title: Vagus nerve-preserving versus conventional laparoscopic splenectomy and azygoportal disconnection.

text: BACKGROUND Conventional open and conventional laparoscopic splenectomy and azygoportal disconnection (CLSD) result in poor quality of life because of damage to the vagal nerve. We have developed vagus nerve-preserving laparoscopic splenectomy and azygoportal disconnection (VLSD). This study aimed to evaluate whether VLSD is effective and safe, and to determine whether a reduction in the incidence of postoperative complications improves postoperative quality of life compared with CLSD. METHODS We retrospectively evaluated outcomes in 72 cirrhotic patients with portal hypertensive bleeding and secondary hypersplenism who underwent CLSD (n = 40) or VLSD (n = 32) between April 2015 and December 2016. Their demographic, intraoperative, and postoperative variables were compared. RESULTS No patients required conversion to laparotomy in CLSD and VLSD. There was no difference in estimated intraoperative blood loss, volume of intraoperative blood transfused, time to first flatus, time to off-bed activity, and postoperative hospital stay between the two groups. VLSD was associated with a shorter operation time (P = 0.020) and less postoperative complications (P < 0.0001), including less diarrhea (P < 0.0001), epigastric fullness (P < 0.0001), and delayed gastric emptying (P < 0.0001), compared with CLSD. With VLSD, there was a significant increase in body weight and plasma albumin levels at 6 months postoperatively compared with preoperative values (all P < 0.05). The curative effect of improving esophageal/gastric variceal bleeding was similar in the groups. CONCLUSIONS VLSD is effective and safe for reducing the incidence of postoperative complications, contributing to improving postoperative quality of life.


title: Robotic-Assisted Laparoscopic Biliopancreatic Diversion, Vertical Sleeve Gastrectomy with Traditional Roux-en-Y Duodenal Switch.

text: BACKGROUND Although effective, duodenal switch can be a complicated and time-consuming operation for surgeons. PURPOSE The purpose of this article is to present our technique of biliopancreatic diversion and vertical sleeve gastrectomy, creating a 150-cm common channel and a 100-cm alimentary limb. MATERIAL AND METHODS A robot-assisted technique was utilized in creating a biliopancreatic diversion and vertical sleeve gastrectomy. RESULTS Laparoscopy was used for marking stitches and then the robot was docked. After creating a window behind the duodenum, sleeve gastrectomy is performed followed by duodeno-ileal anastomosis and ileo-ileal anastomosis. CONCLUSION With the adoption of robots and the described technique, it can be easier to be achieved in less time.


title: C7-Indole Amidations and Alkenylations by Ruthenium(II) Catalysis.

text: C7-H functionalized indoles are ubiquitous structural units of biological and pharmaceutical compounds for numerous antiviral agents against SARS-CoV or HIV-1. Thus, achieving site-selective functionalizations of C7-H of indoles, while discriminating among other bonds, is highly demand. Herein, we disclose site-selective C7-H activations of indoles accomplished by ruthenium(II)biscarboxylate catalysis under mild conditions. Base-assisted internal electrophilic-type substitution C-H ruthenation by weak O-coordination enabled the C7-H functionalizations of indoles, offering ample scope including C-N and C-C bond formation. The versatile ruthenium-catalyzed C7-H activations were characterized by gram-scale syntheses and the traceless removal of directing group, providing easy access to pharmaceutically relevant scaffolds. Detailed mechanistic studies through spectroscopic and spectrometric analyses shed light on the unique nature of robust ruthenium catalysis for C7-H indole functionalizations.


title: Benefits and stressors - Perceived effects of ICT use on employee health and work stress: An exploratory study from Austria and Hong Kong.

text: Stress has become a mass phenomenon in the modern workplace. The use of information and communication technologies is beginning to receive greater attention in the context of occupational stress. An exploratory qualitative study was conducted to examine both stressors and benefits resulting from technologies among practitioners in the advertising, public relations, and journalism industry in Hong Kong and Austria. Results suggest that technologies allow instant availability, which facilitates communication processes as well as information exchange. Notably, modern technologies enable employees to organize their work with greater temporal and spatial flexibility, thus creating an opportunity for better balancing work and private life. However, evolving technologies have come with a cost; the pressure to be constantly available via technologies constitutes a major source of stress, increasing the risk of experiencing prolonged work stress and its adverse consequences on employee health and well-being, such as a burnout. Furthermore, findings suggest that availability pressure may be attributed to an inner obligation rather than to an organizational expectation. Hence, making employees aware of their connectivity behaviour may help to diminish the experience of technology-induced work stress and improve and maintain employees' health and well-being in the long term. Practical implications, limitations, and future research directions are provided.


A case of pulmonary aspergilloma treated with radiofrequency ablation.


title: Smoking is not associated with recurrence and retreatment of intracranial aneurysms after endovascular coiling.

text: OBJECT Tobacco smoking is one of the most important risk factors for the formation of intracranial aneurysms and for aneurysmal subarachnoid hemorrhages. Smoking has also been suggested to contribute to the recurrence of aneurysms after endovascular coiling. To improve the understanding of the impact of smoking on long-term outcomes after coil embolization of intracranial aneurysms, the authors studied a consecutive contemporary series of patients treated at their institution. The aims of this study were to determine whether smoking is an independent risk factor for aneurysm recurrence and retreatment after endovascular coiling. METHODS All patients who had received an intrasaccular coil embolization of an intracranial aneurysm, who had undergone a follow-up imaging exam at least 6 months later, and whose smoking history had been recorded from January 2005 through December 2012 were included in this study. Patients were stratified according to smoking status into 3 groups: 1) never a smoker, 2) current smoker (smoked at the time of treatment), and 3) former smoker (quit smoking before treatment). The 2 primary outcomes studied were aneurysm recurrence and aneurysm retreatment after treatment for endovascular aneurysms. Kruskal-Wallis and chi-square tests were used to test statistical significance of differences in the rates of aneurysm recurrence, retreatment, or of both among the 3 groups. A multivariate logistic regression analysis controlling for smoking status and for several characteristics of the aneurysm was also performed. RESULTS In total, 384 patients with a combined total of 411 aneurysms were included in this study. The aneurysm recurrence rate was not significantly associated with smoking: both former smokers (OR 1.00, 95% CI 0.61-1.65; p = 0.99) and current smokers (OR 0.58, 95% CI 0.31-1.09; p = 0.09) had odds of recurrence that were similar to those who were never smokers. Former smokers (OR 0.78, 95% CI 0.46-1.35; p = 0.38) had odds of retreatment similar to those of never smokers, and current smokers had a lower odds of undergoing retreatment (OR 0.44, 95% CI 0.21-0.91; p = 0.03) than never smokers. Moreover, an analysis adjusting for aneurysm rupture, diameter, and initial occlusion showed that former smokers (OR 0.65, 95% CI 0.33-1.28; p = 0.21) and current smokers (OR 1.04, 95% CI 0.60-1.81; p = 0.88) had odds of aneurysm recurrence similar to those who were never smokers. Adjusting the analysis for aneurysm rupture, diameter, and occlusion showed that both former smokers (OR 0.49, 95% CI 0.23-1.05; p = 0.07) and current smokers (OR 0.82, 95% CI 0.46-1.46; p = 0.50) had odds of retreatment similar to those of patients who were never smokers. CONCLUSIONS The results show that smoking was not an independent risk factor for aneurysm recurrence and aneurysm retreatment among patients receiving endovascular treatment for intracranial aneurysms at the authors' institution. Nonetheless, patients with intracranial aneurysms should continue to be counseled about the risks of tobacco smoking.


title: Prophylactic mesh at end-colostomy construction reduces parastomal hernia rate: a randomized trial.

text: AIM Parastomal hernia (PSH) is the most common complication of an end-colostomy and about one-quarter of patients need operative repair, which is often unsuccessful. A randomized trial was carried out to compare the results of using mesh or no mesh at the time of formation of a colostomy with the clinical identification of PSH as the primary outcome. METHOD In this two-centre randomized trial (Oslo University Hospital and Sykehuset Innlandet Hospital Trust, Norway), patients with rectal cancer undergoing open pelvic surgery were randomized to receive a retromuscular synthetic mesh (study group, n = 32) or no mesh (control group, n = 26) at the time of end-colostomy formation. Postoperative follow up was not blinded and included clinical examination and routine CT. RESULTS The median period of follow up was 40 (range: 84) months. There were no differences in demographic variables or complications between the study and control groups. PSH developed in two patients of the study group and in 12 of the control group [OR = 0.04 (95% CI: 0.01-0.30) and hazard ratio 0.134 (95% CI: 0.030-0.603); P < 0.001]. The number needed to treat to avoid one PSH was 2.5 patients. CT demonstrated an increase over time in the size of the fascial orifice in patients with PSH without mesh prophylaxis, in contrast to a stable size in patients with mesh and in the control patients who did not develop PSH. CONCLUSION The retromuscular insertion of synthetic mesh at the time of formation of an end-colostomy reduced the risk of PSH.


title: Uniportal video-assisted thoracoscopic surgery: safety, efficacy and learning curve during the first 250 cases in Quebec, Canada.

text: BACKGROUND Video-assisted thoracoscopic surgery (VATS) using a single incision (uniportal) may result in better pain control, earlier mobilization and shorter hospital stays. Here, we review the safety and efficiency of our initial experience with uniportal VATS and evaluate our learning curve. METHODS We conducted a retrospective review of uniportal VATS using a prospectively maintained departmental database and analyzed patients who had undergone a lung anatomic resection separately from patients who underwent other resections. To assess the learning curve, we compared the first 10 months of the study period with the second 10 months. RESULTS From January 2014 to August 2015, 250 patients underwent intended uniportal VATS, including 180 lung anatomic resections (72%) and 70 other resections (28%). Lung anatomic resection was successfully completed using uniportal VATS in 153 patients (85%), which comprised all the anatomic segmentectomies (29 patients), 80% (4 of 5) of the pneumonectomies and 82% (120 of 146) of the lobectomies attempted. The majority of lung anatomic resections that required conversion to thoracotomy occurred in the first half of our study period. Seventy patients underwent other uniportal VATS resections. Wedge resections were the most common of these procedures (25 patients, 35.7%). Although 24 of the 70 patients (34%) required the placement of additional ports, none required conversion to thoracotomy. CONCLUSIONS Uniportal VATS was safe and feasible for both standard and complex pulmonary resections. However, when used for pulmonary anatomic resections, uniportal VATS entails a steep learning curve.


