title: Colon cancer during the coronavirus pandemic – recovery from COVID-19 pneumonia of an elderly woman with multiple co-morbidities

text: COVID-19, caused by the new coronavirus, can lead to acute respiratory failure or even sepsis. Patients with multiple co-morbidities are more likely to develop these severe forms of the disease. The aim of this report is to highlight cases the analysis of which might help discover factors that influence the course and mortality of COVID-19 pneumonia. The past medical history of our elderly patient (75-year-old female) includes rectum resection with intraoperative cardiac arrest and successful resuscitation. In January 2020, the patient was diagnosed with adenocarcinoma of the ascending colon and concomittant pulmonary embolism. Following 6 weeks of therapeutic dose low-molecular-weight heparin (LMWH) treatment, the cancerous colonic section was resected. The patient arrested intraoperatively but was successfully resuscitated. On post-operative day 15, the patient developed arterial anastomosis bleed, which necessitated acute right-sided hemicolectomy. Post-operatively she became pyrexial and COVID-19 was confirmed, but later became apyrexial with symptomatic treatment. Subsequently, the patient developed partial anastomosis insufficiency, which resolved with conservative management. Following three negative SARS-CoV-2 tests, she was successfully discharged from hospital. It is worthy of note that due to the active anastomosis bleed the angiotensin-converting enzyme (ACE)-inhibitor treatment was stopped, and later the patient got infected with SARS-CoV-2. A long-lasting LMWH therapy was performed. The timely management of colorectal carcinoms remains important even during an epidemic. The appropriate treatment of these patients during the pandemic presents a great challenge for all doctors, but, as shown in our case report, surgical treatment of even those with multiple co-morbidities can be successful. Orv Hetil. 2020; 161(25): 1059-1062.


title: Outbreaks in the adult ICUs.

text: PURPOSE OF REVIEW Infectious disease outbreaks in the critical care setting are common and serious consequence. This article reviews and summarizes recent outbreaks in the adult ICUs. RECENT FINDINGS Outbreaks of multidrug-resistant bacteria, fungi, and emerging viruses in ICUs from different countries are common. Outbreak investigation relies on epidemiologic methods, microbiologic studies, and molecular typing methods. Overuse of antibiotics, gaps in implementing infection prevention measures, and contaminated environment are common causes of ICU outbreaks. ICU staff awareness of and preparedness for such outbreaks are crucial for outbreak prevention and control. Specific infection control measures vary according to outbreak transmission mode and cause. SUMMARY Outbreaks remain a significant threat to healthcare systems. Proper implementation of infection prevention practices and judicious use of antibiotics are needed for outbreak prevention in adult ICUs. Surveillance, proper outbreak investigation, adherence to infection prevention and control measures, and thorough disinfection of contaminated areas are required to successfully manage outbreaks.


title: Debate: COVID-19 and psychological well-being of children and adolescents in Italy.

text: Italy was the first country in Europe to deal with COVID-19. Measures taken by the government to contain the spread of the virus were based mainly on quarantine and social distancing, with dramatic economic, social and psychological consequences. Since March, Italian children and adolescents are facing school closures, which have caused a disruption in the daily lives of millions of young people and their families. To date, despite the slow reopening, the government has decided to maintain school closures for the entire academic year, leaving the future of young people in uncertainty. There is already some evidence that quarantine and social isolation are having negative impact on children's and adolescents' psychological well-being. Moreover, this situation will mainly affect those children and adolescents with pre-existing vulnerabilities and those suffering of mental disorders. It is imperative to keep young people's needs at the core of reconstruction plans, allowing them to return to school safely, and providing them with some strategies to heal and dealing with this stressful and potentially traumatic situation.


title: Relationship between risk factor control and vascular events in the SAMMPRIS trial.

text: OBJECTIVE The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study is the first stroke prevention trial to include protocol-driven intensive management of multiple risk factors. In this prespecified analysis, we aimed to investigate the relationship between risk factor control during follow-up and outcome of patients in the medical arm of SAMMPRIS. METHODS Data from SAMMPRIS participants in the medical arm (n = 227) were analyzed. Risk factors were recorded at baseline, 30 days, 4 months, and then every 4 months for a mean follow-up of 32 months. For each patient, values for all risk factor measures were averaged and dichotomized as in or out of target. RESULTS Participants who were out of target for systolic blood pressure and physical activity, as well as those with higher mean low-density lipoprotein cholesterol and non-high-density lipoprotein, were more likely to have a recurrent vascular event (stroke, myocardial infarction, or vascular death) at 3 years compared to those who had good risk factor control. In the multivariable analysis, greater physical activity decreased the likelihood of a recurrent stroke, myocardial infarction, or vascular death (odds ratio 0.6, confidence interval 0.4-0.8). CONCLUSIONS Raised blood pressure, cholesterol, and physical inactivity should be aggressively treated in patients with intracranial atherosclerosis to prevent future vascular events. Physical activity, which has not received attention in stroke prevention trials, was the strongest predictor of a good outcome in the medical arm in SAMMPRIS. CLINICALTRIALSGOV IDENTIFIER NCT00576693.


title: Applications in high-content functional protein microarrays.

text: Protein microarray technology provides a versatile platform for characterization of hundreds to thousands of proteins in a parallel and high-throughput manner. Over the last decade, applications of functional protein microarrays in particular have flourished in studying protein function at a systems level and have led to the construction of networks and pathways describing these functions. Relevant areas of research include the detection of various binding properties of proteins, the study of enzyme-substrate relationships, the analysis of host-microbe interactions, and profiling antibody specificity. In addition, discovery of novel biomarkers in autoimmune diseases and cancers is emerging as a major clinical application of functional protein microarrays. In this review, we will summarize the recent advances of functional protein microarrays in both basic and clinical applications.


title: Acellular dermal matrix and subepithelial connective tissue grafts for root coverage: A systematic review.

text: Background The aim of this systematic review was to evaluate whether patients with gingival recession would benefit from an acellular dermal matrix graft (ADMG) in ways that are comparable to the gold standard of the subepithelial connective tissue graft (SCTG). Materials and Methods A systematic review and meta-analysis comparing ADMG to SCTG for the treatment of Miller Class I and II recession defects was conducted according to PRISMA guidelines. PubMed, Excerpta Medica Database, and Cochrane Central Register of Controlled Trials databases were searched up to March 2016 for controlled trials with minimum 6 months duration. The primary outcome was root coverage; secondary outcomes included attachment level change, keratinized tissue (KT) change, and patient-based outcomes. Both authors independently assessed the quality of each included trial and extracted the relevant data. Results From 158 potential titles, 17 controlled trials were included in the meta-analysis. There were no differences between ADMG and SCTG for mean root coverage, percent root coverage, and clinical attachment level gain. ADMG was statistically better than SCTG for gain in width of KT (-0.43 mm; 95% confidence interval: -0.72, -0.15). Only one study compared patient-based outcomes. Conclusion This review found that an ADMG would be a suitable root coverage substitute for an SCTG when avoidance of the second surgical site is preferred.


title: Virological and Immunological Outcomes of Coinfections.

text: Coinfections involving viruses are being recognized to influence the disease pattern that occurs relative to that with single infection. Classically, we usually think of a clinical syndrome as the consequence of infection by a single virus that is isolated from clinical specimens. However, this biased laboratory approach omits detection of additional agents that could be contributing to the clinical outcome, including novel agents not usually considered pathogens. The presence of an additional agent may also interfere with the targeted isolation of a known virus. Viral interference, a phenomenon where one virus competitively suppresses replication of other coinfecting viruses, is the most common outcome of viral coinfections. In addition, coinfections can modulate virus virulence and cell death, thereby altering disease severity and epidemiology. Immunity to primary virus infection can also modulate immune responses to subsequent secondary infections. In this review, various virological mechanisms that determine viral persistence/exclusion during coinfections are discussed, and insights into the isolation/detection of multiple viruses are provided. We also discuss features of heterologous infections that impact the pattern of immune responsiveness that develops.


title: COVID-19 and restrictive lung disease: A deadly combo to trip off the fine balance.

text: Coronavirus Disease (COVID-19) pandemic has so far led to innumerable deaths worldwide. The risk factors so far that have been most studied as poor prognostic factors are old age, individuals with multiple comorbidities and immunocompromised patients. Amongst the chronic lung diseases, most patients with COVID-19 reported so far had asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung disease. Herein, we discuss the significance of restrictive lung disease during the COVID-19 pandemic as a potential risk factor via an example of a patient with kyphoscoliosis who succumbed to death due to COVID-19 pneumonia.


Does comparative-effectiveness research threaten personalized medicine?


docid: owbeneds

title: Assessment of the Double-Staple Technique for Esophagoenteric Anastomosis in Gastric Cancer.

text: INTRODUCTION Reports on outcomes after double-staple technique (DST) for total and proximal gastrectomy are limited, originating mostly from Asian centers. Our objective was to examine anastomotic leak and stricture with DST for esophagoenteric anastomosis in gastric cancer patients. METHODS A single institution review was performed for patients who underwent total/proximal gastrectomy with DST between 2006 and 2015. DST was performed using transoral anvil delivery (OrVil) with end-to-end anastomosis. Clinical characteristics and outcomes, including anastomotic leak and stricture, were recorded. RESULTS Overall, DST was performed in 60 patients [total gastrectomy (81.7%, n = 49/60), proximal gastrectomy (10.0%, n = 6/60), and completion gastrectomy (8.3%, n = 5/60)]. Neoadjuvant chemotherapy was administered to 21 patients (35.0%), and 6 patients (10.0%) received external beam radiation therapy prior to completion gastrectomy. Operative approach was open (51.7%, n = 31/60), laparoscopic (43.3%, n = 26/60), or robotic (5.0%, n = 3/60). Anastomotic leak occurred in 6.7% (n = 4/60), while stricture independent of leak was identified in 19.0% (n = 11/58) of patients. Complications occurred in 38.3% (n = 23/60) of patients, of which 52% were classified as Clavien-Dindo grades III-V complications. CONCLUSION In the largest Western series of DST for esophagoenteric anastomoses in gastric cancer surgery, our experience demonstrates that DST is safe and effective with low rates of leak and stricture.


docid: ofuqcxrb

title: In situ split of the liver when portal venous embolization fails to induce hypertrophy: a report of two cases.

