title: Association of intraoperative cerebral and muscular tissue oxygen saturation with postoperative complications and length of hospital stay after major spine surgery: an observational study.

text: Background. Compromised tissue oxygenation is one of the root causes of dysfunction of various organs and postoperative complications. Oxygenation of different tissue beds may follow different patterns of change during physiological derangement. Methods. Patients undergoing elective major posterior spine surgery participated in this prospective observational study. Cerebral tissue oxygen saturation (SctO 2 ) was monitored on the upper forehead and muscular tissue oxygen saturation (SmtO 2 ) on the lower leg. The associations of various oxygenation indices with postoperative composite complications and length of hospital stay (LOH) were investigated. Results. The number of composite complications per patient was 3 (2) while the LOH was 6 (3) days (n = 102). Multiple SmtO 2 indices (maximum, minimum, mean, median, and area under curve (AUC)) were associated with composite complications (univariate analysis, P < 0.05). No SctO 2 indices were associated with complications. Multiple SmtO 2 indices (maximum, mean, median, and AUC) showed differences ( P < 0.05) between patients with composite complications ≤3 and >3, respectively. SmtO 2 standard deviation, AUC, and AUC weighted, and SctO 2 standard deviation, were associated with LOH (univariate analysis, P < 0.05). Two SmtO 2 indices (AUC and AUC weighted), showed differences ( P < 0.05) between the patients with an LOH ≤6 and >6 days, respectively. SmtO 2 , but not SctO 2 , indices improved the adjusted R 2 for composite complications (+54.0%, P = 0.0001) and LOH (+19.0%, P = 0.02) based on multiple linear models. Conclusions. Muscular tissue oxygenation has a stronger association with postoperative complications and length of hospital stay than cerebral tissue oxygenation after major spine surgery.


title: Transvaginal mesh repair of pelvic organ prolapse by the transobturator-infracoccygeal hammock technique: long-term anatomical and functional outcomes.

text: AIMS To evaluate long-term anatomical and functional outcomes of the transobturator-infracoccygeal hammock repair for complex genital prolapse with a porcine collagen-coated polypropylene mesh. METHODS A prospective observational study comparing pre- and postoperative outcomes, using pelvic organ prolapse quantification (POP-Q) measurements, pelvic floor distress inventory (PFDI), and pelvic floor impact questionnaire (PFIQ) scores. RESULTS One hundred fourteen women with recurrent, advanced, or posthysterectomy genital prolapse were enrolled. During follow-up (median value 57 months), 101 patients were available for assessment. Overall anatomical success rate was 96%, with significant improvement in quality-of-life. Three patients experienced symptomatic recurrent posterior prolapse. Seven had persistent stress urinary incontinence. Mesh exposure occurred in 6.9% of cases, including an infected hematoma that required partial excision of the mesh. No severe adverse event or change in sexual function was observed. CONCLUSIONS The transobturator-infracoccygeal hammock is well tolerated with effective long-term anatomical and functional results for complex genital prolapse. In our experience and compared to the data of the literature, the use of collagen-coated versus uncoated polypropylene meshes seems to decrease local morbidity.


title: Comparison of commercial realtime reverse transcription PCR assays for the detection of SARS-CoV-2.

text: The emergence of a new coronavirus in Wuhan China has triggered a global need for accurate diagnostic assays. Initially, mostly laboratory developed molecular tests were available but shortly thereafter different commercial assays started to appear and are still increasing in number. Although independent performance evaluations are ongoing, available data is still scarce. Here we provide a direct comparison of key performance characteristics of 13 commercial RT-PCR assays. Thirteen RT-PCR assays were selected based on the criteria that they can be used following generic RNA extraction protocols, on common PCR platforms and availability. Using a 10-fold and 2-fold dilution series of a quantified SARS-CoV-2 cell-cultured virus stock, performance was assessed compared to our in house validated assay. Specificity was tested by using RNA extracted from cultured common human coronaviruses. All RT-PCR kits included in this study exhibited PCR efficiencies > 90%, except for the Sentinel Diagnostics B E-gene RUO assay (80%). Analytical sensitivity varied between 3.3 RNA copies to 330 RNA copies. Only one assay cross reacted with another human coronavirus (MERS). This study provides a technical baseline of 13 different commercial PCR assays for SARS-CoV-2 detection that can be used by laboratories interested in purchasing any of these for further full clinical validation.


title: A Coronavirus E Protein Is Present in Two Distinct Pools with Different Effects on Assembly and the Secretory Pathway.

text: UNLABELLED Coronaviruses (CoVs) assemble by budding into the lumen of the early Golgi complex prior to exocytosis. The small CoV envelope (E) protein plays roles in assembly, virion release, and pathogenesis. CoV E has a single hydrophobic domain (HD), is targeted to Golgi complex membranes, and has cation channel activity in vitro. However, the precise functions of the CoV E protein during infection are still enigmatic. Structural data for the severe acute respiratory syndrome (SARS)-CoV E protein suggest that it assembles into a homopentamer. Specific residues in the HD regulate the ion-conducting pore formed by SARS-CoV E in artificial bilayers and the pathogenicity of the virus during infection. The E protein from the avian infectious bronchitis virus (IBV) has dramatic effects on the secretory system which require residues in the HD. Here, we use the known structural data from SARS-CoV E to infer the residues important for ion channel activity and the oligomerization of IBV E. We present biochemical data for the formation of two distinct oligomeric pools of IBV E in transfected and infected cells and the residues required for their formation. A high-order oligomer of IBV E is required for the production of virus-like particles (VLPs), implicating this form of the protein in virion assembly. Additionally, disruption of the secretory pathway by IBV E correlates with a form that is likely monomeric, suggesting that the effects on the secretory pathway are independent of E ion channel activity. IMPORTANCE CoVs are important human pathogens with significant zoonotic potential, as demonstrated by the emergence of SARS-CoV and Middle East respiratory syndrome (MERS)-CoV. Progress has been made toward identifying potential vaccine candidates in mouse models of CoV infection, including the use of attenuated viruses that lack the CoV E protein or express E-protein mutants. However, no approved vaccines or antiviral therapeutics exist. We previously reported that the hydrophobic domain of the IBV E protein, a putative viroporin, causes disruption of the mammalian secretory pathway when exogenously expressed in cells. Understanding the mechanism of this disruption could lead to the identification of novel antiviral therapeutics. Here, we present biochemical evidence for two distinct oligomeric forms of IBV E, one essential for assembly and the other with a role in disruption of the secretory pathway. Discovery of two forms of CoV E protein will provide additional targets for antiviral therapeutics.


Can I receive and store images sent from patients during remote consultations?


title: Acute on Chronic Liver Failure from Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

text: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious viral disease that predominantly causes respiratory symptoms. Elevated liver enzymes have been reported during the course of disease and appear to be common. We present a 56-yearold woman with a history of decompensated alcoholic cirrhosis who presented with abdominal pain, fever and diarrhea and was found to have acute on chronic liver failure secondary to SARS-CoV-2 infection. The patient was treated with empiric antibiotic and supportive care with subsequent improvement.


COVID-19 in prisons: an impossible challenge for public health?


title: Managing a Tertiary Orthopedic Hospital during the COVID-19 Epidemic, Main Challenges and Solutions Adopted.

text: The present paper is a review of the main challenges faced by the management of a tertiary specialty hospital during the COVID-19 pandemic in the northern Italian region of Lombardy, an area of extremely high epidemic impact. The article focuses on the management of patient flows, access to the hospital, maintaining and reallocating staffing levels, and managing urgent referrals, information, and communications from the point of view of the hospital managers over a seven-week period. The objective of the article is to provide beneficial insights and solutions to other hospital managers and medical directors who should find themselves in the same or a similar situation. In such an epidemic emergency, in the authors' opinion, the most important factors influencing the capability of the hospital to maintain operations are (1) sustaining the strict triage of patients, (2) the differentiation of flows and pathways to create what could be regarded as "a hospital inside a hospital", (3) tracing and sharing all available information to face the rapidly changing environment, (4) being able to maintain staffing levels in critical areas by flexibly allocating the workforce, and (5) from a regional perspective, being organized along a hub-and-spoke system for critical and time-sensitive networks was key for focusing the hospital's resources on the most needed services.


title: Laparoscopic pancreaticojejunostomy using a barbed suture: a novel technique.

text: OBJECTIVES The adoption of laparoscopy for the Whipple procedure remains limited in part by its technical difficulty. We sought to develop a superior, simpler pancreaticojejunostomy technique. MATERIALS AND METHODS We applied a running barbed suture (V-Loc™; Covidien, Mansfield, MA) to perform the pancreaticojejunostomy over a stent placed in the pancreatic duct and a small enterotomy in the jejunum. This technique was attempted in the last 19 of 37 patients presenting to two surgeons (M.A.M. and B.H.E.) for a laparoscopic Whipple procedure. Data were collected on operative time, pancreatic leak events, and related complications. RESULTS We successfully applied the modified technique in all 19 patients. Pancreatic leak occurred in 5% of patients with the modified technique (Grade A=0; Grade B=1; Grade C=0) and 11% with the standard technique (Grade A=1; Grade B=1; Grade C=0). All leaks were managed with external drainage. There were no leak-related complications. Mean operative time was shorter for the modified technique (mean, 367 minutes; range, 260-576 minutes) than the standard technique (mean, 440 minutes; range, 300-665 minutes). CONCLUSIONS The use of a running barbed suture for laparoscopic pancreaticojejunostomy is a safe and efficient technique. Our operative times were decreased with this technique, and our outcomes were similar to other laparoscopic Whipple series.


title: Hiatal hernias presenting as a late complication of laparoscopic-assisted cardio-oesophagectomy.

text: The resection of oesophageal cancer offers the only chance of cure. The introduction of minimally invasive oesophagectomy has gained wide acceptance for the surgical treatment of oesophago-gastric cancers. The most commonly reported late complications of minimally invasive oesophagectomy are anastamotic stricture, chylothorax, chronic diarrhoea and delayed gastric emptying. Symptomatic hiatus hernia presenting as a late complication of laparoscopic cardio-oesophagectomy is not a widely reported complication. We have encountered three such cases, two of which were treated laparoscopically.


