory syncytial virus (RSV), human metapneumovirus (MPV) and a threatening virus to China, Middle East Respiratory Syndrome coronavirus (MERS-CoV). Performance of rMLA was evaluated by comparing with real-time RT-PCR. Detection data from clinical specimens showed that the rMLA had diagnostic sensitivities of 97.10% for FluA, 94.59% for FluB, 98.68% for PIV-3, 94.87% for RSV and 95.92% for MPV (No Data for MERS-CoV due to the lack of positive specimens). Data of analytical sensitivities showed that the detection limits of the rMLA assay were 5–25 viral RNA copies per μl for FluA, FluB, PIV-3 and MERS-CoV, approximate to the real-time RT-PCR assay; while the values were 8 and 22copies/μl for MPV and RSV, lower than the real-time RT-PCR(78 and 114 copies/μl respectively). The results indicated that the rMLA is a sensitive, specific detection tool and comparable to real-time RT-PCR, especially suitable for high-throughput detection of respiratory specimens.


title: Clinical value of a combined multi-phase contrast enhanced DOPA-PET/CT in neuroendocrine tumours with emphasis on the diagnostic CT component.

text: OBJECTIVE To assess the clinical value of multi-phase, contrast-enhanced DOPA-PET/CT with emphasis on the diagnostic CT component in patients with neuroendocrine tumours (NET). METHODS Sixty-five patients with NET underwent DOPA-cePET/CT. The DOPA-PET, multi-phase CT and combined DOPA cePET/CT data were evaluated and diagnostic accuracies compared. The value of ceCT in DOPA cePET/CT concerning lesion detection and therapeutic impact was evaluated. Sensitivities, specificities and accuracies were calculated. Histopathology and clinical follow-up served as the standard of reference. Differences were tested for statistical significance by McNemar's test. RESULTS In 40 patients metastatic and/or primary tumour lesions were detected. Lesion-based analysis for the DOPA-PET showed sensitivity, specificity and accuracy of 66%, 100% and 67%, for the ceCT data 85%, 71% and 85%, and for the combined DOPA cePET/CT data 97%, 71% and 96%. DOPA cePET/CT was significantly more accurate compared with dual-phase CT (p < 0.05) and PET alone (p < 0.05). Additional lesion detection was based on ceCT in 12 patients; three patients underwent significant therapeutic changes based on the ceCT findings. CONCLUSION DOPA cePET/CT was significantly more accurate than DOPA-PET alone and ceCT alone. The CT component itself had a diagnostic impact in a small percentage but contributed to the therapeutic strategies in selected patients.


title: Neutralizing antibodies mediate virus-immune pathology of COVID-19.

text: SARS-CoV-2 is a novel beta-coronavirus causing over 200.000 lethal cases within six months of first infecting humans. SARS-CoV-2 causes COVID-19, a form of severe acute respiratory syndrome (SARS). COVID-19 is characterized by two phases: the first resembles the flu with pneumonia, but after about seven or eight days the disease suddenly worsens to a sepsis-like syndrome. It is difficult to explain this virus-immune-pathology sequence from virology or immunology only. This paper hypothesizes that host-produced anti-spike protein antibodies are responsible for immune-induced viral dissemination. Subsequently, systemic distribution of virus-antibodies complexes activates the immune pathology observed in severe COVID-19. This hypothesis may be counterintuitive to immunologist that consider many anti-spike antibodies to be virus-neutralizing antibodies. Although anti-spike antibodies may hinder infection of epithelial cells, antibody binding to the spike protein may facilitate virus infection of myeloid leukocytes. If myeloid leukocytes reenter the circulation, they could spread the virus from a locoregional infection to a systemic disease. Disseminated virus in combination with antibodies results in dispersed virus-antibody complexes that overstimulate the immune system. The hypothesis aligns with the sequences of virus, immune and pathological events in COVID-19. The delay in onset from both syndromes results from an immune system still naïve to the non-cross-reactive spike protein. Details of this hypothesis are in concordance with many clinical characteristics of COVID-19, including its predominant lethality for the elderly, and the mostly asymptomatic course of disease in children. It predicts putative detrimental effects of vaccines that induce virus-neutralizing antibodies against the spike protein, as has been shown for other coronaviruses. This hypothesis has consequences for treatment of patients, evaluation of personal and herd immunity and vaccine development. In patients, cellular immunity should be stimulated. Neutralizing antibodies might not be indicative for immunity. Vaccines should aim to stimulate cellular immunity COVID-19 and/or stimulate humoral immunity against viral proteins except for the immunodominant spike protein.