text: Introduction. Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been reported as an efficient alternative to portal vein embolization (PVE) to induce growth of the future liver remnant (FLR). This method combines portal vein ligation with splitting of the liver parenchyma. Although shown to be efficient in introducing growth of the FLR and allowing for resection of the deportalized part of the liver one to two weeks after the first operation, this approach carries a significant mortality. Presentation of Case. ALPPS was applied to two elderly patients where PVE failed to stimulate sufficient growth of the FLR. In both cases, subsequent growth of the FLR allowed for successful resection of the liver lesions. The postoperative course was uneventful for both patients. Discussion. In both cases, the growth of the FLR was similar to what was previously reported when ALPPS has been performed, both patients underwent radical resections that would probably not have been safe after only the PVE. Conclusion. ALPPS used as rescue technique when PVE fails to stimulate sufficient growth of the FLR can be expected to deliver similar results as ALPPS "Up front". These cases also suggest that ALPPS is applicable to the elderly population.


title: Gaps to bridge: Misalignment between perception, reality and actions in obesity.

text: AIMS Despite increased recognition as a chronic disease, obesity remains greatly underdiagnosed and undertreated. We aimed to identify international perceptions, attitudes, behaviours and barriers to effective obesity care in people with obesity (PwO) and healthcare professionals (HCPs). MATERIALS AND METHODS An online survey was conducted in 11 countries. Participants were adults with obesity and HCPs who were primarily concerned with direct patient care. RESULTS A total of 14 502 PwO and 2785 HCPs completed the survey. Most PwO (68%) and HCPs (88%) agreed that obesity is a disease. However, 81% of PwO assumed complete responsibility for their own weight loss and only 44% of HCPs agreed that genetics were a barrier. There was a median of three (mean, six) years between the time PwO began struggling with excess weight or obesity and when they first discussed their weight with an HCP. Many PwO were concerned about the impact of excess weight on health (46%) and were motivated to lose weight (48%). Most PwO (68%) would like their HCP to initiate a conversation about weight and only 3% were offended by such a conversation. Among HCPs, belief that patients have little interest in or motivation for weight management may constitute a barrier for weight management conversations. When discussed, HCPs typically recommended lifestyle changes; however, more referrals and follow-up appointments are required. CONCLUSIONS Our international dataset reveals a need to increase understanding of obesity and improve education concerning its physiological basis and clinical management. Realization that PwO are motivated to lose weight offers an opportunity for HCPs to initiate earlier weight management conversations.


title: Impacts of school feeding on educational and health outcomes of school-age children and adolescents in low- and middle-income countries: protocol for a systematic review and meta-analysis.

text: BACKGROUND School feeding programs are beneficial for the physical, mental, and psychosocial development of school-age children and adolescents, particularly those in low- and middle-income countries (LMICs). While school feeding programs are ubiquitous in LMICs, the specific benefits of school feeding programs are unclear. The aim of this systematic review and meta-analysis is to evaluate the impacts of school feeding programs on the educational and health outcomes of children and adolescents in LMICs. METHODS Rigorously designed interventional studies on the impacts of school feeding on nutritional and health outcomes of children and adolescents receiving primary or secondary education in LMICs will be included. The following information sources were used to identify relevant published or unpublished studies: MEDLINE, EMBASE, CINAHL, the Cochrane Library, and governmental or organizational websites. The risk of bias of randomized and non-randomized studies will be assessed using the Cochrane Risk of Bias tool and the ROBINS-I tool, respectively. Two reviewers will independently conduct the selection of studies, data extraction, and assessment of the risk of bias. A narrative synthesis of all the included studies will be provided. Meta-analyses will be performed whenever appropriate. Heterogeneity of effects will be assessed by I2, subgroup analyses, and meta-regression. The certainty of evidence for each outcome will be assessed using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. DISCUSSION The design and implementation of school feeding programs in LMICs should be based on the understanding of the benefits of such programs. This work will provide a crucial evidence base for the educational and health benefits of school feeding on children and adolescents in LMICs. SYSTEMATIC REVIEW REGISTRATION This protocol was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) on November 18, 2019 (registration number: pending).


title: Transanal total mesorectal excision for rectal cancer: a preliminary report.

text: BACKGROUND Currently, the majority cases of the novel down-to-up transanal total mesorectal excision (TaTME) were performed in a hybrid approach with conventional laparoscopic assistance because of less operative difficulty. However, although cases are limited, the successes of TaTME in a pure approach (without laparoscopic assistance) indicate that the costly and less mini-invasive hybrid TaTME could be potentially avoided. METHODS In the present single institutional, prospective study, we attempted to demonstrate the safety and feasibility of this approach in rectal cancer by evaluating the short-term results of our first 20 TaTME cases. For the majority of cases, we adopted a strategy that laparoscopic assistance was not introduced unless it was required during the planned pure TaTME procedure. RESULTS A total of 20 patients (12 males and 8 females) were analyzed in this study, including 11 cases (55 %) of pure TaTME and 9 cases (45 %) of hybrid TaTME. Overall, the median operative time was 200 min (range 70-420), along with a median estimated blood loss of 50 ml (range 20-800). Morbidity rate was 20 % (one urethral injury, two urinary retentions, one anastomotic hemorrhage and one mild anastomotic leak). The median number of harvested lymph nodes was 12 (range 1-20). All specimens were intact in mesorectum without positive distal and circumferential resection margins. Among the 15 patients who were preoperatively scheduled to undertake pure TaTME, four patients (26.7 %) required converting to laparoscopic assistance. Moreover, among these 15 patients, the results of the comparative analysis between female and male subgroups favor the former, suggesting easier operation in them. CONCLUSION This preliminary study demonstrates that TaTME in rectal cancer is safe and feasible. The strategy of not introducing laparoscopic assistance unless it is required while performing the planned pTaTME should be cautiously explored. Further studies with larger sample size and longer follow-up are warranted.


title: Correlation of clot imaging with endovascular recanalization in internal carotid artery terminus occlusion.

text: BACKGROUND AND PURPOSE In a swine stroke model we have previously demonstrated a high-intensity fluid attenuated inversion recovery (FLAIR) signal representing the erythrocyte component of the clot. We hypothesized that the intensity of the FLAIR clot signal in patients with acute stroke may predict the efficacy of recanalization by thrombectomy devices. In this study we compared the pretreatment FLAIR signal intensity of the clots in the distal internal carotid artery (ICA) and the degree of angiographic recanalization rate after mechanical thrombectomy. METHODS 25 consecutive acute stroke patients with ICA terminus (ICA-T) occlusion diagnosed with MRI at the UCLA Medical Center between 2002 and 2013 were retrospectively reviewed. The intensity of the FLAIR clot signal at the distal ICA was blindly compared with the angiographic recanalization status (successful recanalization defined as Thrombolysis In Cerebral Infarction (TICI) score of 2b-3) and non-successful recanalization as TICI score 0-2a) after endovascular treatment. Multivariate logistic regression analysis for successful recanalization was performed. RESULTS Successful recanalization was achieved in 40% of patients (10/25) and showed a significantly higher FLAIR intensity (p=0.014). The cut-off value for clot intensity on the FLAIR sequence to predict recanalization was 0.7952, with 70% sensitivity and 80% specificity (95% CI 0.59 to 0.96) using a receiver operating characteristic curve. In multivariate logistic regression analysis, only a high FLAIR clot intensity (>0.7952) was associated with successful recanalization (OR 16.79; 95% CI 1.29 to 218.92; p=0.031). CONCLUSIONS High signal intensity on FLAIR clot imaging may predict successful recanalization after endovascular therapy for ICA-T occlusion.


title: A Novel Configuration of Pipeline Embolization Device for Internal Carotid Bifurcation Region Aneurysms: Horizontal Deployment.

text: PURPOSE To describe a novel configuration of pipeline embolization device for internal carotid bifurcation region aneurysm, named horizontal stenting. CLINICAL PRESENTATION A 64-year-old woman, with visual deficit, harboring a large wide-necked aneurysm located at the junction between left internal carotid artery and left A1 segment of anterior cerebral artery, was submitted to endovascular treatment. As she had pre-existing occlusion of left internal carotid, approach from the contralateral internal carotid was used to advance the pipeline embolization device through the anterior communicating artery and place the flow diverter horizontally across the neck (from M1 to A1). Coil embolization was also performed through a microcatheter navigated via posterior communicating artery. The intervention was uneventful, with total aneurysm occlusion. Patient presented with visual improvement on follow-up. CONCLUSION Horizontal deployment of pipeline embolization device appears to be an acceptable and feasible alternative to treat internal carotid bifurcation aneurysms. Long-term follow-up and a greater number of cases are mandatory to establish the safety of this strategy.


Delayed referral of pediatric brain tumors during COVID-19 pandemic.


Epidemic insurance broker.


title: The effect of single incision laparoscopic cholecystectomy on systemic oxidative stress: a prospective clinical trial.

text: PURPOSE Single incision laparoscopic cholecystectomy (SILC) has become a more frequently performed method for benign gallbladder diseases all over the world. The effects of SILC technique on oxidative stress have not been well documented. The aim of this study was to evaluate the effect of laparoscopic cholecystectomy techniques on systemic oxidative stress by using ischemia modified albumin (IMA). METHODS In total, 70 patients who had been diagnosed with benign gallbladder pathology were enrolled for this prospective study. Twenty-one patients underwent SILC and 49 patients underwent laparoscopic cholecystectomy (LC). All operations were performed under a standard anesthesia protocol. Serum IMA levels were analysed before operation, 45 minutes and 24 hours after operation. RESULTS Demographics and preoperative characteristics of the patients were similiar in each group. The mean duration of operation was 37.5 ± 12.5 and 44.6 ± 14.3 minutes in LC and SILC group, respectively. In both groups, there was no statistically significant difference in hospital stay, operative time, or conversion to open surgery. Operative technique did not effect the 45th minute and 24th hour IMA levels. However, prolonged operative time (>30 minutes) caused an early increase in the level of IMA. Twenty-fourth hour IMA levels were not different. CONCLUSION SILC is an effective and safe surgical prosedure for benign gallbladder diseases. Independent of the surgical technique for cholecystectomy, the prolonged operative time could increase the tissue ischemia.


docid: surskgus

title: Enhanced molecular dynamics sampling of drug target conformations.

