title: Gastrointestinal behavior of itraconazole in humans - Part 1: Supersaturation from a solid dispersion and a cyclodextrin-based solution.

text: This study evaluated the fasted state gastrointestinal behavior of the lipophilic drug itraconazole, orally administered to healthy volunteers as either a solid dispersion (Sporanox® capsules) or a cyclodextrin-based solution (Sporanox® solution). Following intake of the drug products, gastric and duodenal fluids were aspirated and analyzed for itraconazole concentration, total content and solubilizing capacity. Release of itraconazole from the solid dispersion generated high and metastable supersaturated levels in the stomach, but the dissolved fraction in the duodenum remained extremely low (median 2.5%). After intake of the itraconazole solution, precipitation was limited in the stomach but pronounced in the small intestine. Still, the dissolved fraction of itraconazole in the duodenum (median 38%) appeared much higher than after intake of the solid dispersion, possibly explaining the improved absorption of itraconazole from the solution. As for the solid dispersion, the absorption-enabling ability of the solution appeared mainly related to increased intraluminal concentrations by means of supersaturation. Cyclodextrin-based solubilization of itraconazole occurred only in the case of limited intraluminal dilution, but did not further enhance itraconazole absorption. The obtained data will help to understand critical aspects of supersaturating drug delivery systems and act as direct reference for the optimization of in vitro simulation tools for gastrointestinal drug behavior.


title: Presence of the hyperintense acute reperfusion marker on MRI after mechanical thrombectomy for large vessel occlusion is associated with worse early neurological recovery.

text: BACKGROUND Mechanical thrombectomy has become the accepted treatment for large vessel occlusion in acute ischemic stroke. Unfortunately, a large cohort of patients do not achieve functional independence with treatment, even though the results are more robust than with medical management. The hyperintense acute reperfusion marker (HARM) on MRI is an indication of the breakdown of the blood-brain barrier and reperfusion injury. OBJECTIVE To examine the hypothesis that the presence of HARM on MRI correlates with worse neurological recovery after reperfusion therapy. METHODS We retrospectively reviewed 35 consecutive patients who between February 24, 2016 and April 23, 2016 underwent MRI to determine the presence of HARM after thrombectomy for anterior circulation large vessel occlusion. Demographic, radiographic imaging, and outcome data were collected. Univariate and binary logistic regression models were performed to assess predictors for improvement of the National Institutes of Health Stroke Scale (NIHSS) score by ≥8 points at 24 hours. RESULTS The 35 patients studied had an average age of 64±14 years of age with a median NIHSS score of 15 (IQR 9-20). Eighteen patients (51%) were found to have a HARM-positive MRI. In univariate analysis, patients with HARM were older, had lower reperfusion rates and more postprocedural hemorrhages. In binary logistic regression modeling, the absence of HARM was independently associated with a ≥8-point NIHSS score improvement at 24 hours (OR=7.14, 95% CI 1.22 to 41.67). CONCLUSIONS This preliminary analysis shows that the presence of HARM may be linked to worse neurological recovery 24 hours after thrombectomy. Reperfusion injury may affect the number of patients achieving functional independence after treatment.


title: A spiky pattern in the course of electrical thoracic impedance as a very early sign of a developing pneumothorax.

text: A pneumothorax (PTX) is a potentially lethal condition in high-risk intensive care patients. Electrical impedance tomography (EIT) has been proven to detect PTX at the bedside. A so far not described pattern in the course of thoracic impedance at an early state of PTX was observed in a pig model of ventilator-induced lung injury (VILI) used for a more extensive study. EIT was performed at a framerate of 50 Hz. Beginning of PTX at normal ventilation, manifestation of PTX at VILI ventilation (plateau pressure 42 cm H2 O) and final pleural drainage were documented. At ventilation with 8·6 ml kg-1 , early PTX findings prior to any clinical deterioration consisted in a spike-like pattern in the time course of impedance (relative impedance change referred to initial end-expiratory level). Spike amplitudes (mean ± SD) were the following: 0·154 ± 0·059 (right lung) and 0·048 ± 0·050 (left lung). At this state, end-expiratory levels (mean ± SD) were still similar, -0·035 ± 0·010 (right) and -0·058 ± 0·022 (left). After application of VILI ventilation (38 ml kg-1 ), a PTX developed slowly, being confirmed by a continuous increase in the end-expiratory level on the right side and diverging levels of +0·320 ± 0·057 (right) and -0·193 ± 0·147 (left) at full manifestation. We assume that spikes reflect a temporary change in the electrical pathway caused by leakage into the pleural cavity. This newly described phenomenon of spikes is considered to be a potentially useful indicator for a very early detection of an evolving PTX in high-risk ICU patients.


title: Risk Factors for Dehiscence of Stapled Functional End-to-End Intestinal Anastomoses in Dogs: 53 Cases (2001-2012).

text: OBJECTIVE To identify risk factors for dehiscence in stapled functional end-to-end anastomoses (SFEEA) in dogs. STUDY DESIGN Retrospective case series. ANIMALS Dogs (n = 53) requiring an enterectomy. METHODS Medical records from a single institution for all dogs undergoing an enterectomy (2001-2012) were reviewed. Surgeries were included when gastrointestinal (GIA) and thoracoabdominal (TA) stapling equipment was used to create a functional end-to-end anastomosis between segments of small intestine or small and large intestine in dogs. Information regarding preoperative, surgical, and postoperative factors was recorded. RESULTS Anastomotic dehiscence was noted in 6 of 53 cases (11%), with a mortality rate of 83%. The only preoperative factor significantly associated with dehiscence was the presence of inflammatory bowel disease (IBD). Surgical factors significantly associated with dehiscence included the presence, duration, and number of intraoperative hypotensive periods, and location of anastomosis, with greater odds of dehiscence in anastomoses involving the large intestine. CONCLUSION IBD, location of anastomosis, and intraoperative hypotension are risk factors for intestinal anastomotic dehiscence after SFEEA in dogs. Previously suggested risk factors (low serum albumin concentration, preoperative septic peritonitis, and intestinal foreign body) were not confirmed in this study.


title: Conventional Linear versus Purse-string Skin Closure after Loop Ileostomy Reversal: Comparison of Wound Infection Rates and Operative Outcomes.

text: PURPOSE Wound infection after an ileostomy reversal is a common problem. To reduce wound-related complications, purse-string skin closure was introduced as an alternative to conventional linear skin closure. This study is designed to compare wound infection rates and operative outcomes between linear and purse-string skin closure after a loop ileostomy reversal. METHODS Between December 2002 and October 2010, a total of 48 consecutive patients undergoing a loop ileostomy reversal were enrolled. Outcomes were compared between linear skin closure (group L, n = 30) and purse string closure (group P, n = 18). The operative technique for linear skin closure consisted of an elliptical incision around the stoma, with mobilization, and anastomosis of the ileum. The rectus fascia was repaired with interrupted sutures. Skin closure was performed with vertical mattress interrupted sutures. Purse-string skin closure consisted of a circumstomal incision around the ileostomy using the same procedures as used for the ileum. Fascial closure was identical to linear closure, but the circumstomal skin incision was approximated using a purse-string subcuticular suture (2-0 Polysorb). RESULTS Between group L and P, there were no differences of age, gender, body mass index, and American Society of Anesthesiologists (ASA) scores. Original indication for ileostomy was 23 cases of malignancy (76.7%) in group L, and 13 cases of malignancy (77.2%) in group P. The median time duration from ileostomy to reversal was 4.0 months (range, 0.6 to 55.7 months) in group L and 4.1 months (range, 2.2 to 43.9 months) in group P. The median operative time was 103 minutes (range, 45 to 260 minutes) in group L and 100 minutes (range, 30 to 185 minutes) in group P. The median hospital stay was 11 days (range, 5 to 4 days) in group L and 7 days (range, 4 to 14 days) in group P (P < 0.001). Wound infection was found in 5 cases (16.7%) in group L and in one case (5.6%) in group L (P = 0.26). CONCLUSION Based on this study, purse-string skin closure after a loop ileostomy reversal showed comparable outcomes, in terms of wound infection rates, to those of linear skin closure. Thus, purse-string skin closure could be a good alternative to the conventional linear closure.


title: Prevalence and predictors of out-of-range cuff pressure of endotracheal and tracheostomy tubes: a prospective cohort study in mechanically ventilated patients.

text: BACKGROUND Maintaining the cuff pressure of endotracheal tubes (ETTs) within 20-30 cmH2O is a standard practice. The aim of the study was to evaluate the effectiveness of standard practice in maintaining cuff pressure within the target range. METHODS This was a prospective observational study conducted in a tertiary-care intensive care unit, in which respiratory therapists (RTs) measured the cuff pressure 6 hourly by a handheld manometer. In this study, a research RT checked cuff pressure 2-4 h after the clinical RT measurement. Percentages of patients with cuff pressure levels above and below the target range were calculated. We identified predictors of low-cuff pressure. RESULTS We analyzed 2120 cuff-pressure measurements. The mean cuff pressure was 27 ± 2 cmH2O by the clinical RT and 21 ± 5 cmH2O by the research RT (p < 0.0001). The clinical RT documented that 98.0 % of cuff pressures were within the normal range. The research RT found the cuff pressures to be within the normal range in only 41.5 %, below the range in 53 % and above the range in 5.5 %. Low cuff pressure was found more common with lower ETT size (OR, 0.34 per 0.5 unit increase in ETT size; 95 % CI, 0.15-0.79) and with lower peak airway pressure (OR per one cm H2O increment, 0.93; 95 % CI, 0.87-0.99) on multivariate analysis. CONCLUSIONS Cuff pressure is frequently not maintained within the target range with low-cuff pressure being very common approximately 3 h after routine measurements. Low cuff pressure was associated with lower ETT size and lower peak airway pressure. There is a need to redesign the process for maintaining cuff pressure within the target range.


title: A UK-wide survey looking at teaching and trainee confidence in teledermatology: A vital gap in a Covid-19 induced era of rapid digital transformation?

text: Teledermatology has had an explosive impact on provision of dermatology services in recent times, even more so with the unprecedented situation created by the Covid-19 pandemic. Although teledermatology is not presently a feature of the Joint Royal Colleges of Physicians Training Board (JRPCTB) curriculum for dermatology training, this is imminently changing. Specialty trainees need training in this area to be able to confidently and competently meet the demands of the changing face of dermatology services. We surveyed dermatology registrars in training across the UK, prior to Covid-19, to ascertain the teledermatology teaching available and trainee confidence in this area. Our survey found that only 15% of respondents felt slightly confident in their ability to deal with teledermatology referrals and almost all (96%) felt more teaching was needed.