Covid-19 related hospital admissions in the United States: needs and outcomes.


title: Influenza vaccine: a travelers' vaccine?

text: Seasonal influenza affects 5-15% of the world's population annually and is considered to be the second most frequent vaccine-preventable infection in travelers. Despite increasing travel volume worldwide, guidelines on influenza vaccination for international travel are scarce. On the basis of some national recommendations, influenza vaccine should be used based on host criteria to usual risk groups, such as old (>50-65 years) or young (6-23 months) age and those with comorbidities. Additionally, environmental and behavioral factors must be considered. Close contact with high transmission has been documented in cruise ships and during mass gatherings. Travelers crossing to the opposite hemisphere in influenza-peak season may need protection. Those visiting the tropics are at moderate risk of infection and illness during the entire year. A summary on existing traveler recommendations relating to avian influenza is included.


title: Bone preservation in dehiscence-type defects using composite biphasic calcium sulfate plus biphasic hydroxyapatite/β-tricalcium phosphate graft: a histomorphometric case series in canine mandible.

text: OBJECTIVES To examine bone formation in dehiscence defects using biphasic hydroxyapatite/β-tricalcium phosphate plus biphasic calcium sulfate (BCP/BCS). MATERIAL After extractions, 24 mandibular buccal dehiscence defects (3 × 3 mm) were treated with BCP/BCS (E), membrane (MC), or control (NC). Histology and histomorphometric analysis were performed. RESULTS After 6 weeks, bone formation was noticeable in most sites. In subsequent phases, the woven bone was gradually remodeled into lamellar bone and marrow. Vertical new bone height in the E and MC groups (1.06 and 0.85 mm.) was substantially greater than that in the NC group (-0.28 mm). For all groups, there was an overall increase in the height of the newly formed bone through the observation. At week 12, the vertical bone height was 1.95, 2.07, and 0.29 mm, respectively. The mean new bone area in the E and MC groups was much greater than that in the NC group (2.85, 2.80, and -0.20 mm, respectively). Percent new bone in all 3 groups was similar (36.25%, 34.84%, and 28.34%, respectively). CONCLUSIONS This study demonstrates the efficacy of BCP/BCS graft for bone augmentation in dehiscence-type extraction socket defect.


Health surveillance during covid-19 pandemic.


title: Saxifraga spinulosa-Derived Components Rapidly Inactivate Multiple Viruses Including SARS-CoV-2.

text: Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), and norovirus (NV) are highly contagious pathogens that threaten human health. Here we focused on the antiviral potential of the medicinal herb, Saxifraga spinulosa (SS). Water-soluble extracts of SS were prepared, and their virus-inactivating activity was evaluated against the human virus pathogens SARS-CoV-2 and IAV; we also examined virucidal activity against feline calicivirus and murine norovirus, which are surrogates for human NV. Among our findings, we found that SS-derived gallocatechin gallate compounds were capable of inactivating all viruses tested. Interestingly, a pyrogallol-enriched fraction (Fr 1C) inactivated all viruses more rapidly and effectively than did any of the component compounds used alone. We found that 25 µg/mL of Fr 1C inactivated >99.6% of SARS-CoV-2 within 10 s (reduction of ≥2.33 log10 TCID50/mL). Fr 1C resulted in the disruption of viral genomes and proteins as determined by gel electrophoresis, electron microscopy, and reverse transcription-PCR. Taken together, our results reveal the potential of Fr 1C for development as a novel antiviral disinfectant.


title: Meta-analysis on biomechanical properties of meniscus repairs: are devices better than sutures?

text: PURPOSE Meniscal repair devices have been extensively tested during the past decades as reported in the literature. Reviewing the different meniscal repair devices and sutures with their respective biomechanical properties. METHODS For this meta-analysis, we conducted a systematic online search using PubMed, EMBASE, CCTR, and CINAHL using the search terms Meniscus OR Meniscal AND Biomechanics AND Repair). Load-to-failure (LtF), stiffness, and cyclic outcome measures were extracted independently and in duplicate. The systematic search revealed 841 manuscripts in total. After exclusion of duplicates and irrelevant publications, 41 studies remained for final analysis. The studies were published in English and German from 1995 to 2013. Due to differing cyclic force protocols, cyclic outcomes had to be excluded. RESULTS Overall, sutures had a higher LtF [suture: 87.7 ± 0.3 N (weighted mean ± standard error), device: 56.3 ± 0.1 N] and stiffness (suture: 8.9 ± 0.04 N/mm, device: 8.6 ± 0.04 N/mm) than devices, both p < 0.05. In LfT testing, PDS 0 Vertical (145.0 ± 8.1 N), OrthoCord 2-0 (143.6 ± 11.3 N), and Ethibond No 0 Vertical (133.4 ± 7.7 N) were the strongest sutures and Meniscal Viper (140.9 ± 5.1 N), MaxFire Vertical (136.2 ± 11.3 N), and FasT-Fix Vertical (115.2 ± 1.6 N) were the strongest devices. Second-generation devices were significantly stronger and stiffer than first-generation devices (p < 0.001). CLINICAL RELEVANCE Suture repair remains the gold standard with a vertically oriented suture configuration showing superior LtF values compared to a horizontal configuration. Nevertheless, some meniscal repair devices have similar biomechanical properties to suture repairs. Both suture repairs and devices have a place in meniscal restoration. LEVEL OF EVIDENCE None, meta-analysis of controlled laboratory studies.


COVID-19 - "The game changer" of the real world.


title: Weight loss interventions for Hispanic women in the USA: a protocol for a systematic review.

text: BACKGROUND In the U.S., Hispanic women experience a disproportionate rate of obesity and obesity-related chronic diseases. At the same time, Hispanic women remain considerably underrepresented in behavioral weight loss interventions. The purpose of this review is to systematically evaluate the evidence related to the effectiveness of weight loss interventions among Hispanic women in the U.S. This review will identify elements of successful weight loss interventions as well as areas for future research. METHODS/DESIGN The following databases will be searched to identify all relevant articles (from inception onwards): PubMed, Embase, Scopus, Web of Science (Science Citation Index and Social Sciences Citation Index), PsycINFO, CINAHL, Chicano Database, SPORTDiscus, CAB Abstracts, and Google Scholar. We will include randomized controlled trials and quasi-experimental studies of adult women (> 18 years) from Hispanic/Latino background living in the United States. Eligible interventions will target weight-related behaviors (including diet, physical activity, behavior modification and/or their combinations). The review's primary outcome will be weight change (expressed as change in lbs/kg or body mass index (BMI) (kg/m2)). Three reviewers will independently screen and select data and two will extract data. The methodological quality (or risk of bias) of individual studies will be appraised using the Effective Public Health Practice Project Quality Assessment Tool. A narrative synthesis will describe quality and content of the evidence. DISCUSSION The aim of this systematic review is to critically examine existing weight loss interventions for Hispanic women in the U.S. and provide quality evidence for the effectiveness of these interventions on weight loss. Further, this review seeks to identify characteristics of effective interventions and suggest future directions for research efforts targeting weight loss in this population. This review will inform the development of future weight loss interventions for this population. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019119094.


title: Liver Surface Nodularity Quantification from Routine CT Images as a Biomarker for Detection and Evaluation of Cirrhosis.

text: Purpose To determine the accuracy, reproducibility, and intra- and interobserver agreement of a computer-based quantitative method to measure liver surface nodularity (LSN) from routine computed tomographic (CT) images as a biomarker for detection and evaluation of cirrhosis. Materials and Methods For this institutional review board-approved HIPAA-compliant retrospective study, adult patients with healthy livers (n = 24) or various stages of hepatitis C virus-induced chronic liver disease (n = 70) with routine nonenhanced and portal venous phase contrast agent-enhanced liver CT imaging with thick-section (5.0 mm) and thin-section (1.25-1.50 mm) axial images obtained between January 1, 2006, and March 31, 2011, were identified from the electronic medical records. A computer algorithm was developed to measure LSN and derive a score. LSN scores, splenic volume, and the ratio of left lateral segment (LLS) to total liver volume (TLV) were measured from the same multiphasic liver CT examinations. Accuracy for differentiating cirrhotic from noncirrhotic livers was assessed by area under the receiver operating characteristic curve. Intra- and interobserver agreement was assessed by intraclass correlation coefficient. Results Median LSN scores from nonenhanced thick-section CT images in cirrhotic livers (3.16; 56 livers) were significantly higher than in noncirrhotic livers (2.11; 38 livers; P < .001). LSN scores from the four CT imaging types (94 patients for each type) were very strongly correlated (range of Spearman r, 0.929-0.960). LSN scores from portal venous phase contrast-enhanced thick-section CT images had significantly higher accuracy (area under the receiver operating characteristic curve, 0.929) than splenic volume (area under the receiver operating characteristic curve, 0.835) or LLS-to-TLV ratio measurements (area under the receiver operating characteristic curve, 0.753) for differentiating cirrhotic from noncirrhotic livers (P = .038 and .003, respectively; n = 94). Intra- and interobserver agreements that used nonenhanced thick CT images were very good (intraclass correlation coefficient, 0.963 and 0.899, respectively). Conclusion Quantitative measurement of LSN on routine CT images accurately differentiated cirrhotic from noncirrhotic livers and was highly reproducible. (©) RSNA, 2016 Online supplemental material is available for this article.


title: Viral infections in patients with chronic obstructive pulmonary disease.

text: PURPOSE OF REVIEW Chronic obstructive pulmonary disease is a major cause of morbidity and mortality worldwide. There is increasing evidence that implicates viral infections as a major risk factor for exacerbations of chronic obstructive pulmonary disease. Recent studies have attempted to better characterize the epidemiology of viral infections in chronic obstructive pulmonary disease, identify unique clinical manifestations of virus-associated exacerbations, and develop new diagnostic tools and treatments. RECENT FINDINGS Rhinovirus, the organism most often responsible for causing the common cold, is also the most common infectious cause of chronic obstructive pulmonary disease exacerbations. Coronavirus, influenza, respiratory syncytial virus, parainfluenza, adenovirus, and metapneumovirus are other important viral causes of chronic obstructive pulmonary disease exacerbations. These exacerbations can be severe with prolonged recovery times. Although PCR technology has dramatically increased the detection rate of viruses in patients with chronic obstructive pulmonary disease, it does not differentiate infection from colonization. The use of biomarkers represents an exciting new potential diagnostic tool that may lend new insights into the pathogenesis of viral infections in patients with chronic obstructive pulmonary disease. SUMMARY Despite strong epidemiologic evidence linking respiratory virus infection to exacerbations of chronic obstructive pulmonary disease, many of the cellular and molecular mechanisms by which viruses cause exacerbations remain undetermined. Future research efforts to understand these mechanisms would aid the development of novel therapeutics to reduce the morbidity and mortality of this disease.


title: Experimental Infection of Pregnant Female Sheep with Zika Virus During Early Gestation.