text: Computational docking and virtual screening are two main important methods employed in structure-based drug design. Unlike the traditional approach that allows docking of a flexible ligand against a handful of receptor structures, receptor flexibility has now been appreciated and increasingly incorporated in computer-aided docking. Using a diverse set of receptor conformations increases the chances of finding potential drugs and inhibitors. Molecular dynamics (MD) is greatly useful to generate various receptor conformations. However, the diversity of the structures of the receptor, which is usually much larger than the ligand, depends on the sampling efficiency of MD. Enhanced sampling methods based on accelerated molecular dynamics (aMD) can alleviate the sampling limitation of conventional MD and aid in representation of the phase space to a much greater extent. RaMD-db, a variant of aMD that applies boost potential to the rotatable dihedrals and non-bonded diffusive degrees of freedom has been proven to reproduce the equilibrium properties more accurately and efficiently than aMD. Here, we discuss recent advances in the aMD methodology and review the applicability of RaMD-db as an enhanced sampling method. RaMD-db is shown to be able to generate a broad distribution of structures of a drug target, Cyclophilin A. These structures that have never been observed previously in very long conventional MD can be further used for structure-based computer-aided drug discovery, and docking, and thus, in the identification and design of potential novel inhibitors.


title: Right atrial reduction plasty associated with the cox-maze procedure.

text: We performed a right atrial reduction plasty combined with the Cox-maze procedure in a patient with a giant right atrium and permanent atrial fibrillation. The reduction plasty involved excisions of the redundant atrial wall along two ablation lines of the maze procedure, and excision of the redundant thin septum primum. This procedure achieved a 60% dimension reduction and an 80% volume reduction. The reduced atrial size and sinus rhythm were maintained after 3.5 years.


title: Moderate Certainty Evidence Suggests the Use of High-Flow Nasal Cannula Does Not Decrease Hypoxia When Compared With Conventional Oxygen Therapy in the Peri-Intubation Period: Results of a Systematic Review and Meta-Analysis.

text: OBJECTIVE The role of high-flow nasal cannula during and before intubation is unclear despite a number of randomized clinical trials. Our objective was to conduct a systematic review and meta-analysis examining the benefits of high-flow nasal cannula in the peri-intubation period. DATA SOURCES We performed a comprehensive search of relevant databases (MEDLINE, EMBASE, and Web of Science). STUDY SELECTION We included randomized clinical trials that compared high-flow nasal cannula to other noninvasive oxygen delivery systems in the peri-intubation period. DATA EXTRACTION Our primary outcome was severe desaturation (defined as peripheral oxygen saturation reading < 80% during intubation). Secondary outcomes included peri-intubation complications, apneic time, PaO2 before and after intubation, PaCO2 after intubation, ICU length of stay, and short-term mortality. DATA SYNTHESIS We included 10 randomized clinical trials (n = 1,017 patients). High-flow nasal cannula had no effect on the occurrence rate of peri-intubation hypoxemia (relative risk, 0.98; 95% CI, 0.68-1.42; 0.3% absolute risk reduction, moderate certainty), serious complications (relative risk, 0.87; 95% CI, 0.71-1.06), apneic time (mean difference, 10.3 s higher with high-flow nasal cannula; 95% CI, 11.0 s lower to 31.7 s higher), PaO2 measured after preoxygenation (mean difference, 3.6 mm Hg higher; 95% CI, 3.5 mm Hg lower to 10.7 mm Hg higher), or PaO2 measured after intubation (mean difference, 27.0 mm Hg higher; 95% CI, 13.2 mm Hg lower to 67.2 mm Hg higher), when compared with conventional oxygen therapy. There was also no effect on postintubation PaCO2, ICU length of stay, or 28-day mortality. CONCLUSIONS We found moderate-to-low certainty evidence that the use of high-flow nasal cannula likely has no effect on severe desaturation, serious complications, apneic time, oxygenation, ICU length of stay, or overall survival when used in the peri-intubation period when compared with conventional oxygen therapy.


Suffocating in the eye of the storm: attempting to breathe at the epicentre of New York's COVID-19 pandemic.


title: Totally laparoscopic abdominal wall reconstruction: lessons learned and results of a short-term follow-up.

text: PURPOSE Totally Laparoscopic Abdominal Wall Reconstruction (TLAWR) combines the laparoscopic component separation and the laparoscopic ventral hernia repair, with the purpose of further increasing the benefits of a minimally invasive procedure. However, neither the patient selection criteria nor the long-term results of this technique have been reported. Our objective is to discuss our experience with five patients who received a TLAWR. METHODS All patients with a midline incisional hernia who underwent a TLAWR from September 2008 to October 2009 were retrospectively reviewed for early and late postoperative complications. RESULTS A total of five patients underwent the procedure, with a mean age of 48.6 ± 7.9 years. The mean length of stay was 9.2 ± 5.4 days, and follow-up was 12.3 ± 6.8 months. The mean defect size was 175.8 ± 56.2 cm(2). There were no early or late wound complications. Two patients had an early respiratory complication, and one patient developed a port site hernia and small bowel obstruction early after procedure, which required a re-operation. Three patients (60 %) experienced a recurrence. Possible risk factors for recurrence include previous failed hernia repair, loss of domain, large hernias and close proximity to bony structures. CONCLUSIONS Although TLAWR is feasible and improves wound complications, it may be associated with higher recurrence. Appropriate patient selection is imperative in order for the patient to benefit from this technique.


title: Anatomists' views on human body dissection and donation: an international survey.

text: A survey was conducted to test three hypotheses: anatomists believe that dissection by students conveys not just anatomical knowledge but also essential skills and attitudes, including professionalism; anatomists approve of the donation of their own bodies or body parts/organs for medical/health-care training and research; attitudes towards body dissection and donation are not dependent upon gender or upon the extent of teaching experience, but are related to transcendental convictions relating to beliefs in the afterlife. Eighty-one anatomists, from 29 countries responded to the survey; 80% indicated that they required medical/health-care students to dissect human cadavers (60% females-86% males, p=0.02). Most teachers recorded that dissection was an instrument for training undergraduate students, an instrument for the development of professional skills, and an instrument to help to control emotions in the future doctor rather than being only a means of teaching/learning anatomy facts. Males were more receptive to the concept that dissection helps to control emotions in the future doctor (p=0.02). Most teachers (75%) said they were willing to donate their bodies, 41% saying they would donate body organs only, 9% would donate their entire bodies only, 25% would separately donate organs and also the entire body. The willingness to donate increased significantly with the years of teaching experience (p=0.04). Teachers who were not believers in the afterlife were more likely to donate their organs/bodies than were believers (p=0.03). Our findings showed that anatomists' attitudes towards body dissection and donation are dependent upon gender, upon the extent of teaching experience, and upon transcendental convictions.


title: Diagnosis and management of vertebrobasilar insufficiency.

text: OPINION STATEMENT Understanding the anatomical pathways and clinical presentations for VBI are of the utmost importance due to the potential mimics that may occur. After identification of the entity, imaging must be performed to identify the etiology. Distinguishing external compression of the vertebral artery from intrinsic vascular disease due to atherosclerosis or dissection is critical to aid the clinician in the therapeutic decision tree. Patients with an external compression due to an osteophyte may benefit from definitive surgical decompression and excision of the bony structure. Patients with extracranial disease of the vertebral artery who have failed maximal medical therapy may benefit from angioplasty and stenting which appears to carry a low morbidity. Extracranial vertebral artery dissections can be treated with medical therapy using anti-platelet agents or on occasion anti-coagulation. Rarely, endovascular options are required if a patient is having hemodynamic stroke or TIAs due to flow failure. In such circumstances, stenting and angioplasty may be considered. Intracranial atherosclerosis is best managed with maximal medical therapy due to the high rate of complications attributable to stenting and angioplasty.


title: Positional-scanning fluorigenic substrate libraries reveal unexpected specificity determinants of DUBs (deubiquitinating enzymes).

text: DUBs (deubiquitinating enzymes) are a family of proteases responsible for the specific removal of ubiquitin attached to target proteins and thus control the free cellular pools of this molecule. DUB activity is usually assayed using full-length ubiquitin, and these enzymes generally show low activity towards small substrates that constitute the P4-P1 LRGG (Lys-Arg-Gly-Gly) C-terminal motif of ubiquitin. To gain insight into the C-terminal recognition region of ubiquitin by DUBs, we synthesized positional scanning libraries of fluorigenic tetrapeptides and tested them on three examples of human DUBs [OTU-1 (ovarian tumour 1), Iso-T (isopeptidase T) and UCH-L3 (ubiquitin C-terminal hydrolase L3)] and one viral ubiquitin-specific protease, namely PLpro (papain-like protease) from SARS (severe acute respiratory syndrome) virus. In most cases the results show flexibility in the P4 position, very high specificity for arginine in the P3 position and glycine in the P2 position, in accord with the sequence of the natural substrate, ubiquitin. Surprisingly, screening of the P2 position revealed that UCH-L3, in contrast with all the other tested DUBs, demonstrates substantial tolerance of alanine and valine at P2, and a parallel analysis using the appropriate mutation of the full-length ubiquitin confirms this. We have also used an optimal tetrapeptide substrate, acetyl-Lys-Arg-Gly-Gly-7-amino-4-methylcoumarin, to investigate the activation mechanism of DUBs by ubiquitin and elevated salt concentration. Together, our results reveal the importance of the dual features of (1) substrate specificity and (2) the mechanism of ubiquitin binding in determining deubiquitination by this group of proteases.


title: Human placenta as an ex vivo vascular model for neurointerventional research.

text: BACKGROUND Human placenta is a convenient resource for biomedical research, and has not yet been used for neurointerventional surgery research. OBJECTIVE Our objective was to explore the feasibility of using human placenta to test various endovascular interventions and for training. DESIGN 18 placentas soon after delivery were prepared for six pilot studies. (1) Study on anatomical similarity to human cerebral vessel. (2) Simulation of stent assisted coiling and flow diversion on an aneurysm model. (3) Simulation of intra-arterial thrombolysis. (4) Simulation of embolization of arteriovenous malformation with glues. (5) Simulation of mechanical thrombolysis and comparison of different devices. (6) Vascular model for training of neurointerventionalists. RESULTS When the chorionic plate vessels were compared with the cerebral cortical vessels, similarities were found in vascular branch patterns, histological cross sections, and angiographic appearances. Due to the semitransparency of its vessel wall, performance of flow diverter and stent assisted coiling of an aneurysm could be visualized under direct microscopic observation. Similarly, timing of clot lysis and glue polymerization could be estimated. Endothelial change after thrombectomy could be assessed by histological methods. From these pilot studies, the placenta model could be adopted to simulate various clinical situations. It is also ideal for interventional radiology training. CONCLUSIONS It is feasible to adopt the human placenta as an ex vivo vascular model in neurointerventional surgery research due to the fact that its vessels resemble the brain vasculature.