The Challenges of Behavioral Health Integration: The Persistence of the Mind-Body Problem.


title: Risk Factors for Growth of Intracranial Aneurysms: A Systematic Review and Meta-Analysis.

text: BACKGROUND AND PURPOSE Understanding risk factors for intracranial aneurysm growth is important for patient management. We performed a meta-analysis examining risk factors for intracranial aneurysm growth in longitudinal studies and examined the association between aneurysm growth and rupture. MATERIALS AND METHODS We searched the literature for longitudinal studies of patients with unruptured aneurysms. We examined the associations of demographics, multiple aneurysms, prior subarachnoid hemorrhage, family history of aneurysm or subarachnoid hemorrhage, smoking, and hypertension; and aneurysm shape, size, and location with aneurysm growth. We studied the association between aneurysm growth and rupture. A meta-analysis was performed by using a random-effects model by using summary statistics from included studies. RESULTS Twenty-one studies including 3954 patients with 4990 aneurysms with 13,294 aneurysm-years of follow-up were included. The overall proportion of growing aneurysms was 3.0% per aneurysm-year (95% CI, 2.0%-4.0%). Patient risk factors for growth included age older than 50 years (3.8% per year versus 0.9% per year, P < .01), female sex (3.2% per year versus 1.3% per year, P < .01), and smoking history (5.5% per year versus 3.5% per year, P < .01). Characteristics associated with higher growth rates included cavernous carotid artery location (14.4% per year), nonsaccular shape (14.7% per year versus 5.2% per year for saccular, P < .01), and aneurysm size (P < .01). Aneurysm growth was associated with a rupture rate of 3.1% per year compared with 0.1% per year for stable aneurysms (P < .01). CONCLUSIONS Observational evidence provided multiple clinical and anatomic risk factors for aneurysm growth, including age older than 50 years, female sex, smoking history, and nonsaccular shape. These findings should be considered when counseling patients regarding the natural history of unruptured intracranial aneurysms.


Potential influences of obstructive sleep apnea and obesity on COVID-19 severity.


title: A laparoscopic high anterior resection for sigmoid cancer with extraction through incarcerated left inguinal hernia repaired with Permacol mesh.

text: A 65-year-old man presented to the general surgical outpatients with an incarcerated left inguinal hernia. Initial investigations revealed an iron deficiency anaemia that was investigated with a colonoscopy and gastroscopy. This revealed a sigmoid cancer and the staging CT scan confirmed a tumour incarcerated in the sac of the left inguinal hernia. We proceeded with a laparoscopic high anterior resection using the inguinal hernia as the extraction site. The hernia was repaired using Permacol mesh. No postoperative complications occurred.


title: Balancing benefits and risks of glucocorticoids in rheumatic diseases and other inflammatory joint disorders: new insights from emerging data. An expert consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).

text: PURPOSE This consensus review article considers the question of whether glucocorticoid (GC) therapy is still relevant in the treatment of rheumatic diseases, with a particular focus on rheumatoid arthritis (RA), and whether its side effects can be adequately managed. Recent basic and clinical research on the molecular, cellular and clinical effects of GCs have considerably advanced our knowledge in this field. An overview of the subject seems appropriate. METHODS This review is the result of a multidisciplinary expert working group, organised by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. The recent literature was surveyed and the salient evidence synthetized. RESULTS The pathophysiological basis of RA (and other inflammatory rheumatic diseases) now strongly implicates the adaptive immune system in addition to innate mechanisms. The molecular effect of GCs and differential GC sensitivity is better understood, although exploiting this knowledge is still in its infancy. The newer treatment strategies of early and aggressive control of RA have gr eatly improved clinical outcomes, but improvements are still possible. Newer targeted anti-inflammatory drugs have made an important impact, yet they too are associated with numerous side effects. DISCUSSION Short durations of moderate doses of GCs are generally well tolerated and have a positive benefit/risk ratio. Patients should be assessed for fracture risk and bone preserving agents and be prescribed calcium and vitamin D supplementation. CONCLUSIONS Within a strategy of a disease modifying approach to inflammatory disease, combination therapy including a GC is effective approach.


title: Student life - Off on a placement in Zambia.

text: Recent outbreaks of disease, including Ebola, Zika and Middle East Respiratory Syndrome, have shown the need for a collaborative and co-ordinated response to global health issues.


title: GnRHa Before Single-Port Laparoscopic Hysterectomy in a Large Barrel-Shaped Uterus.

text: Background and Objectives Laparoscopic hysterectomy for a large barrel-shaped uterus is difficult. We assessed the feasibility of single-port laparoscopic hysterectomy in a large barrel-shaped uterus after gonadotropin-releasing hormone agonist (GnRHa). Methods We retrospectively reviewed 39 patients with a large barrel-shaped uterus who were treated with GnRHa (leuprolide acetate) before single-port laparoscopic hysterectomy. During the same period, 134 patients without GnRHa pretreatment were included as control subjects. Results Patients with GnRHa treatment had an average increase in hemoglobin of 3.0 mg/dL and a decrease in uterine weight of 330.9 g (40.1%). Ancillary ports were required in 2 patients in the treatment group and none in the control group. There were no differences in uterine weights, operative time, and estimated blood loss in the 2 groups of patients. The estimated average operative time was shortened by 34 min after GnRHa treatment. However, bladder and ureter injuries were marginally higher (10.3% versus 2.2%) and days of hospital stay (3.7 versus 3.1) were significantly longer in the treatment group compared with controls. Complication rates were correlated with previous operative history, pelvic adhesion, and larger uterine weight but not with GnRHa treatment and operative sequence. Conclusions GnRHa pretreatment in patients with a large barrel-shaped uterus during SPH is feasible with shortened operative time. However, the higher complication rates in these patients suggest that a weight-reduced barrel-shaped uterus that is achieved with GnRHa treatment could still be difficult and should be handled in cautious.


title: Epistasis between mutations is host-dependent for an RNA virus.

text: How, and to what extent, does the environment influence the way mutations interact? Do environmental changes affect both the sign and the magnitude of epistasis? Are there any correlations between environments in the variability, sign or magnitude of epistasis? Very few studies have tackled these questions. Here, we addressed them in the context of viral emergence. Most emerging viruses are RNA viruses with small genomes, overlapping reading frames and multifunctional proteins for which epistasis is abundant. Understanding the effect of host species in the sign and magnitude of epistasis will provide insights into the evolutionary ecology of infectious diseases and the predictability of viral emergence.


title: Saturated salt solution method: a useful cadaver embalming for surgical skills training.

text: This article evaluates the suitability of cadavers embalmed by the saturated salt solution (SSS) method for surgical skills training (SST). SST courses using cadavers have been performed to advance a surgeon's techniques without any risk to patients. One important factor for improving SST is the suitability of specimens, which depends on the embalming method. In addition, the infectious risk and cost involved in using cadavers are problems that need to be solved. Six cadavers were embalmed by 3 methods: formalin solution, Thiel solution (TS), and SSS methods. Bacterial and fungal culture tests and measurement of ranges of motion were conducted for each cadaver. Fourteen surgeons evaluated the 3 embalming methods and 9 SST instructors (7 trauma surgeons and 2 orthopedists) operated the cadavers by 21 procedures. In addition, ultrasonography, central venous catheterization, and incision with cauterization followed by autosuture stapling were performed in some cadavers. The SSS method had a sufficient antibiotic effect and produced cadavers with flexible joints and a high tissue quality suitable for SST. The surgeons evaluated the cadavers embalmed by the SSS method to be highly equal to those embalmed by the TS method. Ultrasound images were clear in the cadavers embalmed by both the methods. Central venous catheterization could be performed in a cadaver embalmed by the SSS method and then be affirmed by x-ray. Lungs and intestines could be incised with cauterization and autosuture stapling in the cadavers embalmed by TS and SSS methods. Cadavers embalmed by the SSS method are sufficiently useful for SST. This method is simple, carries a low infectious risk, and is relatively of low cost, enabling a wider use of cadavers for SST.


title: Human rhinovirus spatial-temporal epidemiology in rural coastal Kenya, 2015-2016, observed through outpatient surveillance.

text: Background: Human rhinovirus (HRV) is the predominant cause of upper respiratory tract infections, resulting in a significant public health burden. The virus circulates as many different types (~160), each generating strong homologous, but weak heterotypic, immunity. The influence of these features on transmission patterns of HRV in the community is understudied. Methods: Nasopharyngeal swabs were collected from patients with symptoms of acute respiratory infection (ARI) at nine out-patient facilities across a Health and Demographic Surveillance System between December 2015 and November 2016. HRV was diagnosed by real-time RT-PCR, and the VP4/VP2 genomic region of the positive samples sequenced. Phylogenetic analysis was used to determine the HRV types. Classification models and G-test statistic were used to investigate HRV type spatial distribution. Demographic characteristics and clinical features of ARI were also compared. Results: Of 5,744 NPS samples collected, HRV was detected in 1057 (18.4%), of which 817 (77.3%) were successfully sequenced. HRV species A, B and C were identified in 360 (44.1%), 67 (8.2%) and 390 (47.7%) samples, respectively. In total, 87 types were determined: 39, 10 and 38 occurred within species A, B and C, respectively. HRV types presented heterogeneous temporal patterns of persistence. Spatially, identical types occurred over a wide distance at similar times, but there was statistically significant evidence for clustering of types between health facilities in close proximity or linked by major road networks. Conclusion: This study records a high prevalence of HRV in out-patient presentations exhibiting high type diversity. Patterns of occurrence suggest frequent and independent community invasion of different types. Temporal differences of persistence between types may reflect variation in type-specific population immunity. Spatial patterns suggest either rapid spread or multiple invasions of the same type, but evidence of similar types amongst close health facilities, or along road systems, indicate type partitioning structured by local spread.


title: Single-incision laparoscopic intraperitoneal onlay mesh repair for the treatment of multiple recurrent inguinal hernias.