title: Laparoscopic anterior hemifundoplication and hiatoplasty for the treatment of upside-down stomach: mid- and long-term results after 40 patients.

text: BACKGROUND Treatment of type 4 hiatal hernia using a minimally invasive approach is challenging and requires good familiarity with this technique. METHODS From October 1992 to August 2010, 40 patients with a median age of 68 years underwent laparoscopic anterior hemifundoplication surgery for upside-down stomach and were included in our prospective study. The median symptoms duration was 5 years. The leading clinical symptoms were postprandial, epigastric, or retrosternal pain (80%), heartburn (78%), regurgitation (80%), dysphagia (53%), and anemia (48%). Preoperative evaluation included blood test, chest X-ray, upper endoscopy, and barium swallow. In some patients an esophageal 24-h pH study and esophageal manometry were performed. The median follow-up was 46 months using a standardized questionnaire, including Smiley score, modified Visick score, gastrointestinal quality-of-life index (GQLI), and specific reflux symptoms score. RESULTS Surgery was finished laparoscopically in 39 patients (97%). One patient had to be converted to an open procedure because of severe adhesions. Mesh hiatoplasty had to be performed in one patient due to a large hiatal defect. Median operative time was 160 min (range=90-275) and median blood loss was 5 ml (range=0-300). Seven patients (18%) presented with acute symptoms. Intraoperative technical complications occurred in four patients (10%) and nontechnical complications in two cases (5%). Median postoperative hospital stay was 5 days (range=2-17). Postoperative complications occurred in two patients (5%): one pleural effusion and one surgical emphysema. There was no mortality or symptomatic recurrence. All scores showed significant improvement and patient satisfaction. CONCLUSION Laparoscopic treatment of type 4 hiatal hernia is safe. With respect to the quality of life, anterior hemifundoplication is highly effective.


Is an Ounce of Prevention Worth a Pound of Cure: Postoperative Recurrence of Crohn's Disease?


title: Diagnostic bronchoscopy in solid-organ and hematopoietic stem cell transplantation.

text: Fiberoptic bronchoscopy is a valuable diagnostic tool in solid-organ and hematopoietic stem cell transplant recipients presenting with a range of pulmonary complications. This article provides a comprehensive overview of the utility and potential adverse effects of diagnostic bronchoscopy for transplant recipients. Recommendations are offered on the selection of patients, the timing of bronchoscopy, and the samples to be obtained across the spectrum of suspected pulmonary complications of transplantation. Based on review of the literature, the authors recommend early diagnostic bronchoscopy over empiric treatment in transplant recipients with evidence of certain acute, subacute, or chronic pulmonary processes. This approach may be most critical when an underlying infectious etiology is suspected. In the absence of prompt diagnostic information on which to base effective treatment, the risks associated with empiric antimicrobial therapy, including medication side effects and the development of antibiotic resistance, compound the potential harm of delaying targeted management.


title: Risk factor analysis of additional administration of sedative agent and patient dissatisfaction in intravenous conscious sedation using midazolam for third molar extraction.

text: OBJECTIVES The primary purpose of this study was to investigate the factors related with additional administration of sedative agent during intravenous conscious sedation (IVS) using midazolam (MDZ). The secondary purpose was to analyze the factors affecting patient satisfaction. MATERIALS AND METHODS Clinical data for 124 patients who had undergone surgical extraction of mandibular third molar under IVS using MDZ were retrospectively investigated in this case-control study. The initial dose of MDZ was determined by body mass index (BMI) and weight. In the case of insufficient sedation at the beginning of surgery, additional doses were injected. During surgery, peripheral oxygen saturation, bispectral index score (BIS), heart rate, and blood pressure were monitored and recorded. The predictor variables were sex, age, BMI, sleeping time ratio, dental anxiety, Pederson scale, and initial dose of MDZ. The outcome variables were additional administration of MDZ, observer's assessment of alertness/sedation, intraoperative amnesia, and patient satisfaction. Descriptive statistics were computed, and the P-value was set at 0.05. RESULTS Most patients had an adequate level of sedation with only the initial dose of MDZ and were satisfied with the treatment under sedation; however, 19 patients needed additional administration, and 13 patients were unsatisfied. In multivariable logistic analysis, lower age (odds ratio [OR], 0.825; P=0.005) and higher dental anxiety (OR, 5.744; P=0.003) were related to additional administration; lower intraoperative amnesia (OR, 0.228; P=0.002) and higher BIS right before MDZ administration (OR, 1.379; P=0.029) had relevance to patient dissatisfaction. CONCLUSION The preoperative consideration of age and dental anxiety is necessary for appropriate dose determination of MDZ in the minor oral surgery under IVS. The amnesia about the procedure affects patient satisfaction positively.


title: Clinical findings in 111 cases of influenza A (H7N9) virus infection.

text: BACKGROUND During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).


Pipeline embolization device: lessons learned after 1000 aneurysms.


Ethics preparedness for infectious disease outbreaks research in India: A case for novel coronavirus disease 2019


title: Psoriasis and risk of the COVID-19 infection: Is there a role for Angiotensin Converting Enzyme (ACE)?

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first appeared in Wuhan, China in December 2019 resulting in the COVID-19 pandemic. It has been shown that SARS-CoV-2 spike protein shares a high similarity with SARS-CoV spike protein with a strong binding affinity to human Angiotensin Converting Enzyme 2 (ACE2) receptor. Skin tissue may be a possible specific target for the SARS-CoV-2. Preliminary reports from the COVID-19 infection have shown cutaneous manifestation, including erythematous rash, widespread urticaria, and chickenpox-like vesicles. Moreover, many studies have shown the role of ACE in the development, severity, and complications of psoriasis. Herein, we discuss a possible shared mechanism of psoriasis with SARS-CoV-2; also, we propose a therapeutic approach to balance the effect of ACE activity in these patients.


title: 2018 AAHA Infection Control, Prevention, and Biosecurity Guidelines.

text: A veterinary team's best work can be undone by a breach in infection control, prevention, and biosecurity (ICPB). Such a breach, in the practice or home-care setting, can lead to medical, social, and financial impacts on patients, clients, and staff, as well as damage the reputation of the hospital. To mitigate these negative outcomes, the AAHA ICPB Guidelines Task Force believes that hospital teams should improve upon their current efforts by limiting pathogen exposure from entering or being transmitted throughout the hospital population and using surveillance methods to detect any new entry of a pathogen into the practice. To support these recommendations, these practice-oriented guidelines include step-by-step instructions to upgrade ICPB efforts in any hospital, including recommendations on the following: establishing an infection control practitioner to coordinate and implement the ICPB program; developing evidence-based standard operating procedures related to tasks performed frequently by the veterinary team (hand hygiene, cleaning and disinfection, phone triage, etc.); assessing the facility's ICPB strengths and areas of improvement; creating a staff education and training plan; cataloging client education material specific for use in the practice; implementing a surveillance program; and maintaining a compliance evaluation program. Practices with few or no ICPB protocols should be encouraged to take small steps. Creating visible evidence that these protocols are consistently implemented within the hospital will invariably strengthen the loyalties of clients to the hospital as well as deepen the pride the staff have in their roles, both of which are the basis of successful veterinary practice.


title: Differential mRNA expression profiling in ovarian endometriotic tissue with versus without leuprolide acetate treatment.

text: AIM Leuprolide acetate, an analog of gonadotropin-releasing hormone (GnRH), regresses endometriotic tissue and reduces pain, resulting in clinical improvement upon treatment. The molecular mechanisms involved in the regression of endometriotic tissue, however, remain to be elucidated. In this study, we performed genome-wide gene expression profiling of clinical specimens of ovarian endometrioma to obtain insight into the effects of leuprolide acetate treatment. METHODS We obtained clinical samples from nine normal eutopic endometrium tissues, eight ovarian endometriotic tissues, and 12 leuprolide acetate-treated endometriotic tissues. We compared the gene expression profiles of the three groups using Affymetrix GeneChip Human genome arrays and bioinformatic analysis, including molecular concept analysis. RESULTS Leuprolide acetate-treated endometriotic tissue showed downregulated genes associated with the biological functions of steroid hormone regulation, cell proliferation, inflammation, and intracellular signaling. These genes included PTGDS, GRP, APLP2, PLTP, and FGFRL1. In contrast, genes upregulated by leuprolide acetate treatment were associated with cell growth inhibition and apoptosis. These genes included CARD11 and USP18. CONCLUSIONS These preliminary results based on GeneChip analysis suggest that leuprolide acetate treatment induces a modulation of gene expression that allows for cooperative alterations in disease state. This study gives new insight into the effects of leuprolide acetate treatment. Further investigations with quantitative reverse transcription-polymerase chain reaction and immunohistochemistry are needed to validate this study and to explore new therapeutic targets and biomarkers of endometriosis.


title: Ten-Year Research Update Review: Antiviral Activities from Marine Organisms.

text: Oceans cover more than 70 percent of the surface of our planet and are characterized by huge taxonomic and chemical diversity of marine organisms. Several studies have shown that marine organisms produce a variety of compounds, derived from primary or secondary metabolism, which may have antiviral activities. In particular, certain marine metabolites are active towards a plethora of viruses. Multiple mechanisms of action have been found, as well as different targets. This review gives an overview of the marine-derived compounds discovered in the last 10 years. Even if marine organisms produce a wide variety of different compounds, there is only one compound available on the market, Ara-A, and only another one is in phase I clinical trials, named Griffithsin. The recent pandemic emergency caused by SARS-CoV-2, also known as COVID-19, highlights the need to further invest in this field, in order to shed light on marine compound potentiality and discover new drugs from the sea.


title: Viral phosphodiesterases that antagonize double-stranded RNA signaling to RNase L by degrading 2-5A.

text: The host interferon (IFN) antiviral response involves a myriad of diverse biochemical pathways that disrupt virus replication cycles at many different levels. As a result, viruses have acquired and evolved genes that antagonize the host antiviral proteins. IFNs inhibit viral infections in part through the 2',5'-oligoadenylate (2-5A) synthetase (OAS)/RNase L pathway. OAS proteins are pathogen recognition receptors that exist at different basal levels in different cell types and that are IFN inducible. Upon activation by the pathogen-associated molecular pattern viral double-stranded RNA, certain OAS proteins synthesize 2-5A from ATP. 2-5A binds to the antiviral enzyme RNase L causing its dimerization and activation. Recently, disparate RNA viruses, group 2a betacoronaviruses, and group A rotaviruses, have been shown to produce proteins with 2',5'-phosphodiesterase (PDE) activities that eliminate 2-5A thereby evading the antiviral activity of the OAS/RNase L pathway. These viral proteins are members of the eukaryotic-viral LigT-like group of 2H phosphoesterases, so named for the presence of 2 conserved catalytic histidine residues. Here, we will review the biochemistry, biology, and implications of viral and cellular 2',5'-PDEs that degrade 2-5A. In addition, we discuss alternative viral and cellular strategies for limiting the activity of OAS/RNase L.