Pre-operative Embolization of an Intraventricular Meningioma Using Onyx.


title: The Penumbra Stroke System: a technical review.

text: Major ischemic strokes secondary to proximal artery occlusions are responsible for significant morbidity and mortality. Owing to extensive clot burden, these strokes are poorly responsive to intravenous tissue plasminogen activator. The introduction of endovascular therapy, particularly mechanical devices, has resulted in markedly improved recanalization rates of large vessel occlusions. With increasing experience with the Penumbra Stroke System and the 054 reperfusion catheter, there has been further improvement in TIMI 2 and 3 revascularization rates with faster times to vessel opening. The aim of this technical review is to convey various tips and tricks learnt from this experience.


title: Access to healthcare services for Afghan refugees in Iran in COVID-19 pandemic.

text: In Iran, given the problems Afghan refugees face, special attention needs to be paid to this population in the coronavirus response. The first and ever-existing challenge is the lack of insurance and, consequently, high medical expenses.Other challenges can be mentioned as low level of education and consequently low health literacy, lower access to cyberspace, and not following coronavirus news which might be responsible for observing less safety and health procedures by the refugees.As the next drawback, a majority of refugees may live in groups in different parts of the city, especially in old areas and abandoned houses, which makes it difficult to control these people in the outbreaks, hence the need for accurate planning for monitoring.Given the above, it seems necessary for the Iranian government to take appropriate actions to assist the refugees. Full coverage of all refugees (legal and illegal) with health insurance seems to be essential. Advocacy in international assemblies to attract financial resources can be considered as a way to finance this issue. Free-of-charge treatment for infected refugees can be an alternative to reassuring refugees until full insurance coverage.


title: Transurethral Resection of the Prostate (TURP) Versus Original and PErFecTED Prostate Artery Embolization (PAE) Due to Benign Prostatic Hyperplasia (BPH): Preliminary Results of a Single Center, Prospective, Urodynamic-Controlled Analysis.

text: PURPOSE To compare clinical and urodynamic results of transurethral resection of the prostate (TURP) to original and PErFecTED prostate artery embolization (PAE) methods for benign prostatic hyperplasia. METHODS We prospectively randomized 30 patients to receive TURP or original PAE (oPAE) and compared them to a cohort of patients treated by PErFecTED PAE, with a minimum of 1-year follow-up. Patients were assessed for urodynamic parameters, prostate volume, international prostate symptom score (IPSS), and quality of life (QoL). RESULTS All groups were comparable for all pre-treatment parameters except bladder contractility and peak urine flow rate (Q max), both of which were significantly better in the TURP group, and IIEF score, which was significantly higher among PErFecTED PAE patients than TURP patients. All groups experienced significant improvement in IPSS, QoL, prostate volume, and Q max. TURP and PErFecTED PAE both resulted in significantly lower IPSS than oPAE but were not significantly different from one another. TURP resulted in significantly higher Q max and significantly smaller prostate volume than either original or PErFecTED PAE but required spinal anesthesia and hospitalization. Two patients in the oPAE group with hypocontractile bladders experienced recurrence of symptoms and were treated with TURP. In the TURP group, urinary incontinence occurred in 4/15 patients (26.7 %), rupture of the prostatic capsule in 1/15 (6.7 %), retrograde ejaculation in all patients (100 %), and one patient was readmitted for temporary bladder irrigation due to hematuria. CONCLUSIONS TURP and PAE are both safe and effective treatments. TURP and PErFecTED PAE yield similar symptom improvement, but TURP is associated with both better urodynamic results and more adverse events.


title: Engaging older adults in self-management talk in healthcare encounters: a systematic review protocol.

text: BACKGROUND Clinical practice guidelines for the management of complex chronic conditions in older adults encourage healthcare providers to engage patients in shared decision-making about self-management goals and actions. Yet, healthcare decision-making and communication for this population can pose significant challenges. As a result, healthcare professionals may struggle to help patients define and prioritise their values, goals, and preferences in ways that are clinically and personally meaningful, incorporating physical functioning and quality of life, when faced with numerous diagnostic and treatment alternatives. The aim of this systematic review is to locate and synthesise a body of fine-grained observational research on communication between professionals, older adults, and carers regarding self-management in audio/audio-visually recorded naturalistic interactions. METHODS/DESIGN The paper describes a systematic review of the published conversation analytic and discourse analytic research, using an aggregative thematic approach and following the PRISMA-P guidelines. This review will include studies reporting on adult patients (female or male) aged ≥ 60 years whose consultations are conducted in English in any healthcare setting and stakeholders involved in their care, e.g. general practitioners, nurses, allied health professionals, and family carers. We will search nine electronic databases and the grey literature and two independent reviewers will screen titles and abstracts to identify potential studies. Discrepancies will be resolved via consultation with the review team. The methodological quality of the final set of included studies will be appraised using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research and a detailed description of the characteristics of the included studies using a customised template. DISCUSSION This is the first systematic review to date to locate and synthesise the conversation analytic research on how healthcare professionals raise and pursue talk about self-management with older adults in routine clinical interactions. Amalgamating these findings will enable the identification of effective and potentially trainable communication practices for engaging older adults in healthcare decision-making about the self-management goals and actions that enable the greatest possible health and quality of life in older adulthood. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019139376.