text: INTRODUCTION Despite an exponential rise in laparoscopic surgery for inguinal herniorrhaphy, overall recurrence rates have remained unchanged. Therefore, an increasing number of patients present with recurrent hernias after having failed anterior and laparoscopic repairs. This study reports our experience with single-incision laparoscopic (SIL) intraperitoneal onlay mesh (IPOM) repair for these hernias. MATERIALS AND METHODS All patients referred with multiply recurrent inguinal hernias underwent SIL-IPOM from November 1 2009 to October 30 2013. A 2.5-cm infraumbilical incision was made and a SIL surgical port was placed intraperitoneally. Modified dissection techniques, namely, "chopsticks" and "inline" dissection, 5.5 mm/52 cm/30° angled laparoscope and conventional straight dissecting instruments were used. The peritoneum was incised above the symphysis pubis and dissection continued laterally and proximally raising an inferior flap, below a previous extraperitoneal mesh, while reducing any direct/indirect/femoral/cord lipoma before placement of antiadhesive mesh that was fixed into the pubic ramus as well as superiorly with nonabsorbable tacks before fixing its inferior border with fibrin sealant. The inferior peritoneal flap was then tacked back onto the mesh. RESULTS There were 9 male patients who underwent SIL-IPOM. Mean age was 55 years old and mean body mass index was 26.8 kg/m2. Mean mesh size was 275 cm2. Mean operation time was 125 minutes with hospital stay of 1 day and umbilical scar length of 21 mm at 4 weeks' follow-up. There were no intraoperative/postoperative complications, port-site hernias, chronic groin pain, or recurrence with mean follow-up of 20 months. CONCLUSIONS Multiply recurrent inguinal hernias after failed conventional anterior and laparoscopic repairs can be treated safely and efficiently with SIL-IPOM.


title: Homeopathic Clinical Features of 18 Patients in COVID-19 Outbreaks in Hong Kong.

text: BACKGROUND Hong Kong is geographically located in the province of Guangdong which, after Hubei, has been the region of China second-most affected by the COVID-19 pandemic. Compared to the pathognomonic symptoms of the named disease, homeopathic symptoms are always more helpful for homeopathic prescriptions. AIM This study reports and summarizes the homeopathic symptoms observed in 18 confirmed/suspected epidemiologically related cases in cluster outbreaks of COVID-19 in Hong Kong in early 2020. METHODS Homeopathic symptoms from this case series were collected from 18 consecutive patients who, in addition to their concurrent conventional treatment or traditional Chinese medicine, actively sought help from homeopathy as an adjunctive measure for symptomatic relief from COVID-19. Cases were categorized according to outbreak clusters, focusing mainly on the homeopathic symptoms. In the analysis, frequency of all homeopathic medicines, common rubrics in all the cases, common rubrics in each of the top-ranked remedies, and differentiating symptoms for each top-ranked remedy were determined. RESULTS Homeopathic symptoms of 18 cases, each identified as mild and belonging to one of six separate clusters, are reported. Eighteen common symptoms screened out of 79 selected rubrics constituted two sets of homeopathic symptom pictures: Bryonia alba (n = 4) and Gelsemium sempervirens (n = 12). Eight and seven differentiating features, respectively, were identified for Bryonia alba and Gelsemium sempervirens. CONCLUSION The common symptoms of 18 mild COVID-19 cases constituted two sets of homeopathic symptom pictures, indicating Bryonia alba or Gelsemium sempervirens; they were indicated in 4 and 12 cases, respectively, out of the 18 in total.


title: Alternative technique for clot retrieval: The "tip of the iceberg" technique.

text: We present a variation of the classical technique of stent retriever thrombectomy which we found helpful in two patients presenting with acute stroke. CT angiography in both patients demonstrated thrombus within a middle cerebral artery M2 branch. In both cases the occluded artery was not visualized on DSA and only the proximal tip of the clot could be seen as a filling defect "hanging" into the parent artery reminiscent of a "tip of an iceberg". Rather than selectively catheterizing the occluded branch we placed the stent retriever in the patent parent artery crossing only the tip of the clot. In both cases one pass of the stent retriever was sufficient to retrieve the whole clot by its tip and reopen the occluded branch. We suggest trying this technique whenever the clot is seated in the proximal part of a secondary branch such as an M2 segment of middle cerebral artery. This "tip of the iceberg" technique prevents the need to selectively catheterize the occluded branch which, if difficult, can prolong procedural and ischemic time.


title: An interaction between the nucleocapsid protein and a component of the replicase-transcriptase complex is crucial for the infectivity of coronavirus genomic RNA.

text: The coronavirus nucleocapsid (N) protein plays an essential role in virion assembly via interactions with the large, positive-strand RNA viral genome and the carboxy-terminal endodomain of the membrane protein (M). To learn about the functions of N protein domains in the coronavirus mouse hepatitis virus (MHV), we replaced the MHV N gene with its counterpart from the closely related bovine coronavirus (BCoV). The resulting viral mutant was severely defective, even though individual domains of the N protein responsible for N-RNA, N-M, or N-N interactions were completely interchangeable between BCoV and MHV. The lesion in the BCoV N substitution mutant could be compensated for by reverting mutations in the central, serine- and arginine-rich (SR) domain of the N protein. Surprisingly, a second class of reverting mutations were mapped to the amino terminus of a replicase subunit, nonstructural protein 3 (nsp3). A similarly defective MHV N mutant bearing an insertion of the SR region from the severe acute respiratory syndrome coronavirus N protein was rescued by the same two classes of reverting mutations. Our genetic results were corroborated by the demonstration that the expressed amino-terminal segment of nsp3 bound selectively to N protein from infected cells, and this interaction was RNA independent. Moreover, we found a direct correlation between the N-nsp3 interaction and the ability of N protein to stimulate the infectivity of transfected MHV genomic RNA (gRNA). Our results suggest a role for this previously unknown N-nsp3 interaction in the localization of genomic RNA to the replicase complex at an early stage of infection.


Authors' response re: From the frontlines of COVID-19-How prepared are we as obstetricians: a commentary.


title: Membrane fixation for osseous graft stabilization in periodontally accelerated osteogenic orthodontics: a comparative study.

text: BACKGROUND Periodontally accelerated osteogenic orthodontics (PAOO) is a treatment for bone defects associated with a lack of bone graft stability, especially in coronal locations. This study aimed to compare a modified technique of membrane fixation that utilizes periosteal sutures (using a pouch design) with the traditional approach, which does not use membrane fixation. METHODS Twenty-eight patients with a total of 168 teeth treated were divided into two groups: 1-A, in which patients were treated using the modified technique (with membrane fixation), and group 2-B, in which patients were treated using the traditional technique (without membrane fixation). The postoperative bone thickness was evaluated via radiographic examination. RESULTS Postoperative improvements in bone augmentation were detected in both groups. At 12 months, the values of the CHBT (measured from the midpoint of the coronal third to the labial cortical surface, 0.84 ± 0.33 mm) and the values of VBL (measured from the alveolar crest to the cemento-enamel junction, - 2.35 ± 0.80 mm)were significantly greater in the modified technique group than those in the traditional technique group (CHBT:0.12 ± 0.21 mm and VBL:-1.39 ± 0.99 mm; P = 0.00 and P = 0.01). CONCLUSIONS This study shows that compared to the traditional technique, the modified PAOO technique with membrane fixation using periosteal sutures provides improved graft stabilization, superior coronal augmentation and satisfactory vertical volume.


title: Intravenous rtPA versus mechanical thrombectomy in acute ischemic stroke: A historical cohort in Joinville, Brazil.

text: Groundbreaking results concerning ischemic stroke (IS) hyperacute treatment worldwide were published in 2014 and 2015. We aimed to compare functional status after 3 months in patients treated with intra-arterial thrombectomy (IAT) and those treated with intravenous thrombolysis (IVT) alone in Joinville, Brazil. From the Joinville Stroke Registry, we extracted and compared all consecutive IVT patients treated with r-tPA within 4.5 h in the period 2009-2011 versus all consecutive IAT treated within 6 h with the Solitaire FR device plus IVT in the period 2012-2014. We registered 82 patients in the IVT group and 31 patients in the IAT group. At hospital admission, patients in the IAT group were significantly younger (p < 0.001), had a higher educational level (p = 0.001), had a slightly higher prevalence of atrial fibrillation (p = 0.057) and had more severe strokes measured by the NIH stroke scale (p = 0.011). After 90 days, 45% of patients in the IAT group and 27% in the IVT group were independent (0-1 points) according to the modified Rankin scale (adjusted odds ratio: 4.53; 95% CI: 1.22 to 16.75). Symptomatic hemorrhage was diagnosed in 10% of patients in both groups (p = 1.0). The 90-day case-fatality was 39% (32/82) in the IVT group and 26% (8/31) in the IAT group (p = 0.27). In this small cohort, a greater rate of functional independence was achieved in patients treated with IAT plus IVT, compared with patients treated with IVT lysis alone. Our "real-world" findings are consistent with results of controlled, randomized clinical trials.


title: Benzodiazepines for antipsychotic-induced tardive dyskinesia.

text: BACKGROUND Tardive dyskinesia (TD) is a disfiguring movement disorder, often of the orofacial region, frequently caused by using antipsychotic drugs. A wide range of strategies have been used to help manage TD, and for those who are unable to have their antipsychotic medication stopped or substantially changed, the benzodiazepine group of drugs have been suggested as a useful adjunctive treatment. However, benzodiazepines are very addictive. OBJECTIVES To determine the effects of benzodiazepines for antipsychotic-induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder, or other chronic mental illnesses. SEARCH METHODS On 17 July 2015 and 26 April 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (including trial registers), inspected references of all identified studies for further trials and contacted authors of each included trial for additional information. SELECTION CRITERIA We included all randomised controlled trials (RCTs) focusing on people with schizophrenia (or other chronic mental illnesses) and antipsychotic-induced TD that compared benzodiazepines with placebo, no intervention, or any other intervention for the treatment of TD. DATA COLLECTION AND ANALYSIS We independently extracted data from the included studies and ensured that they were reliably selected, and quality assessed. For homogenous dichotomous data, we calculated random effects, risk ratio (RR), and 95% confidence intervals (CI). We synthesised continuous data from valid scales using mean differences (MD). For continuous outcomes, we preferred endpoint data to change data. We assumed that people who left early had no improvement. MAIN RESULTS The review now includes four trials (total 75 people, one additional trial since 2006, 21 people) randomising inpatients and outpatients in China and the USA. Risk of bias was mostly unclear as reporting was poor. We are uncertain about all the effects as all evidence was graded at very low quality. We found no significant difference between benzodiazepines and placebo for the outcome of 'no clinically important improvement in TD' (2 RCTs, 32 people, RR 1.12, 95% CI 0.60 to 2.09, very low quality evidence). Significantly fewer participants allocated to clonazepam compared with phenobarbital (as active placebo) experienced no clinically important improvement (RR 0.44, 95% CI 0.20 to 0.96, 1 RCT, 21 people, very low quality evidence). For the outcome 'deterioration of TD symptoms,' we found no clear difference between benzodiazepines and placebo (2 RCTs, 30 people, RR 1.48, 95% CI 0.22 to 9.82, very low quality evidence). All 10 participants allocated to benzodiazepines experienced any adverse event compared with 7/11 allocated to phenobarbital (RR 1.53, 95% CI 0.97 to 2.41, 1 RCT, 21 people, very low quality evidence). There was no clear difference in the incidence of participants leaving the study early for benzodiazepines compared with placebo (3 RCTs, 56 people, RR 2.73, 95% CI 0.15 to 48.04, very low quality evidence) or compared with phenobarbital (as active placebo) (no events, 1 RCT, 21 people, very low quality evidence). No trials reported on social confidence, social inclusion, social networks, or personalised quality of life, which are outcomes designated important by patients. No trials comparing benzodiazepines with placebo or treatment as usual reported on adverse effects. AUTHORS' CONCLUSIONS There is only evidence of very low quality from a few small and poorly reported trials on the effect of benzodiazepines as an adjunctive treatment for antipsychotic-induced TD. These inconclusive results mean routine clinical use is not indicated and these treatments remain experimental. New and better trials are indicated in this under-researched area; however, as benzodiazepines are addictive, we feel that other techniques or medications should be adequately evaluated before benzodiazepines are chosen.