title: Lead Molecule Prediction and Characterization for Designing MERS-CoV 3C-like Protease Inhibitors: An In silico Approach.

text: BACKGROUND 3C-like protease also called the main protease is an essential enzyme for the completion of the life cycle of Middle East Respiratory Syndrome Coronavirus. In our study we predicted compounds which are capable of inhibiting 3C-like protease, and thus inhibit the lifecycle of Middle East Respiratory Syndrome Coronavirus using in silico methods. METHODS Lead like compounds and drug molecules which are capable of inhibiting 3C-like protease was identified by structure-based virtual screening and ligand-based virtual screening method. Further, the compounds were validated through absorption, distribution, metabolism and excretion filtering. RESULTS Based on binding energy, ADME properties, and toxicology analysis, we finally selected 3 compounds from structure-based virtual screening (ZINC ID: 75121653, 41131653, and 67266079) having binding energy -7.12, -7.1 and -7.08 Kcal/mol, respectively and 5 compounds from ligandbased virtual screening (ZINC ID: 05576502, 47654332, 04829153, 86434515 and 25626324) having binding energy -49.8, -54.9, -65.6, -61.1 and -66.7 Kcal/mol respectively. All these compounds have good ADME profile and reduced toxicity. Among eight compounds, one is soluble in water and remaining 7 compounds are highly soluble in water. All compounds have bioavailability 0.55 on the scale of 0 to 1. Among the 5 compounds from structure-based virtual screening, 2 compounds showed leadlikeness. All the compounds showed no inhibition of cytochrome P450 enzymes, no blood-brain barrier permeability and no toxic structure in medicinal chemistry profile. All the compounds are not a substrate of P-glycoprotein. CONCLUSION Our predicted compounds may be capable of inhibiting 3C-like protease but need some further validation in wet lab.


Response of anti-SARS-CoV-2 total antibodies to nucleocapsid antigen in COVID-19 patients: a longitudinal study.


title: Radiofrequency ablation in the treatment of large hepatic hemangiomas: a comparison of multitined and internally cooled electrodes.

text: OBJECTIVE Radiofrequency (RF) ablation is an accepted nonsurgical treatment of hepatic hemangiomas, but with an appreciable complication rate. Our study aimed to assess the safety and efficacy of RF ablation, administered with either multitined expandable electrodes or with internally cooled cluster electrodes, in the treatment of large (≥10 cm diameter) hepatic hemangiomas. METHODS We retrospectively reviewed our sequential experience of treating 43 large hepatic hemangiomas in 42 patients with RF ablation/multitined expandable electrodes or with RF ablation/internally cooled electrodes. Twenty-two hemangiomas in 21 patients were treated with expandable electrode (multitined electrode group), and 21 hemangiomas in 21 patients were treated with internally cooled cluster electrode (internally cooled electrode group). RESULTS Among the 43 large hepatic hemangiomas, 27 subcapsular lesions were treated by a laparoscopic approach, and 16 lesions located in liver parenchyma were treated by a computed tomography-guided percutaneous approach. In the multitined electrode group, RF ablation treatment was performed in all 21 patients in 1 session. In the internally cooled electrode group, 18 patients were treated by RF ablation in 1 session, and 3 patients, with ≥14.0-cm single hemangioma, were treated with RF ablation in 2 sessions. Complete ablation was achieved in 81.8% (18/22) and 90.5% (19/21) in the multitined electrode group and the internally cooled electrode group, respectively (P>0.05). Ablation time for single hemangioma was shorter with the internally cooled electrode than with the multitined electrode (P<0.05). There were 79 complications related to ablation (2 major and 77 minor) in 31 patients. All 21 patients in the multitined electrode group experienced complications, compared with 10 of 21 patients (47.6%) in the internally cooled electrode group (P<0.05). Both of the 2 major complications occurred in the multitined electrode group. All the complications were treated successfully with conservative measures. CONCLUSIONS RF ablation is a safe and effective treatment for large hepatic hemangiomas. Use of the internally cooled cluster electrodes and a more defensive treatment algorithm can reduce the complications.


title: Reduced cerebrovascular reserve is associated with an increased risk of postoperative ischemic lesions during carotid artery stenting.

text: BACKGROUND Reduced cerebrovascular reserve (CVR) is associated with increased risk of ischemic events in carotid steno-occlusive diseases. OBJECTIVE To determine whether pretreatment CVR can predict postoperative ischemic lesions after carotid artery stenting (CAS) by retrospective analysis. METHODS We retrospectively reviewed the medical records of 46 patients (42 men; mean age 74.2±8.3 years) who underwent CAS and preprocedural cerebral blood flow measurement by quantitative single-photon emission CT. Ischemic lesions were evaluated by diffusion-weighted image (DWI) within 72 h after the intervention. We also evaluated plaque characteristics using black-blood MR plaque imaging. RESULTS New ipsilateral DWI-positive lesions were found in 11 cases (23.9%). Patients were classified into two groups based on the presence or absence of new DWI-positive lesions, and no significant differences in characteristics were found between the DWI-positive and DWI-negative groups, except for age and CVR of the ipsilateral middle cerebral artery (MCA) territory. The DWI-positive group was significantly older than the DWI-negative group (79.7±4.1 vs 72.5±8.6 years; p=0.0085) and had lower average regional CVR (1.4±18.2% vs 22.4±25.8%; p=0.016). MR plaque imaging showed no significant difference in relative overall plaque MR signal intensity between the two groups (1.53±0.37 vs 1.34±0.26; p=0.113). In multivariate logistic regression analysis, lower CVR of the ipsilateral MCA territory (<11%) was the only independent risk factor for new ischemic lesions following CAS (OR=6.99; 95% CI 1.17 to 41.80; p=0.033). CONCLUSIONS Impaired pretreatment CVR was associated with increased incidence of new infarction after CAS.


docid: abxozmze

title: Haemorrhagic enteritis of turkeys - current knowledge.

text: Haemorrhagic enteritis virus (HEV), an adenovirus associated with acute haemorrhagic gastro-intestinal disease of 6-11-week old turkeys predominantly hampers both humoral and cellular immunity. Affected birds are more prone to secondary complications (e.g. colibacillosis and clostridiosis) and failure to mount an effective vaccine-induced immune response. HEV belongs to the new genus Siadenovirus. Feco-oral transmission is the main route of entry of the virus and it mainly colonizes bursa, intestine and spleen. Both naturally occurring virulent and avirulent strains of HEVs are serologically indistinguishable. Recent findings revealed that ORF1, E3 and fib genes are the key factors affecting virulence. The adoption of suitable diagnostic tools, proper vaccination and biosecurity measures have restrained the occurrence of disease epidemics. For diagnostic purposes, the best source of HEV is either intestinal contents or samples from spleen. For rapid detection highly sensitive and specific tests such as quantitative real-time PCR based on Taq man probe has been designed. Avirulent strains of HEV or MSDV can be effectively used as live vaccines. Novel vaccines include recombinant hexon protein-based subunit vaccines or recombinant virus-vectored vaccines using fowl poxvirus (FPV) expressing the native hexon of HEV. Notably, subunit vaccines and recombinant virus vectored vaccines altogether offer high protection against challenge or field viruses. Herein, we converse a comprehensive analysis of the HEV genetics, disease pathobiology, advancements in diagnosis and vaccination along with appropriate prevention and control strategies.


title: Histopathologic and molecular evaluation of the Organ Procurement and Transplantation Network selection criteria for intestinal graft donation.

text: BACKGROUND The Organ Procurement and Transplantation Network (OPTN) has formulated criteria for the selection of donors for intestinal transplantation. To date, however, no study has correlated histologic findings of intestinal injury with the OPTN criteria. We aimed to describe histopathologic and molecular features of allograft injury in relation to donor conditions defined by the OPTN criteria. MATERIALS AND METHODS Graft histology (Park Score), Claudin-3 staining, systemic inflammatory markers (C-reactive protein/lipopolysaccharide-binding protein) and expression of heat shock protein 70, heme oxygenase 1, and interleukin 6 were evaluated in multiorgan deceased donors (donation after brain death [DBD] and donation after cardiac death [DCD]). RESULTS Ninety-seven samples (52 jejunum/45 ileum) were recovered from 59 donors (46 DBD/13 DCD). The OPTN criterion cold ischemia time correlated with histologic injury (Park score) to which the jejunum appeared more susceptible than the ileum. Claudin-3 staining was higher, and heat shock protein 70 expression lower in donors meeting the OPTN criteria compared with donors not meeting the criteria and in DBD versus DCD. In DBD donors, interleukin 6 expression was higher compared with DCD donors and inversely related to C-reactive protein. CONCLUSIONS Our multiparameter analysis suggests that the OPTN criteria can be discriminative concerning intestinal graft quality. Our data suggest that DCD intestinal allografts are qualitatively inferior and that the jejunum is more sensitive to ischemia than the ileum.


title: Cortical thickness is not associated with current depression in a clinical treatment study.

text: BACKGROUND Reduced cortical thickness is a candidate biological marker of depression, although findings are inconsistent. This could reflect analytic heterogeneity, such as use of region-wise cortical thickness based on the Freesurfer Desikan-Killiany (DK) atlas or surface-based morphometry (SBM). The Freesurfer Destrieux (DS) atlas (more, smaller regions) has not been utilized in depression studies. This could also reflect differential gender and age effects. METHODS Cortical thickness was collected from 170 currently depressed adults and 52 never-depressed adults. Visually inspected and approved Freesurfer-generated surfaces were used to extract cortical thickness estimates according to the DK atlas (68 regions) and DS atlas (148 regions) for region-wise analysis (216 total regions) and for SBM. RESULTS Overall, except for small effects in a few regions, the two region-wise approaches generally failed to discriminate depressed adults from nondepressed adults or current episode severity. Differential effects by age and gender were also rare and small in magnitude. Using SBM, depressed adults showed a significantly thicker cluster in the left supramarginal gyrus than nondepressed adults (P = 0.047) but there were no associations with current episode severity. CONCLUSIONS Three analytic approaches (i.e., DK atlas, DS atlas, and SBM) converge on the notion that cortical thickness is a relatively weak discriminator of current depression status. Differential age and gender effects do not appear to represent key moderators. Robust associations with demographic factors will likely hinder translation of cortical thickness into a clinically useful biomarker. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. Hum Brain Mapp 38:4370-4385, 2017. © 2017 Wiley Periodicals, Inc.