text: Zika virus (ZIKV) is a vertically and sexually transmissible virus resulting in severe congenital malformation. The goal of this study was to develop an ovine model of ZIKV infection. Between 28-35 days gestation (DG), four pregnant animals were infected with two doses of 6 × 106 PFU of ZIKV; four control animals received PBS. Animals were evaluated for 45 days (D) post-infection (PI) and necropsies were performed. Viral RNA was detected in infected ewe peripheral blood mononuclear cells (PBMC) during the first week PI; however, all fluids and tissues were negative upon culture. Anti-ZIKV IgM (1:400) and neutralizing antibodies were detected in all infected animals. Clinical disease, virus, or ZIKV antibodies were not detected in control ewes. After two weeks PI, fetal loss occurred in two infected animals, and at necropsy, three infected animals had placental petechiation and ecchymosis and one had hydramnion. Fetal morphometrics revealed smaller cranial circumference to crown-rump length ratios (p < 0.001) and relative brain weights (p = 0.038) in fetuses of infected animals compared with control fetuses. Immunophenotyping indicated an increase in B cells (p = 0.012) in infected sheep. Additionally, in vitro experiments using both adult and fetal cell lines demonstrated that ovine cells are highly permissive to ZIKV infection. In conclusion, ZIKV infection of pregnant sheep results in a change in fetal growth and gestational outcomes.


title: Radiofrequency ablation: a safe and effective treatment in nonoperative patients with early-stage lung cancer.

text: Surgical resection remains the treatment of choice for patients with early-stage non-small cell lung cancer. However, some patients are not surgical candidates because of medical problems. Therefore, alternative therapies are considered in these medically inoperable patients. Radiofrequency ablation has been used clinically for more than 12 years, with many studies reporting its safety and efficacy. Because there are no large prospective clinical trials comparing the efficacy and long-term survival of the different treatment modalities, the choice of therapy is often based on a combination of tumor location, available technology and expertise, and patient preference. Here we review the principles, procedure, follow up, and clinical outcomes published to date on radiofrequency ablation in the treatment of early-stage non-small cell lung cancer.


title: Radiofrequency ablation for subcardiac hepatocellular carcinoma: therapeutic outcomes and risk factors for technical failure.

text: OBJECTIVES To compare the therapeutic outcomes and safety of radiofrequency (RF) ablation for subcardiac and non-subcardiac hepatocellular carcinoma (HCC) and to evaluate the risk factors for technical failure of the procedure. METHODS This retrospective study was approved by the institutional review board. Between September 2002 and May 2016, 73 patients with subcardiac HCC and the same number of patients with non-subcardiac HCC matched by tumor size were included. Subcardiac HCC was defined as an index tumor that was located ≤ 1 cm from the pericardium in axial or coronal images. Cumulative local tumor progression (LTP) was compared between the two groups using the log-rank test. Prognostic factors for technical failure were assessed using multivariable logistic analysis. RESULTS Technical success rates between both groups were not significantly different (91.8% in the subcardiac HCC group vs. 95.9% in the non-subcardiac HCC group; p = 0.494). The cumulative LTP rates were 15.4% and 19.1% at 3 and 5 years, respectively, in the subcardiac HCC group, and 10.7% and 15.5% in the non-subcardiac HCC group, without significant difference (p = 0.862). The distance between the index tumor and pericardium (odds ratio [OR], 0.14; p = 0.023) and tumor in segment IV (reference, left lateral sector; OR, 36.53; p = 0.029) were significant factors for technical failure in patients with subcardiac HCC. CONCLUSIONS RF ablation was an effective treatment for subcardiac HCC. However, tumor location should be considered in the planning of treatment to avoid technical failure. KEY POINTS • RF ablation for subcardiac HCC is technically feasible without major complications. • RF ablation was an effective treatment for subcardiac HCC in terms of LTP. • Risk factors for technical failure were distance of the index tumor from the heart (cutoff value of 0.5 cm) and the location of the tumor (segment IV).


title: Lipoplasty Combined with Percutaneous Radiofrequency Dermaplasty: A New Strategy for Body Contouring.

text: BACKGROUND A new technique in plastic surgery termed percutaneous radiofrequency dermaplasty (PRD) is described. Customized radiofrequency energy is applied via the percutaneous route to produce skin tightening and fascia contraction at body temperature, avoiding thermal injury. We combine PRD with lipoplasty and call this combined procedure dermaplasty-assisted lipoplasty (DAL). The purpose of this study was to review both the safety and efficacy of DAL. METHODS We developed the required novel device and technique to perform DAL and then performed a clinical trial including Type I and Type II lipodystrophy female patients undergoing a primary liposuction of the circumferential trunk. The trial comprised two phases. In Phase I, 51 patients were included in a prospective, comparative, controlled trial and divided into two groups. In Group 1, 29 patients underwent DAL, and in Group 2, 22 patients underwent a standard suction-assisted lipectomy (SAL) alone. In Phase II, 84 patients underwent DAL, including 9 cases initially scheduled for a mini-abdominoplasty. RESULTS Phase I: We found better aesthetic results with DAL (93.1%) than with SAL alone (72.7%) [p < .05]. Postoperative correction of flaccid skin was superior with DAL (93.1%) than with SAL alone (36.4%) [p < .01]. Phase II: DAL achieved good-to-excellent aesthetic results in 94% of the cases. CONCLUSIONS DAL was found to be a reliable and safe treatment for fat removal with concomitant skin and fascia tightening but without compromising the viability of the overlying skin. LEVEL OF EVIDENCE IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


title: Hemorrhagic Posterior Reversible Encephalopathy Syndrome as a Manifestation of COVID-19 Infection.

text: We describe 2 hospitalized patients with confirmed coronavirus 19 (COVID-19) infection in whom brain imaging showed hemorrhagic posterior reversible encephalopathy syndrome, and we discuss the possible reasons for these findings and their relationship to the infection.


title: Evaluation of six videolaryngoscopes in 720 patients with a simulated difficult airway: a multicentre randomized controlled trial.

text: BACKGROUND Videolaryngoscopes are aggressively marketed, but independent evaluation in difficult airways is scarce. This multicentre, prospective randomized controlled trial evaluates six videolaryngoscopes in patients with a simulated difficult airway. METHODS With ethics committee approval and written informed consent, 12 senior anaesthetists intubated the trachea of 720 patients. A cervical collar limited mouth opening and neck movement, making intubation difficult. We evaluated three unchannelled (C-MAC™ D-blade, GlideScope™, and McGrath™) and three channelled videolaryngoscopes (Airtraq™, A.P. Advance™ difficult airway blade, and KingVision™). The primary outcome was first-attempt intubation success rate. Secondary outcomes included overall success rate, laryngeal view, intubation times, and side-effects. The primary hypothesis for every videolaryngoscope was that the 95% confidence interval of first-attempt success rate is ≥90%. RESULTS Mouth opening was decreased from 46 (sd 7) to 23 (3) mm with the cervical collar. First-attempt success rates were 98% (McGrath™), 95% (C-MAC™ D-blade), 87% (KingVision™), 85% (GlideScope™ and Airtraq™), and 37% (A.P. Advance™, P<0.01). The 95% confidence interval of first-attempt success rate was >90% only for the McGrath™. Overall success, laryngeal view, and intubation times differed significantly between videolaryngoscopes (all P<0.01). Side-effects were minor. CONCLUSIONS This trial revealed differences in the performance of six videolaryngoscopes in 720 patients with restricted neck movement and limited mouth opening. In this setting, first-attempt success rates were 85-98%, except for the A.P. Advance™ difficult airway blade. Highest success and lowest tissue trauma rates were achieved by the McGrath™ and C-MAC™ D-blade, highlighting the importance of the videolaryngoscope blade design. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov: identifier NCT01692535.


title: Neural mass model-based tracking of anesthetic brain states.

text: Neural mass model-based tracking of brain states from electroencephalographic signals holds the promise of simultaneously tracking brain states while inferring underlying physiological changes in various neuroscientific and clinical applications. Here, neural mass model-based tracking of brain states using the unscented Kalman filter applied to estimate parameters of the Jansen-Rit cortical population model is evaluated through the application of propofol-based anesthetic state monitoring. In particular, 15 subjects underwent propofol anesthesia induction from awake to anesthetised while behavioral responsiveness was monitored and frontal electroencephalographic signals were recorded. The unscented Kalman filter Jansen-Rit model approach applied to frontal electroencephalography achieved reasonable testing performance for classification of the anesthetic brain state (sensitivity: 0.51; chance sensitivity: 0.17; nearest neighbor sensitivity 0.75) when compared to approaches based on linear (autoregressive moving average) modeling (sensitivity 0.58; nearest neighbor sensitivity: 0.91) and a high performing standard depth of anesthesia monitoring measure, Higuchi Fractal Dimension (sensitivity: 0.50; nearest neighbor sensitivity: 0.88). Moreover, it was found that the unscented Kalman filter based parameter estimates of the inhibitory postsynaptic potential amplitude varied in the physiologically expected direction with increases in propofol concentration, while the estimates of the inhibitory postsynaptic potential rate constant did not. These results combined with analysis of monotonicity of parameter estimates, error analysis of parameter estimates, and observability analysis of the Jansen-Rit model, along with considerations of extensions of the Jansen-Rit model, suggests that the Jansen-Rit model combined with unscented Kalman filtering provides a valuable reference point for future real-time brain state tracking studies. This is especially true for studies of more complex, but still computationally efficient, neural models of anesthesia that can more accurately track the anesthetic brain state, while simultaneously inferring underlying physiological changes that can potentially provide useful clinical information.


Hematological changes in Covid-19 infections.