title: Does COVID19 infect the brain? If so, smokers might be at a higher risk.

text: COVID19 is a devastating global pandemic with epicenters in China, Italy, Spain, and now the United States. While the majority of infected cases appear mild, in some cases individuals present serious cardiorespiratory complications with possible long-term lung damage. Infected individuals report a range of symptoms from headaches to shortness of breath to taste and smell loss. To that end, less is known about the how the virus may impact different organ systems. The SARS-CoV2 virus, which is responsible for COVID19, is highly similar to SARS-CoV. Both viruses have evolved an ability to enter host cells through direct interaction with the angiotensin converting enzyme 2 (ACE2) protein at the surface of many cells. Published findings indicate that SARS-CoV can enter the human nervous system with evidence from both postmortem brains and detection in cerebrospinal fluid of infected individuals. Here we consider the ability of SARS-CoV2 to enter and infect the human nervous system based on the strong expression of the ACE2 target throughout the brain. Moreover, we predict that nicotine exposure through various kinds of smoking (cigarettes, e-cigarettes, or vape) can increase the risk for COVID19 neuroinfection based on known functional interactions between the nicotinic receptor and ACE2. We advocate for higher surveillance and analysis of neuro-complications in infected cases.


title: COVID-19 response measures - a Singapore Neurosurgical Academic Medical Centre experience segregated team model to maintain tertiary level neurosurgical care during the COVID-19 outbreak.

text: Aim: This article aims to inform and share the experience of a Singaporean tertiary level neurosurgical unit in an academic medical centre during the COVID-19 outbreak. Method: This is a descriptive study of our segregation team model which is designed with the aim of optimizing manpower and ensuring the safety and welfare of the neurosurgical unit, while maintaining and prioritizing excellent patient care. Result: We describe our method of team segregation, rostering, and outline some principles that we adhere to in its design. We also summarise the restructuring of our inpatient and outpatient service, including the operating theatre and protocols for specific procedures, intensive care and general wards, as well as clinic services and multidisciplinary meetings. Conclusion: We end with a commentary on residency training and anticipated challenges. Given the likely protracted course of the pandemic, it is key to account for sustainability of such measures and the conservation of resource via the reduction of pateint volume, upkeep of staff emotional and physical health and harnessing technologies such as telemedicine.


CT Is Not a Screening Tool for Coronavirus Disease (COVID-19) Pneumonia.


title: The Canadian Association for Interventional Radiology (CAIR) and Canadian Association of Radiologists (CAR) Guidelines for Interventional Radiology Procedures for Patients With Suspected or Confirmed COVID-19.

text: The current coronavirus disease 2019 (COVID-19) pandemic is creating significant challenges to the Canadian health system, including the practice of interventional radiology (IR). Interventional radiology will continue to play an important role in patient care, during this crisis. This document serves to guide interventional and general radiologists in safely performing IR procedures on patients with suspected or confirmed COVID-19, using the best evidence, guidelines and expert recommendations available. These strategies include reviewing procedural indications, development of tactics to minimize cross contamination prior to the intervention, appropriate usage of personal protection equipment according to the type of procedure (along with defining aerosol-generating procedures in IR), along with developing the appropriate work environment during the COVID-19 pandemic. By adopting the policies described, hospitals will protect the interventional radiologists, medical radiation technologists, nurses, ancillary staff, along with patients who benefit from their care.


title: Status of sentinel lymph node mapping in non-small cell lung cancer.

text: Sentinel lymph node mapping has become the standard of care in melanoma and breast cancer, contributing to marked improvements in accurate staging and targeted treatment, while decreasing morbidity of aggressive nodal bed dissections. Since 1999, several groups have proposed similar mapping in lung cancer models with mixed success. This article reviews the research up to date and discusses opportunities to improve accuracy of sentinel lymph node biopsy in non-small cell lung cancer.


title: Current understanding of middle east respiratory syndrome coronavirus infection in human and animal models.

text: Middle East respiratory syndrome (MERS) is a highly lethal respiratory disease caused by a novel betacoronavirus (MERS coronavirus, MERS-CoV). Since its first emergence in 2012, multiple transmission events of MERS-CoV (dromedary to human and human to human) have been reported, indicating that MERS-CoV has the potential to cause widespread outbreak. However, the epidemiology of MERS as well as immune responses against the virus in animal models and patients are still not well understood, hindering the vaccine and therapeutic developments. In this review, we summarize recent genetic and epidemic findings of MERS-CoV and the progress in animal model development, immune response studies in both animals and humans. At last, we discussed the breakthrough on vaccine and therapeutic development which are important against potential future MERS outbreak.