Lichenoid drug reaction to antituberculosis drugs treated through with topical steroids and phototherapy.


title: MAVS Expressed by Hematopoietic Cells Is Critical for Control of West Nile Virus Infection and Pathogenesis.

text: UNLABELLED West Nile virus (WNV) is the most important cause of epidemic encephalitis in North America. Innate immune responses, which are critical for control of WNV infection, are initiated by signaling through pathogen recognition receptors, RIG-I and MDA5, and their downstream adaptor molecule, MAVS. Here, we show that a deficiency of MAVS in hematopoietic cells resulted in increased mortality and delayed WNV clearance from the brain. In Mavs(-/-) mice, a dysregulated immune response was detected, characterized by a massive influx of macrophages and virus-specific T cells into the infected brain. These T cells were polyfunctional and lysed peptide-pulsed target cells in vitro However, virus-specific T cells in the brains of infected Mavs(-/-) mice exhibited lower functional avidity than those in wild-type animals, and even virus-specific memory T cells generated by prior immunization could not protect Mavs(-/-) mice from WNV-induced lethal disease. Concomitant with ineffective virus clearance, macrophage numbers were increased in the Mavs(-/-) brain, and both macrophages and microglia exhibited an activated phenotype. Microarray analyses of leukocytes in the infected Mavs(-/-) brain showed a preferential expression of genes associated with activation and inflammation. Together, these results demonstrate a critical role for MAVS in hematopoietic cells in augmenting the kinetics of WNV clearance and thereby preventing a dysregulated and pathogenic immune response. IMPORTANCE West Nile virus (WNV) is the most important cause of mosquito-transmitted encephalitis in the United States. The innate immune response is known to be critical for protection in infected mice. Here, we show that expression of MAVS, a key adaptor molecule in the RIG-I-like receptor RNA-sensing pathway, in hematopoietic cells is critical for protection from lethal WNV infection. In the absence of MAVS, there is a massive infiltration of myeloid cells and virus-specific T cells into the brain and overexuberant production of proinflammatory cytokines. These results demonstrate the important role that MAVS expression in hematopoietic cells has in regulating the inflammatory response in the WNV-infected brain.


docid: rwcvkhiy

title: Impact of COVID-19 pandemic on paediatric services at a referral centre in Pakistan: lessons from a low-income and middle-income country setting.


title: A survey of current practice of vascular surgeons in venous disease management.

text: OBJECTIVE Acute venous thromboembolism and chronic venous diseases are common conditions that affect a large proportion of the United States population. The diagnosis of venous disease has improved, and the treatment options have rapidly evolved over the past decade. To date, it is unclear to what extent vascular surgeons have become involved in the modern management of venous disorders. This survey was undertaken to explore the current interest and practice of vascular surgeons in the contemporary care of venous disease. METHODS A survey was administered via a web-based platform to active and candidate members of the Society for Vascular Surgery (SVS). The survey included 30 questions investigating the characteristics of venous surgeons and scope of venous practice. Open-ended questions were also included for commentary. RESULTS A total of 1879 surveys were sent to SVS members nationwide, and 385 members participated (response rate of 20.5%). The participants were mostly men (89.6%) with 37.7% practicing in an academic setting and 59.2% in private practice. The respondents treated superficial veins (92.9%) and deep veins (85.8%) in clinical practice, with 89.9% having their own vascular laboratory. A wide spectrum of interventions for superficial (91.9%), deep (85.8%), and perforator veins (52.7% endovenous, 19.4% subfascial endoscopic perforator surgery) are being performed by respondents. Only 26.2% had learned endovenous thermal ablation in their training program; however, over 96% of those performing venous interventions utilized this technique. Overall, the majority (85.5%) devoted 50% or less of practice to venous disorders. Respondents indicated that limitations to expansion of vein practices mainly involved challenges with third party payers, local competition, and existing large volumes of arterial interventions needing to be performed. Despite the widespread incorporation of venous disease into current vascular practices, 66.1% are not members of the American Venous Forum (AVF) or other venous society. Many believe there is still a lack of standardization of care and guidelines for venous disease. CONCLUSIONS The care of patients with venous disease has become more widespread among SVS members, with most offering both deep and superficial venous interventions as well as incorporation of minimally invasive techniques into their treatment armamentarium. Dissemination and incorporation of protocols and guidelines into clinical practice as well as postgraduate courses in venous disease may be areas in which the SVS could facilitate members' involvement in the care of patients with venous disease.


title: Social representations, identity threat, and coping amid COVID-19.

text: This article describes an integrative social psychological framework within which human reactions to COVID-19 can be understood and predicted. It is argued that social representations of COVID-19 (and its mitigation strategies) must resonate among diverse communities, not be too threatening, and provide clear pathways for action and engagement. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Science in the time of COVID-19.


title: Impact of balanced versus unbalanced fluid resuscitation on clinical outcomes in critically ill children: protocol for a systematic review and meta-analysis.

text: BACKGROUND Isotonic crystalloid fluid bolus therapy is used in critically ill children to restore or maintain hemodynamic stability. However, the ideal choice of crystalloid remains to be determined. The most easily available and most frequently used crystalloid is 0.9% saline, an unbalanced crystalloid, that has been associated with hyperchloremic metabolic acidosis and acute kidney injury (AKI). Balanced fluids such as Ringer's lactate (RL) were developed to be closer to the composition of serum. However, they are more expensive and less readily available than 0.9% saline. Few trials have found RL to be associated with more favorable outcomes, but pediatric data is limited and inconsistent. The objective of the present systematic review is to review existing literature to determine the effect of balanced versus unbalanced fluid bolus therapy on metabolic acidosis in critically ill children. METHODS Using the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines, we will conduct a systematic review to retrieve all controlled trials and observational studies comparing balanced and unbalanced resuscitative fluids in critically ill children from age 28 days to 18 years old in any resuscitation settings. Search strategy was developed in collaboration with an experienced clinical research librarian. The primary outcome is the incidence and/or time to resolution of metabolic acidosis. Secondary outcomes included the incidence of hyperchloremia, AKI, duration of renal replacement therapy, vasopressors, mechanical ventilation, total volume of rehydration needed per day, extracorporeal membrane oxygenation, and length of stay and mortality. Study screening, inclusion, data extraction, and assessment of risk of bias will be performed independently by two authors. We intend to perform a meta-analysis with studies that are compatible on the basis of population and outcomes. DISCUSSION Isotonic crystalloid fluid bolus therapy is a ubiquitous treatment in resuscitation of critically ill pediatric patients and yet there is no clear recommendation to support the choice of balanced versus unbalanced fluid. The present review will summarize current available data in the literature and assess whether recommendations can be generated regarding the choice of crystalloids or otherwise identify knowledge gaps which will open the door to a large-scale randomized controlled trial (RCT).


Pandemics show us what government is for.


title: [Technical guideline for disinfection of wastewater and wastes of medical organizations during COVID-19 outbreak].

text: This technical guideline is applicable to disinfection of wastewater and wastes of medical organizations during COVID-19 outbreak. The purpose of the guideline is to eliminate various pathogenic bacteria, fungi, and viruses, effectively block the virus transmission pathways, and guide medical organizations to carry out the prevention and control of COVID-19.


docid: hulgvfjj

title: Clinical strategies for treating pediatric cancer during the outbreak of 2019 novel coronavirus infection.


Covid-19: democracy and hard choices in public health.


title: Randomised clinical trial: enteral nutrition does not improve the long-term outcome of alcoholic cirrhotic patients with jaundice.

text: BACKGROUND Malnutrition and jaundice are independent prognostic factors in cirrhosis. AIM To assess the impact of enteral nutrition on the survival of alcoholic cirrhotic patients with jaundice but without acute alcoholic hepatitis. METHODS The study was a multicentre prospective randomised controlled trial comparing effects of enteral nutrition vs. a symptomatic support in patients with alcoholic cirrhosis and jaundice (bilirubin ≥51 µmol/L) but without severe acute alcoholic hepatitis. A total of 99 patients were randomised to receive either the conventional symptomatic treatment (55 patients) or the symptomatic support associated with 35 kcal/Kg/day of enteral nutrition during 4 weeks followed by an oral nutritional support during 2 months (44 patients). Randomisation was stratified on nutritional status. One-year survival curves were compared using the Kaplan-Meier method and Logrank test. RESULTS Populations in both arms were similar. One-year survival was similar in the overall population (27/44 patients (61.4%) in the enteral nutrition arm vs. 36/55 (65.5%) in the control arm; Logrank P = 0.60) and in the subgroup suffering from malnutrition [18/29 patients (62.1%) in the enteral nutrition arm vs. 20/32 (62.5%) in the control arm; Logrank P = 0.99]. There was no statistical difference for bilirubin, prothrombin rate, Child-Pugh score, albumin or nutritional assessment. Complications during treatment (bleeding, encephalopathy, infection) occurred in 23% of patients in the enteral nutrition group (10/44) vs. 16% (9/55) of the control patients (P = 0.59). CONCLUSION Enteral nutrition does not improve the survival and hepatic or nutritional parameters of cirrhotic patients with jaundice.


title: Severe metapneumovirus infections among immunocompetent and immunocompromised patients admitted to hospital with respiratory infection.

text: Human metapneumovirus (hMPV) is considered an important cause of acute respiratory infections. hMPV can cause morbidity in hematopoietic stem cell transplant recipients and recent research has demonstrated that it is an important virus in patients admitted to hospital with respiratory infections and suspected of having pandemic 2009 influenza A (H1N1pdm09) virus. The purpose of this study was to investigate infections caused by hMPV in two groups of patients admitted to hospital: Immunocompromized patients with a potential risk of severe outcomes and immunocompetent patients with severe acute respiratory syndrome. A total of 288 samples were tested: 165 samples were collected from patients with suspected influenza A (H1N1) pdm09 infection during the first pandemic wave in 2009; and 123 samples were collected from patients of a hematopoietic stem cell transplantation program in 2008-2009. Amplification of the hMPV genes was performed by polymerase chain reaction. This was followed by sequencing and phylogenetic analysis. hMPV was detected in 14.2% (41/288) of all samples: 17% (28/165) of immunocompetent patients with suspected H1N1 infection and 10.6% (13/123) among hematopoietic stem cell transplant recipients. hMPV accounted for 12.1% (8/66) of immunocompetent adults patients with severe respiratory infections (median age, 55.9 years). Two hMPV subtypes were identified, A2 (26.9%; 7/26) and B2 (73.1%; 19/26) but no difference was observed between the patient groups in terms of age or immunosuppression level. This study highlights the significance of hMPV in immunocompetent adult patients with severe infections and further investigations are recommended for understanding the impact of this virus.