Virucidal activity of cell-penetrating peptides of viral origin.


title: Laparoendoscopic single-site nephrectomy: initial clinical experience in children.

text: OBJECTIVE To present the initial clinical experience in children undergoing unilateral and bilateral laparoendoscopic single-site nephrectomy. PATIENTS AND METHODS We reviewed our experience with pediatric patients who had undergone single-port nephrectomy (SPN) at our institution since August of 2009. Access was obtained by using the Hassan technique to place a 2-cm SILS™ Port (Covidien Surgical Devices, Norwalk, CT), which contains a gas insufflation channel and three individual cannulas that can readily accommodate laparoscopic instruments up to 12 mm in diameter. Nephrectomy was performed using a standard set of laparoscopic instruments and a rigid 5 mm 30 degree laparoscope (Karl Storz, Tuttlingen, Germany) with an end-on light source. Patient demographics, operative details, and postoperative treatment parameters were collected and recorded. RESULTS SPN was successfully performed in three consecutive pediatric patients (one female and two male patients: aged 11, 10, and 13 years, respectively) without placement of additional trocars or conversion to open surgery. The operative time for the unilateral SPN was 188 minutes, whereas bilateral SPNs required 214 and 300 minutes, respectively. Estimated blood loss for the unilateral and bilateral SPNs was 25, 20, and 30 mL; whereas patients were discharged on postoperative days 1, 3, and 12, respectively. The prolonged hospital stay was secondary to fever and pseudomembranous colitis in a patient with dialysis who also required a blood transfusion. CONCLUSIONS Laparoendoscopic single-site simple nephrectomy is a technically demanding yet feasible procedure in children. Further studies are necessary to define the indications, advantages, and limitations of this technique as compared with standard laparoscopy.


title: Identification and characterization of the Onchocerca volvulus Excretory Secretory Product Ov28CRP, a putative GM2 activator protein.

text: Onchocerca volvulus is the nematode pathogen responsible for human onchocerciasis also known as "River blindness", a neglected tropical disease that affects up to 18 million people worldwide. Helminths Excretory Secretory Products (ESPs) constitute a rich repertoire of molecules that can be exploited for host-parasite relationship, diagnosis and vaccine studies. Here, we report, using a range of molecular techniques including PCR, western blot, recombinant DNA technology, ELISA, high performance thin-layer chromatography and mass spectrometry that the 28 KDa cysteine-rich protein (Ov28CRP) is a reliable component of the O. volvulus ESPs to address the biology of this parasite. We showed that (1) Ov28CRP is a putative ganglioside GM2 Activator Protein (GM2AP) conserved in nematode; (2) OvGM2AP gene is transcriptionally activated in all investigated stages of the parasitic life cycle, including larval and adult stages; (3) The full-length OvGM2AP was detected in in-vitro O. volvulus ESPs of adult and larval stages; (4) the mass expressed and purified recombinant OvGM2AP purified from insect cell culture medium was found to be glycosylated at asparagine 173 and lacked N-terminal signal peptide sequence; (5) the recombinant OvGM2AP discriminated serum samples of infected and uninfected individuals; (6) OvGM2AP competitively inhibits MUG degradation by recombinant β-hexosaminidase A but not MUGS, and could not hydrolyze the GM2 to GM3; (7) humoral immune responses to the recombinant OvGM2AP revealed a negative correlation with ivermectin treatment. Altogether, our findings suggest for the first time that OvGM2AP is an antigenic molecule whose biochemical and immunological features are important to gain more insight into our understanding of host-parasite relationship, as well as its function in parasite development at large.


title: Pediatric transumbilical laparoendoscopic single-site nephroureterectomy: initial report.

text: OBJECTIVE To present a case of laparoendoscopic single-site surgery (LESS) nephroureterectomy (NUx), a type of embroyonic natural orifice translumenal endoscopic surgery, which is one of the recent innovations in the era of laparoscopy, in a child. METHODS A 10-year-old girl underwent left nephroureterectomy by LESS due to end-stage reflux nephropathy on December 25, 2008. The surgery is performed transperitoneally, through a 2-cm semicircular incision in the left inner curve of the umbilicus using three 5-mm trocars. NUx with LESS was performed duplicating standard laparoscopic steps with the help of flexible and straight laparoscopic instruments. RESULTS Operation time was 140 minutes and the blood loss was minimal. There was no intraoperative or postoperative complication. The patient was discharged at the 24th postoperative hour. The postoperative cosmetic result was excellent as the incision scar was hidden inside the belly button. CONCLUSIONS NUx with LESS is a feasible technique with the advantages of less pain, shortened convalescence, improved cosmesis, and absence of wound complications in children. However, clear indications of LESS in children remain to be clarified.


title: A novel dromedary camel enterovirus in the family Picornaviridae from dromedaries in the Middle East.

text: The recent emergence of Middle East respiratory syndrome coronavirus from the Middle East and the discovery of the virus from dromedary camels have boosted interest in the search for novel viruses in dromedaries. Whilst picornaviruses are known to infect various animals, their existence in dromedaries was unknown. We describe the discovery of a novel picornavirus, dromedary camel enterovirus (DcEV), from dromedaries in Dubai. Among 215 dromedaries, DcEV was detected in faecal samples of four (1.9 %) dromedaries [one (0.5 %) adult dromedary and three (25 %) dromedary calves] by reverse transcription PCR. Analysis of two DcEV genomes showed that DcEV was clustered with other species of the genus Enterovirus and was most closely related to and possessed highest amino acid identities to the species Enterovirus E and Enterovirus F found in cattle. The G+C content of DcEV was 45 mol%, which differed from that of Enterovirus E and Enterovirus F (49-50 mol%) by 4-5 %. Similar to other members of the genus Enterovirus, the 5' UTR of DcEV possessed a putative type I internal ribosome entry site. The low ratios of the number of nonsynonymous substitutions per non-synonymous site to the number of synonymous substitutions per synonymous site (Ka/Ks) of various coding regions suggested that dromedaries are the natural reservoir in which DcEV has been stably evolving. These results suggest that DcEV is a novel species of the genus Enterovirus in the family Picornaviridae. Western blot analysis using recombinant DcEV VP1 polypeptide showed a high seroprevalence of 52 % among serum samples from 172 dromedaries for IgG, concurring with its much higher infection rates in dromedary calves than in adults. Further studies are important to understand the pathogenicity, epidemiology and genetic evolution of DcEV in this unique group of animals.


Covid-19: how to use your time when clinical placements are postponed.


title: Is the skillset obtained in surgical simulation transferable to the operating theatre?

text: BACKGROUND Simulated surgical training offers a safe and accessible way of learning surgical procedures outside the operating room. Training programs have been developed using simulated laboratories to train surgical trainees to proficiency outside the operating room. Despite the global enthusiasm among educators to enhance training through simulation-based learning, it remains to be elucidated whether the skill set obtained is transferrable to the operating room. METHODS Using standardized search methods, the authors searched the Cochrane Central Register of Controlled Trials, PubMed, Embase, and Web-Based Knowledge, as well as the reference lists of relevant articles, and retrieved all published randomized controlled trials. RESULTS Sixteen randomized controlled trials involving 309 participants were identified to be suitable for qualitative analysis using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The mean Consolidated Standards of Reporting Trials score was 16 (range, 12-22). The studies showed considerable clinical and methodologic diversity. Operative time improved consistently in all trials after training and was the only objective parameter measurable in the live setting. Studies that used the Objective Structured Assessment of Technical Skills as their primary outcome showed improved scores in 80% of trials, and studies that used performance indicators to assess participants all showed improved scores after simulation training in all of the trials, with 88% showing statistical significance. CONCLUSIONS The current literature consistently demonstrates the positive impact of simulation on operative time and predefined performance scores. However, these reproducible measures alone are insufficient to demonstrate transferability of skills from the laboratory to the operating room. The authors advocate a multimodal assessment, including metrics, the Objective Structured Assessment of Technical Skills, and critical step completion. This may provide a more complete assessment of operative performance. Only then can it be concluded that simulation skills are transferable to the live operative setting.


Progress toward a vaccine for Middle-Eastern respiratory syndrome.


title: Factors affecting recurrence and management of recurrent cerebral aneurysms after initial coiling.

text: OBJECTIVE To investigate factors affecting recurrence and effects and safety of endovascular retreatment for aneurysms recurrent after embolization. METHODS Among 815 aneurysms treated with embolization, recurrence was in 114 aneurysms (14.0%). Forty-three recurrent aneurysms were managed with re-embolization. Procedural complications, angiographic, and clinical results of retreatment were analyzed. RESULTS Patients with recurrent aneurysms were significantly (P < 0.01) younger than without recurrence (51.09 ± 10.46 vs. 53.88 ± 9.61 years). Recurrent aneurysms (n = 114) were significantly (P = 0.00) greater (11.12 ± 8.35 vs. 5.81 ± 3.44 mm) with a significantly (P = 0.00) greater neck (4.34 ± 2.26 vs. 2.90 ± 1.44 mm) than without recurrence. The rupture status of aneurysms significantly (P = 0.00) affected recurrence at follow-up. Significantly (P = 0.00) more aneurysms without recurrence were treated with advanced embolization techniques (81.0% vs. 62.3%) and got complete occlusion at the first embolization than those with recurrence (93.7% vs. 36.8%). In treating 43 recurrent aneurysms, stent-assisted recoiling was used in 48.8% in the first retreatment and 50% in the second and third retreatment procedures. Angiographic follow-up in 38 (88.4%) cases showed complete or near complete occlusion in 30 aneurysms, with the rest eight aneurysms experiencing a second recurrence (21.1%). Of the eight aneurysms with the second recurrence, five underwent the second endovascular retreatment, with complete aneurysm occlusion achieved in three cases (60%), near-complete occlusion in one (20%), and incomplete occlusion in one case at immediate angiography and six-month follow-up. Procedure-related complications occurred in three patients. CONCLUSIONS Endovascular retreatment of recurrent previously coiled aneurysms is safe and effective even though advanced embolization techniques are frequently involved especially for large and giant aneurysms.


title: Double-barrelled wet colostomy formation after pelvic exenteration for locally advanced or recurrent rectal cancer.

text: AIM In advanced pelvic cancer it may be necessary to perform a total pelvic exenteration. In such cases urinary tract reconstruction is usually achieved with the creation of an ileal conduit with a urinary stoma on the right side of the patient's abdomen and an end colostomy separately on the left. The potential morbidity from a second stoma may be avoided by the use of a double-barrelled wet colostomy (DBWC), as a single stoma. Another advantage is the possibility of using a vertical rectus abdominis muscle flap for perineal reconstruction. METHOD All patients undergoing formation of a DBWC were included. RESULT A DBWC was formed in 10 patients. One patient underwent formation of a double-barrelled wet ileostomy. CONCLUSIONS In this technical note we present our early experience in 11 cases and a video of DBWC formation in a male patient.


title: Unruptured intracranial aneurysms: management strategy and current endovascular treatment options.

text: INTRODUCTION Unruptured intracranial aneurysms (UIA) have a high prevalence (3.2%) and are increasingly diagnosed with modern imaging tools. The main risk of UIA is their rupture associated with intracranial bleeding with often severe clinical consequences. Areas covered: This review discusses the management strategy of UIAs, based on the large series of the literature (ISUIA, ATENA, UCAS, …), knowing that no randomized controlled trial is available to compare different strategies. The different endovascular treatments are described. Expert commentary: Due to the relatively scarce data regarding the risk of rupture of UIAs, the strategy of management is often difficult to define. It has to be multidisciplinary and has to take into account several factors related to the patient and the aneurysm. Beside the surgical approach, several endovascular tools are available to treat UIAs, that includes standard coiling, balloon-assisted coiling, stent-assisted coiling, flow diversion, and flow disruption.


title: Structural and functional conservation of the programmed -1 ribosomal frameshift signal of SARS coronavirus 2 (SARS-CoV-2).