title: Butcherbird polyomavirus isolated from a grey butcherbird (Cracticus torquatus) in Queensland, Australia.

text: A novel avian polyomavirus was detected in peri-ocular skin lesions collected from a grey butcherbird (Cracticus torquatus), using a combination of multiply primed rolling circle amplification, nested PCR and long range PCR. The sequence of Butcherbird polyomavirus was determined by combining next generation sequencing and primer walking techniques. The circular double-stranded DNA genome of Butcherbird polyomavirus consisted of 5084 bp, and encoded six open reading frames (ORF-X, VP2, VP3, VP1, small T-antigen and large T-antigen). Phylogenetic analysis placed it amongst other members of the genus Avipolyomavirus, most closely related to Crow polyomavirus. Next generation sequencing enabled the detection of DNA fragments similar to, but distinct from, Canarypox virus within the same lesion from which Butcherbird polyomavirus was amplified, thus confirming an avipolyomavirus-avipoxvirus co-infection in the peri-ocular skin lesions of this grey butcherbird.


docid: tftbcyfk

title: Real-time ultrasound-guided percutaneous dilatational tracheostomy: a feasibility study.

text: INTRODUCTION Ultrasound (US) performed prior to percutaneous tracheostomy (PT) may be useful in avoiding injury to pretracheal vascular structures and in avoiding high placement of the tube. Bedside real-time US guidance with visualization of needle path is routinely utilized for other procedures such as central venous catheterization, and may enhance the safety and accuracy of PT without causing airway occlusion or hypercarbia. Our objective was to demonstrate that PT performed under real-time US guidance with visualization of needle path during tracheal puncture is feasible, including in patients with features that increase the technical difficulty of PT. METHODS Mechanically ventilated patients with acute brain injury requiring tracheostomy underwent US guided PT. The orotracheal tube was withdrawn using direct laryngoscopy. The trachea was punctured under real-time US guidance (with visualization of the needle path) while using the acoustic shadows of the cricoid and the tracheal rings to identify the level of puncture. After guidewire passage the site and level of entry was verified using the bronchoscope, which was then withdrawn. Following dilatation and tube placement, placement in the airway was confirmed using auscultation and the "lung sliding" sign on US. Bronchoscopy and chest X-ray were then performed to identify any complications. RESULTS Thirteen patients successfully underwent US guided PT. Three patients were morbidly obese, two were in cervical spine precautions and one had a previous tracheostomy. In all 13 patients bronchoscopy confirmed that guidewire entry was through the anterior wall and between the first and fifth tracheal rings. There was no case of tube misplacement, pneumothorax, posterior wall injury, significant bleeding or other complication during the procedure. CONCLUSIONS Percutaneous tracheostomy performed under real-time ultrasound guidance is feasible and appears accurate and safe, including in patients with morbid obesity and cervical spine precautions. Larger studies are required to further define the safety and relative benefits of this technique. TRIAL REGISTRATION UMIN Clinical Trials Registry, UMIN000005023.


title: COVID-19, chronic inflammatory respiratory diseases and eosinophils - Observationsfrom reported clinical case series.

text: Currently, the world is facinga global pandemicwith a new coronavirus SARS-CoV- 2 (Severe Acute Respiratory Syndrome CoronaVirus Type 2) causing infectious disease named COVID-19 (CoronaVirus Infectious Disease 2019). Comparing the clinical presentation and epidemiological characteristics of COVID-19 with previous coronavirus-associated respiratory diseases (SARS-CoV1 and MERS) revealedsome remarkable findings and differences. Moreover, the clinical course of SARS-CoV-2 infection showed the complexity of COVID-19 profile with the variable clinical presentations.


title: Gastric diverticulum and halitosis-A case for surgery?

text: INTRODUCTION Gastric diverticulum is a rare and frequently asymptomatic condition. Symptoms include vague pain, fullness, dyspepsia, vomiting, hemorrhage and perforation. Occasionally, the patient can present with belching and oral fetor. PRESENTATION OF CASE We report a 58-year-old woman with a gastric diverticulum who was suffering from a socially disabling oral fetor. After a thorough evaluation, a laparoscopic resection of the diverticulum was offered and completed successfully. At follow-up, the oral fetor had disappeared. The patient had no complaints and regarded herself as cured. DISCUSSION Although indications for the treatment of asymptomatic patients remain to be defined, pharmacological therapies including protein pump inhibitors and histamine receptor blockers have been employed, with limited effects in patients with miscellaneous symptoms. Surgery is required when serious complications such as hemorrhage or perforation of the diverticulum occur. CONCLUSION Surgery is required when serious complications such as hemorrhage or perforation of the diverticulum occur. Therapy resistent social disabling oral fetor may add to the indications for surgery.


docid: vczklgym

title: Single-incision laparoscopic gastric resection for submucosal tumors: report of three cases.

text: Between March and April 2009, three consecutive patients underwent single-incision laparoscopic gastric wedge resection for a submucosal tumor located in the anterior wall or greater curvature of the stomach. First, we placed two or three trocars through the same infra-umbilical skin incision. Then, we either elevated the tumor with a mini-loop retractor or retracted the gastric wall near the tumor with a laparoscopic grasper. Finally, we resected the tumor using an endoscopic linear stapler. Single-incision laparoscopic gastric resection was successfully completed in all three patients without the need for any extraumbilical skin incisions or conversion to conventional laparoscopic procedures. There was no morbidity. The mean operating time and blood loss were 86 min and 4 ml, respectively, and the mean tumor size and surgical margin were 34 mm and 8 mm, respectively. Histopathologically, two tumors were diagnosed as gastrointestinal stromal tumors and one as a carcinoid tumor. Thus, single-incision laparoscopic gastric resection for submucosal tumors is safe and feasible when performed by experienced laparoscopic surgeons using conventional laparoscopic instruments.


title: Enhancing in vivo circulation and siRNA delivery with biodegradable polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) copolymers.

text: The purpose of this study was to enhance the in vivo blood circulation time and siRNA delivery efficiency of biodegradable copolymers polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) (hy-PEI-g-PCL-b-PEG) by introducing high graft densities of PCL-PEG chains. SYBR(®) Gold and heparin assays indicated improved stability of siRNA/copolymer-complexes with a graft density of 5. At N/P 1, only 40% siRNA condensation was achieved with non-grafted polymer, but 95% siRNA was condensed with copolymer PEI25k-(PCL570-PEG5k)(5). Intracellular uptake studies with confocal laser scanning microscopy and flow cytometry showed that the cellular uptake was increased with graft density, and copolymer PEI25k-(PCL570-PEG5k)(5) was able to deliver siRNA much more efficiently into the cytosol than into the nucleus. The in vitro knockdown effect of siRNA/hyPEI-g-PCL-b-PEG was also significantly improved with increasing graft density, and the most potent copolymer PEI25k-(PCL570-PEG5k)(5) knocked down 84.43% of the GAPDH expression. Complexes of both the copolymers with graft density 3 and 5 circulated much longer than unmodified PEI25 kDa and free siRNA, leading to a longer elimination half-life, a slower clearance and a three- or fourfold increase of the AUC compared to free siRNA, respectively. We demonstrated that the graft density of the amphiphilic chains can enhance the siRNA delivery efficiency and blood circulation, which highlights the development of safe and efficient non-viral polymeric siRNA nanocarriers that are especially stable and provide longer circulation in vivo.


title: Arteriography for Lower Gastrointestinal Hemorrhage: Role of Preceding Abdominal Computed Tomographic Angiogram in Diagnosis and Localization.

text: IMPORTANCE Optimizing the nature and sequence of diagnostic imaging when managing lower gastrointestinal hemorrhage may reduce subsequent morbidity and mortality. OBJECTIVES To determine if preceding visceral arteriography with computed tomographic angiography (CTA) in acute lower gastrointestinal hemorrhage increases hemorrhage identification and localization and to determine if CTA was superior to nuclear scintigraphy when used as a pre-angiogram test. DESIGN, SETTING, AND PARTICIPANTS Analysis was conducted of prospectively acquired data from an interventional radiology database and of individual electronic medical records from an academic tertiary medical center. On January 1, 2009, a new, evidence-based, institutional protocol that formally incorporated CTA to manage acute lower gastrointestinal hemorrhage was launched after multidisciplinary consultation. All records of patients who underwent visceral angiography (VA) for acute lower gastrointestinal hemorrhage from January 1, 2005, to December 31, 2012, were evaluated. EXPOSURES Imaging, procedural, and operative details were abstracted from the medical records of all patients who underwent VA for lower gastrointestinal hemorrhage. MAIN OUTCOMES AND MEASURES Visceral angiography results and efficacy were compared in patients before and after protocol implementation and compared based on which imaging method was used prior to angiography. RESULTS A total of 161 angiographic procedures were performed during the study period (78 before and 83 after protocol implementation). Use of CTA increased from 3.8% to 56.6%, and use of nuclear scintigraphy decreased from 83.3% to 50.6% following protocol implementation (P < .001). Preceding angiography with CTA resulted in similar angiography contrast administration (mean [SD] amount for CTA prior to VA, 135 [63] vs 160 [77] mL; P = .18) and fluoroscopy time (mean [SD], 26.3 [16.8] vs 32.2 [34.9] minutes; P = .34). Although nuclear scintigraphy and CTA had similar sensitivity and specificity, localization of hemorrhage site by CTA was more precise and consistent with angiography findings. As a pre-angiography test, compared with nuclear scintigraphy, CTA reduced overall the number of imaging studies required (mean [SD] number per patient admission, 2.1 [0.3] vs 2.5 [0.8]; P = .005) and resulted in administration of more overall contrast (mean [SD], 220 [80] vs 130 [70] mL; P < .001) without worsening renal function. CONCLUSIONS AND RELEVANCE Preceding VA with a diagnostic study improves positive localization of the site of lower gastrointestinal hemorrhage compared with VA alone. Increasing the use of CTA for pre-angiography imaging may reduce overall imaging studies while appearing to increase positive yield at VA. Computed tomographic angiography can be used as part of a lower intestinal hemorrhage management algorithm and does not appear to worsen renal function despite the additional contrast load.


