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

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


docid: nazgwskr

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

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


docid: wjlikodp

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

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


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

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


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

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


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

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


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

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


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

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


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

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


Burnout in the age of COVID-19.


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

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


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

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


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


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

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


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

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


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

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


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

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


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

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


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

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


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

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


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

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


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

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


title: Effect of bariatric surgery on cardiovascular risk profile.

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


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

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


How to demystify COVID-19 and reduce social stigma.


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

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


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

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


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

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


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

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


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

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


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

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


COVID 19 and its mental health consequences.


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

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


title: Robotic ileal ureter: a completely intracorporeal technique.

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


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

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


title: Optimal Dexmedetomidine Dose to Prevent Emergence Agitation Under Sevoflurane and Remifentanil Anesthesia During Pediatric Tonsillectomy and Adenoidectomy.

text: Background: Emergence agitation (EA) is a common pediatric complication after sevoflurane anesthesia that can be prevented with dexmedetomidine. However, an inappropriate dose of dexmedetomidine can cause prolonged sedation and cardiovascular complications. Thus, we evaluated the optimal dose (ED95) of dexmedetomidine for preventing EA with sevoflurane and remifentanil anesthesia after pediatric tonsillectomy and adenoidectomy. Methods: We enrolled American Society of Anesthesiologists (ASA) I and II children 3-7 years of age who underwent tonsillectomy with adenoidectomy. During induction, dexmedetomidine was infused for 10 min. Anesthesia was induced with sevoflurane and maintained with sevoflurane and remifentanil, resulting in a bispectral spectrum index (BIS) range from 40 to 60. Extubation time, surgical and anesthetic duration time, and duration time in the postanesthesia care unit (PACU) stay were recorded. EA [measured with Pediatric Anaesthesia Emergence Delirium (PAED) scores] and pain [measured with Face, Legs, Activity, Cry, Consolability (FLACC) scores] were assessed at extubation (E0), 15 min after extubation (E1), and 30 min after extubation (E2). If EA occurred, the next surgical procedure included increased dexmedetomidine by 0.1 μg/kg, and if not, the drug was reduced by 0.1 μg/kg. Results: The 50% effective dose (ED50) of dexmedetomidine for preventing EA after sevoflurane and remifentanil anesthesia for tonsillectomy and adenoidectomy was 0.13 μg/kg, and its 95% confidence interval is 0.09-0.19 μg/kg; ED95 was 0.30 μg/kg, and its 95% confidence interval is 0.21-1.00 μg/kg. Conclusion: Intravenous dexmedetomidine infusion at ED50 (0.13 μg/kg) or ED95 (0.30 μg/kg) during induction for 10 min can prevent half or almost all EA after sevoflurane and remifentanil anesthesia during pediatric tonsillectomy and adenoidectomy.


title: Early middle cerebral artery stenosis following stent-assisted thrombectomy.

text: Stent-assisted thrombectomy (SAT) is an extensively used endovascular treatment method for stroke in which the thrombectomy stents come into direct contact with the vascular intimal surface and entrap the thrombus causing the arterial occlusion. Although there are a few studies that demonstrate that the vessel wall changes in the arteries where stroke intervention is performed, we observed progressive stenosis in early follow-up imaging studies in a case. We present a middle cerebral artery (MCA) stroke patient who had four repetitive stent passes during SAT and developed distal MCA stenosis 2 months after SAT at the control magnetic resonance angiography (MRA). Inclusion of early follow-up MRA studies would be helpful in defining the silent vascular changes in patients who have undergone repetitive SAT.


title: Inhibition by local bupivacaine-releasing microspheres of acute postoperative pain from hairy skin incision.