title: Periprocedural cost-effectiveness analysis of mechanical thrombectomy for acute ischemic stroke in the stent retriever era.

text: BACKGROUND Early reperfusion is critical for favorable outcomes in acute ischemic stroke (AIS). Stent retrievers lead to faster and more complete reperfusion than previous technologies. Our aim is to compare the cost-effectiveness of stent retrievers to the previous mechanical thrombectomy devices. METHODS Retrospective review of endovascularly treated large-vessel AIS. Data from all consecutive patients who underwent thrombectomy from January 2012 through November 2012 were collected. Baseline characteristics, the total procedural cost, the rates of successful recanalization [modified thrombolysis in cerebral ischemia (mTICI) scores of 2b or 3], and the length of stay at the hospital were compared between the stent retriever (SR) and the non-stent retriever (NSR) groups. RESULTS After excluding the patients who underwent concomitant extracranial stenting (n = 22) or received intra-arterial tissue plasminogen activator only (n = 6), the entire cohort included 150 patients. The cost of the reperfusion procedure was significantly higher in the SR compared to the NSR group (USD 13,419 vs. 9,308, p <0.001). We were unable to demonstrate a statistically significant difference in the rates of mTICI 2b/3 reperfusion (81 vs. 74%, p = 0.337) or the length of stay (11.1 ± 9.1 vs. 12.8 ± 9.6 days, p = 0.260) amongst the SR and the NSR patients. CONCLUSION The procedural costs of thrombectomy for AIS are increasing and account for the bulk of hospitalization reimbursement. The impact of these expenditures in the long-term sustainability of stroke centers deserves greater consideration. While it is likely that the SR technology results in higher rates of optimal reperfusion, better clinical outcomes, and shorter lengths of stay, larger studies are needed to prove its cost-effectiveness.


title: Systematic review of risk prediction models for diabetes after bariatric surgery.

text: BACKGROUND Diabetes remission is an important outcome after bariatric surgery. The purpose of this study was to identify risk prediction models of diabetes remission after bariatric surgery. METHODS A systematic literature review was performed in MEDLINE, MEDLINE-In-Process, Embase and the Cochrane Central Register of Controlled Trials databases in April 2015. All English-language full-text published derivation and validation studies for risk prediction models on diabetic outcomes after bariatric surgery were included. Data extraction included population, outcomes, variables, intervention, model discrimination and calibration. RESULTS Of 2330 studies retrieved, eight met the inclusion criteria. Of these, six presented development of risk prediction models and two reported validation of existing models. All included models were developed to predict diabetes remission. Internal validation using tenfold validation was reported for one model. Two models (ABCD score and DiaRem score) had external validation using independent patient cohorts with diabetes remission assessed at 12 and 14 months respectively. Of the 11 cohorts included in the eight studies, calibration was not reported in any cohort, and discrimination was reported in two. CONCLUSION A variety of models are available for predicting risk of diabetes following bariatric surgery, but only two have undergone external validation.


title: Impact of bacterial culture positivity of the drainage fluid during the early postoperative period on the development of intra-abdominal abscesses after gastrectomy.

text: PURPOSE The aim of this study was to evaluate the impact of positive bacterial cultures of the drainage fluid (D-cultures) during the early postoperative period on the incidence of intra-abdominal abscess formation following gastrectomy. METHODS From January 2012 to June 2013, we prospectively performed D-cultures on postoperative day (POD) 1 in consecutive gastric cancer patients who underwent gastrectomy. The univariate and multivariate analyses were performed to identify the risk factors for intra-abdominal abscess formation without anastomotic leakage. RESULTS The rate of positive D-cultures was 6.4 % on POD 1. According to a univariate analysis, the use of combined organ resection (P = 0.011), the drain amylase level on POD 1 (P = 0.016) and the D-culture status on POD 1 (P = 0.004) were found to be significantly associated with the incidence of intra-abdominal abscesses. A multivariate analysis demonstrated that D-culture positivity on POD 1 was the only independent predictor of intra-abdominal abscess formation (P = 0.011). CONCLUSIONS The present study demonstrated that bacterial culture positivity of drainage fluid during the early postoperative period has a significant impact on the development of intra-abdominal abscesses after gastrectomy.


title: DWI reversal is associated with small infarct volume in patients with TIA and minor stroke.

text: BACKGROUND AND PURPOSE More than half of patients with TIA/minor stroke have ischemic lesions on early DWI, which represent irreversibly damaged tissue. The presence and volume of DWI lesions predict early deterioration in this population. We aimed to study the rate and implications of DWI reversal in patients with TIA/minor stroke. MATERIALS AND METHODS Patients with TIA/minor stroke were prospectively enrolled and imaged within 24 hours of onset. Patients were followed for 3 months with repeat MR imaging either at day 30 or 90. Baseline DWI/PWI and follow-up FLAIR final infarct volumes were measured. RESULTS Of 418 patients included, 55.5% had DWI and 37% had PWI (time-to-peak of the impulse response ≥2 seconds' delay) lesions at baseline. The median time from symptom onset to baseline and follow-up imaging was 13.4 (interquartile range, 12.7) and 78.73 hours (interquartile range, 60.2), respectively. DWI reversal occurred in 5.7% of patients. The median DWI lesion volume was significantly smaller in those with reversal (0.26 mL, interquartile range = 0.58 mL) compared with those without (1.29 mL, interquartile range = 3.6 mL, P = .002); 72.7% of DWI reversal occurred in cortically based lesions. Concurrent tissue hypoperfusion (time-to-peak of the impulse response ≥2 seconds) was seen in 36.4% of those with DWI reversal versus 62.4% without (P = .08). DWI reversal occurred in 3.3% of patients with penumbral patterns (time-to-peak of the impulse response ≥6 seconds - DWI) > 0 and in 6.8% of those without penumbral patterns (P = .3). The severity of hypoperfusion, defined as greater prolongation of time-to-peak of the impulse response (≥2, ≥4, ≥6, ≥8 seconds), did not affect the likelihood of DWI reversal (linear trend, P = .147). No patient with DWI reversal had an mRS score of ≥2 at 90 days versus 18.2% of those without reversal (P = .02). CONCLUSIONS DWI reversal is uncommon in patients with TIA/minor stroke and is more likely to occur in those with smaller baseline lesions. DWI reversal should not have a significant effect on the accuracy of penumbra definition.


docid: gtdonvuo

title: Incisional hernia after single-incision laparoscopic cholecystectomy: incidence and predictive factors.

text: AIM To access the incidence and predictive factors of incisional hernia after single-incision laparoscopic cholecystectomy (SILC). METHODS Eighty-two consecutive patients operated on for uncomplicated cholelithiasis between 2009 and 2013 were eligible for the study. Clinical outcome was assessed by a combination of case notes review, office consultation and telephone interview. Long-term incisional hernia rate was the major outcome of the study. Secondary outcome was the evaluation of predictive factors. Univariate and multivariate statistical analyses were performed using the following variables: age, gender, ASA score, BMI, risk, or comorbidity factors and surgical site infection. RESULTS Six patients (7 %) were lost to follow-up after the 1-month office visit and excluded. The study group consisted of 16 men and 60 women with a median age of 42 years (range 18-69) and a BMI of 25 (range 19-34). Eight patients had risk or comorbidity factors, 46 were classified ASA I, and 30 ASA II. Early postoperative course was uneventful in all cases but two patients developed a superficial wound abscess after hospital discharge. With a median follow-up of 44 months (range 12-72), incisional hernia was noted in six patients (7.9 %). Multivariate logistic analysis revealed that age (OR 1.08, 95 % CI 1.00-1.16, p < 0.038) and BMI (OR 1.37, 95 % CI 1.03-1.82, p < 0.029) were independent predictive factors of developing an incisional hernia. The incidence of hernia was, respectively, 15 % in patients with an age ≥ 50 and 33 % in patients with a BMI ≥ 30. CONCLUSION After SILC, we noted an incisional hernia rate of 8 %. To decrease the risk of developing that specific complication, SILC should only be proposed to young and non-obese patients.


title: Detecting and controlling foodborne infections in humans: lessons for China from the United States experience.

text: In the past 50 years, the United States has made major advances in human health surveillance, research and outbreak investigation that have helped reduce microbial contamination of food. In China, food safety has emerged as one of the country's most prominent domestic concerns, but there has been limited investment in surveillance, inter-agency coordination, outbreak investigation and data synthesis. After large outbreaks of Salmonella in the 1960s and E. coli O157:H7 in the 1990s, the United States transformed its approach to detecting and investigating foodborne infections, including deployment of a national, laboratory-based surveillance system that uses molecular subtyping. In China, the absence of a national, laboratory-based surveillance system means that it is difficult to rapidly detect a widely dispersed foodborne infection outbreak or the emergence of new foodborne infections. Based on lessons learned in the United States, we propose policy and administrative changes that China can adopt to strengthen detection and control of foodborne infections.


title: Identification of new ligands for the methionine biosynthesis transcriptional regulator (MetJ) by FAC-MS.

text: We have developed a high-throughput approach using frontal affinity chromatography coupled to mass spectrometry (FAC-MS) for the identification and characterization of the small molecules that modulate transcriptional regulator (TR) binding to TR targets. We tested this approach using the methionine biosynthesis regulator (MetJ). We used effector mixtures containing S-adenosyl-L-methionine (SAM) and S-adenosyl derivatives as potential ligands for MetJ binding. The differences in the elution time of different compounds allowed us to rank the binding affinity of each compound. Consistent with previous results, FAC-MS showed that SAM binds to MetJ with the highest affinity. In addition, adenine and 5'-deoxy-5'-(methylthio)adenosine bind to the effector binding site on MetJ. Our experiments with MetJ demonstrate that FAC-MS is capable of screening complex mixtures of molecules and identifying high-affinity binders to TRs. In addition, FAC-MS experiments can be used to discriminate between specific and nonspecific binding of the effectors as well as to estimate the dissociation constant (K(d)) for effector-TR binding.


title: Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial.