title: Curettage and aspiration in splenic hilar lymph node dissection for spleen-preserving radical D2 gastrectomy.

text: D2 radical gastrectomy is the standard procedure for gastric cancer in the middle or upper part of the stomach. According to the latest Japanese treatment guidelines for gastric cancer, dissection of the splenic hilar lymph nodes is required during the radical treatment for this condition. This study reports a D2 radical total gastrectomy employing the curettage and dissection techniques, in which the resection of the anterior lobe of transverse mesocolon, vascular denudation and splenic hilar lymph node dissection were successfully completed.


title: Application of mid-frequency ventilation in an animal model of lung injury: a pilot study.

text: BACKGROUND Mid-frequency ventilation (MFV) is a mode of pressure control ventilation based on an optimal targeting scheme that maximizes alveolar ventilation and minimizes tidal volume (VT). This study was designed to compare the effects of conventional mechanical ventilation using a lung-protective strategy with MFV in a porcine model of lung injury. Our hypothesis was that MFV can maximize ventilation at higher frequencies without adverse consequences. We compared ventilation and hemodynamic outcomes between conventional ventilation and MFV. METHODS This was a prospective study of 6 live Yorkshire pigs (10 ± 0.5 kg). The animals were subjected to lung injury induced by saline lavage and injurious conventional mechanical ventilation. Baseline conventional pressure control continuous mandatory ventilation was applied with V(T) = 6 mL/kg and PEEP determined using a decremental PEEP trial. A manual decision support algorithm was used to implement MFV using the same conventional ventilator. We measured P(aCO2), P(aO2), end-tidal carbon dioxide, cardiac output, arterial and venous blood oxygen saturation, pulmonary and systemic vascular pressures, and lactic acid. RESULTS The MFV algorithm produced the same minute ventilation as conventional ventilation but with lower V(T) (-1 ± 0.7 mL/kg) and higher frequency (32.1 ± 6.8 vs 55.7 ± 15.8 breaths/min, P < .002). There were no differences between conventional ventilation and MFV for mean airway pressures (16.1 ± 1.3 vs 16.4 ± 2 cm H2O, P = .75) even when auto-PEEP was higher (0.6 ± 0.9 vs 2.4 ± 1.1 cm H2O, P = .02). There were no significant differences in any hemodynamic measurements, although heart rate was higher during MFV. CONCLUSIONS In this pilot study, we demonstrate that MFV allows the use of higher breathing frequencies and lower V(T) than conventional ventilation to maximize alveolar ventilation. We describe the ventilatory or hemodynamic effects of MFV. We also demonstrate that the application of a decision support algorithm to manage MFV is feasible.


docid: gemxlczm

title: Initial Alpha-Fetoprotein Response Predicts Prognosis in Hepatitis B-related Solitary HCC Patients After Radiofrequency Ablation.

text: BACKGROUND Radiofrequency ablation (RFA) is effective for early-stage hepatocellular carcinoma but recurrence is problem. GOALS To identify prognostic factors including alpha-fetoprotein (AFP) for overall survival and intrahepatic recurrence after RFA. PATIENTS AND METHODS Not only naïve but also previously treated patients with solitary hepatitis B virus-related hepatocellular carcinoma <5 cm were prospectively enrolled and a ≥50% decrease from baseline to 1 month after RFA was defined as an initial AFP response. Tumor responses were assessed by the modified response evaluation criteria in solid tumors. RESULTS Among 255 patients, 156 patients (61.2%) developed intrahepatic recurrence. Radiologic progression occurred in 54.8% (86/157) in the AFP responders and 71.4% (70/98) in the AFP nonresponders. In multivariate analysis, a history of previous treatment [hazard ratio (HR), 2.037; P=0.015 for percutaneous ethanol injection vs. none; and HR, 2.642; P<0.001 for transarterial chemoembolization vs. none] and an initial AFP nonresponse (HR, 1.899; P<0.001) were independent predictors of accelerated progression after RFA. Moreover, those who had a history of previous treatment and did not achieve an initial AFP response had significantly unfavorable overall survival (HR, 3.581; P<0.001) and the increased risk of intrahepatic remote recurrence (HR, 5.385; P<0.001) compared with those with an initial AFP response and no history of previous treatment. CONCLUSIONS Biological response evaluation by the measurement of serial AFP levels is a useful predictor of overall survival and intrahepatic remote recurrence after RFA. Therefore, an initial AFP response may aid in determining the need of closer follow-up as a therapeutic response indicator of RFA.


title: Multiple Sensor Monitoring of CFRP Drilling to Define Cutting Parameters Sensitivity on Surface Roughness, Cylindricity and Diameter.

text: Machining parameters affects the final quality of components made in carbon fiber reinforced plastic (CFRP) composite materials. In this framework, the work here presented aims at studying the right combination of cutting speed (vc) and feed rate (vf), for dry drilling of carbon fiber reinforced plastic composite materials, which obtained better results regarding roughness, hole cylindricity, and diameter. A series of experimental tests were carried out under different drilling conditions (vc/vf), monitoring the thrust force (Fz), torque (T), and electric power (EP), to define which one can help more for industrial daily life production. Results validation was carried out using the analysis of variance, in order to relate main machining parameters cutting speed and linear feed, with thrust force, drilling torque, main spindle electric power and hole quality parameters (average roughness, cylindricity and diameter). The conclusions show that thrust force is not proportional to the cutting speed and the best combinations of cutting speed and feed were found out around the average values of tested parameters. Spindle electric power is an interesting element to take into account because it is easy to consider in real production.


title: Time-delay when updating infusion rates in the Graseby 3400 pump results in reduced drug delivery.

text: Infusion pumps are commonly used for infusion of drugs for physiologic control, and infusion rate has been demonstrated to affect the parameters of pharmacokinetic models. In attempting to develop a model that explained this behavior, we examined the behavior of the Graseby 3400 syringe pump under a range of flow conditions and with variations in syringe characteristics. Two issues were identified: start-up loss (the difference between actual and ideal delivery on initial infusion) and update loss (the difference between actual and ideal delivery when transmitting a command to change infusion rate). Under worst-case conditions, this may result in a 20-second period of zero delivery during start-up, and when updating infusion rates once per second, zero output. These effects are influenced by syringe characteristics and vary sufficiently as to make it impossible to isolate this effect from the pharmacokinetic process being controlled. The implications of this for previous published results and clinical application of target-controlled infusions are discussed.


title: Exposure to crises and resiliency of health care workers in Singapore.

text: BACKGROUND Health care workers are exposed to various work-related traumatic incidents and crises, so building emotional resiliency is important. AIMS To examine exposure to work-related crises and resiliency of health care workers in public hospitals in Singapore. METHODS We sent questionnaires to health care workers in seven public hospitals. Participation was voluntary and anonymous. We asked about mental health training and exposure to work-related and personal crises. We measured resiliency using a pilot 5-point Likert questionnaire reflecting resistance and resilience constructs. RESULTS We received 496 responses, a response rate of 58%. More than 70% of hospital staff experienced aggression or violence from patients and relatives, and about a third experienced significant personal crises, most commonly interpersonal conflicts. Those with mental health training were twice as likely to be resistant (OR = 1.8, 95% CI 1.2-2.7) and resilient (OR = 1.9, 95% CI 1.3-2.7) and also more likely to have experienced sudden/unexpected patient deaths (OR = 2.7, 95% CI 1.9-4.0) and aggression or violence from patients and relatives (OR = 5.1, 95% CI 3.0-8.7). CONCLUSIONS Mental health training appears to improve individuals' perception of resistance and resilience. Hospitals should consider providing mental health and crisis intervention training to improve the emotional resiliency of health care workers.


title: Eukaryotic life without tQCUG: the role of Elongator-dependent tRNA modifications in Dictyosteliumdiscoideum.

text: In the Elongator-dependent modification pathway, chemical modifications are introduced at the wobble uridines at position 34 in transfer RNAs (tRNAs), which serve to optimize codon translation rates. Here, we show that this three-step modification pathway exists in Dictyostelium discoideum, model of the evolutionary superfamily Amoebozoa. Not only are previously established modifications observable by mass spectrometry in strains with the most conserved genes of each step deleted, but also additional modifications are detected, indicating a certain plasticity of the pathway in the amoeba. Unlike described for yeast, D. discoideum allows for an unconditional deletion of the single tQCUG gene, as long as the Elongator-dependent modification pathway is intact. In gene deletion strains of the modification pathway, protein amounts are significantly reduced as shown by flow cytometry and Western blotting, using strains expressing different glutamine leader constructs fused to GFP. Most dramatic are these effects, when the tQCUG gene is deleted, or Elp3, the catalytic component of the Elongator complex is missing. In addition, Elp3 is the most strongly conserved protein of the modification pathway, as our phylogenetic analysis reveals. The implications of this observation are discussed with respect to the evolutionary age of the components acting in the Elongator-dependent modification pathway.


title: Prevention of unplanned extubations in neonates through process standardization.

text: OBJECTIVE Unplanned extubation events (UPEs) in neonates are hazardous to patient safety. Our goal was to reduce UPE rate (#UPEs per 100 ventilator days) by 50% in 12 months at our 25-bed level III inborn unit. STUDY DESIGN Baseline data were gathered prospectively for 7 months. Three Plan-Do-Study-Act (PDSA) cycles targeting main causes of UPEs were developed over the next 20 months. Causes of UPEs were analyzed using Pareto charts; and a U control chart was created with QI Charts(©). Standard rules for detecting special cause variation were applied. RESULT Mean UPE rate decreased from 16.1 to 4.5 per 100 ventilator days, a 72% decrease, exceeding our goal. Analysis of U-chart demonstrated special cause variation, with eight consecutive points below the mean. Improvement was sustained throughout the study period. CONCLUSION UPEs in neonates can be reduced with process standardization and frontline staff education, emphasizing vigilant endotracheal tube (ETT) maintenance.


A "Deep Breath In" for GPs.