text: BACKGROUND Acute postoperative pain causes physiological deficits and slows recovery. Reduction of such pain by local anesthetics that are delivered for several days postoperatively is a desirable clinical objective, which is approached by a new formulation and applied in animal studies reported here. METHODS We subcutaneously injected a new formulation of poly-lactic-co-glycolic acid polymer microspheres, which provides steady drug release for 96+ hours into rats at the dorsal region 2 hours before surgery. A single 1.2-cm-long skin incision was followed by blunt dissection of skin away from the underlying fascia, and closed by 2 sutures, followed by 14 days of testing. Microspheres containing 5, 10, 20, and 40 mg bupivacaine were injected locally 2 hours before surgery; bupivacaine-free microspheres were the vehicle control, and bupivacaine HCl solution (0.5%), the positive control. Mechanical sensitivity was determined by the frequency of local muscle contractions to repeated pokes with nylon monofilaments (von Frey hairs) exerting 4 and 15 g forces, testing, respectively, allodynia and hyperalgesia, and by pinprick. RESULTS Injection of bupivacaine microspheres (40 mg drug) into intact skin reduced responses to 15 g von Frey hairs for 6 hours and to pinprick for 36 hours. Respective reductions from bupivacaine HCl lasted for 3 and 2 hours. Skin incision and dissection alone caused mechanical allodynia and hyperalgesia for 14 days. Microspheres containing 20 or 40 mg bupivacaine suppressed postoperative hypersensitivity for up to 3 days, reduced integrated allodynia (area under curve of response versus time) over postoperative days 1 to 5 by 51% ± 20% (mean ± SE) and 78% ± 12%, and reduced integrated hyperalgesia by 55% ± 13% and 64% ± 11%, for the respective doses. Five and ten milligrams bupivacaine in microspheres and the 0.5% bupivacaine solution were ineffective in reducing postoperative hypersensitivity, as were 40 mg bupivacaine microspheres injected contralateral to the incision. CONCLUSIONS Significant suppression of postoperative pain by the slow-release bupivacaine preparation outlasts its anesthetic action on intact skin. These findings demonstrate preventive analgesia and indicate the importance of acute processes in the development of chronic postoperative pain.


title: Laparoscopic total extraperitoneal repair of recurrent inguinal hernias.

text: BACKGROUND This study aimed to compare the outcome and morbidity parameters of laparoscopic total extraperitoneal (TEP) repair for recurrent and primary inguinal hernias. METHODS A retrospective analysis was conducted over a 3-year period. The recurrence rate; pain scores at 24 h, 1 week, and 4 weeks; hospital stay; days to resumption of normal activities; seroma formation; and urinary retention rates were noted. RESULTS Of 937 patients, 52 underwent recurrent and 885 underwent primary hernia repair. The follow-up period was 12 to 40 months (median, 25 months). The mean operating time was longer in the recurrent group (32.7 +/- 6.3 min) than in the primary group (30.1 +/- 6.1 min; p = 0.015). The mean pain scores at 24 h were similar in the two groups (2.28 +/- 0.5 for the recurrent group vs. 2.20 +/- 0.4 for the primary group; nonsignificant difference). However the pain scores at 1 week were significantly higher in the recurrent group (1.35 +/- 0.5) than in the primary group (1.20 +/- 0.4; p = 0.017). The hospital stay (1.19 +/- 0.4 vs. 1.07 +/- 0.3 days; p = 0.002) and the time to resumption of normal activities (8.62 +/- 2.6 vs. 7.67 +/- 1.4 days; p < 0.0001) were significantly longer in the recurrent group than in the primary group. The urinary retention (9.6% vs. 5.4%; nonsignificant difference) and seroma formation (3.8% vs. 3.5%; p = 0.5) were similar in the recurrent and the primary groups, respectively. There were two recurrences and two conversions to open procedure in the primary group and none in the recurrent group. CONCLUSIONS Laparoscopic TEP repair of recurrent inguinal hernia is safe and effective, with recurrence and conversion rates similar to those for primary hernia repair. However, the operative time, pain at 1 week and 1 month postoperatively, hospital stay, and time to resumption of normal activities with recurrent repair were significantly greater than with laparoscopic primary hernia repair.


title: Human Coronavirus HKU1 Spike Protein Uses O-Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme.