Going viral: how to boost the spread of coronavirus science on social media.


title: An exploratory study on the social and genotypic clustering of HIV infection in men having sex with men.

text: OBJECTIVE To explore the clustering of HIV infected men having sex with men (MSM) using social network approach in conjunction with the phylogenetic relationship of the virus strains. DESIGN An exploratory study incorporating social network and phylogenetic analysis. METHODS Recently diagnosed HIV-infected MSM attending one major HIV specialist clinic in Hong Kong were recruited in the study involving the administration of a self-administered questionnaire on behaviours and partnership patterns using a Likert Scale, the results of which were assessed using social network analysis and in context of the phylogenetic analysis from sequencing the HIV-1 pol gene, as part of the clinical investigation for genotypic resistance. Clusters were defined using social and molecular methods. RESULTS An 'Internet-centred' cluster and 'Sauna-centred' cluster could be delineated using correspondence analysis and network diagrams. The main distinguishing features of MSM in the 'Internet-centred' social cluster were: younger age, higher education level, and multiple partner types. Three genetic clusters could be identified in the phylogenetic tree, two of which associated with Internet use and one with sauna for sex partnership. There were partial overlaps between social and genetic clusters. Characteristically, the virus strains in sauna users were more disperse compared with the closely knit configuration of those using Internet. CONCLUSION The principle of the duality of place and person can be strategically applied in epidemiologic investigation. The characterization of MSM cluster using anonymized network data provides a potentially powerful tool for informing public health intervention.


title: Intraoperative carcinoid syndrome during small-bowel neuroendocrine tumour surgery.

text: Only few descriptions of Intraoperative carcinoid syndrome (ioCS) have been reported. The primary objective of this study was to describe ioCS. A second aim was to identify risk factors of ioCS. We retrospectively analyzed patients operated for small-bowel neuroendocrine tumour in our institution between 2007 and 2015, and receiving our preventive local regimen of octreotide continuous administration. ioCS was defined as highly-probable in case of rapid (<5min) arterial blood pressure changes ≥ 40%, not explained by surgical/anaesthetic management and regressive ≥ 20% after octreotide bolus injection. Probable cases were ioCS which did not meet all criteria of highly-probable ioCS. Suspected ioCS were detected on the anaesthesia record by an injection of octreotide due to a manifestation which did not meet the criteria for highly-probable or probable ioCS. A total of 81 patients (liver metastases: 59, prior carcinoid syndrome: 49, carcinoid heart disease: 7) were included; 139 ioCS occurred in 45 patients: 45 highly-probable, 67 probable, and 27 suspected. ioCs was hypertensive (91%) and/or hypotensive (29%). There was no factor, including the use of vasopressors, significantly associated with the occurrence of an ioCS. All surgeries were completed and one patient died from cardiac failure four days after surgery. After preoperative octreotide continuous infusion, ioCS were mainly hypertensive. No ioCS risk factors, including vasopressor use, were identified. No intraoperative carcinoid crisis occurred, suggesting the clinical relevance of a standardized octreotide prophylaxis protocol.


title: Safety and Efficacy of Permacol Injection in the Treatment of Fecal Incontinence.

text: PURPOSE Permacol has been gaining popularity in recent times for the treatment of fecal incontinence (FI). This study aims to evaluate the safety and efficacy of anal submucosal Permacol injection in the treatment of FI. METHODS All consecutive patients who underwent Permacol injection for FI over a 3-year period were included. Patients' data relating to obstetric history, anorectal/pelvic operations, type of FI, preoperative anorectal physiology results and follow-up details for outcome measures were collected. Preoperative and postoperative Cleveland Clinic Florida Incontinence Scores (CCFISs) were noted. Patients were surveyed by using a telephone questionnaire to assess the quality of life and other outcome measures. Data were analysed using SPSS ver.19.0. RESULTS Thirty patients (28 females and 2 males) with a median age of 67 years were included in the study. Of those patients, 37%, 50%, and 13% were noted to have passive, mixed and urge FI, respectively. Six of the patients (20%) had repeat Permacol injections, 5 of whom had sustained responses to the first Permacol injection for a mean of 11 months. There was a significant improvement in the CCFIS from a baseline median of 12.5, mean 12.8 interquartile range [IQR], 6-20), to a median of 3.5, mean 4.8 (IQR, 0-20), P < 0.001. Of the patients surveyed by telephone 89% were satisfied with their overall experience and the improvement in their symptoms following Permacol injections. CONCLUSION This study has demonstrated that Permacol injection for the treatment of FI is safe and effective and has no associated major complications. However, the results are not permanent; consequently, a significant proportion of the patients with an initial response may require repeat injections.