The COVID-19 Pandemic: Everything Old Is New Again in Public Health Education.


title: Quantitative proteomic analysis reveals that transmissible gastroenteritis virus activates the JAK-STAT1 signaling pathway.

text: Transmissible gastroenteritis virus (TGEV), a porcine enteropathogenic coronavirus, causes lethal watery diarrhea and severe dehydration in piglets. In this study, liquid chromatography-tandem mass spectrometry coupled to isobaric tags for relative and absolute quantification labeling was used to quantitatively identify differentially expressed cellular proteins after TGEV infection in PK-15 cells. In total, 162 differentially expressed cellular proteins were identified, including 60 upregulated proteins and 102 downregulated proteins. These differentially expressed proteins were involved in the cell cycle, cellular growth and proliferation, the innate immune response, etc. Interestingly, many upregulated proteins were associated with interferon signaling, especially signal transducer and activator of transcription 1 (STAT1) and interferon-stimulated genes (ISGs). Immunoblotting and real-time quantitative reverse transcription polymerase chain reaction demonstrated that TGEV infection induces STAT1 phosphorylation and nuclear translocation, as well as ISG expression. This study for the first time reveals that TGEV induces interferon signaling from the point of proteomic analysis.


title: Turning neglected tropical diseases into forgotten maladies.

text: Because they afflict mostly poor people in poor countries, killing relatively few compared to the many who suffer from severe chronic disabilities, a large cluster of infections deserve the label of neglected tropical diseases (NTDs). That is changing as these diseases' enormous health, educational, and economic toll is better understood, including how they interact with HIV/AIDS, malaria, and other illnesses. Several NTDs could be controlled or even eliminated within a decade, using integrated, highly cost-effective mass drug administration programs together with nondrug interventions. Research is needed to provide additional means of control for these conditions and make elimination feasible for still others.


title: Monitoring cerebral oxygenation of preterm infants using a neonatal specific sensor.

text: INTRODUCTION Cerebral oxygenation (rcSO2) monitoring in preterm infants may identify periods of cerebral hypoxia or hyperoxia. We hypothesised that there was a relationship between rcSO2 values and short term outcome in infants of GA < 32weeks. METHODS RcSO2 values were recorded for the first 48 h of life using an INVOS monitor with a neonatal sensor. The association between cranial ultrasound scan measured brain injury and rcSO2 was assessed. RESULTS 120 infants were included. Sixty-nine percent (83) of infants had a normal outcome (no IVH, no PVL, and survival at 1 month); less than one-quarter, 22% (26), had low grade IVH 1 or 2 (moderate outcome); and 9% (11) of infants had a severe outcome (IVH ≥ 3, PVL or died before 1 month age). rcSO2 values were lower for infants GA < 28weeks when compared with those GA 28-32, p < 0.001. There was no difference in absolute rcSO2 values between the three outcome groups but a greater degree of cerebral hypoxia was associated with preterm infants who had low grade 1 or 2 IVH. CONCLUSION Infants of GA < 28 weeks have lower cerebral oxygenation in the first 2 days of life. A greater degree of hypoxia was seen in infants with grade 1 or 2 haemorrhage. Normative ranges need to be gestation specific.


docid: nvpnfbds

title: Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites.

text: The coronavirus spike protein (S) plays a key role in the early steps of viral infection, with the S1 domain responsible for receptor binding and the S2 domain mediating membrane fusion. In some cases, the S protein is proteolytically cleaved at the S1-S2 boundary. In the case of the severe acute respiratory syndrome coronavirus (SARS-CoV), it has been shown that virus entry requires the endosomal protease cathepsin L; however, it was also found that infection of SARS-CoV could be strongly induced by trypsin treatment. Overall, in terms of how cleavage might activate membrane fusion, proteolytic processing of the SARS-CoV S protein remains unclear. Here, we identify a proteolytic cleavage site within the SARS-CoV S2 domain (S2', R797). Mutation of R797 specifically inhibited trypsin-dependent fusion in both cell-cell fusion and pseudovirion entry assays. We also introduced a furin cleavage site at both the S2' cleavage site within S2 793-KPTKR-797 (S2'), as well as at the junction of S1 and S2. Introduction of a furin cleavage site at the S2' position allowed trypsin-independent cell-cell fusion, which was strongly increased by the presence of a second furin cleavage site at the S1-S2 position. Taken together, these data suggest a novel priming mechanism for a viral fusion protein, with a critical proteolytic cleavage event on the SARS-CoV S protein at position 797 (S2'), acting in concert with the S1-S2 cleavage site to mediate membrane fusion and virus infectivity.


Middle East respiratory syndrome coronavirus infection: a short note on cases with renal failure problem.


title: Totally endoscopic ventricular septal defect repair using bilateral femoral arterial cannulation in an 8-year-old girl.

text: INTRODUCTION There are few reports on applying totally endoscopic surgery (TES) for repairing ventricular septal defect (VSD), especially in children. CASE PRESENTATION We described an 8-year-old girl, weighing 17 kg, who was diagnosed with peri-membranous VSD and patent ductus arteriosus (PDA). The patient had undergone trans-catheter PDA closure first, and 3 weeks later, TES was performed for VSD repair through 4 small trocars (one 12 mm trocar and three 5 mm trocars) without robotic assistance. Arterial line was set up indirectly to the right femoral artery (FA) through a graft with an additional line to the left side for reducing arterial pressure. DISCUSSION FA cannulation in small children induce some risks, such as: FA trauma, critical lower limb ischaemia, and iliac or femoral arterial stenosis. Our new method of FA cannulation was safe with 13 months of follow-up. The major concerns in this case were repairing VSD through small trocars in a small child. CONCLUSION Bilateral FA cannulation and the way to set up small trocars may facilitate totally endoscopic VSD repair in small children. However, the safety and efficacy of these approaches needs to be validated by larger studies preferably randomised controlled trials.


title: Residents' resuscitation training and theoretical knowledge in a Greek General Hospital.

text: The objective of this paper was to assess the resuscitation training and knowledge status of medical and surgical residents (SRs). A questionnaire of 23 questions was answered by medical and SRs in an Athens General Hospital. The questionnaire was designed based on the 2005 resuscitation guidelines. The questionnaire was answered by 137 residents (53.3% medical and 46.7% surgical). With regard to the knowledge questions, the mean score, on a maximum scale of 10, was 5.39±1.93 for the medical residents and 5.27±2.33 for the SRs. Their resuscitation knowledge was positively influenced by their attendance of Basic Life Support (P=0.005) and Advanced Life Support/Advanced Cardiac Life Support courses (P=0.013). Residents in this tertiary general hospital in Athens had inadequate knowledge of resuscitation guidelines and the majority of them were not currently certified in any of these courses.


title: Zerobot®: A Remote-controlled Robot for Needle Insertion in CT-guided Interventional Radiology Developed at Okayama University.

text: Since 2012, we have been developing a remote-controlled robotic system (Zerobot®) for needle insertion during computed tomography (CT)-guided interventional procedures, such as ablation, biopsy, and drainage. The system was designed via a collaboration between the medical and engineering departments at Okayama University, including various risk control features. It consists of a robot with 6 degrees of freedom that is manipulated using an operation interface to perform needle insertions under CT-guidance. The procedure includes robot positioning, needle targeting, and needle insertion. Phantom experiments have indicated that robotic insertion is equivalent in accuracy to manual insertion, without physician radiation exposure. Animal experiments have revealed that robotic insertion of biopsy introducer needles and various ablation needles is safe and accurate in vivo. The first in vivo human trial, therefore, began in April 2018. After its completion, a larger clinical study will be conducted for commercialization of the robot. This robotic procedure has many potential advantages over a manual procedure: 1) decreased physician fatigue; 2) stable and accurate needle posture without tremor; 3) procedure automation; 4) less experience required for proficiency in needle insertion skills; 5) decreased variance in technical skills among physicians; and 6) increased likelihood of performing the procedure at remote hospitals (i.e., telemedicine).


title: The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease.

text: Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissue. Cervical tissue samples were collected from women with healthy, human papilloma virus (HPV) ± cervical intraepithelial neoplasia (CIN), or cervical cancer. A handheld diathermy device generated surgical aerosol, which was transferred into a mass spectrometer for subsequent chemical analysis. Combination of principal component and linear discriminant analysis and least absolute shrinkage and selection operator was employed to study the spectral differences between groups. Significance of discriminatory m/z features was tested using univariate statistics and tandem MS performed to elucidate the structure of the significant peaks allowing separation of the two classes. We analyzed 87 samples (normal = 16, HPV ± CIN = 50, cancer = 21 patients). The iKnife discriminated with 100% accuracy normal (100%) vs. HPV ± CIN (100%) vs. cancer (100%) when compared to histology as the gold standard. When comparing normal vs. cancer samples, the accuracy was 100% with a sensitivity of 100% (95% CI 83.9 to 100) and specificity 100% (79.4 to 100). Univariate analysis revealed significant MS peaks in the cancer-to-normal separation belonging to various classes of complex lipids. The iKnife discriminates healthy from premalignant and invasive cervical lesions with high accuracy and can improve oncological outcomes and fertility preservation of women treated surgically for cervical cancer. Larger in vivo research cohorts are required to validate these findings.


title: Transarterial embolization (TAE) as add-on to percutaneous radiofrequency ablation (RFA) for the treatment of renal tumors: Review of the literature, overview of state-of-the-art embolization materials and further perspective of advanced image-guided tumor ablation.

text: Percutaneous radiofrequency ablation (RFA) for the treatment of stage I renal cell carcinoma has recently gained significant attention as the now available long-term and controlled data demonstrate that RFA can result in disease-free and cancer-specific survival comparable with partial and/or radical nephrectomy. In the non-controlled single center trials, however, the rates of treatment failure vary. Operator experience and ablation technique may explain some of the different outcomes. In the controlled trials, a major limitation is the lack of adequate randomization. In case reports, original series and overview articles, transarterial embolization (TAE) before percutaneous RFA was promising to increase tumor control and to reduce complications. The purpose of this study was to systematically review the literature on TAE as add-on to percutaneous RFA for renal tumors. Specific data regarding technique, tumor and patient characteristics as well as technical, clinical and oncologic outcomes have been analyzed. Additionally, an overview of state-of-the-art embolization materials and the radiological perspective of advanced image-guided tumor ablation (TA) will be discussed. In conclusion, TAE as add-on to percutaneous RFA is feasible and very effective and safe for the treatment of T1a tumors in difficult locations and T1b tumors. Advanced radiological techniques and technologies such as microwave ablation, innovative embolization materials and software-based solutions are now available, or will be available in the near future, to reduce the limitations of bland RFA. Clinical implementation is extremely important for performing image-guided TA as a highly standardized effective procedure even in the most challenging cases of localized renal tumors.


title: Detection of Sclerotinia sclerotiorum using a monomeric and dimeric single-chain fragment variable (scFv) antibody.