text: UNLABELLED Human coronavirus (hCoV) HKU1 is one of six hCoVs identified to date and the only one with an unidentified cellular receptor. hCoV-HKU1 encodes a hemagglutinin-esterase (HE) protein that is unique to the group a betacoronaviruses (group 2a). The function of HKU1-HE remains largely undetermined. In this study, we examined binding of the S1 domain of hCoV-HKU1 spike to a panel of cells and found that the S1 could specifically bind on the cell surface of a human rhabdomyosarcoma cell line, RD. Pretreatment of RD cells with neuraminidase (NA) and trypsin greatly reduced the binding, suggesting that the binding was mediated by sialic acids on glycoproteins. However, unlike other group 2a CoVs, e.g., hCoV-OC43, for which 9-O-acetylated sialic acid (9-O-Ac-Sia) serves as a receptor determinant, HKU1-S1 bound with neither 9-O-Ac-Sia-containing glycoprotein(s) nor rat and mouse erythrocytes. Nonetheless, the HKU1-HE was similar to OC43-HE, also possessed sialate-O-acetylesterase activity, and acted as a receptor-destroying enzyme (RDE) capable of eliminating the binding of HKU1-S1 to RD cells, whereas the O-acetylesterase-inactive HKU1-HE mutant lost this capacity. Using primary human ciliated airway epithelial (HAE) cell cultures, the only in vitro replication model for hCoV-HKU1 infection, we confirmed that pretreatment of HAE cells with HE but not the enzymatically inactive mutant blocked hCoV-HKU1 infection. These results demonstrate that hCoV-HKU1 exploits O-Ac-Sia as a cellular attachment receptor determinant to initiate the infection of host cells and that its HE protein possesses the corresponding sialate-O-acetylesterase RDE activity. IMPORTANCE Human coronaviruses (hCoV) are important human respiratory pathogens. Among the six hCoVs identified to date, only hCoV-HKU1 has no defined cellular receptor. It is also unclear whether hemagglutinin-esterase (HE) protein plays a role in viral entry. In this study, we found that, similarly to other members of the group 2a CoVs, sialic acid moieties on glycoproteins are critical receptor determinants for the hCoV-HKU1 infection. Interestingly, the virus seems to employ a type of sialic acid different from those employed by other group 2a CoVs. In addition, we determined that the HKU1-HE protein is an O-acetylesterase and acts as a receptor-destroying enzyme (RDE) for hCoV-HKU1. This is the first study to demonstrate that hCoV-HKU1 uses certain types of O-acetylated sialic acid residues on glycoproteins to initiate the infection of host cells and that the HKU1-HE protein possesses sialate-O-acetylesterase RDE activity.


title: Gender Differences in Antithrombotic Treatment for Newly Diagnosed Atrial Fibrillation: The GLORIA-AF Registry Program.

text: AIMS Data on gender differences in oral anticoagulation for stroke prevention in patients with atrial fibrillation are conflicting, largely limited to regional reports and vitamin K antagonist use. We aimed to analyze gender-specific anticoagulant prescription patterns early following the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) in a large, global registry on atrial fibrillation. METHODS The Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is an international registry program involving patients with newly diagnosed atrial fibrillation (<3 months from arrhythmia onset). We used data from 15,092 consecutive patients (median age, 71.0 years; 45.5% were women) enrolled between 2011 and 2014. Globally, 79.7% of women and 80.2% of men were anticoagulated; the absolute between-gender difference in prevalence of anticoagulant use was -0.5% (95% confidence interval, -1.8% to 0.8%). Vitamin K antagonists were prescribed to 32.8% and 31.9% (NOACs 46.8% and 48.3%) of women and men, respectively. RESULTS No confounder for the association between gender and anticoagulant prescription was identified. Between-gender differences in anticoagulant use (lower use in women compared with men by decreasing order of magnitude of the difference) were found for CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category [female]) score = 1; CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke) score = 0; previous bleeding; age <65 years; no history of hypertension; myocardial infarction; coronary artery disease; North America region; and specialist office setting. CONCLUSION Globally, the prevalence of anticoagulant use is similar in women and men. The decision to prescribe oral anticoagulation seems to depend predominantly on guideline-related differences in stroke risk stratification rather than on gender.