Potential Implications of COVID-19 for the 2020-2021 Residency Application Cycle.


title: Facial and neck hematoma after carotid artery stenting: an uncommon misadventure in endovascular carotid revascularization.

text: The complication rates of carotid artery stenting (CAS) vary from 3.0% to 4.4%, and most commonly include ischemic stroke, intracranial hemorrhage, or groin complications. We present the rare complication of a patient who underwent CAS for a symptomatic 90% left internal carotid artery stenosis and developed an expanding cervical hematoma after the procedure with imminent respiratory compromise. After intubation, an arteriogram revealed perforation of the external carotid artery trunk, proximal to the origin of the internal maxillary artery. The artery was subsequently embolized and the hematoma resolved without further intervention. We present a potential catastrophic complication and suggest potential causes and treatment options available.


title: Endoscopic, endonasal, transclival resection of a pontine cavernoma: case report.

text: BACKGROUND AND IMPORTANCE Hemorrhagic, symptomatic cavernous malformations in the brainstem are difficult to access. Conventional approaches such as the transpetrosal approach often require significant brain retraction. We present the successful purely endoscopic, endonasal, transclival resection of a symptomatic cavernoma located in the ventromedial pons. CLINICAL PRESENTATION A 17-year-old male patient presented with acute onset of headache, facial numbness, and tingling. Magnetic resonance imaging demonstrated an enhancing lesion in the pons consistent with a cavernous malformation. Over the course of the next 3 weeks, the patient had 2 additional episodes of acutely worsening neurological deficits that left him with left-sided hemiparesis, a right sixth nerve palsy, and dysphagia. A purely endoscopic, endonasal, transclival approach was used to resect the cavernoma. Postoperatively, he had a transient worsening of his left-side motor function and restricted horizontal gaze, but at the last follow-up, his hemiparesis had improved and his magnetic resonance imaging demonstrated a radiographic cure. He developed a cerebrospinal fluid (CSF) leak despite prophylactic lumbar CSF drainage for 2 days and the use of bilateral vascularized nasoseptal flaps. The CSF leak was repaired with CSF diversion and a second surgical procedure; at the last follow-up, he had no recurrence of the leak. CONCLUSION An endoscopic, endonasal, transclival approach is a novel and effective approach to cavernous malformations presenting to the ventral surface of the pons. Recently developed techniques for closure and repair of the skull base defect have minimized but have not eliminated the risk of CSF leak in these procedures.


title: Sequential kidney-liver transplantation from the same living donor for lecithin cholesterol acyl transferase deficiency.

text: BACKGROUND Lecithin cholesterol acyl transferase (LCAT) deficiency is a rare autosomal recessive disorder of lipoprotein metabolism that results in end-stage renal disease (ESRD) necessitating transplantation. As LCAT is produced in the liver, combined kidney and liver transplantation was proposed to cure the clinical syndrome of LCAT deficiency. METHODS A 29-year-old male with ESRD secondary to LCAT deficiency underwent a sequential kidney-liver transplantation from the same living donor (LD). One year following the kidney transplant, auxiliary partial orthotopic liver transplant (APOLT) of a left lateral segment from the same donor was performed. RESULTS At 5 years follow-up, there have been no major complications, readmissions, or rejection episodes. Serum lipid abnormalities recurred within the first year, but liver and kidney allograft function remains intact. CONCLUSION Few cases of sequential transplantation from the same LD have been performed in adults. This is the first APOLT and multi-organ transplant performed for LCAT deficiency. Sequential organ transplant from the same LD for ESRD secondary to a metabolic disorder of the liver is feasible in adults and should be further investigated.


title: Absence of hydrogen sulfide-induced hypometabolism in pigs: a mechanistic explanation in relation to small nonhibernating mammals.

text: Artificially induced hypometabolism in nonhibernating mammals may have considerable clinical implications. Numerous studies in small rodent models have demonstrated that hydrogen sulfide (H2S) induces hypometabolism, supposedly as a result of histotoxic hypoxia. However, the induction of hypometabolism is absent in large animals following H2S administration. To determine the cause of this animal size-dependent discrepancy in H2S pharmacodynamics, the effects of sodium H2S (NaSH; 5 mg/kg/h, 4-hour intravenous administration) on systemic, pneumocardial, hematological, biochemical, microvascular (sublingual), and histological parameters were investigated in pigs. After 4 h, no differences were observed between the NaSH and control group with respect to systemic, pneumocardial, hematological, biochemical, and histological parameters. However, NaSH triggered significant hyperperfusion in the sublingual microcirculation, as evidenced by an increased blood vessel diameter (154 ± 16 and 85 ± 25% vs. baseline for NaSH and NaCl, respectively), total vessel density (139 ± 18 and 98 ± 13%, respectively), and perfused vessel density (139 ± 18 and 99 ± 13%, respectively). These phenomena are consistent with microvascular changes that occur during a panting response, an important heat loss mechanism (i.e., thermoregulatory effector) in pigs that is controlled by the thermoneutral zone (Ztn). On the basis of our findings and the literature, a mechanistic explanation is provided for the differential manifestation of hypometabolism between small and large animals. In large animals, H2S does not act via histotoxic hypoxia but likely triggers carotid bodies to transmit a hypoxic signal, which subsequently lowers the Ztn and activates heat loss mechanisms (e.g., panting) to align ATP consumption with ATP production through hypothermia. Since large animals have a small surface:size ratio, the cooling rate is too inefficient to accommodate hypothermia and subsequent hypometabolism. This is why large animals do not exhibit hypometabolism, despite the activation of thermoregulatory effectors. This is also a reason for the poor translatability of artificial hypometabolism to the clinical setting.