title: Does Sex/Gender Play a Role in Placebo and Nocebo Effects? Conflicting Evidence From Clinical Trials and Experimental Studies.

text: Sex has been speculated to be a predictor of the placebo and nocebo effect for many years, but whether this holds true or not has rarely been investigated. We utilized a placebo literature database on various aspects of the genuine placebo/nocebo response. In 2015, we had extracted 75 systematic reviews, meta-analyses, and meta-regressions performed in major medical areas (neurology, psychiatry, internal medicine). These meta-analyses were screened for whether sex/gender differences had been noted to contribute to the placebo/nocebo effect: in only 3 such analyses female sex was associated with a higher placebo effect, indicating poor evidence for a contribution of sex to it in RCTs. This was updated with another set of meta-analyses for the current review, but did not change the overall conclusion. The same holds true for 18 meta-analyses investigating adverse event (nocebo) reporting in RCT in the placebo arm of trials. We also screened our database for papers referring to sex/gender and the placebo effect in experimental studies, and identified 28 papers reporting 29 experiments. Their results can be summarized as follows: (a) Despite higher sensitivity of pain in females, placebo analgesia is easier to elicit in males; (b) It appears that conditioning is effective specifically eliciting nocebo effects; (c) Conditioning works specifically well to elicit placebo and nocebo effects in females and with nausea; (d) Verbal suggestions are not sufficient to induce analgesia in women, but work in men. These results will be discussed with respect to the question why nausea and pain may be prone to be responsive to sex/gender differences, while other symptoms are less. Lastly, we will discuss the apparent discrepancy between RCT with low relevance of sex, and higher relevance of sex in specific experimental settings. We argue that the placebo response is predominantly the result of a conditioning (learning) response in females, while in males it predominantly may be generated via (verbal) manipulating of expectancies. In RCT therefore, the net outcome of the intervention may be the same despite different mechanisms generating the placebo effect between the sexes, while in experimental work when both pathways are separated and explicitly explored, such differences may surface.


title: Minimally Invasive Repair of Pediatric Morgagni Hernias Using Transfascial Sutures with Extracorporeal Knot Tying.

text: BACKGROUND Morgagni hernias are rare, with a reported incidence of 2% to 5% of congenital diaphragmatic hernias. OBJECTIVES To review a laparoscopic technique to repair Morgagni hernias in pediatric patients. METHODS Retrospective chart review of pediatric patients who underwent minimally invasive repair of a Morgagni hernia from November 2009 to September 2017 within a defined population. RESULTS During an 8-year period, 15 patients with Morgagni hernias were identified. Four patients with Morgagni hernias were excluded because they had open repairs. Eleven Morgagni hernias were repaired through a completely minimally invasive approach. Three repairs were completed using a soft-tissue patch (Gore-Tex patch, W L Gore & Associates Inc, Flagstaff, AZ). All minimally invasive repairs were completed with transfascial sutures using an endoscopic suturing device (Endo Close, Covidien/Medtronic, Fridley, MN) and 2-0 nonabsorbable synthetic sutures with extracorporeal knot tying. Median follow-up was 40 months (range = 2.6 months to 7.3 years). No patients had postoperative pectus excavatum defects. There were no recurrences. CONCLUSION Morgagni hernias are amenable to minimally invasive repair with this simple technique. With large defects, synthetic patches should be used. Recurrences are rare, and morbidity is low.


The Challenges Wrought by COVID-19.


title: DNA vaccines for targeting bacterial infections.

text: DNA vaccination has been of great interest since its discovery in the 1990s due to its ability to elicit both humoral and cellular immune responses. DNA vaccines consist of a DNA plasmid containing a transgene that encodes the sequence of a target protein from a pathogen under the control of a eukaryotic promoter. This revolutionary technology has proven to be effective in animal models and four DNA vaccine products have recently been approved for veterinary use. Although few DNA vaccines against bacterial infections have been tested, the results are encouraging. Because of their versatility, safety and simplicity a wider range of organisms can be targeted by these vaccines, which shows their potential advantages to public health. This article describes the mechanism of action of DNA vaccines and their potential use for targeting bacterial infections. In addition, it provides an updated summary of the methods used to enhance immunogenicity from codon optimization and adjuvants to delivery techniques including electroporation and use of nanoparticles.


title: Tough adhesives for diverse wet surfaces.

text: Adhesion to wet and dynamic surfaces, including biological tissues, is important in many fields but has proven to be extremely challenging. Existing adhesives are cytotoxic, adhere weakly to tissues, or cannot be used in wet environments. We report a bioinspired design for adhesives consisting of two layers: an adhesive surface and a dissipative matrix. The former adheres to the substrate by electrostatic interactions, covalent bonds, and physical interpenetration. The latter amplifies energy dissipation through hysteresis. The two layers synergistically lead to higher adhesion energies on wet surfaces as compared with those of existing adhesives. Adhesion occurs within minutes, independent of blood exposure and compatible with in vivo dynamic movements. This family of adhesives may be useful in many areas of application, including tissue adhesives, wound dressings, and tissue repair.


title: Use of Pipeline Flex is associated with reduced fluoroscopy time, procedure time, and technical failure compared with the first-generation Pipeline embolization device.

text: BACKGROUND Flow diversion with the Pipeline embolization device is a well-established method of intracranial aneurysm treatment. However, deployment of the first-generation device (Pipeline Classic) can be technically challenging. The Pipeline Flex contains the same flow-diverting stent with a modified delivery system. OBJECTIVE To compare procedural outcomes between the first-generation device (Pipeline Classic) and the Pipeline Flex. METHODS Thirty-eight of the first 40 consecutive patients who underwent intracranial aneurysm treatment with the Pipeline Flex and 58 of the most recent 60 consecutive patients who underwent treatment with the Pipeline Classic at our institution were evaluated. Patient demographics, aneurysm characteristics, technical procedural details, and early outcomes were analyzed. RESULTS The two groups were comparable for age, gender, and location of target aneurysms. Use of Pipeline Flex decreased procedure time by 44.2 min (p≤0.001) and fluoroscopy time by 22.0 min (p=0.001) compared with the Pipeline Classic. Similarly, radiation exposure was less in the Flex group with a mean difference of 3473.5 Gy cm2 (p=0.002), while contrast usage was decreased with a mean difference of 22.3 mL (p=0.007). These differences remained significant in multivariate regression analysis. Finally, the rate of device deployment failure was lower in the Flex group (7.1%) than in the Classic group (23.9%) (p=0.034). CONCLUSIONS Use of Pipeline Flex significantly reduces the total procedure and fluoroscopy time, contrast usage, patient radiation exposure, and proportion of recaptured devices in comparison with the Pipeline Classic, probably owing to an enhanced delivery system that allows for more reliable and controlled deployment.


title: A meta-analysis of intracranial hemorrhage in patients with brain tumors receiving therapeutic anticoagulation.

text: UNLABELLED Essentials Clinicians may be hesitant to administer anticoagulation in the setting of brain metastases or glioma. In this meta-analysis, we identified nine retrospective cohort studies that met inclusion criteria. Anticoagulation did not increase the risk of intracranial hemorrhage in brain metastasis. In the setting of glioma, anticoagulation resulted in 3.8-fold increase in intracranial hemorrhage. SUMMARY Background Venous thromboembolism commonly occurs in patients with brain tumors. Because of the high rate of spontaneous intracranial hemorrhage (ICH), the safety of therapeutic anticoagulation is commonly questioned. Objective We performed a meta-analysis to evaluate whether therapeutic anticoagulation is associated with an increased risk of intracranial hemorrhage in patients with brain tumors. Patients/Methods A systematic literature search strategy was conducted. Summary statistics for ICH were obtained by calculating the odds ratio using a random effects model and heterogeneity across studies was estimated by the I(2) statistic. Results A total of nine retrospective cohort studies met the criteria for inclusion. The odds ratio (OR) for ICH in patients receiving therapeutic anticoagulation versus those who did not receive anticoagulation was 2.13 (95% confidence interval [CI], 1.00-4.56; I(2) = 46%). In studies evaluating anticoagulation in patients with brain metastases, there was no apparent increased risk of ICH (OR, 1.07; 95% CI, 0.61-1.88; I(2) = 0%). However, in patients with glioma there was an increase in risk of ICH associated with the administration of anticoagulation (OR, 3.75; 95% CI, 1.42-9.95; I(2) = 33%). Conclusions The risk of ICH in patients with brain tumors receiving therapeutic anticoagulation depends on the diagnosis of primary or metastatic brain tumors. Although anticoagulation was not associated with an increased risk of ICH in the setting of brain metastasis, its use resulted in a greater than 3-fold increased risk of ICH in patients with glioma.


title: An overview of early investigational drugs for the treatment of human papilloma virus infection and associated dysplasia.

text: INTRODUCTION High-risk HPV (HR-HPV) related invasive cervical cancer (ICC) causes >270,000 deaths per annum world-wide with over 85% of these occurring in low-resource countries. Ablative and excisional treatment modalities are restricted for use with high-grade pre-cancerous cervical disease with HPV infection and low-grade dysplasia mostly managed by a watch-and-wait policy. AREAS COVERED Various pharmacological approaches have been investigated as non-destructive alternatives for the treatment of HR-HPV infection and associated dysplasia. These are discussed dealing with efficacy, ease-of-use (physician or self-applied), systemic or locally applied, side-effects, cost and risks. The main focus is the perceived impact on current clinical practice of a self-applied, effective and safe pharmacological anti-HPV treatment. EXPERT OPINION Current prophylactic HPV vaccines are expensive, HPV type restricted and have little effect in already infected women. Therapeutic vaccines are under development but are also HPV type-restricted. At present, the developed nations use national cytology screening and surgical procedures to treat only women identified with HPV-related high-grade dysplastic disease. However, since HPV testing is rapidly replacing cytology as the test-of-choice, a suitable topically-applied and low-cost antiviral treatment could be an ideal solution for treatment of HPV infection per se with test-of-cure carried out by repeat HPV testing. Cytology would only then be necessary for women who remained HPV positive. Although of significant benefit in the developed countries, combining such a treatment with self-sampled HPV testing could revolutionise the management of this disease in the developing world which lack both the infrastructure and resources to establish national cytology screening programs.