text: About 17 years after the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic, the world is currently facing the COVID-19 pandemic caused by SARS coronavirus 2 (SARS-CoV-2). According to the most optimistic projections, it will take more than a year to develop a vaccine, so the best short-term strategy may lie in identifying virus-specific targets for small molecule-based interventions. All coronaviruses utilize a molecular mechanism called programmed -1 ribosomal frameshift (-1 PRF) to control the relative expression of their proteins. Previous analyses of SARS-CoV have revealed that it employs a structurally unique three-stemmed mRNA pseudoknot that stimulates high -1 PRF rates and that it also harbors a -1 PRF attenuation element. Altering -1 PRF activity impairs virus replication, suggesting that this activity may be therapeutically targeted. Here, we comparatively analyzed the SARS-CoV and SARS-CoV-2 frameshift signals. Structural and functional analyses revealed that both elements promote similar -1 PRF rates and that silent coding mutations in the slippery sites and in all three stems of the pseudoknot strongly ablate -1 PRF activity. We noted that the upstream attenuator hairpin activity is also functionally retained in both viruses, despite differences in the primary sequence in this region. Small-angle X-ray scattering analyses indicated that the pseudoknots in SARS-CoV and SARS-CoV-2 have the same conformation. Finally, a small molecule previously shown to bind the SARS-CoV pseudoknot and inhibit -1 PRF was similarly effective against -1 PRF in SARS-CoV-2, suggesting that such frameshift inhibitors may be promising lead compounds to combat the current COVID-19 pandemic.


title: Moderation of the Relationship Between Reward Expectancy and Prediction Error-Related Ventral Striatal Reactivity by Anhedonia in Unmedicated Major Depressive Disorder: Findings From the EMBARC Study.

text: OBJECTIVE Anhedonia, disrupted reward processing, is a core symptom of major depressive disorder. Recent findings demonstrate altered reward-related ventral striatal reactivity in depressed individuals, but the extent to which this is specific to anhedonia remains poorly understood. The authors examined the effect of anhedonia on reward expectancy (expected outcome value) and prediction error- (discrepancy between expected and actual outcome) related ventral striatal reactivity, as well as the relationship between these measures. METHOD A total of 148 unmedicated individuals with major depressive disorder and 31 healthy comparison individuals recruited for the multisite EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study underwent functional MRI during a well-validated reward task. Region of interest and whole-brain data were examined in the first- (N=78) and second- (N=70) recruited cohorts, as well as the total sample, of depressed individuals, and in healthy individuals. RESULTS Healthy, but not depressed, individuals showed a significant inverse relationship between reward expectancy and prediction error-related right ventral striatal reactivity. Across all participants, and in depressed individuals only, greater anhedonia severity was associated with a reduced reward expectancy-prediction error inverse relationship, even after controlling for other symptoms. CONCLUSIONS The normal reward expectancy and prediction error-related ventral striatal reactivity inverse relationship concords with conditioning models, predicting a shift in ventral striatal responding from reward outcomes to reward cues. This study shows, for the first time, an absence of this relationship in two cohorts of unmedicated depressed individuals and a moderation of this relationship by anhedonia, suggesting reduced reward-contingency learning with greater anhedonia. These findings help elucidate neural mechanisms of anhedonia, as a step toward identifying potential biosignatures of treatment response.


title: Precautionary measures needed for ophthalmologists during pandemic of the coronavirus disease 2019 (COVID-19).

text: The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 2019 in Wuhan, China has spread to over 113 countries with 118,326 infected and 4,292 died as of 11 March 2020 and the World Health Organization (WHO) has just announced COVID-19 a global pandemic. A person under investigation (PUI) for COVID-19 is less likely to present initially to the ophthalmologists compared to emergency care or internal medicine physicians. However, in late February 2020, 2 patients presented simultaneously to our eye casualty with sudden onset of unilateral painful red eye associated with a decline in visual acuity, their intraocular pressure (IOP) were over 40 mmHg and slit-lamp examination findings were suggestive of acute primary angle closure (APAC).


title: Repeat liver resection for recurrent colorectal metastases: a single-centre, 13-year experience.

text: OBJECTIVES Isolated intrahepatic recurrence is noted in up to 40% of patients following curative liver resection for colorectal liver metastases (CLM). The aims of this study were to analyse the outcomes of repeat hepatectomy for recurrent CLM and to identify factors predicting survival. METHODS Data for all liver resections for CLM carried out at one centre between 1998 and 2011 were analysed. RESULTS A total of 1027 liver resections were performed for CLM. Of these, 58 were repeat liver resections performed in 53 patients. Median time intervals were 10.5 months between the primary resection and first hepatectomy, and 15.4 months between the first and repeat hepatectomies. The median tumour size was 3.0 cm and the median number of tumours was one. Six patients had a positive margin (R1) resection following first hepatectomy. There were no perioperative deaths. Significant complications included transient liver dysfunction in one and bile leak in two patients. Rates of 1-, 3- and 5-year overall survival following repeat liver resection were 85%, 61% and 52%, respectively, at a median follow-up of 23 months. R1 resection at first hepatectomy (P = 0.002), a shorter time interval between the first and second hepatectomies (P = 0.02) and the presence of extrahepatic disease (P = 0.02) were associated with significantly worse overall survival. CONCLUSIONS Repeat resection of CLM is safe and can achieve longterm survival in carefully selected patients. A preoperative knowledge of poor prognostic factors helps to facilitate better patient selection.


title: Total Extraperitoneal Hernia Repair: Residency Teaching Program and Outcome Evaluation.

text: BACKGROUND Total extraperitoneal (TEP) hernia repair has been shown to offer less pain, shorter postoperative hospital stay and earlier return to work when compared to open surgery. Our institution routinely performs TEP procedures for patients with primary or recurrent inguinal hernias. The aim of this study was to show that supervised senior residents can safely perform TEP repairs in a teaching setting. METHODS All consecutive patients treated for inguinal hernias by laparoscopic approach from October 2008 to June 2012 were retrospectively analyzed from a prospective database. RESULTS A total of 219 TEP repairs were performed on 171 patients: 123 unilateral and 48 bilateral. The mean patient age was 51.6 years with a standard deviation (SD) of ± 15.9. Supervised senior residents performed 171 (78 %) and staff surgeons 48 (22 %) TEP repairs, respectively. Thirty-day morbidity included cases of inguinal paresthesias (0.4 %, n = 1), umbilical hematomas (0.9 %, n = 2), superficial wound infections (0.9 %, n = 2), scrotal hematomas (2.7 %, n = 6), postoperative urinary retentions (2.7 %, n = 6), chronic pain syndromes (5 %, n = 11) and postoperative seromas (6.7 %, n = 14). Overall, complication rates were 18.7 % for staff surgeons and 19.3 % for residents (p = 0.83). For staff surgeons and residents, mean operative times for unilateral hernia repairs were 65 min (SD ± 18.9) and 77.6 min (SD ± 29.8) (p = 0.043), respectively, while mean operative times for bilateral repairs were 115 min (SD ± 40.1) and 103.6 (SD ± 25.9) (p = 0.05). CONCLUSIONS TEP repair is a safe procedure when performed by supervised senior surgical trainees. Teaching of TEP should be routinely included in general surgery residency programs.


title: [Working together to overcome coronavirus disease 2019: salute to the burn surgeons and nurses fighting against coronavirus disease 2019].

text: Since the outbreak and spread of coronavirus disease 2019 (COVID-19) pandemic, Chinese government has taken various steps to protect people's health. Medical workers across the country including medical and nursing staffs from burn departments have taken active actions and participated in the battles against COVID-19.


title: Mechanical Thrombectomy-Ready Comprehensive Stroke Center Requirements and Endovascular Stroke Systems of Care: Recommendations from the Endovascular Stroke Standards Committee of the Society of Vascular and Interventional Neurology (SVIN).

text: Five landmark multicenter, prospective, randomized, open-label, blinded end point clinical trials have recently demonstrated significant clinical benefit of endovascular therapy with mechanical thrombectomy in acute ischemic stroke (AIS) patients presenting with proximal intracranial large vessel occlusions. The Society of Vascular and Interventional Neurology (SVIN) appointed an expert writing committee to summarize this new evidence and make recommendations on how these data should guide emergency endovascular therapy for AIS patients.


title: Impact of Anesthesia on the Outcome of Acute Ischemic Stroke after Endovascular Treatment with the Solitaire Stent Retriever.

text: BACKGROUND AND PURPOSE General anesthesia during endovascular treatment of acute ischemic stroke may have an adverse effect on outcome compared with conscious sedation. The aim of this study was to examine the impact of the type of anesthesia on the outcome of patients with acute ischemic stroke treated with the Solitaire stent retriever, accounting for confounding factors. MATERIALS AND METHODS Four-hundred one patients with consecutive acute anterior circulation stroke treated with a Solitaire stent retriever were included in this prospective analysis. Outcome was assessed after 3 months by the modified Rankin Scale. RESULTS One-hundred thirty-five patients (31%) underwent endovascular treatment with conscious sedation, and 266 patients (69%), with general anesthesia. Patients under general anesthesia had higher NIHSS scores on admission (17 versus 13, P < .001) and more internal carotid artery occlusions (44.6% versus 14.8%, P < .001) than patients under conscious sedation. Other baseline characteristics such as time from symptom onset to the start of endovascular treatment did not differ. Favorable outcome (mRS 0-2) was more frequent with conscious sedation (47.4% versus 32%; OR, 0.773; 95% CI, 0.646-0.925; P = .002) in univariable but not multivariable logistic regression analysis (P = .629). Mortality did not differ (P = .077). Independent predictors of outcome were age (OR, 0.95; 95% CI, 0.933-0.969; P < .001), NIHSS score (OR, 0.894; 95% CI, 0.855-0.933; P < .001), time from symptom onset to the start of endovascular treatment (OR, 0.998; 95% CI, 0.996-0.999; P = .011), diabetes mellitus (OR, 0.544; 95% CI, 0.305-0.927; P = .04), and symptomatic intracerebral hemorrhage (OR, 0.109; 95% CI, 0.028-0.428; P = .002). CONCLUSIONS In this single-center study, the anesthetic management during stent retriever thrombectomy with general anesthesia or conscious sedation had no impact on the outcome of patients with large-vessel occlusion in the anterior circulation.


title: Catheter-directed thrombolysis vs. anticoagulation for the prevention and treatment of post-thrombotic syndrome in deep vein thrombosis: An updated systematic review and meta-analysis of randomized trials.

text: BACKGROUND Oral anticoagulation therapy was the mainstay of deep vein thrombosis treatment but recently, catheter-directed thrombolysis has emerged as an alternative. OBJECTIVE To compare the efficacy and safety of the two strategies. METHODS Medline, Embase and Cochrane CENTRAL were reviewed. Outcomes of interest included post-thrombotic syndrome, thromboembolic events, mortality, bleeding risk and iliofemoral patency. A random effects model meta-analysis was performed. Heterogeneity was assessed with I square. RESULTS Four randomized controlled trials (RCTs) including 1005 patients met the inclusion criteria. Catheter-directed thrombolysis was more likely to prevent overall post-thrombotic syndrome compared to anticoagulation only (OR: 0.32; 95% CI: 0.12-0.85; I2=87.2%), and to lead to iliofemoral vein patency (OR: 2.7; 95% CI: 1.08-6.75; I2=55.3%) but no difference was noted in thromboembolic events (OR = 0.5; 95% CI: 0.08-3.02, I2=55.1%), bleeding and mortality rates. CONCLUSIONS Catheter-directed thrombolysis can decrease post-thrombotic syndrome rates and improve iliofemoral vein patency compared to anticoagulation when used for the treatment of deep vein thrombosis.