Health Care Tax Inversions--Robbing Both Peter and Paul.


docid: izegbayd

title: Covid-19 and infection in health-care workers: An emerging problem.

text: The 2019 coronavirus infection (called SARS-CoV-2) began in Wuhan, spread rapidly throughout the world. In many countries the exponential growth of Covid-19 cases is overwhelming health care systems with overcrowding of hospitals and overflowing Intensive Care Units. While people must stay at home to reduce the spread of this virus health-care workers do the exact opposite. In some countries doctors are working with insufficient protection and are constantly at risk of contracting Covid-19. Health-care workers should be constantly monitored because if they are infected they may spread the virus to colleagues, hospitalized patients and even family members. Increased rates of infection in health-care workers could cause the health-care system to collapse and a further worsening of the pandemic; if there are too few doctors it will be even more difficult to manage.


title: Highly efficient nitrate and phosphorus removal and adsorption of tetracycline by precipitation in a chitosan/polyvinyl alcohol immobilized bioreactor.

text: Single denitrification using bacteria has been widely investigated, but few studies have focused on the simultaneous removal of nitrate, phosphorus. and tetracycline. Strain L2, an iron-reducing bacteria, was immobilized using chitosan/polyvinyl alcohol to simultaneously remove nitrate and phosphorus. The effects of carbon/nitrogen ratio (1:1, 1.5:1, and 2:1), initial Fe2+ concentration (0, 15, and 30 mg·L-1), and HRT (2, 4, and 6 h) were assessed in bioreactors and optimum conditions were established. Results showed that the nitrate and phosphorus removal efficiency reached 100.00% (2.697 mg·L-1·h-1) and 81.93% (1.533 mg·L-1·h-1) under the conditions of carbon/nitrogen of 2:1, Fe2+ concentration of 30 mg·L-1 and HRT of 6 h. The precipitation of bioreactor, which identified as FeOOH by XRD, had significant adsorption on tetracycline. The results of high-throughput sequencing indicated that strain L2 played a significant role in denitrification. This bioreactor provided effective method for the treatment of polluted water contaminated by nitrate, phosphorus, and tetracycline.


title: Overtraining in Resistance Exercise: An Exploratory Systematic Review and Methodological Appraisal of the Literature.

text: BACKGROUND The balance between training stress and recovery is important for inducing adaptations to improve athletic performance. However, continuously high training loads with insufficient recovery may cause fatigue to accumulate and result in overtraining. A comprehensive systematic review is required to collate overtraining literature and improve the current understanding of the mechanisms underlying functional overreaching (FOR), non-functional overreaching (NFOR) and the overtraining syndrome (OTS) in resistance training. OBJECTIVE The objective of this systematic review was to establish markers of overtraining and elucidate the mechanisms underlying maladaptive resistance training conditions. Furthermore, this review aims to critically evaluate the methodological approaches of the overtraining literature. METHODS A systematic literature search was performed on PubMed, Web of Science and SPORTDiscus to identify studies up to June 2019. Electronic databases were searched using terms related to resistance training and overtraining. Records were included if they attempted to induce a state of overreaching or overtraining through resistance exercise in healthy participants. RESULTS A total of 22 studies were selected for review. Among these studies, eight resulted in decrements in performance and measured changes in performance during a follow-up period. There were four studies that reported decrease in performance yet failed to implement follow-up measures. A total of 10 studies reported no decline in performance. Overall, a lack of standardisation in methodology (follow-up performance testing) and diagnostic criteria prevents consistent determination of FOR, NFOR and OTS in resistance training. CONCLUSIONS Few studies have appropriately established FOR, NFOR or OTS in resistance training. Overtraining may be related to frequent high-intensity and monotonous resistance training. However, no marker other than a sustained decrease in performance has been established as a reliable indicator of overtraining in resistance exercise. REGISTRATION This systematic review was registered on the Open Science Framework (https://osf.io/) (https://doi.org/10.17605/osf.io/5bmsp).