title: Vaccines against Coronaviruses: The State of the Art.

text: The emerging epidemic caused by the new coronavirus SARS-CoV-2 represents the most important socio-health threat of the 21st century. The high contagiousness of the virus, the strong impact on the health system of the various countries and the absence to date of treatments able to improve the prognosis of the disease make the introduction of a vaccine indispensable, even though there are currently no approved human coronavirus vaccines. The aim of the study is to carry out a review of the medical literature concerning vaccine candidates for the main coronaviruses responsible for human epidemics, including recent advances in the development of a vaccine against COVID-19. This extensive review carried out on the vaccine candidates of the main epidemic coronaviruses of the past has shown that the studies in animal models suggest a high efficacy of potential vaccines in providing protection against viral challenges. Similar human studies have not yet been carried out, as the main trials are aimed at assessing mainly vaccine safety and immunogenicity. Whereas the severe acute respiratory syndrome (SARS-CoV) epidemic ended almost two decades ago and the Middle East respiratory syndrome (MERS-CoV) epidemic is now better controlled, as it is less contagious due to the high lethality of the virus, the current SARS-CoV-2 pandemic represents a problem that is certainly more compelling, which pushes us to accelerate the studies not only for the production of vaccines but also for innovative pharmacological treatments. SARS-CoV-2 vaccines might come too late to affect the first wave of this pandemic, but they might be useful if additional subsequent waves occur or in a post-pandemic perspective in which the virus continues to circulate as a seasonal virus.


title: Treating multiple sclerosis and neuromyelitis optica spectrum disorder during the COVID-19 pandemic.

text: The emergence of novel Coronavirus 2019 (COVID-19)1 and the subsequent pandemic present a unique challenge to Neurologists managing patients with multiple sclerosis (MS) and related neuroinflammatory disorders, such as neuromyelitis spectrum disorder (NMOSD).


title: Superficial non-ampullary duodenal cancer identified by small-bowel capsule endoscopy: a case report (with video).

text: Herein, we report for the first time a case of a surficial superficial non-ampullary duodenal cancer causing obscure intestinal bleeding that was identified by small-bowel capsule endoscopy and treated by endoscopic mucosal resection. A 73-year-old man underwent upper gastrointestinal endoscopy to identify the cause of anemia. Although conventional duodenoscopy revealed a flat, elevated 5-mm lesion with a central recess and "milk-white mucosa" at the inferior duodenal angulus, capsule endoscopy revealed a white nodular 5-mm lesion with central recess at the duodenum slightly to the anal side from the major duodenal papilla. Pathohistological examination revealed a low-grade well-differentiated tubular adenocarcinoma growing locally in the mucosal layer. Although capsule endoscopy detected a nodular lesion, conventional endoscopy revealed a flat, elevated lesion. The cause of this difference in endoscopic findings is considered to be the degree of extension of the intestinal mucosa. In contrast, "milk-white mucosa" as a typical finding of superficial duodenal tumor in conventional endoscopy could be identified as a white mucosal color tone in capsule endoscopy. Conventional endoscopic findings of irregular surface structure in the lesion suggested malignancy. Pathohistologically, the ductal structure of the adenocarcinoma was also distorted. Unfortunately, it was difficult to suggest that the lesion was adenocarcinoma based on the endoscopic findings alone.


title: Sedation with Dexmedetomidine or Propofol Impairs Hypoxic Control of Breathing in Healthy Male Volunteers: A Nonblinded, Randomized Crossover Study.

text: BACKGROUND In contrast to general anesthetics such as propofol, dexmedetomidine when used for sedation has been put forward as a drug with minimal effects on respiration. To obtain a more comprehensive understanding of the regulation of breathing during sedation with dexmedetomidine, the authors compared ventilatory responses to hypoxia and hypercapnia during sedation with dexmedetomidine and propofol. METHODS Eleven healthy male volunteers entered this randomized crossover study. Sedation was administered as an intravenous bolus followed by an infusion and monitored by Observer's Assessment of Alertness/Sedation (OAA/S) scale, Richmond Agitation Sedation Scale, and Bispectral Index Score. Hypoxic and hypercapnic ventilatory responses were measured at rest, during sedation (OAA/S 2 to 4), and after recovery. Drug exposure was verified with concentration analysis in plasma. RESULTS Ten subjects completed the study. The OAA/S at the sedation goal was 3 (3 to 4) (median [minimum to maximum]) for both drugs. Bispectral Index Score was 82 ± 8 and 75 ± 3, and the drug concentrations in plasma at the sedation target were 0.66 ± 0.14 and 1.26 ± 0.36 μg/ml for dexmedetomidine and propofol, respectively. Compared with baseline, sedation reduced hypoxic ventilation to 59 and 53% and the hypercapnic ventilation to 82 and 86% for dexmedetomidine and propofol, respectively. In addition, some volunteers displayed upper airway obstruction and episodes of apnea during sedation. CONCLUSIONS Dexmedetomidine-induced sedation reduces ventilatory responses to hypoxia and hypercapnia to a similar extent as sedation with propofol. This finding implies that sedation with dexmedetomidine interacts with both peripheral and central control of breathing.


title: Effects of mast cell modulation on early host response to implanted synthetic meshes.

text: INTRODUCTION Mast cells (MCs) and their products (e.g., histamine, serotonin, heparin, prostaglandins, cytokines, etc.) play key roles in controlling local inflammation, wound healing, and foreign body reactions in vivo. Investigation of the role of MCs in mediating local tissue responses to synthetic hernia meshes has been very limited to date. We aimed to determine the effects of MCs/MC products in mice undergoing synthetic mesh implantation. MATERIALS AND METHODS Circular samples (5 mm) of heavyweight microporous polypropylene (Trelex), midweight microporous polypropylene (ProLite), lightweight macroporous polypropylene with poliglecaprone (Ultrapro), and 3-dimensional macroporous polyester (Parietex) meshes were implanted subcutaneously in C57BL/6 J mice with and without cromolyn (MC stabilizer/suppressant) treatment (50 mg/kg, daily IP). Two weeks post-implantation, all meshes were explanted and evaluated histologically using H&E and trichrome stains. RESULTS Chronic inflammation was focused around individual mesh fibers; inter-fiber inflammation and fibrosis diminished as mesh porosity increased. MC accumulation was seen at the periphery of inflammatory reactions, and in association with mesh-induced fibrosis and neovascularization. Cromolyn treatment resulted in significantly decreased fibrotic responses to all four meshes and reduced inflammation induced by Trelex, ProLite, and Parietex meshes but not Ultrapro. CONCLUSION We demonstrated that MCs play important roles in mesh-induced host tissue reactions. Blocking MC degranulation decreased early inflammation and fibrosis induced by most synthetic meshes in this study. Further evaluation and understanding of the role of MCs in mesh-induced tissue reactions will provide new therapeutic approaches to enhance the biocompatibility of surgical meshes and ultimately improve clinical outcomes in patients undergoing hernia repair with synthetic biomaterials.


title: Long-term outcomes of laparoscopic adjustable silicone gastric banding (LAGB) in moderately obese patients with and without co-morbidities.

text: BACKGROUND Overweight and obesity independently increase cardiovascular risk, while even modest weight loss can result in clinically significant improvements in cardiovascular risk and reduce long-term mortality. Lowering the body mass index (BMI) threshold for bariatric surgery to those with moderate obesity might be one way to lower the burden of this disease. The aim of this study was to evaluate the efficacy and safety of laparoscopic adjustable silicone gastric banding (LAGB) in moderately obese subjects with or without obesity-related co-morbidities. METHODS Thirty-four patients with BMI between 30 and 35 kg/m(2) (5 males/29 females, mean age 36 ± 10 years, mean preoperative weight 87.9 ± 7.1 kg, mean BMI 32.6 ± 1.6 kg/m(2) and mean percentage excess weight 48.7 ± 9 %) who underwent LAGB via pars flaccida between June 1, 2002 and August 31, 2010 were included. Good response was defined as BMI <30 kg/m(2) or percentage estimated weight loss (%EWL) >50. Poor response was defined as BMI >30 kg/m(2) or %EWL less than 50 after a minimum of 1 year. RESULTS Mean weight, BMI and %EWL were recorded at 1, 3, 5 and 7 years and were 77.4 ± 7.6, 69.9 ± 10.8, 70.9 ± 9.3 and 73.3 ± 12.0 kg; 28.8 ± 2.9, 26.4 ± 3.2, 26.5 ± 3.4 and 27.4 ± 5.0 kg/m(2); and 36 ± 23, 46.1 ± 33.8, 58.6 ± 31.5 and 45 ± 57, respectively (p < 0.01). Co-morbidities were diagnosed in 17/34 (50 %) patients at baseline and underwent remission or improvement in all cases after 1 year. CONCLUSIONS LAGB in a safe and effective procedure in patients with a BMI <35 kg/m(2).