text: BACKGROUND Findings from the Look AHEAD trial showed no significant reductions in the primary outcome of cardiovascular disease incidence in adults with type 2 diabetes randomly assigned to an intensive lifestyle intervention for weight loss compared with those randomly assigned to diabetes support and education (control). We examined whether the incidence of cardiovascular disease in Look AHEAD varied by changes in weight or fitness. METHODS Look AHEAD was a randomised clinical trial done at 16 clinical sites in the USA, recruiting patients from Aug 22, 2001, to April 30, 2004. In the trial, 5145 overweight or obese adults aged 45-76 years with type 2 diabetes were assigned (1:1) to an intensive lifestyle intervention or diabetes support and education. In this observational, post-hoc analysis, we examined the association of magnitude of weight loss and fitness change over the first year with incidence of cardiovascular disease. The primary outcome of the trial and of this analysis was a composite of death from cardiovascular causes, non-fatal acute myocardial infarction, non-fatal stroke, or admission to hospital for angina. The secondary outcome included the same indices plus coronary artery bypass grafting, carotid endartectomy, percutaneous coronary intervention, hospitalisation for congestive heart failure, peripheral vascular disease, or total mortality. We adjusted analyses for baseline differences in weight or fitness, demographic characteristics, and risk factors for cardiovascular disease. The Look AHEAD trial is registered with ClinicalTrials.gov, number NCT00017953. FINDINGS For the analyses related to weight change, we excluded 311 ineligible participants, leaving a population of 4834; for the analyses related to fitness change, we excluded 739 participants, leaving a population of 4406. In analyses of the full cohort (ie, combining both study groups), over a median 10·2 years of follow-up (IQR 9·5-10·7), individuals who lost at least 10% of their bodyweight in the first year of the study had a 21% lower risk of the primary outcome (adjusted hazard ratio [HR] 0·79, 95% CI 0·64-0·98; p=0·034) and a 24% reduced risk of the secondary outcome (adjusted HR 0·76, 95% CI 0·63-0·91; p=0·003) compared with individuals with stable weight or weight gain. Achieving an increase of at least 2 metabolic equivalents in fitness change was associated with a significant reduction in the secondary outcome (adjusted HR 0·77, 95% CI 0·61-0·96; p=0·023) but not the primary outcome (adjusted HR 0·78, 0·60-1·03; p=0·079). In analyses treating the control group as the reference group, participants in the intensive lifestyle intervention group who lost at least 10% of their bodyweight had a 20% lower risk of the primary outcome (adjusted HR 0·80, 95% CI 0·65-0·99; p=0·039), and a 21% lower risk of the secondary outcome (adjusted HR 0·79, 95% CI 0·66-0·95; p=0·011); however, change in fitness was not significantly associated with a change in the primary outcome. INTERPRETATION The results of this post-hoc analysis of Look AHEAD suggest an association between the magnitude of weight loss and incidence of cardiovascular disease in people with type 2 diabetes. These findings suggest a need to continue to refine approaches to identify individuals who are most likely to benefit from lifestyle interventions and to develop strategies to improve the magnitude of sustained weight loss with lifestyle interventions. FUNDING US National Institute of Diabetes and Digestive and Kidney Diseases.


title: Attenuation and restoration of severe acute respiratory syndrome coronavirus mutant lacking 2'-o-methyltransferase activity.

text: UNLABELLED The sudden emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and, more recently, Middle Eastern respiratory syndrome CoV (MERS-CoV) underscores the importance of understanding critical aspects of CoV infection and pathogenesis. Despite significant insights into CoV cross-species transmission, replication, and virus-host interactions, successful therapeutic options for CoVs do not yet exist. Recent identification of SARS-CoV NSP16 as a viral 2'-O-methyltransferase (2'-O-MTase) led to the possibility of utilizing this pathway to both attenuate SARS-CoV infection and develop novel therapeutic treatment options. Mutations were introduced into SARS-CoV NSP16 within the conserved KDKE motif and effectively attenuated the resulting SARS-CoV mutant viruses both in vitro and in vivo. While viruses lacking 2'-O-MTase activity had enhanced sensitivity to type I interferon (IFN), they were not completely restored in their absence in vivo. However, the absence of either MDA5 or IFIT1, IFN-responsive genes that recognize unmethylated 2'-O RNA, resulted in restored replication and virulence of the dNSP16 mutant virus. Finally, using the mutant as a live-attenuated vaccine showed significant promise for possible therapeutic development against SARS-CoV. Together, the data underscore the necessity of 2'-O-MTase activity for SARS-CoV pathogenesis and identify host immune pathways that mediate this attenuation. In addition, we describe novel treatment avenues that exploit this pathway and could potentially be used against a diverse range of viral pathogens that utilize 2'-O-MTase activity to subvert the immune system. IMPORTANCE Preventing recognition by the host immune response represents a critical aspect necessary for successful viral infection. Several viruses, including SARS-CoV, utilize virally encoded 2'-O-MTases to camouflage and obscure their viral RNA from host cell sensing machinery, thus preventing recognition and activation of cell intrinsic defense pathways. For SARS-CoV, the absence of this 2'-O-MTase activity results in significant attenuation characterized by decreased viral replication, reduced weight loss, and limited breathing dysfunction in mice. The results indicate that both MDA5, a recognition molecule, and the IFIT family play an important role in mediating this attenuation with restored virulence observed in their absence. Understanding this virus-host interaction provided an opportunity to design a successful live-attenuated vaccine for SARS-CoV and opens avenues for treatment and prevention of emerging CoVs and other RNA virus infections.


docid: ryizurmk

title: Use of transaortic, transapical, and transcarotid transcatheter aortic valve replacement in inoperable patients.

text: BACKGROUND Transcatheter aortic valve replacement (TAVR) is an effective treatment in patients with severe aortic stenosis unsuitable for surgical aortic valve replacement (SAVR). This study evaluated the early experience with the posttrial application of TAVR, with specific focus on non-transfemoral (TF) access. METHODS All patients who underwent posttrial TAVR at Emory University from November 2011 to April 2012 were reviewed. During this time, 44 posttrial TAVRs were performed: TF in 18, transapical in 11, transaortic in 12, and transcarotid in 3. RESULTS A total of 40.9% of all patients were candidates for TF implantation. Mean age was 78.2 ± 11.3 years, and 34.1% were women. Mean ejection fraction was 0.463 ± 0.164, and 90.2% had New York Heart Association class III to IV heart failure. Fifty percent were diabetic, 27.3% had moderate to severe chronic obstructive pulmonary disease, and 20.5% had a prior stroke. The mean creatinine was 1.63 ± 1.74 mg/dL, 9.1% required preoperative dialysis, and 61.4% had undergone prior cardiac operations. No patients had postoperative myocardial infarction, stroke, or required new dialysis. Intraoperative vascular complications occurred in 11.4%. No patient had more than mild perivalvular leak by transthoracic echocardiography at discharge. Mean postoperative ventilator time was 17.8 ± 40.1 hours. Intensive care unit length of stay was 58.0 ± 67.0 hours. Postoperative hospital length of stay was 6.1 ± 4.7 days. The 30-day mortality was 6.8% (3 of 44) for all patients, despite a mean The Society of Thoracic Surgeons Predicted Risk of Mortality score of 12.6. CONCLUSIONS Less than half of patients deemed appropriate for posttrial TAVR were candidates for TF implantation. The use of all available access routes leads to excellent outcomes in patients deemed inoperable.


title: Changes in cerebral autoregulation in the second half of pregnancy and compared to non-pregnant controls.

text: OBJECTIVE The mechanism by which pregnancy affects the cerebral circulation is unknown, but it has a central role in the development of neurological complications in preeclampsia, which is believed to be related to impaired autoregulation. We evaluated the cerebral autoregulation in the second half of pregnancy, and compared this with a control group of healthy, fertile non-pregnant women. METHODS In a prospective cohort analysis, cerebral blood flow velocity of the middle cerebral artery (determined by transcranial Doppler), blood pressure (noninvasive arterial volume clamping), and end-tidal carbon dioxide (EtCO2) were simultaneously collected for 7min. The autoregulation index (ARI) was calculated. ARI values of 0 and 9 indicated absent and perfect autoregulation, respectively. ANOVA and Pearson's correlation coefficient were used, with p<0.05 considered significant. RESULTS A total of 76 pregnant and 18 non-pregnant women were included. The ARI did not change during pregnancy, but pregnant women had a significantly higher ARI than non-pregnant controls (ARI 6.7±0.9 vs. 5.3±1.4, p<0.001). This remained significant after adjusting for EtCO2 (p<0.001). CONCLUSION Cerebral autoregulation functionality is enhanced in the second half of pregnancy, when compared to non-pregnant fertile women, even after controlling for EtCO2. The autoregulation does not change with advancing gestational age.


title: Bipolar Sealing Device Use in Pancreas Graft Preparation: A Novel Tieless Backtable Surgery Technique.

text: Supplemental digital content is available in the text.


title: Respiratory RNA Viruses.

text: Acute upper and lower respiratory infections are a major public health problem and a leading cause of morbidity and mortality worldwide. At greatest risk are young children, the elderly, the chronically ill, and those with suppressed or compromised immune systems. Viruses are the predominant cause of respiratory tract illnesses and include RNA viruses such as respiratory syncytial virus, influenza virus, parainfluenza virus, metapneumovirus, rhinovirus, and coronavirus. Laboratory testing is required for a reliable diagnosis of viral respiratory infections, as a clinical diagnosis can be difficult since signs and symptoms are often overlapping and not specific for any one virus. Recent advances in technology have resulted in the development of newer diagnostic assays that offer great promise for rapid and accurate detection of respiratory viral infections. This chapter emphasizes the fundamental characteristics and clinical importance of the various RNA viruses that cause upper and lower respiratory tract diseases in the immunocompromised host. It highlights the laboratory methods that can be used to make a rapid and definitive diagnosis for the greatest impact on the care and management of ill patients, and the prevention and control of hospital-acquired infections and community outbreaks.


title: Evaluation of bone regeneration using the rat critical size calvarial defect.

text: Animal models that are reliably reproducible, appropriate analogs to the clinical condition they are used to investigate, and that offer minimal morbidity and periprocedural mortality to the subject, are the keystone to the preclinical development of translational technologies. For bone tissue engineering, a number of small animal models exist. Here we describe the protocol for one such model, the rat calvarial defect. This versatile model allows for evaluation of biomaterials and bone tissue engineering approaches within a reproducible, non-load-bearing orthotopic site. Crucial steps for ensuring appropriate experimental control and troubleshooting tips learned through extensive experience with this model are provided. The surgical procedure itself takes ∼30 min to complete, with ∼2 h of perioperative care, and tissue collection is generally performed 4-12 weeks postoperatively. Several analytical techniques are presented, which evaluate the cellular and extracellular matrix components, functionality and mineralization, including histological, mechanical and radiographic methods.