text: Sclerotinia sclerotiorum (Lib.) de Bary is a phytopathogenic fungus capable of causing significant yield losses in numerous crops, including canola, in which the fungus causes sclerotinia stem rot. Immunological detection methods to rapidly determine the presence of S. sclerotiorum on plants may provide growers with a viable diagnostic tool to aid with fungicide use decisions. This paper discusses the generation of a monomeric and dimeric single-chain, variable fragment (scFv) antibody with affinity for S. sclerotiorum using phage display technology. The bacterially expressed and purified scFv is shown to bind S. sclerotiorum with some cross-reactivity with the closely related phytopathogen Botrytis cinerea (Pers.:Fr.). The dimeric scFv displayed improved binding to the fungus as compared to the monomer and could detect the presence of mycelia in inoculated canola petals. To the authors' knowledge, this is the first report of a scFv dimer with affinity for S. sclerotiorum that has the potential for use in the development of a new diagnostic test.


title: Assessment of Th1/Th2 cytokines among patients with Middle East respiratory syndrome coronavirus infection.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a member of the beta-coronavirus genus of zoonotic origin that emerged in the Arabian Peninsula and is associated with significant morbidity and mortality. This study was conducted to assess the plasma levels of cytokines to evaluate the Th1/Th2 status among 46 MERS-CoV infected patients (19 asymptomatic and 27 symptomatic) and 52 normal healthy controls using a customized luminex kit. Comparative analysis of data between MERS-CoV infected patients and normal healthy controls revealed that whereas no difference was observed between asymptomatic MERS-CoV patients and controls, the mean plasma levels of IL-10 (44.69 ± 40.04 pg/mL vs 14.84 ± 6.96 pg/mL; p<0.0001), IL-4 (22.46 ± 8.02 pg/mL vs 16.01 ± 9.97 pg/mL; p<0.0001), IL-5 (10.78 ± 2.86 pg/mL vs 8.06 ± 1.41 pg/mL; p<0.0001) and IL-13 (14.51 ± 3.97 pg/mL vs 11.53 ± 4.16 pg/mL; p<0.003) in MERS-CoV symptomatic patients were significantly higher than the normal controls. The mean plasma levels of IFN-γ and IL-12 were no different among the study groups. The cytokine profile among symptomatic MERS-CoV infected patients was skewed to Th2 type immune response.


title: The host microRNA miR-301a blocks the IRF1-mediated neuronal innate immune response to Japanese encephalitis virus infection.

text: Effective recognition of viral components and the subsequent stimulation of the production of type I interferons (IFNs) is crucial for the induction of host antiviral immunity. The failure of the host to efficiently produce type I IFNs in response to infection by the Japanese encephalitis virus (JEV) is linked with an increased probability for the disease to become lethal. JEV is a neurotropic virus of the Flaviviridae family that causes encephalitis in humans. JEV infection is regulated by several host factors, including microRNAs, which are conserved noncoding RNAs that participate in various physiological and pathological processes. We showed that the JEV-induced expression of miR-301a led to inhibition of the production of type I IFN by reducing the abundances of the transcription factor IFN regulatory factor 1 (IRF1) and the signaling protein suppressor of cytokine signaling 5 (SOCS5). Mechanistically, induction of miR-301a expression during JEV infection required the transcription factor nuclear factor κB. In mouse neurons, neutralization of miR-301a restored the host innate immune response by enabling IFN-β production, thereby restricting viral propagation. Inhibition of miR-301a in mouse brain rescued the production of IRF1 and SOCS5, increased the generation of IFN-β, and reduced the extent of JEV replication, thus improving mouse survival. Thus, our study suggests that the JEV-induced expression of miR-301a assists viral pathogenesis by suppressing IFN production, which might be targeted by antiviral therapies.


Covid-19: Brazil now has third highest number of cases behind US and Russia.


title: Repeatability of gallium-68 DOTATOC positron emission tomographic imaging in neuroendocrine tumors.

text: OBJECTIVE To evaluate the repeatability of gallium-68 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic (DOTA)-D-Phe1-Try3-octreotide (68Ga-DOTATOC) positron emission tomography (PET) in neuroendocrine tumors. METHODS Five patients with neuroendocrine tumors were imaged with 68Ga-DOTATOC PET twice within 5 days. Maximum and mean standardized uptake values (SUVmax and SUVmean) and kinetic parameters (K-Patlak and K-influx) of target lesions were measured. The repeatability of these measurements was investigated. RESULTS Forty-seven target lesions were identified on whole-body PET and 21 lesions on dynamic images. There was excellent repeatability with intraclass correlation coefficient of 0.99 for SUVmax, SUVmean, and K-Patlak, and 0.85 for K-influx. The median absolute percent differences and the interquartile ranges (IQR) between 2 scans for SUVmax and SUVmean were 7.4% (IQR, 14.1%) and 9.3% (IQR, 10.6%), respectively. The median absolute percent differences for K-Patlak and K-influx were 12.5% (IQR, 12.6%) and 29.9% (IQR, 22.4%), respectively. The SUVmax of target lesions did not differ by more than 25% between the 2 scans. CONCLUSIONS 68Ga-DOTATOC PET imaging of neuroendocrine tumors is highly reproducible. A difference of more than 25% in SUVmax represents a change that is larger than the measurement error observed on repeated studies and should reflect a significant change in the biological character of the tumor.


title: Surveillance of Wildlife Diseases: Lessons from the West Nile Virus Outbreak.

text: The West Nile virus outbreak of 1999 revealed many weaknesses in this country's ability to respond to disease threats that cross species lines. There were issues of poor communication among human, domestic animal, and wildlife health agencies that delayed diagnosis; a lack of diagnostic capacity of wildlife agencies at the state level; the exclusion of captive wildlife from any surveillance efforts; an inability to visualize the geospatial relationship between the human and avian outbreaks in a timely manner; and marked disparities of funding levels across agencies. Wildlife has played an important role in recent emerging infectious diseases, and it is clear that a One Health approach will be necessary to respond to future threats. The question is, are we any better prepared to recognize and respond to a wildlife-related emerging infectious disease than we were 14 years ago? Have the lessons of WNV been learned?


Subintimal angioplasty and stenting of chronic total femoropopliteal occlusions: is distal protection needed?


title: The heptad repeat 2 domain is a major determinant for enhanced human immunodeficiency virus type 1 (HIV-1) fusion and pathogenicity of a highly pathogenic HIV-1 Env.

text: Human immunodeficiency virus type 1 (HIV-1)-mediated depletion of CD4+ lymphocytes in an infected individual is the hallmark of progression to AIDS. However, the mechanism for this depletion remains unclear. To identify mechanisms of HIV-1-mediated CD4 T-cell death, two similar viral isolates obtained from a rapid progressor patient with significantly different pathogenic phenotypes were studied. One isolate (R3A) demonstrates enhanced pathogenesis in both in vivo models and relevant ex vivo lymphoid organ model systems compared to another isolate, R3B. The pathogenic determinants were previously mapped to the V5-gp41 envelope region, correlating functionally with enhanced fusion activity and elevated CXCR4 binding affinity. To further elucidate specific differences between R3A and R3B within the V5-gp41 domains that enhance CD4 depletion, R3A-R3B chimeras to study the V5-gp41 region were developed. Our data demonstrate that six residues in the ectodomain of R3A provide the major determinant for both enhanced Env-cell fusion and pathogenicity. Furthermore, three amino acid differences in the heptad repeat 2 (HR-2) domain of R3A determined its fusion activity and significantly elevated its pathogenic activity. The chimeric viruses with enhanced fusion activity, but not elevated CXCR4 affinity, correlated with high pathogenicity in the thymus organ. We conclude that the functional domain of a highly pathogenic HIV-1 Env is determined by mutations in the HR-2 region that contribute to enhanced fusion and CD4 T-cell depletion.


title: Pancreas Transplantation: Past, Present, Future.

text: Diabetes is the pandemic disease of the modern era, with 10% of these patients having type 1 diabetes mellitus. Despite the prevalence, morbidities, and associated financial burden, treatment options have not changed since the introduction of injectable insulin. To date, over 40,000 pancreas transplants have been performed globally. It remains the only known method for restoring glycemic control and thus curing type 1 diabetes mellitus. The aim of this review is to bring pancreatic transplantation out of the specialist realm, informing practitioners about this important procedure, so that they feel better equipped to refer suitable patients for transplantation and manage, counsel, and support when encountering them within their own specialty. This study was a narrative review conducted in October 2015, with OVID interface searching EMBASE and MEDLINE databases, using Timeframe: Inception to October 2015. Articles were assessed for clinical relevance and most up-to-date content, with articles written in English as the only inclusion criterion. Other sources used included conference proceedings/presentations and unpublished data from our institution (Oxford Transplant Centre). Pancreatic transplantation is growing and has quickly become the gold standard of care for patients with type 1 diabetes mellitus and renal failure. Significant improvements in quality of life and life expectancy make pancreatic transplant a viable and economically feasible intervention. It remains the most effective method of establishing and maintaining euglycemia, halting and potentially reversing complications associated with diabetes.


title: Clinical and oncological outcomes of single-incision vs. conventional laparoscopic surgery for rectal cancer.

text: BACKGROUND To evaluate the clinical and oncological outcomes of single-incision laparoscopic surgery (SILS) vs. conventional laparoscopic surgery (CLS) for patients with rectal cancer (RC) who underwent total mesorectal excision (TME) surgery. METHODS This was a retrospective case-control study of patients with RC operated between 12/2013 and 12/2017 in Ruijin Hospital North, Shanghai Jiaotong University School of Medicine. In total, 177 patients who underwent CLS and 51 who underwent SILS met the inclusion and exclusion criteria and were matched 1:1 using propensity score matching method (PSM). RESULTS Compared with the CLS group, the SILS group showed shorter operation time [105 (40) vs. 125 (55) min, P = 0.045], shorter total incision length [4 (1) vs. 6.5 (1.5) cm, P < 0.001], lower VAS score on POD2 [1 (1) vs. 2 (1), P < 0.001], shorter time to soft diet [7 (1) vs. 8 (2) days, P = 0.048], and shorter length of hospital stay [9 (2) vs. 11 (3) days, P < 0.001]. The postoperative complications were similar between two groups [1(2%) vs. 5 (9.8%), P = 0.205]. No readmissions or mortality in either group occurred within 30 days of surgery. All 102 specimens met the requirements of TME. No significant differences were observed in the pathologic outcomes between the two groups. The median follow-up period was 32.6 months in the SILS group and 36.8 months in the CLS group (P = 0.053). The 3-year disease-free survival rates and overall survival rates of the SILS and CLS groups were 89.8% vs. 96.0% (P = 0.224) and 90.9% vs. 96.9% (P = 0.146), respectively. CONCLUSIONS Compared with CLS, TME surgery for rectal cancer can be performed safely and effectively using the SILS technique with better cosmetic results, less postoperative pain, faster postoperative recovery, and acceptable clinical and oncological outcomes.