Burnout in the age of COVID-19.


title: Changes in pediatric tracheostomy tubes exposed to home dishwashing.

text: OBJECTIVE Determine the effects of household dishwashing on Tracheostomy Tube safety. INTRODUCTION Tracheostomy tubes accumulate biofilms, which may limit their lifespan. Frequent cleaning of the tubes is a method for biofilm prevention. Cleaning practices vary widely. Some families prefer dishwashing of tubes, but its effects are currently unknown. We hypothesize that dishwashing has no significant effect on the physical properties of tracheostomy tubes and can be recommended as a safe way to clean tracheostomy tubes. METHODS Twenty 4.0 Shiley™ pediatric tracheostomy tubes were randomly assigned into dishwashed (DW) and non-dishwashed (NDW) groups, 10/group. DW tubes were subjected to 12 wash cycles. Each tube's hardness along with the surface spectra were analyzed to assess for chemical composition changes. Three cannula samples from each group were also randomly assessed with scanning-electron microscopy and scored by blinded examiners to assess for changes in surface heterogeneity. RESULTS Hardness testing revealed a statistically significant difference (p = 0.0009) between the NDW and the DW group indicating increased fragility in the dishwashed tubes. Spectral analysis revealed loss of plasticizers, indicating decreased flexibility. Blinded electron microscopy scoring revealed increased surface heterogeneity in the DW group (p = 0.00007). CONCLUSION A significant decrease in tube hardness and increased surface heterogeneity were found with dishwashing. The spectral analysis demonstrated increasing fragility. We believe these effects could potentially lead to decreased mechanical safety. With increased surface heterogeneity there is a greater potential for biofilm formation. At this time, dishwashing cannot be recommended as a tracheostomy tube cleaning method.


title: Coxsackievirus can exploit LC3 in both autophagy-dependent and -independent manners in vivo.

text: RNA viruses modify intracellular membranes to produce replication scaffolds. In pancreatic cells, coxsackievirus B3 (CVB3) hijacks membranes from the autophagy pathway, and in vivo disruption of acinar cell autophagy dramatically delays CVB3 replication. This is reversed by expression of GFP-LC3, indicating that CVB3 may acquire membranes from an alternative, autophagy-independent, source(s). Herein, using 3 recombinant CVB3s (rCVB3s) encoding different proteins (proLC3, proLC3(G120A), or ATG4B(C74A)), we show that CVB3 is, indeed, flexible in its utilization of cellular membranes. When compared with a control rCVB3, all 3 viruses replicated to high titers in vivo, and caused severe pancreatitis. Most importantly, each virus appeared to subvert membranes in a unique manner. The proLC3 virus produced a large quantity of LC3-I which binds to phosphatidylethanolamine (PE), affording access to the autophagy pathway. The proLC3(G120A) protein cannot attach to PE, and instead binds to the ER-resident protein SEL1L, potentially providing an autophagy-independent source of membranes. Finally, the ATG4B(C74A) protein sequestered host cell LC3-I, causing accumulation of immature phagophores, and massive membrane rearrangement. Taken together, our data indicate that some RNA viruses can exploit a variety of different intracellular membranes, potentially maximizing their replication in each of the diverse cell types that they infect in vivo.


Phylogenetic evidence for a mild H1 pandemic in the early 1900s.


title: Multidetector CT of expected findings and early postoperative complications after current techniques for ventral hernia repair.

text: UNLABELLED Current techniques for ventral hernia repair (VHR) rely on prosthetic mesh implantation and are increasingly performed laparoscopically. Potentially serious iatrogenic complications may occur following VHR, though these are rare compared to the vast number of procedures performed each year. This paper provides an overview of contemporary open and laparoscopic surgical techniques and biomaterials, then reviews and illustrates the expected postoperative imaging appearances, and common and unusual early complications after VHR. Emphasis is placed on multidetector computed tomography (CT), which comprehensively visualizes the operated anterior abdominal wall and deeper intra-abdominal structures. CT consistently allows diagnosis of postoperative seromas, abdominal wall abscesses and fistulas, haemorrhages with or without active bleeding, bowel obstruction, peritonitis and recurrent hernias, and thus providing a reliable basis for an appropriate choice between conservative, interventional, or surgical treatment. Familiarity with early post-surgical CT is warranted to avoid misinterpretation of the expected imaging appearance and correctly elucidate postoperative complications after VHR. TEACHING POINTS • Open and laparoscopic repair of ventral hernias rely on prosthetic mesh implantation. • Potentially serious iatrogenic complications occasionally occur after ventral hernioplasty. • Multidetector CT consistently evaluates the operated abdominal wall and deeper structures. • Familiarity with the expected early postoperative imaging appearance is required. • Complications include seroma, infections, haemorrhage, bowel obstruction, peritonitis, and recurrence.


title: Exploring Opportunities for Household-Level Chronic Care Management Using Linked Electronic Health Records of Adults and Children: A Retrospective Cohort Study.

text: OBJECTIVE Linking electronic health records (EHR) of pediatric and adult patients living in the same household has the potential to improve chronic care management efficiencies by facilitating the delivery of services to multiple household members at once. However, little is known about relationship between the chronic medical (CM) and behavioral health (CBH) of adults and children living in common households. METHODS EHR data for children were linked to the EHR data of adults living at the same address during the same time in a retrospective cohort study from 2006 to 2014 to evaluate associations between adult and child CM and CBH conditions within a Boston safety-net primary care patient sample. RESULTS Of the 13,845 included children, 61.6% lived with at least one adult with ≥ 1 CM or CBH condition. Compared to children living with an adult(s) without a chronic condition, children living with an adult with a CM or CBH condition had a respective 16.2% and 18.1% increased likelihood of having a chronic condition themselves, with multiple adult chronic conditions in adults increasing children's likelihood. CONCLUSIONS FOR PRACTICE We found a positive association between the chronic diseases of adult and child household members. Given the clustering of child and adult chronic disease within households, using EHR data to support the care management needs of multiple members of households may be a promising approach to improving child and adult health in safety-net settings.


title: Minilaparoscopy-assisted transrectal low anterior resection (LAR): a preliminary study.

text: BACKGROUND Natural orifice translumenal endoscopic surgery (NOTES) represents the evolution of surgery towards less invasive procedures. The feasibility of NOTES transrectal approach has increased its clinical applicability. This report describes a first series of minilaparoscopy-assisted transrectal low anterior resection with double purse-string end-to-end circular stapler anastomoses. METHODS Between March and April 2012 three selected patients underwent transrectal minilaparoscopy-assisted natural orifice surgery total mesorectal excision for rectal cancer. All the oncologic principles of open/laparoscopic low anterior resection for rectal cancer were strictly fulfilled. Two patients underwent neoadjuvant treatment. Laparoscopic visualization and assistance was provided through one 10-mm umbilical port and two ports, one of which was used as stoma site (5 mm) and the other as a drain site (2 mm needle port). The specimen was transected transanally followed by the confection of double purse-string lateral/end-to-end anastomoses. There were no intraoperative complications. RESULTS Mean operative time was 143 min. Oral intake was initiated on the second postoperative day. Patients were discharged home by day 5. The pathology unit confirmed that distal and circumferential margins were free of tumor invasion, and quality of mesorectum resection was reported satisfactory. One patient had to be readmitted because of severe dehydration due to increased ileostomy output. The patient was discharged at the third day after the readmission without renal failure. CONCLUSIONS In this preliminary report, transrectal minilaparoscopy-assisted low anterior resection was feasible and safe. Lateral/end-to-end anastomoses can be considered an interesting alternative to the double-stapling technique. However, it is necessary to further study and develop these procedures, along with careful patient selection, before transrectal low anterior resection may be considered for routine clinical use.


title: Antibody responses to SARS-CoV-2 in patients with COVID-19.

text: We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.


title: Nonnucleoside inhibitors of norovirus RNA polymerase: scaffolds for rational drug design.

text: Norovirus (NoV) is the leading cause of acute gastroenteritis worldwide, causing over 200,000 deaths a year. NoV is nonenveloped, with a single-stranded RNA genome, and is primarily transmitted person to person. The viral RNA-dependent RNA polymerase (RdRp) is critical for the production of genomic and subgenomic RNA and is therefore a prime target for antiviral therapies. Using high-throughput screening, nearly 20,000 "lead-like" compounds were tested for inhibitory activity against the NoV genogroup II, genotype 4 (GII.4) RdRp. The four most potent hits demonstrated half-maximal inhibitory concentrations (IC50s) between 5.0 μM and 9.8 μM against the target RdRp. Compounds NIC02 and NIC04 revealed a mixed mode of inhibition, while NIC10 and NIC12 were uncompetitive RdRp inhibitors. When examined using enzymes from related viruses, NIC02 demonstrated broad inhibitory activity while NIC04 was the most specific GII.4 RdRp inhibitor. The antiviral activity was examined using available NoV cell culture models; the GI.1 replicon and the infectious GV.1 murine norovirus (MNV). NIC02 and NIC04 inhibited the replication of the GI.1 replicon, with 50% effective concentrations (EC50s) of 30.1 μM and 71.1 μM, respectively, while NIC10 and NIC12 had no observable effect on the NoV GI.1 replicon. In the MNV model, NIC02 reduced plaque numbers, size, and viral RNA levels in a dose-dependent manner (EC50s between 2.3 μM and 4.8 μM). The remaining three compounds also reduced MNV replication, although with higher EC50s, ranging from 32 μM to 38 μM. In summary, we have identified novel nonnucleoside inhibitor scaffolds that will provide a starting framework for the development and future optimization of targeted antivirals against NoV.


title: Efficacy and safety of antiviral treatment for COVID-19 from evidence in studies of SARSCoV-2 and other acute viral infections: a systematic review and meta-analysis.

text: BACKGROUND Antiviral medications are being given empirically to some patients with coronavirus disease 2019 (COVID-19). To support the development of a COVID-19 management guideline, we conducted a systematic review that addressed the benefits and harms of 7 antiviral treatments for COVID-19. METHODS We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and 3 Chinese databases (CNKI, WANFANG and SinoMed) through Apr. 19, medRxiv and Chinaxiv through Apr. 27, and Chongqing VIP through Apr. 30, 2020. We included studies of ribavirin, chloroquine, hydroxychloroquine, umifenovir (arbidol), favipravir, interferon and lopinavir/ritonavir. If direct evidence from COVID-19 studies was not available, we included indirect evidence from studies of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for efficacy outcomes and other acute respiratory viral infections for safety outcomes. RESULTS In patients with nonsevere COVID-19 illness, the death rate was extremely low, precluding an important effect on mortality. We found only very low-quality evidence with little or no suggestion of benefit for most treatments and outcomes in both nonsevere and severe COVID-19. An exception was treatment with lopinavir/ritonavir, for which we found low-quality evidence for a decrease in length of stay in the intensive care unit (risk difference 5 d shorter, 95% confidence interval [CI] 0 to 9 d) and hospital stay (risk difference 1 d shorter, 95% CI 0 to 2 d). For safety outcomes, evidence was of low or very low quality, with the exception of treatment with lopinavir/ritonavir for which moderate-quality evidence suggested likely increases in diarrhea, nausea and vomiting. INTERPRETATION To date, persuasive evidence of important benefit in COVID-19 does not exist for any antiviral treatments, although for each treatment evidence has not excluded important benefit. Additional randomized controlled trials involving patients with COVID-19 will be needed before such treatments can be administered with confidence.


title: Optimize the interactions at S4 with efficient inhibitors targeting 3C proteinase from enterovirus 71.