title: Mask versus nasal tube for stabilization of preterm infants at birth: a randomized controlled trial.

text: OBJECTIVE Positive-pressure ventilation (PPV) using a manual ventilation device and a face mask is recommended for compromised newborn infants in the delivery room (DR). Mask ventilation is associated with airway obstruction and leak. A nasal tube is an alternative interface, but its safety and efficacy have not been tested in extremely preterm infants. METHODS An unblinded randomized controlled trial was conducted in Australia, and the Netherlands. Infants were stratified by gestational age (24-25/26-29 weeks) and center. Immediately before birth infants were randomly assigned to receive PPV and/or continuous positive airway pressure with either a nasal tube or a size 00 soft, round silicone mask. Resuscitation protocols were standardized; respiratory support was provided using a T-piece device commencing in room air. Criteria for intubation included need for cardiac compressions, apnea, continuous positive airway pressure >7 cm H2O, and fraction of inspired oxygen >0.4. Primary outcome was endotracheal intubation in the first 24 hours from birth. RESULTS Three hundred sixty-three infants were randomly assigned; the study terminated early on the grounds of futility. Baseline variables were similar between groups. Intubation rates in the first 24 hours were 54% and 55% in the nasal tube and face mask groups, respectively (odds ratio: 0.97; 95% confidence interval: 0.63-1.50). There were no important differences in any of the secondary outcomes within the whole cohort or between the 2 gestational age subgroups. CONCLUSIONS In infants at <30 weeks' gestation receiving PPV in the DR, there were no differences in short-term outcomes using the nasal tube compared with the face mask.


title: Viral surveillance and discovery.

text: The field of virus discovery has burgeoned with the advent of high throughput sequencing platforms and bioinformatics programs that enable rapid identification and molecular characterization of known and novel agents, investments in global microbial surveillance that include wildlife and domestic animals as well as humans, and recognition that viruses may be implicated in chronic as well as acute diseases. Here we review methods for viral surveillance and discovery, strategies and pitfalls in linking discoveries to disease, and identify opportunities for improvements in sequencing instrumentation and analysis, the use of social media and medical informatics that will further advance clinical medicine and public health.


title: Carotid cavernous fistula after Pipeline placement: a single-center experience and review of the literature.

text: OBJECTIVE Carotid cavernous fistula (CCF) development after Pipeline Embolization Device (PED) treatment of cavernous carotid aneurysms (CCA) can be a challenging pathology to treat for the neurointerventionalist. METHODS A database of all patients whose aneurysms were treated with the PED since its approval by the Food and Drug Administration in 2011 was retrospectively reviewed. Demographic information, aneurysm characteristics, treatment technique, antiplatelet regimen, and follow-up data were collected. A literature review of all papers that describe PED treatment of CCA was then completed. RESULTS A total of 44 patients with 45 CCAs were identified (38 women, 6 men). The mean age was 59.9±9.0 years. The mean maximal aneurysm diameter was 15.9±6.9 mm (mean neck 7.1±3.6 mm). A single PED was deployed in 32 patients, with two PEDs deployed in 10 patients and three PEDs in 3 patients. Adjunctive coiling was performed in 3 patients. Mean follow-up duration based on final imaging (MR angiography or digital subtraction angiography) was 14.1±12.2 months. Five patients (11.4%) developed CCFs in the post-procedural period after PED treatment, all within 2 weeks of device placement. These CCFs were treated with a balloon test occlusion followed by parent artery sacrifice. Our literature review yielded only three reports of CCFs after PED placement, with the largest series having a CCF rate of 2.3%. CONCLUSIONS CCF formation is a known risk of PED treatment of CCA. Although transvenous embolization can be used for treating CCFs, parent artery sacrifice remains a viable option on the basis of these data. Studies support the view that adjunctive coiling may have a protective effect against post-PED CCF formation. None of the coiled aneurysms in our database or in the literature have ruptured. Follow-up data will lead to a better understanding of the safety profile of the PED for CCA.


title: Clinical and laboratory findings from patients with COVID-19 pneumonia in Babol North of Iran: a retrospective cohort study.