The aftermath.


title: In vitro evaluation of heat and moisture exchangers designed for spontaneously breathing tracheostomized patients.

text: BACKGROUND Heat and moisture exchangers (HMEs) are commonly used in chronically tracheostomized spontaneously breathing patients, to condition inhaled air, maintain lower airway function, and minimize the viscosity of secretions. Supplemental oxygen (O2) can be added to most HMEs designed for spontaneously breathing tracheostomized patients. We tested the efficiency of 7 HMEs designed for spontaneously breathing tracheostomized patients, in a normothermic model, at different minute ventilations (VE) and supplemental O2 flows. METHODS HME efficiency was evaluated using an in vitro lung model at 2 VE (5 and 15 L/min) and 4 supplemental O2 flows (0, 3, 6, and 12 L/min). Wet and dry temperatures of the inspiratory flow were measured, and absolute humidity was calculated. In addition, HME efficiency at 0, 12, and 24 h use was evaluated, as well as resistance to flow at 0 and 24 h. RESULTS The progressive increase in O2 flow from 0 to 12 L/min was associated with a reduction in temperature and absolute humidity. Under the same conditions, this effect was greater at lower VE. The HME with the best performance provided an absolute humidity of 26 mg H2O/L and a temperature of 27.8 °C. No significant changes in efficiency or resistance were detected during the 24 h evaluation. CONCLUSIONS The efficiency of HMEs in terms of temperature and absolute humidity is significantly affected by O2 supplementation and V(E).


title: Fast Identification of Possible Drug Treatment of Coronavirus Disease -19 (COVID-19) Through Computational Drug Repurposing Study.

text: The recent outbreak of novel coronavirus disease -19 (COVID-19) calls for and welcomes possible treatment strategies using drugs on the market. It is very efficient to apply computer-aided drug design techniques to quickly identify promising drug repurposing candidates, especially after the detailed 3D-structures of key virous proteins are resolved. Taking the advantage of a recently released crystal structure of COVID-19 protease in complex with a covalently-bonded inhibitor, N3,1 I conducted virtual docking screening of approved drugs and drug candidates in clinical trials. For the top docking hits, I then performed molecular dynamics simulations followed by binding free energy calculations using an endpoint method called MM-PBSA-WSAS.2-4 Several promising known drugs stand out as potential inhibitors of COVID-19 protease, including Carfilzomib, Eravacycline, Valrubicin, Lopinavir and Elbasvir. Carfilzomib, an approved anti-cancer drug acting as a proteasome inhibitor, has the best MM-PBSA-WSAS binding free energy, -13.82 kcal/mol. Streptomycin, an antibiotic and a charged molecule, also demonstrates some inhibitory effect, even though the predicted binding free energy of the charged form (-3.82 kcal/mol) is not nearly as low as that of the neutral form (-7.92 kcal/mol). One bioactive, PubChem 23727975, has a binding free energy of -12.86 kcal/mol. Detailed receptor-ligand interactions were analyzed and hot spots for the receptor-ligand binding were identified. I found that one hotspot residue HIS41, is a conserved residue across many viruses including COVID-19, SARS, MERS, and HCV. The findings of this study can facilitate rational drug design targeting the COVID-19 protease.


title: Effect of surgical masks worn concurrently over N95 filtering facepiece respirators: extended service life versus increased user burden.

text: Growing concern over the availability of Respiratory protective devices (eg, filtering facepiece Respirators), in the face of the probable extreme demand brought on by a pandemic influenza, has prompted the suggestion that useful life of N95 filtering facepiece Respirator can be extended by the concurrent use of a surgical mask as an outer protective barrier over the Respirator. Personal protective equipment generally places a strain on the user, and the detrimental physiological and psychological burdens normally imposed by Respirator use could be magnified by the addition of an extra layer of protection such as a surgical mask. The issue of this potentially increased burden of the concurrent use of a surgical facemask with an N95 filtering facepiece Respirator is investigated to afford users the necessary information to make informed decisions Regarding the use of this Respiratory personal protective equipment in the face of large-scale outbreaks of Respiratory pathogens.


title: The Effect of Initial High vs. Low FiO2 on Breathing Effort in Preterm Infants at Birth: A Randomized Controlled Trial.

text: Background: Infants are currently stabilized at birth with initial low FiO2 which increases the risk of hypoxia and suppression of breathing in the first minutes after birth. We hypothesized that initiating stabilization at birth with a high O2 concentration, followed by titration, would improve breathing effort when compared to a low O2 concentration, followed by titration. Methods: In a bi-center randomized controlled trial, infants <30 weeks gestation were stabilized at birth with an initial O2 concentration of 30 or 100%, followed by oxygen titration. Primary outcome was minute volume of spontaneous breathing. We also assessed tidal volumes, mean inspiratory flow rate (MIFR) and respiratory rate with a respiratory function monitor in the first 5 min after birth, and evaluated the duration of mask ventilation in the first 10 min after birth. Pulse oximetry was used to measure heart rate and SpO2 values in the first 10 min. Hypoxemia was defined as SpO2 < 25th percentile and hyperoxemia as SpO2 >95%. 8-iso-prostaglandin F2α (8iPGF2α) was measured to assess oxidative stress in cord blood and 1 and 24 h after birth. Results: Fifty-two infants were randomized and recordings were obtained in 44 infants (100% O2-group: n = 20, 30% O2-group: n = 24). Minute volumes were significantly higher in the 100% O2-group (146.34 ± 112.68 mL/kg/min) compared to the 30% O2-group (74.43 ± 52.19 mL/kg/min), p = 0.014. Tidal volumes and MIFR were significantly higher in the 100% O2-group, while the duration of mask ventilation given was significantly shorter. Oxygenation in the first 5 min after birth was significantly higher in infants in the 100% O2-group [85 (64-93)%] compared to the 30% O2-group [58 (46-67)%], p < 0.001. The duration of hypoxemia was significantly shorter in the 100% O2-group, while the duration of hyperoxemia was not different between groups. There was no difference in oxidative stress marker 8iPGF2α between the groups. Conclusion: Initiating stabilization of preterm infants at birth with 100% O2 led to higher breathing effort, improved oxygenation, and a shorter duration of mask ventilation as compared to 30% O2, without increasing the risk for hyperoxia or oxidative stress. Clinical Trial Registration: This study was registered in www.trialregister.nl, with registration number NTR6878.


Letter: the irony of oral iron - not an underdog for post-gastrointestinal bleeding anaemia.


title: Managing Barrett's esophagus with radiofrequency ablation.

text: Barrett's esophagus (BE) is a well-established pre-malignant lesion for esophageal adenocarcinoma, a condition that carries a dismal five-year overall survival rate of less than 15%. Among several available methods to eliminate BE, radiofrequency ablation (RFA) provides the most efficient modality, since it has been demonstrated to successfully eradicate BE with or without dysplasia with acceptable safety, efficacy and durability profiles. In conjunction with proton pump therapy, this new technology has quickly become the standard care for patients with dysplastic BE. However, several technical questions remain about how to deploy RFA therapy for maximum effectiveness and long-term favorable outcomes for all stages of the disease. These include how to select patient for therapy, what the best protocol for RFA is, when to use other modalities, such as endoscopic mucosal resection, and what should be considered for refractory BE. This review addresses these questions with the perspective of the best available evidence matched with the authors' experience with the technology.


title: Assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a "gray zone" approach.

text: BACKGROUND Respiratory arterial pulse pressure variations (PPV) are the best predictors of fluid responsiveness in mechanically ventilated patients during general anesthesia. However, previous studies were performed in a small number of patients and determined a single cutoff point to make clinical discrimination. The authors sought to test the predictive value of PPV in a large, multicenter study and to express it using a gray zone approach. METHODS The authors studied 413 patients during general anesthesia and mechanical ventilation in four centers. PPV, central venous pressure, and cardiac output were recorded before and after volume expansion (VE). Response to VE was defined as more than 15% increase in cardiac output after VE. The following approaches were used to determine the gray zones: resampled and two-graph receiver operator characteristic curves. The impact of changes in the benefit-risk balance of VE on the gray zone was also evaluated. RESULTS The authors observed 209 responders (51%) and 204 nonresponders (49%) to VE. The area under receiver operating characteristic curve was 0.89 (95% CI: 0.86-0.92) for PPV, compared with 0.57 (95% CI: 0.54-0.59) for central venous pressure (P < 10). The gray zone approach identified a range of PPV values (between 9% and 13%) for which fluid responsiveness could not be predicted reliably. These PPV values were seen in 98 (24%) patients. Changes in the cost ratio of VE moderately affected the gray zone limits. CONCLUSION Despite a strong predictive value, PPV may be inconclusive (between 9% and 13%) in approximately 25% of patients during general anesthesia.


title: Hysterectomy and salphingoopherectomy by Transvaginal Natural Orifice Transluminal Endoscopic Surgery(NOTES): Turkish surgeons' initial experience.

text: BACKGROUND The aim of this study was to evaluate the feasibility, safety, and early postoperative outcomes of hysterectomies and salpingo-oophorectomies using transvaginal natural orifice transluminal endoscopic surgery (vNOTES). MATERIALS AND METHODS The women undergoing vNOTES hysterectomies and salpingo-oophorectomies at a tertiary referral medical center between April 2016 and April 2017 were retrospectively analyzed. In all of the vNOTES procedures, a handmade glove port system comprised of a glove-wound retractor NOTES port was used. RESULTS Thirteen patients underwent gynecological procedures with benign indications via vNOTES. Of the 13 operations, 6 of the patients had salpingo-oophorectomies and 7 had hysterectomies, and all of the surgeries were performed by the same surgeon (Dr. Ahmet Kale). No conversion to a conventional laparoscopy or even a laparotomy was needed in any of the procedures. The mean operation time was 73.14 min in the hysterectomy patients and 40.8 min in the salpingo-oophorectomy patients. The mean drop in the hemoglobin (Hb) level was 1.4 g/dl in the hysterectomy patients and 1.6 g/dl in the salpingo-oophorectomy patients. For these patients undergoing vNOTES, the mean postoperative visual analog scale (VAS) pain score at 6 h was 4.38 and at 24 h it was 0.62. There were no intraoperative complications in any of the cases. The mean length of the hospital stay was 1.8 days in the hysterectomy patients and 1.5 days in the salpingo-oophorectomy patients. CONCLUSION The vNOTES procedure overcomes the surgical and technical difficulties of conventional vaginal surgery by incorporating the advantages of endoscopic surgery. Moreover, vNOTES uses inexpensive, reusable, handmade conventional laparoscopic instruments and avoids those problems related to abdominal wall incisions and trocar-related complications. Overall, this procedure results in high patient satisfaction, cosmetic advantages, and decreased postoperative pain.