text: Enterovirus 71 (EV71) is the causative agent of hand, foot and mouth disease and can spread its infections to the central nervous and other systems with severe consequences. The replication of EV71 depends on its 3C proteinase (3Cpro ), a significant drug target. By X-ray crystallography and functional assays, the interactions between inhibitors and EV71 3Cpro were evaluated. It was shown that improved interactions at S4 for the substrate binding could significantly enhance the potency. A new series of potent inhibitors with high ligand efficiency was generated for developing antivirals to treat and control the EV71-associated diseases. Copyright © 2016 John Wiley & Sons, Ltd.


title: Poly(dopamine)-assisted immobilization of Arg-Gly-Asp peptides, hydroxyapatite, and bone morphogenic protein-2 on titanium to improve the osteogenesis of bone marrow stem cells.

text: Osteointegration of titanium implants in bone defects is clinically important for long-term performance of orthopaedic implants. In this work, we developed a facile and effective "one-pot" deposition method based on dopamine polymerization for the development of cell-adhesive, osteoconductive, and osteoinductive titanium implants. Arg-Gly-Asp (RGD)-conjugated polymers, hydroxyapatite (HAp) nanoparticles, and bone morphogenic protein-2 (BMP-2) were mixed with an alkaline dopamine solution, and then, titanium substrates were immersed in the mixture for an hour. During poly(dopamine) coating, the three types of bioactive substances were immobilized on the titanium surfaces. Our results indicate that RGD conjugation enhanced the adhesion of human bone marrow stem cell line, while HAp incorporation facilitated cellular osteodifferentiation. The immobilization of BMP-2 induced the osteogenesis of the stem cells, indicated by reverse-transcriptase polymerase chain reaction (RT-PCR) analysis. The mineralization on the deposited substrates was also enhanced greatly. This functionalized layer on titanium substrate promoted mesenchymal stem cell to osteoblast and improved osteogenic differentiation and mineralization. In conclusion, the surface modification method shows a great potential for enhancement of osteointegration of orthopaedic and dental implants.


title: Cell recruiting chemokine-loaded sprayable gelatin hydrogel dressings for diabetic wound healing.

text: UNLABELLED In this study, we developed horseradish peroxidase (HRP)-catalyzed sprayable gelatin hydrogels (GH) as a bioactive wound dressing that can deliver cell-attracting chemotactic cytokines to the injured tissues for diabetic wound healing. We hypothesized that topical administration of chemokines using GH hydrogels might improve wound healing by inducing recruitment of the endogenous cells. Two types of chemokines (interleukin-8; IL-8, macrophage inflammatory protein-3α; MIP-3α) were simply loaded into GH hydrogels during in situ cross-linking, and then their wound-healing effects were evaluated in streptozotocin-induced diabetic mice. The incorporation of chemokines did not affect hydrogels properties including swelling ratio and mechanical stiffness, and the bioactivities of IL-8 and MIP-3α released from hydrogel matrices were stably maintained. In vivo transplantation of chemokine-loaded GH hydrogels facilitated cell infiltration into the wound area, and promoted wound healing with enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or the GH hydrogel alone. Based on our results, we suggest that cell-recruiting chemokine-loaded GH hydrogel dressing can serve as a delivery platform of various therapeutic proteins for wound healing applications. STATEMENT OF SIGNIFICANCE Despite development of materials combined with therapeutic agents for diabetic wound treatment, impaired wound healing by insufficient chemotactic responses still remain as a significant problem. In this study, we have developed enzyme-catalyzed gelatin (GH) hydrogels as a sprayable dressing material that can deliver cell-attracting chemokines for diabetic wound healing. The chemotactic cytokines (IL-8 and MIP-3α) were simply loaded within hydrogel during in situ gelling, and wound healing efficacy of chemokine-loaded GH hydrogels was investigated in STZ-induced diabetic mouse model. These hydrogels significantly promoted wound-healing efficacy with faster wound closure, neovascularization, and thicker granulation. Therefore, we expect that HRP-catalyzed in situ forming GH hydrogels can serve as an injectable/sprayable carrier of various therapeutic agents for wound healing applications.


title: Effect of bariatric surgery on cardiovascular risk profile.

text: Obesity is associated with increased risk for cardiovascular (CV) disease (CVD) and CV mortality. Bariatric surgery has been shown to resolve or improve CVD risk factors, to varying degrees. The objective of this systematic review was to determine the impact of bariatric surgery on CV risk factors and mortality. A systematic review of the published research was performed to evaluate evidence regarding CV outcomes in morbidly obese bariatric patients. Two major databases (PubMed and the Cochrane Library) were searched. The review included all original reports reporting outcomes after bariatric surgery, published in English, from January 1950 to July 2010. In total, 637 studies were identified from the initial screen. After applying inclusion and exclusion criteria, 52 studies involving 16,867 patients were included (mean age 42 years, 78% women). The baseline prevalence of hypertension, diabetes, and dyslipidemia was 49%, 28%, and 46%, respectively. Mean follow-up was 34 months (range 3 to 155), and the average excess weight loss was 52% (range 16% to 87%). Most studies reported significant decreases postoperatively in the prevalence of CV risk factors, including hypertension, diabetes, and dyslipidemia. Mean systolic pressure reduced from to 139 to 124 mm Hg and diastolic pressure from 87 to 77 mm Hg. C-reactive protein decreased, endothelial function improved, and a 40% relative risk reduction for 10-year coronary heart disease risk was observed, as determined by the Framingham risk score. In conclusion, this review highlights the benefits of bariatric surgery in reducing or eliminating risk factors for CVD. It provides further evidence to support surgical treatment of obesity to achieve CVD risk reduction.


title: Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature.

text: There must be something unique about a class of drugs (discovered and developed in the mid-1940s) where there are more than 130 ongoing clinical trials currently listed. Tetracyclines were developed as a result of the screening of soil samples for antibiotic organisms. The first of these compounds chlortetracycline was introduced in 1948. Soon after their development tetracyclines were found to be highly effective against various pathogens including rickettsiae, Gram-positive, and Gram-negative bacteria, thus, becoming a class of broad-spectrum antibiotics. The mechanism of action of tetracyclines is thought to be related to the inhibition of protein synthesis by binding to the 30S bacterial ribosome. Tetracyclines are also an effective anti-malarial drug. Over time, many other "protective" actions have been described for tetracyclines. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Its mechanism of action appears to relate to specific effects exerted on apoptosis signaling pathways. Another tetracycline, doxycycline is known to exert antiprotease activities. Doxycycline can inhibit matrix metalloproteinases, which contribute to tissue destruction activities in diseases such as gingivitis. A large body of literature has provided additional evidence for the "beneficial" actions of tetracyclines, including their ability to act as oxygen radical scavengers and anti-inflammatory agents. This increasing volume of published work and ongoing clinical trials supports the notion that a more systematic examination of their possible therapeutic uses is warranted. This review provides a summary of tetracycline's multiple mechanisms of action and while using the effects on the heart as an example, this review also notes their potential to benefit patients suffering from various pathologies such as cancer, Rosacea, and Parkinson's disease.


How to demystify COVID-19 and reduce social stigma.


title: Protocol for a scoping review study to identify and map treatments for dysphagia following moderate to severe acquired brain injury.

text: INTRODUCTION Dysphagia is highly prevalent in patients with acquired brain injury (ABI) and is associated with high morbidity and mortality. However, dysphagia management varies greatly between units and internationally, and there is currently no consensus, standard intervention or treatment. A review mapping the existing literature on dysphagia treatment is needed. In this paper, the protocol for a scoping review to identify and map dysphagia treatment following ABI is outlined. OBJECTIVE The objective of the scoping review is to systematically map the existing research literature to answer the research question: Which non-surgical, non-pharmacological interventions are used in the treatment of dysphagia in patients with moderate and severe acquired brain injury in the acute and subacute phase? METHODS AND ANALYSIS: The methodological framework for the study is based on methodology by Arksey and O'Malley and methodological advancement by Levac et al. We will search electronic databases in June 2019: MEDLINE (Ovid); Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library); EMBASE (Ovid); CINAHL (EBSCO); PsycINFO; Science Citation Index Expanded on Web of Science; OTseeker; Speechbite and PEDro. The search terms will be limited to patients with moderate to severe ABI and dysphagia. Four review authors will independently conduct an initial screening of title and abstract and subsequent full-text review of included studies. Data will be extracted and summarised in diagrammatic or tabular form (numerical summary), and a descriptive format (narrative summary). The strategy for data synthesis entails qualitative methods to categorise the interventions based on the treatment modality and subgroup diagnosis. ETHICS AND DISSEMINATION Scoping the existing literature will provide a foundation for further evaluating and developing our dysphagia treatment and inform future studies assessing the effectiveness of treatments. The review is part of an ongoing expansive research into dysphagia. The results will be disseminated through a peer-reviewed publication and conference presentations.


title: Single-incision laparoscopic cholecystectomy: a comparison with the gold standard.

text: BACKGROUND Single-incision laparoscopic cholecystectomy (SILC) may be a comparable alternative to conventional multiport laparoscopic cholecystectomy (LC). This study compared procedural outcomes and costs between SILC and LC. METHODS A retrospective review of patients undergoing SILC over an 8-month period was performed. A cohort of LC patients from the same surgeons over the preceding 8 months was used as historic controls. Demographics, comorbidities, diagnosis, operative data, pain control in the recovery room, complications, length of hospital stay, and cost were compared between the two groups. RESULTS Of the 285 patients, 177 underwent LC and 108 underwent SILC. The mean age was 49.7 years for the LC patients and 48.2 years for the SILC patients (p = 0.44). Two of the LC patients underwent conversion to open surgery. None of SILC patients were converted to open procedure, although nine had additional ports placed. After multivariate adjustment, SILC was associated with a 15% longer operative time (p = 0.053) and a 66% shorter hospital stay (p = 006) than LC. Biliary dyskinesia and biliary colic were independently associated with shorter operative times and a reduced hospital stay. No significant differences were noted in pain score, narcotics used in the postanesthesia care unit (PACU), 30-day complication rates (1.7 vs 1.9%; p = 1), hospital charges, or cost between the two groups. CONCLUSIONS Single-incision LC is safe, significantly reduces the hospital stay, and is an acceptable alternative to traditional LC. Although further study is warranted, initial results indicate that SILC may offer the most benefit for outpatient procedures.


title: Performance Characteristics of FilmArray Respiratory Panel v1.7 for Detection of Adenovirus in a Large Cohort of Pediatric Nasopharyngeal Samples: One Test May Not Fit All.