Role of Permacol Injection in the Treatment of Patients With Fecal Incontinence.


title: Trans-subxiphoid robotic thymectomy.

text: Minimally invasive surgery has replaced median sternotomy for resectable anterior mediastinal masses and is performed by various approaches. We developed a new minimally invasive surgical procedure by combining the subxiphoid approach performed through a midline camera port with the use of a robotic surgery system (Intuitive Surgical, Sunnyvale, CA, USA). A 3-cm transverse incision was made 1 cm below the xiphoid process. Then, a port designed for single-port surgery was inserted. Through this port, CO2 gas was injected at 8 mmHg. The thymus was then detached from the back of the sternum. A 1-cm skin incision was made bilaterally in the sixth intercostal space, followed by insertion of a port for the robotic system. A camera port was inserted into the subxiphoid port, to which the camera scope was mounted, and thymectomy was performed. We have performed the operation in 3 patients. In our experience, this procedure provides a good operative view in the neck region and makes verification of the phrenic nerve easy. Furthermore, with the da Vinci surgical system, which enables surgical manipulation from a correct angle due to the multijoint robotic arms, trans-subxiphoid robotic thymectomy may be a promising new thymectomy procedure.


title: Safety and outcomes of simultaneous vasospasm and endovascular aneurysm treatment (SVAT) in subarachnoid hemorrhage.

text: BACKGROUND Simultaneous vasospasm and endovascular aneurysm treatment (SVAT) has been shown to be effective with good clinical outcomes in small series, but these studies have not examined predictive factors for clinical outcome after treatment. OBJECTIVE To identify the safety and efficacy of SVAT in a large multicenter patient cohort and evaluate prognostic markers of clinical outcome following SVAT. METHODS This study retrospectively enrolled 50 consecutive patients undergoing SVAT at 11 different centers. We analyzed Hunt and Hess and Fisher grades, aneurysm location, angiographic vasospasm grade, Glasgow Outcome Scale (GOS) at discharge, and 90-day modified Rankin Scale (mRS) scores. RESULTS A total of 50 patients undergoing SVAT between the years 2003 and 2009 were identified. Patients presented, on average, 6.48±4.45 days after subarachnoid hemorrhage. Hunt and Hess and Fisher grades were 1 (n=7), 2 (n=12), 3 (n=14), 4 (n=15), 5 (n=2), and 3 and 4 (n=33), respectively. Aneurysm location was distributed as follows: anterior (n=32), posterior (n=16), anterior and posterior (n=2). Patients with good clinical condition (Hunt and Hess score 1-3) had significantly higher odds of surviving (OR=17.5, 95% CI 1.9 to 161.5), favorable GOS (OR=4.2, 95% CI 1.2 to 14.8), and favorable 90-day mRS (OR=4.2, 95% CI 1.2 to 14.8). CONCLUSIONS SVAT is safe, with the majority of patients achieving good clinical outcome. Patients with lower Hunt and Hess grades have higher odds of surviving and favorable clinical prognosis.


title: Identification of residual metabolic-active areas within NSCLC tumours using a pre-radiotherapy FDG-PET-CT scan: a prospective validation.

text: It was recently described that high FDG-uptake areas pre-radiotherapy largely correspond with residual metabolic-active areas post-radiotherapy. Here, an independent prospective validation of these results was performed using an overlap-fraction (OF) calculation of various FDG-uptake based thresholds. Data from twelve patients treated at Radboud University Nijmegen Medical Center with lung cancer were analyzed. All patients underwent two FDG-PET-CT scans, one pre-radiotherapy (pre-RT) and one approximately three months after treatment (post-RT). Of the twelve analyzed patients, eight patients showed residual FDG uptake on the post-RT scan and were included for analysis. One of these patients had a residue that was not clearly distinguishable from the surrounding tissue due to FDG avid inflammation. Therefore, seven patients remained for further analysis. The mean volume of the residual metabolic-active areas post-RT was 14.6±10.0% (mean±SD) of the mean volume of the gross tumour volume (GTV) pre-RT. The residual metabolic-active areas largely corresponded with the pre-RT GTV (OF=93.7±7.2%). The pre-RT-scan threshold delineations of 34%, 40% and 50% of the SUV(max) had a large OF with the residual region, 86.9±8.3%, 77.4±8.1% and 67.9±6.8%, respectively. In this independent dataset, we confirmed that the location of residual FDG-uptake areas after radiotherapy corresponds with the high FDG-uptake areas pre-radiotherapy. Therefore, a pre-radiotherapy FDG-PET-CT scan can potentially be used for radiotherapy dose redistribution.


title: How sequential studies inform drug development: evaluating the effect of food intake on optimal bioavailability of ziprasidone.

text: Determining a drug dosing regimen that produces consistent bioavailability and patient effects is one of the goals of the drug development process. Food consumption is one factor that can significantly alter the bioavailability of some drugs. This manuscript describes a research approach to determine what recommendations to give patients regarding taking oral ziprasidone in relation to food consumption. Four pharmacokinetic studies, the first three in volunteers and the fourth in patients at steady-state on the maximum recommended daily dose of ziprasidone, investigated the relationship between food intake and ziprasidone absorption. These studies illustrate how sequential studies are used in drug development to investigate increasingly precise questions using data from one study to refine the question being addressed by the next. In the first study, the absorption of ziprasidone was shown to double when taken following a high-calorie, high-fat meal versus the fasting state. The second study showed that the difference in absorption between the fasting and fed states increased with dose. The third study suggested that calorie rather than fat content was the critical variable. This finding was confirmed in the fourth study over a wider variety of meals and under clinically relevant dosing conditions. That study also found reduced pharmacokinetic variability (i.e., more consistent absorption) when ziprasidone was administered with 500-1000 kcal meals without regard to fat content rather than under fasting or low-calorie meal conditions. These results have several clinically important implications. First, the effect of taking ziprasidone in a fasting state cannot be overcome simply by increasing the dose. Second, significant swings in ziprasidone concentration and hence efficacy and tolerability may occur on a day-to-day basis if diet is not controlled. Third, patients should be advised to take ziprasidone with a meal containing at least 500 calories (without regard to fat content) to ensure adequate ziprasidone bioavailability and thus achieve optimal efficacy. These four studies illustrate the sequential and incremental nature of drug development research and what is meant by the concept of bioequivalence.


title: Utility of prenatal Doppler ultrasound to predict neonatal impaired cerebral autoregulation.

text: OBJECTIVE Determine if abnormal prenatal Doppler ultrasound indices are predictive of postnatal impaired cerebral autoregulation. STUDY DESIGN Prospective cohort study of 46 subjects, 240-296 weeks' gestation. Utilizing near-infrared spectroscopy and receiver-operating characteristic analysis, impaired cerebral autoregulation was defined as >16.5% time spent in a dysregulated state within 96 h of life. Normal and abnormal Doppler indices were compared for perinatal outcomes. RESULTS Subjects with abnormal cerebroplacental ratio (n = 12) and abnormal umbilical artery pulsatility index (n = 13) were likely to develop postnatal impaired cerebral autoregulation (p ≤ 0.02). Abnormal cerebroplacental ratio was associated with impaired cerebral autoregulation between 24 and 48 h of life (p = 0.016). These subjects have increased risk for fetal growth restriction, lower birth weight, lower Apgar scores, acidosis, and severe intraventricular hemorrhage and/or death (p < 0.05). CONCLUSION Abnormal cerebroplacental ratio and umbilical artery pulsatility index are associated with postnatal impairment in cerebral autoregulation and adverse outcome.


title: Laparoscopic nephroureterectomy with transvesical single-port distal ureter and bladder cuff dissection: points of technique and initial surgical outcomes with five patients.

text: Although a variety of techniques have been used to manage the distal ureter during laparoscopic radical nephroureterectomy (LNU), a consensus has not yet been established. Recently, some authors have used a single-port transvesical approach to excise the distal ureter and bladder cuff following LNU. The aim of the study was to present our initial experience in "en bloc" dissection of the distal ureter and bladder cuff during LNU, using a transvesical single-port approach (T-LESS) and standard laparoscopic instruments. From April to October 2012, 5 patients aged 45 to 73 years with upper urinary tract urothelial tumors were subjected to LNU/T-LESS. After a standard LNU was performed, a TriPort+(®) device was introduced into the bladder and the pneumovesicum was established. A bladder cuff with a distal ureter was dissected and put in the paravesical tissue. The bladder wall defect was closed with the V-loc(®) 3/0 suture. The LNU was then completed in the flank position. All procedures were completed successfully. No significant blood loss or complications were observed. The mean operative time was 250 min (range: 200-370) for a total procedure and 59 min (range: 42-80) for the T-LESS stage. The postoperative hospital stay was 5.2 days (range: 4-9). Pathologic examination revealed no positive margin in any of the cases. The LNU/T-LESS approach is an efficient and safe procedure. A well-visualized dissection of the distal ureter, closing the defect of the bladder, the use of standard laparoscopic instruments and a good cosmesis are advantages of the method.


title: Apelin is a positive regulator of ACE2 in failing hearts.

text: Angiotensin converting enzyme 2 (ACE2) is a negative regulator of the renin-angiotensin system (RAS), catalyzing the conversion of Angiotensin II to Angiotensin 1-7. Apelin is a second catalytic substrate for ACE2 and functions as an inotropic and cardioprotective peptide. While an antagonistic relationship between the RAS and apelin has been proposed, such functional interplay remains elusive. Here we found that ACE2 was downregulated in apelin-deficient mice. Pharmacological or genetic inhibition of angiotensin II type 1 receptor (AT1R) rescued the impaired contractility and hypertrophy of apelin mutant mice, which was accompanied by restored ACE2 levels. Importantly, treatment with angiotensin 1-7 rescued hypertrophy and heart dysfunctions of apelin-knockout mice. Moreover, apelin, via activation of its receptor, APJ, increased ACE2 promoter activity in vitro and upregulated ACE2 expression in failing hearts in vivo. Apelin treatment also increased cardiac contractility and ACE2 levels in AT1R-deficient mice. These data demonstrate that ACE2 couples the RAS to the apelin system, adding a conceptual framework for the apelin-ACE2-angiotensin 1-7 axis as a therapeutic target for cardiovascular diseases.