title: Sequential exposure to bovine viral diarrhea virus and bovine coronavirus results in increased respiratory disease lesions: clinical, immunologic, pathologic, and immunohistochemical findings.

text: Bovine coronaviruses (BoCVs) have been found in respiratory tissues in cattle and frequently associated with bovine respiratory disease (BRD); however, pathogenesis studies in calves are limited. To characterize the pathogenesis and pathogenicity of BoCV isolates, we used 5 different BoCV strains to inoculate colostrum-deprived calves, ~ 2-5 wk of age. Later, to determine if dual viral infection would potentiate pathogenicity of BoCV, calves were inoculated with BoCV alone, bovine viral diarrhea virus (BVDV) alone, or a series of dual-infection (BVDV-BoCV) schemes. A negative control group was included in all studies. Clinical signs and body temperature were monitored during the study and samples collected for lymphocyte counts, virus isolation, and serology. During autopsy, gross lesions were recorded and fixed tissues collected for histopathology and immunohistochemistry; fresh tissues were collected for virus isolation. Results suggest increased pathogenicity for isolate BoCV OK 1776. Increased body temperature was found in all virus-inoculated groups. Lung lesions were present in calves in all dual-infection groups; however, lesions were most pronounced in calves inoculated with BVDV followed by BoCV inoculation 6 d later. Lung lesions were consistent with mild-to-moderate interstitial pneumonia, and immunohistochemistry confirmed the presence of BoCV antigen. Our studies demonstrated that BVDV-BoCV dual infection may play an important role in BRD pathogenesis, and timing between infections seems critical to the severity of lesions.


Redesigning Italy's regional Neurosciences networks in the COVID-19 era: a model for a future healthcare system or skating on thin ice?


title: The use of pyrosequencing for detection of hemagglutinin mutations associated with increased pathogenicity of H5N1 avian influenza viruses in mammals.

text: Hemagglutinin (HA) cleavage is critical for virulence of influenza viruses. The amino acid residue at the P6 position of the HA cleavage site (HACS) has been shown to be most variable and to have a direct correlation with the cleavage efficiency and pathogenicity of H5N1 avian influenza viruses (AIVs) in mammals. Among these amino acid variants, serine has been associated with the highest virulence in mammals, and its detection may serve as an indicator for H5N1 AIVs with high pathogenicity and potential public risk. We developed a rapid detection method based on reverse-transcription (RT)-PCR and pyrosequencing to detect a mutation at the HACS that is associated with increased pathogenicity of H5N1 AIVs in mammals. Herein, we provide a specific, sensitive, and reliable method for rapid detection of one of the virulence determinants associated with increased pathogenicity of H5N1 AIVs in mammals.


Patterns of IgG and IgM antibody response in COVID-19 patients.


Covid-19: doctors' visas are automatically extended for one year.


title: Crystal structure and carbohydrate analysis of Nipah virus attachment glycoprotein: a template for antiviral and vaccine design.

text: Two members of the paramyxovirus family, Nipah virus (NiV) and Hendra virus (HeV), are recent additions to a growing number of agents of emergent diseases which use bats as a natural host. Identification of ephrin-B2 and ephrin-B3 as cellular receptors for these viruses has enabled the development of immunotherapeutic reagents which prevent virus attachment and subsequent fusion. Here we present the structural analysis of the protein and carbohydrate components of the unbound viral attachment glycoprotein of NiV glycoprotein (NiV-G) at a 2.2-A resolution. Comparison with its ephrin-B2-bound form reveals that conformational changes within the envelope glycoprotein are required to achieve viral attachment. Structural differences are particularly pronounced in the 579-590 loop, a major component of the ephrin binding surface. In addition, the 236-245 loop is rather disordered in the unbound structure. We extend our structural characterization of NiV-G with mass spectrometric analysis of the carbohydrate moieties. We demonstrate that NiV-G is largely devoid of the oligomannose-type glycans that in viruses such as human immunodeficiency virus type 1 and Ebola virus influence viral tropism and the host immune response. Nevertheless, we find putative ligands for the endothelial cell lectin, LSECtin. Finally, by mapping structural conservation and glycosylation site positions from other members of the paramyxovirus family, we suggest the molecular surface involved in oligomerization. These results suggest possible pathways of virus-host interaction and strategies for the optimization of recombinant vaccines.


title: Endoscopic management of acute necrotizing pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) evidence-based multidisciplinary guidelines.

text: 1: ESGE suggests using contrast-enhanced computed tomography (CT) as the first-line imaging modality on admission when indicated and up to the 4th week from onset in the absence of contraindications. Magnetic resonance imaging (MRI) may be used instead of CT in patients with contraindications to contrast-enhanced CT, and after the 4th week from onset when invasive intervention is considered because the contents (liquid vs. solid) of pancreatic collections are better characterized by MRI and evaluation of pancreatic duct integrity is possible. Weak recommendation, low quality evidence. 2: ESGE recommends against routine percutaneous fine needle aspiration (FNA) of (peri)pancreatic collections. Strong recommendation, moderate quality evidence. FNA should be performed only if there is suspicion of infection and clinical/imaging signs are unclear. Weak recommendation, low quality evidence. 3: ESGE recommends initial goal-directed intravenous fluid therapy with Ringer's lactate (e. g. 5 - 10 mL/kg/h) at onset. Fluid requirements should be patient-tailored and reassessed at frequent intervals. Strong recommendation, moderate quality evidence. 4: ESGE recommends against antibiotic or probiotic prophylaxis of infectious complications in acute necrotizing pancreatitis. Strong recommendation, high quality evidence. 5: ESGE recommends invasive intervention for patients with acute necrotizing pancreatitis and clinically suspected or proven infected necrosis. Strong recommendation, low quality evidence.ESGE suggests that the first intervention for infected necrosis should be delayed for 4 weeks if tolerated by the patient. Weak recommendation, low quality evidence. 6: ESGE recommends performing endoscopic or percutaneous drainage of (suspected) infected walled-off necrosis as the first interventional method, taking into account the location of the walled-off necrosis and local expertise. Strong recommendation, moderate quality evidence. 7: ESGE suggests that, in the absence of improvement following endoscopic transmural drainage of walled-off necrosis, endoscopic necrosectomy or minimally invasive surgery (if percutaneous drainage has already been performed) is to be preferred over open surgery as the next therapeutic step, taking into account the location of the walled-off necrosis and local expertise. Weak recommendation, low quality evidence. 8: ESGE recommends long-term indwelling of transluminal plastic stents in patients with disconnected pancreatic duct syndrome. Strong recommendation, low quality evidence. Lumen-apposing metal stents should be retrieved within 4 weeks to avoid stent-related adverse effects.Strong recommendation, low quality evidence.


Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: An ARIA-EAACI statement.


title: The pig as an experimental model for mid-dermal burns research.

text: This was a novel, prospective and interventional animal study designed to develop and evaluate a new infliction device for the experimental burn model. Four paired sets of contact burns measuring 36mm diameter were inflicted on the dorsum of an anesthetized pig using a stainless steel round bar heated up to 80-110°C. The bar was applied using a push-pull force gauge designed to control 1kgf mechanical force applied to the skin for a period of 20s. The left dorsum was used for macroscopic observation and the right dorsum was used for histopathological evaluation. A total of eight burns were covered with moist saline dressings and given daily treatments of xylocaine (lidocaine HCl) gel. This procedure was followed for a period of 24 days. Full-thickness biopsies were obtained for histologic analysis to determine the extent of injury. Statistical analysis showed a high correlation between the exposure temperature and histopathological assessment. The results found the depth of injury to the collagen (Seg1) correlated with the temperature (Ti) at which the burns was inflicted, Seg1=0.038Ti-2.57 (r=0.973, P<0.05). Also, the histological studies show a high correlation between the depth of collagen denaturation in wounds and the exposure temperature, Seg1=0.0268Ti-0.165 (r=0.991, P<0.05). This model is useful to assess more closely the therapeutic agents used for wound healing in experimental burn wounds.


title: Outcome of patients with large vessel occlusion in the anterior circulation and low NIHSS score.

text: BACKGROUND Optimal management of patients with large vessel occlusion (LVO) and low NIHSS score is unknown, which was the aim to investigate in this study. METHODS This is a retrospective analysis of a prospective single tertiary care centre 14-year cohort of patients with LVO in the anterior circulation and NIHSS score ≤ 5 on admission. Outcome was analysed according to primary intended therapy. RESULTS Among 185 patients (median age 67.4 years), 52.4% received primary conservative therapy (including 26.8% secondary reperfusion in case of secondary neurological deterioration), 12.4% IV thrombolysis (IVT) only and 35.1% primary endovascular therapy (EVT). 95 (51.4%) patients experienced neurological deterioration until 3 months. Primary-IVT-only and primary-EVT compared to conservative-therapy patients had better 3 months' outcome (54.5% vs. 30.8%: adjustedOR 6.02; adjustedp = 0.004 for mRS 0-1 and 54.7% vs. 30.8%: adjustedOR 5.09; adjustedp = 0.002, respectively). Also mRS shift analysis favored primary-IVT-only and primary-EVT patients (adjustedOR 6.25; adjustedp = 0.001 and adjustedOR 3.14; adjustedp = 0.003). Outcome in primary-IVT-only vs. primary-EVT patients did not differ significantly. Patients who received secondary EVT because of neurological deterioration after primary-conservative-therapy had worse 3 months' outcome than primary-EVT patients (20.8% vs. 30.8%: adjustedOR 0.24; adjustedp = 0.047 for mRS 0-1 and adjustedOR 0.31; adjustedp = 0.019 in mRS shift analysis). Survival and symptomatic intracranial haemorrhage did not differ amongst groups. CONCLUSIONS Our data indicate that primary IVT and/or EVT may be better than primary conservative therapy in patients with LVO in the anterior circulation and low NIHSS score. Furthermore, primary EVT was better than secondary EVT in case of neurological deterioration. There is an unmet need for RCTs to find the optimal therapy for this patient group.