Circulation of QX-like infectious bronchitis virus in the Middle East.


title: The emergence and diversification of panzootic H5N1 influenza viruses.

text: The Asian highly pathogenic avian influenza H5N1 virus was first detected in the goose population of Guangdong, China in 1996. The viruses in this lineage are unique in their ecological success, demonstrating an extremely broad host range and becoming established in poultry over much of Asia and in Africa. H5N1 viruses have also diverged into multiple clades and subclades that generally do not cross neutralize, which has greatly confounded control measures in poultry and pre-pandemic vaccine strain selection. Although H5N1 viruses currently cannot transmit efficiently between mammals they exhibit high mortality in humans and recent experimental studies have shown that it is possible to generate an H5N1 virus that is transmissible in mammals. In addition to causing unprecedented economic losses, the long-term presence of the H5N1 virus in poultry and its frequent introductions to humans continue to pose a significant pandemic threat. Here we provide a summary of the genesis, molecular epidemiology and evolution of this H5N1 lineage, particularly the factors that have contributed to the continued diversification and ecological success of H5N1 viruses, with particular reference to the poultry production systems they have emerged from.


title: Increased Post-procedural Non-gastrointestinal Adverse Events After Outpatient Colonoscopy in High-risk Patients.

text: BACKGROUND & AIMS The incidence and predictors of non-gastrointestinal (GI) adverse events (AEs) after colonoscopy are not well-understood. We studied the effects of antithrombotic agents, cardiopulmonary comorbidities, and age on risk of non-GI AEs after colonoscopy. METHODS We performed a retrospective longitudinal analysis to assess the diagnosis, procedure, and prescription drug codes in a United States commercial claims database (March 2010-March 2012). Data from patients at increased risk (n = 82,025; defined as patients with pulmonary comorbidities or cardiovascular disease requiring antithrombotic medications) were compared with data from 398,663 average-risk patients. In a 1:1 matched analysis, 51,932 patients at increased risk, examined by colonoscopy, were compared with 51,932 matched (on the basis of age, sex, and comorbidities) patients at increased risk who did not undergo colonoscopy. We tracked cardiac, pulmonary, and neurovascular events 1-30 days after colonoscopy. RESULTS Thirty days after outpatient colonoscopy, non-GI AEs were significantly higher in patients taking antithrombotic medications (7.3%; odds ratio [OR], 10.75; 95% confidence interval, 10.13-11.42) or those with pulmonary comorbidities (1.8%; OR, 2.44; 95% confidence interval, 2.27-2.62) vs average-risk patients (0.7%) and in patients 60-69 years old (OR, 2.21; 95% confidence interval, 2.01-2.42) or 70 years or older (OR, 6.45; 95% confidence interval, 5.89-7.06), compared with patients younger than 50 years. The 30-day incidence of non-GI AEs in patients at increased risk who underwent colonoscopy was also significantly higher than in matched patients at increased risk who did not undergo colonoscopy in the anticoagulant group (OR, 2.31; 95% confidence interval, 2.01-2.65) and in the chronic obstructive pulmonary disease group (OR, 1.33; 95% confidence interval, 1.13-1.56). CONCLUSIONS Increased number of comorbidities and older age (older than 60 years) are associated with increased risk of non-GI AEs after colonoscopy. These findings indicate the importance of determining comorbid risk and evaluating antithrombotic management before colonoscopy.


title: Comparison of heart rate and oxygen saturation measurements from Masimo and Nellcor pulse oximeters in newly born term infants.

text: AIM To compare heart rate (HR) measurements from Masimo and Nellcor pulse oximeters (POs) against HR measured via a three lead electrocardiograph (ECG) (HRECG ). We also compared peripheral oxygen saturation (SpO2 ) measurements between Nellcor and Masimo oximeters. METHOD Term infants born via elective caesarean section were studied. ECG leads were placed on the infant's chest and abdomen. Masimo and Nellcor PO sensors were randomly allocated to either foot. The monitors were placed on a trolley, and data from each monitor screen captured by a video camera. HR, SpO2 measurements and signal quality were extracted. Bland-Altman analysis was used to determine agreement between HR from the ECG and each oximeter, and between SpO2 from the oximeters. RESULTS We studied 44 infants of whom 4 were resuscitated. More than 8000 pairs of observations were used for each comparison of HR and SpO2. The mean difference (±2SD) between HRECG and HRN ellcor was -0.8 (±11) beats per minute (bpm); between HRECG and HRM asimo was 0.2 (±9) bpm. The mean (±2SD) difference between SpO2Masimo and SpO2Nellcor was -3 (±15)%. The Nellcor PO measured 20% higher than the Masimo PO at SpO2 <70%. CONCLUSION Both oximeters accurately measure HR. There was good agreement between SpO2 measurements when SpO2 ≥70%. At lower SpO2 , agreement was poorer.


title: SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans.

text: Previous studies have reported associations of IFITM3 SNP rs12252 with severe influenza, but evidence of association and the mechanism by which risk is conferred remain controversial. We prioritized SNPs in IFITM3 on the basis of putative biological function and identified rs34481144 in the 5' UTR. We found evidence of a new association of rs34481144 with severe influenza in three influenza-infected cohorts characterized by different levels of influenza illness severity. We determined a role for rs34481144 as an expression quantitative trait locus (eQTL) for IFITM3, with the risk allele associated with lower mRNA expression. The risk allele was found to have decreased IRF3 binding and increased CTCF binding in promoter-binding assays, and risk allele carriage diminished transcriptional correlations among IFITM3-neighboring genes, indicative of CTCF boundary activity. Furthermore, the risk allele disrupts a CpG site that undergoes differential methylation in CD8+ T cell subsets. Carriers of the risk allele had reduced numbers of CD8+ T cells in their airways during natural influenza infection, consistent with IFITM3 promoting accumulation of CD8+ T cells in airways and indicating that a critical function for IFITM3 may be to promote immune cell persistence at mucosal sites.Our study identifies a new regulator of IFITM3 expression that associates with CD8+ T cell levels in the airways and a spectrum of clinical outcomes.


title: Air travel and pregnancy outcomes: a review of pregnancy regulations and outcomes for passengers, flight attendants, and aviators.

text: To review flight regulations and gestational complications associated with air travel in pregnant passengers, flight attendants, and aviators. A literature search was undertaken on the relationship of air travel and spontaneous pregnancy losses, intrauterine fetal demise (IUFD), birth weight<10th percentile, preterm delivery, and neonatal intensive care unit admissions. The literature search identified 128 abstracts, of which 9 evaluated air travel and pregnancy outcomes. The risk of a pregnancy loss (spontaneous abortion or IUFD) was greater in flight attendants than controls (odds ratio [OR]: 1.62, 95% confidence interval [CI]: 1.29, 2.04). The risk of preterm birth<37 weeks was greater in passengers than controls (OR: 1.44, 95% CI: 1.07, 1.93). However, the risk of preeclampsia (OR: 0.86, 95% CI: 0.58, 1.27), neonatal intensive care unit admissions (OR: 1.19, 95% CI: 0.78, 1.82), or birth weight<10th percentile (OR: 1.25, 95% CI: 0.62, 2.48) was not increased. Flight attendants did not have an increased risk of preterm birth compared to controls (OR: 1.37, 95% CI: 0.85, 2.22) or delivering infants with birth weight<10th percentile (OR: 1.57, 95% CI: 0.68, 3.74). The risks of spontaneous abortions and other adverse pregnancy outcomes have been poorly studied in a limited number of investigations. An analysis of the available information suggests a greater risk of spontaneous abortions or IUFD in flight attendants, and a greater risk of preterm birth<37 weeks in air passengers. However, the literature on which these findings are based is generally not of high methodologic quality.


docid: hosimstu

title: The case for philanthropic investment to increase colorectal cancer screening rates: A novel paradigm to address a public health challenge.

text: BACKGROUND Colorectal cancer (CRC) remains a leading cause of cancer-related death despite being highly preventable. Efforts to increase participation in CRC screening have not met national goals. We developed a novel approach: building a business case for philanthropic investment in CRC screening. METHODS A taskforce representing the public health community, professional societies, charitable foundations, academia, and industry was assembled to: (a) quantify the impact of improving CRC screening rates; (b) identify barriers to screening; (c) estimate the "activation cost" to overcome barriers and screen one additional person; (d) develop a holistic business case that is attractive to philanthropists; and (e) launch a demonstration project. RESULTS We estimated that of 50 600 CRC deaths annually in the US, 55% occur in 50- to 85-year-olds and are potentially addressable by improvements in CRC screening. Barriers to screening were identified in all patient journey phases, including lack of awareness or insurance and logistical challenges in the pre-physician phase. The cost to activate one person to undergo screening was $25-175. This translated into a cost of $6000-36 000 per CRC death averted by philanthropic investment. Based on this work, the Colorectal Cancer Alliance launched the effort "March Forth" to prevent 100 000 CRC deaths in the US over 10 years, with the first pilot in Philadelphia. CONCLUSIONS A holistic business plan can attract philanthropy to promote CRC screening. A simple message of "You can save a life from CRC with a $25 000 donation" can motivate demonstration projects in regions with high CRC rates and low screening participation.


title: Repurposing of the antihistamine chlorcyclizine and related compounds for treatment of hepatitis C virus infection.

text: Hepatitis C virus (HCV) infection affects an estimated 185 million people worldwide, with chronic infection often leading to liver cirrhosis and hepatocellular carcinoma. Although HCV is curable, there is an unmet need for the development of effective and affordable treatment options. Through a cell-based high-throughput screen, we identified chlorcyclizine HCl (CCZ), an over-the-counter drug for allergy symptoms, as a potent inhibitor of HCV infection. CCZ inhibited HCV infection in human hepatoma cells and primary human hepatocytes. The mode of action of CCZ is mediated by inhibiting an early stage of HCV infection, probably targeting viral entry into host cells. The in vitro antiviral effect of CCZ was synergistic with other anti-HCV drugs, including ribavirin, interferon-α, telaprevir, boceprevir, sofosbuvir, daclatasvir, and cyclosporin A, without significant cytotoxicity, suggesting its potential in combination therapy of hepatitis C. In the mouse pharmacokinetic model, CCZ showed preferential liver distribution. In chimeric mice engrafted with primary human hepatocytes, CCZ significantly inhibited infection of HCV genotypes 1b and 2a, without evidence of emergence of drug resistance, during 4 and 6 weeks of treatment, respectively. With its established clinical safety profile as an allergy medication, affordability, and a simple chemical structure for optimization, CCZ represents a promising candidate for drug repurposing and further development as an effective and accessible agent for treatment of HCV infection.