title: Diagnosis of non-effusive feline infectious peritonitis by reverse transcriptase quantitative PCR from mesenteric lymph node fine-needle aspirates.

text: OBJECTIVES The aim of this study was to evaluate a feline coronavirus (FCoV) reverse transcriptase quantitative PCR (RT-qPCR) on fine-needle aspirates (FNAs) from mesenteric lymph nodes (MLNs) collected in sterile saline for the purpose of diagnosing non-effusive feline infectious peritonitis (FIP) in cats. METHODS First, the ability of the assay to detect viral RNA in MLN FNA preparations compared with MLN biopsy preparations was assessed in matched samples from eight cats. Second, a panel of MLN FNA samples was collected from a series of cats representing non-effusive FIP cases (n = 20), FCoV-seropositive individuals (n = 8) and FCoV seronegative individuals (n = 18). Disease status of the animals was determined using a combination of gross pathology, histopathology and/or 'FIP profile', consisting of serology, clinical pathology and clinical signs. RESULTS Viral RNA was detected in 18/20 non-effusive FIP cases; it was not detected in two cases that presented with neurological FIP. Samples from 18 seronegative non-FIP control cats and 7/8 samples from seropositive non-FIP control cats contained no detectable viral RNA. Thus, as a method for diagnosing non-effusive FIP, MLN FNA RT-qPCR had an overall sensitivity of 90.0% and specificity of 96.1%. CONCLUSIONS AND RELEVANCE In cases with a high index of suspicion of disease, RT-qPCR targeting FCoV in MLN FNA can provide important information to support the ante-mortem diagnosis of non-effusive FIP. Importantly, viral RNA can be reliably detected in MLN FNA samples in saline submitted via the national mail service. When applied in combination with biochemistry, haematology and serological tests in cases with a high index of suspicion of disease the results of this assay may be used to support a diagnosis of non-effusive FIP.


The H7N9 influenza virus in China--changes since SARS.


title: Overdiagnosis across medical disciplines: a scoping review.

text: OBJECTIVE To provide insight into how and in what clinical fields overdiagnosis is studied and give directions for further applied and methodological research. DESIGN Scoping review. DATA SOURCES Medline up to August 2017. STUDY SELECTION All English studies on humans, in which overdiagnosis was discussed as a dominant theme. DATA EXTRACTION Studies were assessed on clinical field, study aim (ie, methodological or non-methodological), article type (eg, primary study, review), the type and role of diagnostic test(s) studied and the context in which these studies discussed overdiagnosis. RESULTS From 4896 studies, 1851 were included for analysis. Half of all studies on overdiagnosis were performed in the field of oncology (50%). Other prevalent clinical fields included mental disorders, infectious diseases and cardiovascular diseases accounting for 9%, 8% and 6% of studies, respectively. Overdiagnosis was addressed from a methodological perspective in 20% of studies. Primary studies were the most common article type (58%). The type of diagnostic tests most commonly studied were imaging tests (32%), although these were predominantly seen in oncology and cardiovascular disease (84%). Diagnostic tests were studied in a screening setting in 43% of all studies, but as high as 75% of all oncological studies. The context in which studies addressed overdiagnosis related most frequently to its estimation, accounting for 53%. Methodology on overdiagnosis estimation and definition provided a source for extensive discussion. Other contexts of discussion included definition of disease, overdiagnosis communication, trends in increasing disease prevalence, drivers and consequences of overdiagnosis, incidental findings and genomics. CONCLUSIONS Overdiagnosis is discussed across virtually all clinical fields and in different contexts. The variability in characteristics between studies and lack of consensus on overdiagnosis definition indicate the need for a uniform typology to improve coherence and comparability of studies on overdiagnosis.


title: Single-Use Energy Sources and Operating Room Time for Laparoscopic Hysterectomy: A Randomized Controlled Trial.

text: STUDY OBJECTIVES To compare the intraoperative direct costs of a single-use energy device with reusable energy devices during laparoscopic hysterectomy. DESIGN A randomized controlled trial (Canadian Task Force Classification I). SETTING An academic hospital. PATIENTS Forty-six women who underwent laparoscopic hysterectomy from March 2013 to September 2013. INTERVENTIONS Each patient served as her own control. One side of the uterine attachments was desiccated and transected with the single-use device (Ligasure 5-mm Blunt Tip LF1537 with the Force Triad generator). The other side was desiccated and transected with reusable bipolar forceps (RoBi 5 mm), and transected with monopolar scissors using the same Covidien Force Triad generator. The instrument approach used was randomized to the attending physician who was always on the patient's left side. Resident physicians always operated on the patient's right side and used the converse instruments of the attending physician. MEASUREMENTS AND MAIN RESULTS Start time was recorded at the utero-ovarian pedicle and end time was recorded after transection of the uterine artery on the same side. Costs included the single-use device; amortized costs of the generator, reusable instruments, and cords; cleaning and packaging of reusable instruments; and disposal of the single-use device. Operating room time was $94.14/min. We estimated that our single use-device cost $630.14 and had a total time savings of 6.7 min per case, or 3.35 min per side, which could justify the expense of the device. The single-use energy device had significant median time savings (-4.7 min per side, p < .001) and total intraoperative direct cost savings ($254.16 per case). CONCLUSIONS A single-use energy device that both desiccates and cuts significantly reduced operating room time to justify its own cost, and it also reduced total intraoperative direct costs during laparoscopic hysterectomy in our institution. Operating room cost per minute varies between institutions and must be considered before generalizing our results.


title: A prospective, multicentre, randomised controlled study of human fibroblast-derived dermal substitute (Dermagraft) in patients with venous leg ulcers.

text: This was an open-label, prospective, multicentre, randomised controlled study to evaluate the efficacy and safety of human fibroblast-derived dermal substitute (HFDS) plus four-layer compression therapy compared with compression therapy alone in the treatment of venous leg ulcers. The primary outcome variable was the proportion of patients with completely healed study ulcers by 12 weeks. The number healed was further summarised by ulcer duration and baseline ulcer size. Sixty-four (34%) of 186 patients in the HFDS group experienced healing by week 12 compared with 56 (31%) of 180 patients in the control group (P = 0·235). For ulcers ≤ 12 months duration, 49 (52%) of 94 patients in the HFDS group versus 36 (37%) of 97 patients in the control group healed at 12 weeks (P = 0·029). For ulcers ≤ 10 cm(2), complete healing at week 12 was observed in 55 (47%) of 117 patients in the HFDS group compared with 47 (39%) of 120 patients in the control group (P = 0·223). The most common adverse events (AEs) were wound infection, cellulitis and skin ulcer. The frequency of AEs did not markedly differ between the treatment and control groups.


title: As We Went to Press: COVID-19 Continues to Spread.

text: Updates on the coronavirus.


title: Glycogen synthase kinase-3 regulates the phosphorylation of severe acute respiratory syndrome coronavirus nucleocapsid protein and viral replication.

text: Coronavirus (CoV) nucleocapsid (N) protein is a highly phosphorylated protein required for viral replication, but whether its phosphorylation and the related kinases are involved in the viral life cycle is unknown. We found the severe acute respiratory syndrome CoV N protein to be an appropriate system to address this issue. Using high resolution PAGE analysis, this protein could be separated into phosphorylated and unphosphorylated isoforms. Mass spectrometric analysis and deletion mapping showed that the major phosphorylation sites were located at the central serine-arginine (SR)-rich motif that contains several glycogen synthase kinase (GSK)-3 substrate consensus sequences. GSK-3-specific inhibitor treatment dephosphorylated the N protein, and this could be recovered by the constitutively active GSK-3 kinase. Immunoprecipitation brought down both N and GSK-3 proteins in the same complex, and the N protein could be phosphorylated directly at its SR-rich motif by GSK-3 using an in vitro kinase assay. Mutation of the two priming sites critical for GSK-3 phosphorylation in the SR-rich motif abolished N protein phosphorylation. Finally, GSK-3 inhibitor was found to reduce N phosphorylation in the severe acute respiratory syndrome CoV-infected VeroE6 cells and decrease the viral titer and cytopathic effects. The effect of GSK-3 inhibitor was reproduced in another coronavirus, the neurotropic JHM strain of mouse hepatitis virus. Our results indicate that GSK-3 is critical for CoV N protein phosphorylation and suggest that it plays a role in regulating the viral life cycle. This study, thus, provides new avenues to further investigate the specific role of N protein phosphorylation in CoV replication.


title: Distribution of CD10-positive epithelial and mesenchymal cells in human mid-term fetuses: a comparison with CD34 expression.

text: CD10, a marker of immature B lymphocytes, is expressed in the developing epithelium of mammary glands, hair follicles, and renal tubules of human fetuses. To assess mesenchymal and stromal expression of CD10, we performed immunohistochemical assays in whole body sections from eight fetuses of gestational ages 15-20 weeks. In addition to expression in urinary tract and intestinal epithelium, CD10 was strongly expressed at both gestational ages in fibrous tissues surrounding the airways from the larynx to lung alveoli, in the periosteum and ossification center, and in the glans of external genitalia. CD10 was not expressed, however, in other cavernous tissues. These findings suggest that mesenchymal, in addition to epithelial cells at specific sites, are likely to express CD10. The glomeruli, alveoli, and glans are all end products of budding or outgrowth processes in the epithelium or skin. However, in contrast to the CD34 marker of stromal stem cells, CD10 was not expressed in vascular progenitor cells and in differentiated vascular endothelium. The alternating pattern of CD10 and CD34 expression suggests that these factors play different roles in cellular differentiation and proliferation of the kidneys, airway and external genitalia.


title: Docking study of Chloroquine and Hydroxychloroquine interaction with SARS-CoV-2 spike glycoprotein-An in silico insight into the comparative efficacy of repurposing antiviral drugs.