text: The FilmArray Respiratory Panel (RP) v1.7 assay has improved sensitivity for detection of human adenovirus (HAdV), compared to an earlier version (RP v1.6). RP v1.7 was designed for detection of species B, C, and E but may show variable detection of species A, D, and F. We sought to evaluate the clinical and analytical performance of RP v1.7 for detection of HAdV in a large pediatric cohort. Respiratory specimens obtained from a tertiary care children's hospital between February 2014 and February 2015 were tested for HAdV by RP v1.7. If the RP v1.7 results were negative for HAdV, then the specimens were reflexed to a HAdV-specific laboratory-developed PCR (LD-PCR) assay for confirmation. A subset of specimens underwent secondary confirmatory testing using another commercially available HAdV PCR assay and a molecular typing assay for species identification. Among 4,750 specimens, a total of 146 specimens (3.1%) were HAdV positive by RP v1.7. HAdV was detected by LD-PCR in an additional 220 specimens that were negative by RP v1.7. Overall, a nearly 5% increase in HAdV detection was observed when RP v1.7-negative specimens were reflexed to LD-PCR testing. RP v1.7 did not detect HAdV with either low viral burden (threshold cycle values of >30) or nonrespiratory species (species A, D, and F), as shown in both clinical and analytic data. While the level of sensitivity of RP v1.7 may be adequate for testing among otherwise healthy children, the decreased sensitivity may be problematic for immunocompromised patients, in whom low levels of HAdV in the respiratory tract may precede systemic infection and require early intervention.


title: Doing Our Part to Conserve Resources: Determining Whether All Personal Protective Equipment Is Mandatory for Closed Reduction and Percutaneous Pinning of Supracondylar Humeral Fractures.

text: BACKGROUND Closed reduction and percutaneous pinning (CRPP) of supracondylar humeral fractures is one of the most common procedures performed in pediatric orthopaedics. The use of full, standard preparation and draping with standard personal protective equipment (PPE) may not be necessary during this procedure. This is of particular interest in the current climate as we face unprecedented PPE shortages due to the current COVID-19 pandemic. METHODS This is a retrospective chart review of 1,270 patients treated with CRPP of a supracondylar humeral fracture at 2 metropolitan pediatric centers by 10 fellowship-trained pediatric orthopaedic surgeons. One surgeon in the group did not wear a mask when performing CRPP of supracondylar humeral fractures, and multiple surgeons in the group utilized a semisterile preparation technique (no sterile gown or drapes). Infectious outcomes were compared between 2 groups: full sterile preparation and semisterile preparation. We additionally analyzed a subgroup of patients who had semisterile preparation without surgeon mask use. Hospital cost data were used to estimate annual cost savings with the adoption of the semisterile technique. RESULTS In this study, 1,270 patients who underwent CRPP of a supracondylar humeral fracture and met inclusion criteria were identified. There were 3 deep infections (0.24%). These infections all occurred in the group using full sterile preparation and surgical masks. No clinically relevant pin-track infections were noted. There were no known surgeon occupational exposures to bodily fluid. It is estimated that national adoption of this technique in the United States could save between 18,612 and 22,162 gowns and masks with costs savings of $3.7 million to $4.4 million annually. CONCLUSIONS We currently face critical shortages of PPE due to the COVID-19 pandemic. Data from this large series suggest that a semisterile technique during CRPP of supracondylar humeral fractures is a safe practice. We anticipate that this could preserve approximately 20,000 gowns and masks in the United States over the next year. Physicians are encouraged to reevaluate their daily practice to identify safe opportunities for resource preservation. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


title: The occurrence of enteric viruses in Light Turkey Syndrome.

text: Two studies were conducted to determine the role of enteric viruses in Light Turkey Syndrome (LTS), which is characterized by lower weight in market age turkeys than their standard breed character. In the surveillance study, we selected four LTS and two non-LTS turkey flocks in Minnesota and collected faecal samples at 2, 3, 5 and 8-weeks of age. Astrovirus, rotavirus, and reovirus were detected alone or in various combinations in both LTS and non-LTS flocks. No coronavirus was detected in LTS flocks and no corona- or reovirus was detected in non-LTS flocks. In the second study, 2-week-old turkey poults were divided into two groups; Group A (challenged) was inoculated orally with 10% pooled faecal suspension from LTS flocks and group B (control) was inoculated with phosphate buffered saline (PBS). Clinical signs of depression, huddling, and lack of uniform size were observed in the challenged group but not in the control group. diarrhoea was observed in both groups but was more severe in the challenged group than in the control group. Birds in the challenged group shed astrovirus, rotavirus and reovirus, while the control group shed only astrovirus. Virus shedding in both groups was observed for up to nine weeks of age. Significantly lower body weights were seen in the challenged group starting at seven weeks of age and lasting until 20 weeks of age. These findings suggest that viral enteritis at an early age may set up conditions for the development of LTS in adult turkeys.


title: Advance care planning: A systematic review about experiences of patients with a life-threatening or life-limiting illness.

text: BACKGROUND Advance care planning is seen as an important strategy to improve end-of-life communication and the quality of life of patients and their relatives. However, the frequency of advance care planning conversations in practice remains low. In-depth understanding of patients' experiences with advance care planning might provide clues to optimise its value to patients and improve implementation. AIM To synthesise and describe the research findings on the experiences with advance care planning of patients with a life-threatening or life-limiting illness. DESIGN A systematic literature review, using an iterative search strategy. A thematic synthesis was conducted and was supported by NVivo 11. DATA SOURCES The search was performed in MEDLINE, Embase, PsycINFO and CINAHL on 7 November 2016. RESULTS Of the 3555 articles found, 20 were included. We identified three themes in patients' experiences with advance care planning. 'Ambivalence' refers to patients simultaneously experiencing benefits from advance care planning as well as unpleasant feelings. 'Readiness' for advance care planning is a necessary prerequisite for taking up its benefits but can also be promoted by the process of advance care planning itself. 'Openness' refers to patients' need to feel comfortable in being open about their preferences for future care towards relevant others. CONCLUSION Although participation in advance care planning can be accompanied by unpleasant feelings, many patients reported benefits of advance care planning as well. This suggests a need for advance care planning to be personalised in a form which is both feasible and relevant at moments suitable for the individual patient.


COVID 19 and its mental health consequences.


title: Impact of single phase CT angiography collateral status on functional outcome over time: results from the MR CLEAN Registry.

text: BACKGROUND Collateral status modified the effect of endovascular treatment (EVT) for stroke in several randomized trials. We assessed the association between collaterals and functional outcome in EVT treated patients and investigated if this association is time dependent. METHODS We included consecutive patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN) Registry (March 2014-June 2016) with an anterior circulation large vessel occlusion undergoing EVT. Functional outcome was measured on the modified Rankin Scale (mRS) at 90 days. We investigated the association between collaterals and mRS in the MR CLEAN Registry with ordinal logistic regression and if this association was time dependent with an interaction term. Additionally, we determined modification of EVT effect by collaterals compared with MR CLEAN controls, and also investigated if this was time dependent with multiplicative interaction terms. RESULTS 1412 patients were analyzed. Functional independence (mRS score of 0-2) was achieved in 13% of patients with grade 0 collaterals, in 27% with grade 1, in 46% with grade 2, and in 53% with grade 3. Collaterals were significantly associated with mRS (adjusted common OR 1.5 (95% CI 1.4 to 1.7)) and significantly modified EVT benefit (P=0.04). None of the effects were time dependent. Better collaterals corresponded to lower mortality (P<0.001), but not to lower rates of symptomatic intracranial hemorrhage (P=0.14). CONCLUSION In routine clinical practice, better collateral status is associated with better functional outcome and greater treatment benefit in EVT treated acute ischemic stroke patients, independent of time to treatment. Within the 6 hour time window, a substantial proportion of patients with absent and poor collaterals can still achieve functional independence.


title: Robotic ileal ureter: a completely intracorporeal technique.

text: INTRODUCTION The first laparoscopic case of ileal interposition was reported in 2000, proving the feasibility of the procedure in a minimally invasive fashion by duplicating the principles of open surgery. Robotic applications in urology are expanding worldwide, given the unique features of the robotic platform, which facilitates more advanced laparoscopic procedures. In this study, we report a case of completely intracorporeal robotic ileal ureter and thoroughly describe our technique for this complex minimally invasive procedure. TECHNICAL CONSIDERATIONS A 50-year-old gentleman with a history of right renal stones underwent multiple right ureteroscopies and thereafter developed 2 proximal ureteral strictures of 5 mm. Preoperative estimated glomerular filtration rate was 71 mL/min/1.73 m(2). Renal scan showed preserved function. The treatment options were discussed, and the patient elected to undergo a robotic ileal ureter interposition. Total operative time was 7 hours, the estimated blood loss was approximately 50 mL, and the patient progressed to regular diet on postoperative day 4 without any problem, being discharged without complications. On the postoperative day 12, a cystogram demonstrated no extravasation, and the Foley catheter was removed. After 1 month, renal scan showed the left kidney with 60.1% and the right kidney with 39.9% of total renal function. At 2 years follow-up, his serum creatinine was 1.14 and estimated glomerular filtration rate was 70 mL/min/1.73 m(2). CONCLUSION Robot-assisted laparaoscopic ileal ureter with a completely intracorporeal technique is feasible and appears to be safe. A larger number of procedures using this technique and longer follow-up are needed to further define its role in the treatment of ureteral strictures.


title: Decision-making on management of ms and nmosd patients during the COVID-19 pandemic: A latin american survey.

text: BACKGROUND The emergence of COVID-19 and its vertiginous spreading speed represents a unique challenge to neurologists managing multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). The need for data on the impact of the virus on these patients grows rapidly. There is an urgent necessity of sharing information to enable evidence-based decision making on the clinical management. There are no data on what physicians are doing on clinical practice in Latin American countries. AIM to investigate current management opinion of Latin American MS and/or NMOSD expert neurologists based on their experience and recommendations. METHODS we developed a voluntary web-based survey based on hypothetical situations that these patients may encounter, while taking into account the potential risk of developing severe COVID-19 infection. RESULTS 60% of the experts had the possibility of monitoring their patients by telemedicine. Most neurologists postpone magnetic resonance. Laboratory blood tests delay is associated with the type of treatment. Platform therapies, dimethyl-fumarate and natalizumab are considered safe options to initiate in naive patients. CONCLUSION decision-making about MS and NMOSD patients has become even more complex in order to adapt to the COVID-19 pandemic. Risks and benefits should be taken into consideration throughout the patient follow-up.