text: BACKGROUND In December, 2019, China, has experienced an outbreak of novel coronavirus disease 2019 (COVID-19). Coronavirus has now spread to all of the continents. We aimed to consider clinical characteristics, laboratory data of COVID-19 that provided more information for the research of this novel virus. METHODS We performed a retrospective cohort study on the clinical symptoms and laboratory findings of a series of the 100 confirmed patients with COVID-19. These patients were admitted to the hospitals affiliated to Babol University of Medical Sciences (Ayatollah Rohani, Shahid Beheshti and Yahyanejad hospitals) form 25 February 2020 to 12 March 2020. RESULTS Nineteen patients died during hospitalization and 81 were discharged. Non-survivor patients had a significantly higher C-reactive protein (CRP) (MD: 46.37, 95% CI: 20.84, 71.90; P= 0.001), white blood cells (WBCs) (MD: 3.10, 95% CI: 1.53, 4.67; P< 0.001) and lower lymphocyte (MD: -8.75, 95% CI: -12.62, -4.87; P< 0.001) compared to survivor patients Data analysis showed that comorbid conditions (aRR: 2.99, 95%CI: 1.09, 8.21, P= 0.034), higher CRP levels (aRR: 1.02, 95%CI: 1.01, 1.03, P= 0.044), and lower lymphocyte (aRR: 0.82, 95%CI: 0.73, 0.93, P= 0.003) were associated with increased risk of death. CONCLUSIONS Based on our findings, most non-survivors are elderly with comorbidities. Lymphopenia and increased levels of WBCs along with elevated CRP were associated with increased risk of death. Therefore, it is best to be regularly assessed these markers during treatment of COVID-19 patients.


title: [Epidemiology, Treatment, and Epidemic Prevention and Control of the Coronavirus Disease 2019: a Review].

text: This review summarizes the ongoing researches regarding etiology, epidemiology, transmission dynamics, treatment, and prevention and control strategies of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with comparison to severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and pandemic H1N1 virus. SARS-CoV-2 may be originated from bats, and the patients and asymptomatic carriers are the source of epidemic infection. The virus can be transmitted human-to-human through droplets and close contact, and people at all ages are susceptible to this virus. The main clinical symptoms of the patients are fever and cough, accompanied with leukocytopenia and lymphocytopenia. Effective drugs have been not yet available thus far. In terms of the prevention and control strategies, vaccine development as the primary prevention should be accelerated. Regarding the secondary prevention, ongoing efforts of the infected patients and close contacts quarantine, mask wearing promotion, regular disinfection in public places should be continued. Meanwhile, rapid detection kit for serological monitoring of the virus in general population is expected so as to achieve early detection, early diagnosis, early isolation and early treatment. In addition, public health education on this disease and prevention should be enhanced so as to mitigate panic and mobilize the public to jointly combat the epidemic.


title: Trends in Door-to-Thrombolysis Time in the Safe Implementation of Stroke Thrombolysis Registry: Effect of Center Volume and Duration of Registry Membership.

text: BACKGROUND AND PURPOSE Shorter delays between symptom onset and treatment translate into better outcomes after ischemic stroke thrombolysis. There are considerable intercenter variations in treatment delivery. We analyzed the trends of door-to-needle times (DNTs) in the Safe Implementation of Thrombolysis in Stroke registry between 2003 and 2011. METHODS We extracted from the Safe Implementation of Thrombolysis in Stroke registry (n=45 079) year of treatment, center code, DNT, sex, age, National Institutes of Health Stroke Scale, and comorbidity. For each center, the year they joined the registry and the annual volume of patients were determined (<5, 5-24, 25-49, 50-74, 75-99, and ≥100 patients/y). RESULTS DNT was not available for 720 (1.6%) patients. The overall mean (SD) DNT was 73 (37) minutes with a median (interquartile range) of 67 (47-91) minutes. The DNT was 65 (46-90), 68 (50-92), and 72 (51-98) minutes for centers joined early (2003-2005), later (2006-2009), and recently (2009-2011), respectively. Center volume had more robust effect on DNT than year of treatment, and the shortest DNTs were seen in centers with volumes ≥100 patients/y. Earlier enrollment period was also associated with shorter delays. CONCLUSIONS Centers that joined the registry earlier and those with high annual volume achieved shorter DNT than centers that joined later and low-volume centers. However, in most of the centers, DNT did not change much during the registry period. A multicenter project aiming to reduce DNT is warranted.


What the United States has to gain from global health research.


title: Direct endovascular recanalization of chronic carotid occlusion: should we do it? Case report.

text: BACKGROUND AND IMPORTANCE Patients with chronic carotid artery occlusion face a significant risk of stroke. It is believed that treatment is indicated if medical therapy fails or even as prophylaxis in high-risk patients. Direct surgical repair with carotid endarterectomy has a considerable failure rate and significant associated risks. Indirect repair with an extracranial-to-intracranial bypass has become the mainstay of surgical treatment. In this case study, the authors assess the feasibility of direct endovascular recanalization in the setting of chronic carotid occlusion, and discuss technical nuances and indications in comparison with the world literature and alternative options. CLINICAL PRESENTATION Two patients presented with symptomatic, chronic, complete occlusion of the proximal carotid artery. The duration of documented occlusion exceeded 3 years in one patient and 6 months in the other. METHODS Endovascular recanalization was attempted using extracranial and intracranial stenting with proximal protection (flow arrest/reversal). Both patients had an excellent radiographic result, improving from Thrombolysis in Cerebral Infarction (TICI) grade 0 (no perfusion) to grade 3 (complete perfusion). The first patient's clinical symptoms resolved. The second patient remained unchanged with a mild facial droop. CONCLUSION These preliminary results show potential for the endovascular management of this complicated disease. Long-term results and more data will determine the ultimate place of endovascular recanalization for symptomatic chronic carotid occlusion among other therapies.