text: Recent outbreak of novel Coronavirus disease (Covid-19) pandemic around the world is associated with severe acute respiratory syndrome. The death toll associated with the pandemic is increasing day by day. SARS-CoV-2 is an enveloped virus and there are ample evidences that its Spike protein (S-protein) is mainly associated with pathogenesis as it is surface-exposed and mediates entry into host cells by binding to angiotensin-converting enzyme-2 (ACE-2) receptor. Therefore, it is the main target of neutralizing antibodies upon infection and there is always a quest to inhibit the S-protein which in turn may help in controlling diseases caused by SARS-CoV-2 in humans. The role of Chloroquine and Hydroxychloroquine as potential treatments for Covid-19 is still under debate globally because of some side effects associated with it. This study involves the In silico interactions of Chloroquine and Hydroxychloroquine with the S-protein of SARS-CoV-2. With the help of various computational methods, we have re-explored the potential role of both of these antiviral drugs for the treatment of Covid-19 patients by comparing the efficacy of both of the drugs to bind to S-protein at its host receptor region. In our research Hydroxychloroquine exhibited potential inhibitory effectsof S-protein with binding energy -7.28 kcal/mol than Chloroquine (-6.30 kcal/mol) at SARS-CoV-2 receptor recognition of susceptible cells. The outcomes of this research strongly appeal for in vivo trials of Hydroxychloroquine for the patients infected with Covid-19. Furthermore, the recommended doses of Hydroxychloroquine may reduce the chances of catching Covid-19 to the healthcare workers and staff who are in contact with or delivering direct care to coronavirus patients as long as they have not been diagnosed with Covid-19. We further hypothesize that the comparative S-protein-drug docking interactions may help to understand the comparative efficacy of other candidate repurposing drugs until discovery of a proper vaccine.


title: Phase II study of the effectiveness and safety of trastuzumab and paclitaxel for taxane- and trastuzumab-naïve patients with HER2-positive, previously treated, advanced, or recurrent gastric cancer (JFMC45-1102).

text: Paclitaxel is a standard second-line gastric cancer treatment in Japan. Trastuzumab could be active as second-line chemotherapy for taxane/trastuzumab-naïve patients with epidermal growth factor 2 (HER2)-positive advanced gastric cancer. Patients aged ≥20 years with HER2-positive, previously treated (except for trastuzumab and taxane), unresectable or recurrent gastric adenocarcinoma underwent combined trastuzumab (first and subsequent doses of 8 and 6 mg kg-1 , respectively, every 3 weeks) and paclitaxel (days 1, 8, 15, every 4 weeks) treatment. Study endpoints were best overall response, progression-free survival, overall survival, and safety. From September 2011 to March 2012, 47 Japanese patients were enrolled. Forty patients discontinued treatment after a median of 128.5 (range 4-486) days. Complete and partial responses were obtained in one and 16 patients (response rate of 37% [95% CI 23-52]), respectively. Median progression-free survival and overall survival were 5.1 (95% CI 3.8-6.5) and 17.1 (95% CI 13.5-18.6) months, respectively. Grade 3/4 adverse events were neutropenia (32.6%), leukopenia (17.4%), anemia (15.2%) and hypoalbuminemia (8.7%). There was no clinically significant cardiotoxicity or cumulative toxicity. Three (disturbed consciousness, pulmonary fibrosis, and rapid disease progression) grade 5 events occurred. In conclusion, trastuzumab combined with paclitaxel was well tolerated and was a promising regimen for patients with HER2-positive, previously treated, advanced or recurrent gastric cancer.


title: What is the current evidence of the impact on quality of life whilst waiting for management/treatment of orthopaedic/musculoskeletal complaints? A systematic scoping review.

text: PURPOSE To describe quality of life (QoL) outcome measures that are reported in the literature in patients waiting for outpatient orthopaedic/musculoskeletal specialist care and how waiting impacts on QoL in these terms. METHODS A subset of studies reporting on QoL outcome measures were extracted from literature identified in a recent scoping search of Medline, Embase, Pubmed, NHS Economic Evaluation Database (Prospero registration CRD42016047332). The systematic scoping search examined impacts on patients waiting for orthopaedic specialist care. Two independent reviewers ranked study design using the National Health and Medical Research Council aetiology evidence hierarchy, and appraised study quality using Critical Appraisal Skills Programme tools. QoL measures were mapped against waiting period timepoints. RESULTS The scoping search yielded 142 articles, of which 18 reported on impact on QoL. These studies reported only on patients waiting for hip and/or knee replacement surgery. The most recent study reported on data collected in 2006/7. The Western Ontario and McMaster Universities Arthritis Index and the SF-36 were the most commonly reported QoL measures. QoL was measured at variable timepoints in the waiting period (from a few weeks to greater than 12 months). The impact of waiting on QoL was inconsistent. CONCLUSION The evidence base was over 10 years old, reported only on patients with hip and knee problems, and on limited QoL outcome measures, and with inconsistent findings. A better understanding of the impact on QoL for patients waiting for specialist care could be gained by using standard timepoints in the waiting period, patients with other orthopaedic conditions, comprehensive QoL measures, as well as expectations, choices and perspectives of patients waiting for specialist care.


title: The role of opioid receptor agonists in ischemic preconditioning.

text: Opioids and their receptor agonists have been widely used because of their beneficial effects on pain management and control. Over the past decade, there has been an increasing interest on the experimental use of opioid agonists in the laboratory setting of ischemia and reperfusion; existing data suggest that there is a potential association between opioid agonism and the reduction of infarct size in several animal models of regional ischemia similar to that following ischemic preconditioning. Most of these studies seem to attribute these beneficial and cardioprotective effects to the stimulation of a specific opioid receptor type, the delta (δ) opioid receptor. This review focuses on the role of the delta opioid receptor agonism in several models of ischemia and reperfusion, as well as on hemorrhagic shock models, on the potential mechanisms of action following delta opioid receptor activation and on the time window for opioid administration in various animal studies.


title: Telemedicine and Neurological Practice in the COVID-19 Era.

text: Background The COVID-19 pandemic has within months turned the world upside down. With personal distancing and shortage of personal protective equipment, face-to-face health care encounters are increasingly becoming problematic. Neurological manifestations are also being observed in clinical presentations. Objective Worldwide most countries, the World Health Organization (WHO) and Centre for Disease Control (USA) have recommended use of Telemedicine during the current pandemic.With acute shortage of neurologists and neurosurgeons and their lopsided distribution, it becomes more difficult to provide neurological care to those who need it the most, particularly with travel restrictions. The author has since 2002 been advocating use of Telemedicine in Neurosciences. Materials and Methods This article reviews the increasing deployment of Telemedicine in neurological practice in the last few years, particularly the radical exponential use in the last few months due to COVID-19. Conclusions With possible reduction in face-to-face consultations, remote evaluation may become mainstream. Webinars will play an increasing role. CME's and resident training will become more and more digital. The world will never be the same again. It is imperative that we accept and start deploying the "New Normal".


Impact of delayed diagnoses at the time of COVID-19: increased rate of preventable bilateral blindness in giant cell arteritis.


title: The impact of financial incentives on physical activity in adults: a systematic review protocol.

text: BACKGROUND Most adults fail to meet global physical activity guidelines set out by the World Health Organization. In recent years, behavioural economic principles have been used to design novel interventions that increase physical activity. Immediate financial rewards, for instance, can motivate an individual to change physical activity behaviour by lowering the opportunity costs of exercise. This systematic review will summarise the evidence about the effectiveness of financial incentive interventions for improving physical activity in adults. METHODS We will search MEDLINE, Embase, Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, Web of Science, Scopus, PsycINFO, EconLit, SPORTDiscus, the National Health Service Economic Evaluation Database, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform from inception using a comprehensive, electronic search strategy. The search strategy will include terms related to 'financial incentive' and 'physical activity'. Only randomised controlled trials that investigate the effect of financial incentives on physical activity in adult populations and that are written in the English language will be included. Two review authors will independently screen abstracts and titles, complete full text reviews and extract data on objective and self-reported physical activity outcomes. The authors will also assess the study quality using the Cochrane risk of bias tool and provide a systematic presentation and synthesis of the included studies' characteristics and results. If more than two studies are sufficiently similar in population, settings and interventions, we will pool the data to conduct a meta-analysis. If we are unable to perform a meta-analysis, we will conduct a narrative synthesis of the results and produce forest plots for individual studies. Our subgroup analyses will examine the differential effects of an intervention in healthy populations compared to populations with disease pathology and compare the effects of interventions using financial rewards to interventions using financial penalties. DISCUSSION This systematic review will determine the effectiveness of positive and negative financial incentives on physical activity in adults. Findings will help inform the development of public health interventions and research in this field. SYSTEMATIC REVIEW REGISTRATION PROSPERO 2017: CRD42017068263.


title: Non-parametric frequency response function tissue modeling in bipolar electrosurgery.

text: High-frequency radio energy is applied to tissue therapeutically in a number of different medical applications. The ability to model the effects of RF energy on the collagen, elastin, and liquid content of the target tissue would allow for the refinement of the control of the energy in order to improve outcomes and reduce negative side-effects. In this paper, we study the time-varying impedance spectra of the circuit. It is expected that the collagen/elastin ratio does not change over time such that the time-varying impedance is a function of the liquid content. We apply a non-parametric model in which we characterize the measured impedance spectra by its frequency response function. The measurements indicate that the changing impedance as a function of time exhibit a polynomial shift which we characterize by a polynomial regression. Finally, we quantify the uncertainty to obtain prediction intervals for the estimated polynomial describing the time variation of the impedance spectra.


title: Induction of a type I interferon signature in normal human monocytes by gadolinium-based contrast agents: comparison of linear and macrocyclic agents.

text: The gadolinium-based contrast agent (GdBCA) Omniscan activates human macrophages through Toll-like receptor (TLR)-4 and TLR-7 signalling. To explore the mechanisms responsible we compared the ability of linear and macrocyclic GdBCA to induce a type I interferon signature and a proinflammatory/profibrotic phenotype in normal human monocytes in vitro. Expression of genes associated with type I interferon signalling and inflammation and production of their corresponding proteins were determined. Both linear and macrocyclic GdBCA stimulated expression of multiple type I interferon-regulated genes and the expression of numerous chemokines, cytokines and growth factors in normal human peripheral blood monocytes. There was no correlation between the magnitude of the measured response and the Gd chelate used. To explore the mechanisms responsible for GdBCA induction of fibrosis in nephrogenic systemic fibrosis (NSF) in vitro, normal human dermal fibroblasts were incubated with GdBCA-treated monocyte culture supernatants and the effects on profibrotic gene expression were examined. Supernatants from monocytes exposed to all GdBCA stimulated types I and III collagen, fibronectin and α-smooth muscle actin (α-SMA) expression in normal dermal fibroblasts. The results indicate that the monocyte activation induced by GdBCA may be the initial step in the development of GdBCA associated fibrosis in NSF.


Coronavirus and children, deep-sea microbes and a bold new climate law.


New rules for biosecurity.