title: Retrograde trans-posterior communicating artery snare-assisted rescue of lost access to a foreshortened pipeline embolization device: complication management.

text: BACKGROUND AND IMPORTANCE The Pipeline embolization device (PED; Covidien Vascular Therapies, Mansfield, Massachusetts) is a promising, yet experimental, vascular reconstruction device for the treatment of complex intracranial aneurysms. We present a PED-related complication and describe a salvage strategy. CLINICAL PRESENTATION A 64-year-old woman underwent PED-assisted parent vessel reconstruction for her giant cavernous internal carotid artery (ICA) aneurysm. During placement of the first PED, the proximal part of the PED foreshortened and was displaced into the aneurysm sac. Multiple subsequent attempts to recatheterize the PED failed, and, ultimately, distal access through and beyond the PED was lost. Therefore, completion of the Pipeline construct by stacking PEDs for definitive treatment was prevented. Retrograde access of the PED was gained from the distal ICA through a microwire that was advanced from the basilar artery through the posterior communicating artery. The microwire from the distal ICA was grasped with a snare from the proximal ICA and pulled down to the cervical ICA. The opened snare around the microwire was used as a lasso to advance a microcatheter from the cervical ICA through the PED to regain distal access. Five more PEDs were used to achieve complete parent vessel reconstruction and aneurysm obliteration. CONCLUSION Maintaining distal access is critical until the entire parent vessel is reconstructed, especially when multiple PEDs are required. The salvage technique described may help regain distal access if it is lost during the procedure.


title: MR-PET evaluation of 1-month post-ablation therapy for hepatocellular carcinoma: preliminary observations.

text: PURPOSE The purpose of the study was to evaluate the feasibility and protocol optimization of whole-body hybrid MR-PET system performed 1-month after post-locoregional thermoablative procedures for hepatocellular carcinomas (HCCs). MATERIALS AND METHODS Eight patients (6 men and 2 women; mean age, 56.6 ± 5.5 years) with 9 ablated HCCs constituted our study population. Three readers interpreted the studies to determine the presence or absence of residual malignancy. Two readers independently assessed the fused MR-PET images to compare registration accuracy of two types of T2-weighted (triggered T2 half-Fourier acquisition single-shot turbo spin-echo and turbo spin-echo) and T1-weighted [Cartesian and radial 3D gradient echo (GRE)]. Image quality evaluation of both 3D-GRE T1-weighted sequences was evaluated. Kappa statistics were used to measure inter-observer agreement. Non-parametric Kruskal-Wallis and Wilcoxon signed-rank tests were used for qualitative data analysis. RESULTS Definite residual tumor was observed in 3/9 ablations; two were PET positive. All residual tumors were isovascular on MRI. Radial 3D-GRE demonstrated significantly superior MR-PET subjective co-registration in comparison with the remaining sequences and showed a non-significant trend toward higher image quality scores than Cartesian GRE. CONCLUSION Whole-body hybrid MR-PET is feasible as a part of 1-month follow-up post-locoregional thermoablative treatment for HCC. Radial 3D-GRE offers improved co-registration with PET data, with overall good image quality.


title: Traditional chinese medicine: an update on clinical evidence.

text: BACKGROUND As an alternative medical system, Traditional Chinese Medicine (TCM) has been increasingly used over the last several decades. Such a consumer-driven development has resulted in introduction of education programs for practitioner training, development of product and practitioner regulation systems, and generation of an increasing interest in research. Significant efforts have been made in validating the quality, effectiveness, and safety of TCM interventions evidenced by a growing number of published trials and systematic reviews. Commonly, the results of these studies were inconclusive due to the lack of quality and quantity of the trials to answer specific and answerable clinical questions. OBJECTIVES The methodology of a randomized clinical trial (RCT) is not free from bias, and the unique features of TCM (such as individualization and holism) further complicate effective execution of RCTs in TCM therapies. Thus, data from limited RCTs and systematic reviews need to be interpreted with great caution. Nevertheless, until new and specific methodology is developed that can adequately address these methodology challenges for RCTs in TCM, evidence from quality RCTs and systematic reviews still holds the credibility of TCM in the scientific community. CONCLUSIONS This article summarizes studies on TCM utilization, and regulatory and educational development with a focus on updating the TCM clinical evidence from RCTs and systematic reviews over the last decade. The key issues and challenges associated with evidence-based TCM developments are also explored.