docid: jzqhooei

title: INTRAUTERINE TRANSMISSION OF SARS-COV-2 INFECTION IN A PRETERM INFANT.

text: We present a preterm infant who developed a fever and mild respiratory disease on the second day of life. Infant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nasopharyngeal testing was positive at 24 and 48 hours of life. Placenta histopathology revealed SARS-CoV-2 infection by electron microscopy and immunohistochemistry. Further understanding of the risk factors that lead to in utero transmission of SARS-CoV-2 infection is needed.


title: Randomized double-blinded trial of laparoscopic gastric imbrication v laparoscopic sleeve gastrectomy at a single Indian institution.

text: BACKGROUND Currently, there is a debate whether the laparoscopic gastric imbrication (LGI) offers similar weight loss when compared to the laparoscopic sleeve gastrectomy (LSG). On the surface, they seem to offer similar-sized stomachs after the procedures are performed. We chose to perform a randomized double-blinded trial to see if similar-sized pouches result in similar types of weight loss. Our belief was that sleeve gastrectomy would offer at least a 10% better weight loss over a 3-year period. METHODS Thirty patients were randomized to one of two arms. The patients and the third party administrator following the patients were blinded as to which procedure was chosen. The surgeon had full knowledge of the patients' surgery throughout the treatment. The decision of which arm to place them was made by a single employee of the third party administrator and not shared with the employees following the patients. Patients were then followed for 3 years. RESULTS There were no differences in weight, age, or BMI preoperatively. There were no differences between the two groups at any follow-up time point from 6 months to 3 years. Follow-up was 100%. CONCLUSION Due to the large standard deviations present in both groups, there was no statistical difference between either of the groups in terms of weight loss.


title: Retrograde transvenous balloon-assisted Onyx embolization of mandibular arteriovenous malformation after hemorrhage.

text: Mandibular arteriovenous malformation (AVM) is a rare lesion, but it often can be presented with life-threatening bleedings. Endovascular treatment of mandibular AVMs has multiple approaches including transarterial embolization, transvenous embolization, direct puncture, and sclerotherapy. In this case study, we present a patient with mandibular AVM complicated by hemorrhage. The patient was treated with transarterial embolization, followed by transvenous sclerotherapy with balloon occlusion of venous outflow. But radical occlusion of AVM was achieved only by transvenous embolization of AVM with Onyx via double lumen balloon, which occluded the venous outflow.


title: Structural Biology of the Arterivirus nsp11 Endoribonucleases.

text: Endoribonuclease (NendoU) is unique and conserved as a major genetic marker in nidoviruses that infect vertebrate hosts. Arterivirus nonstructural protein 11 (nsp11) was shown to have NendoU activity and play essential roles in the viral life cycle. Here, we report three crystal structures of porcine reproductive and respiratory syndrome virus (PRRSV) and equine arteritis virus (EAV) nsp11 mutants. The structures of arterivirus nsp11 contain two conserved compact domains: the N-terminal domain (NTD) and C-terminal domain (CTD). The structures of PRRSV and EAV endoribonucleases are similar and conserved in the arterivirus, but they are greatly different from that of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoV), representing important human pathogens in the Nidovirales order. The catalytic center of NendoU activity is located in the CTD, where a positively charged groove is next to the key catalytic residues conserved in nidoviruses. Although the NTD is nearly identical, the catalytic region of the arterivirus nsp11 family proteins is remarkably flexible, and the oligomerization may be concentration dependent. In summary, our structures provide new insight into this key multifunctional NendoU family of proteins and lay a foundation for better understanding of the molecular mechanism and antiviral drug development. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) and equine arteritis virus are two major members of the arterivirus family. PRRSV, a leading swine pathogen, causes reproductive failure in breeding stock and respiratory tract illness in young pigs. Due to the lack of a suitable vaccine or effective drug treatment and the quick spread of these viruses, infected animals either die quickly or must be culled. PRRSV costs the swine industry around $644 million annually in the United States and almost €1.5 billion in Europe every year. To find a way to combat these viruses, we focused on the essential viral nonstructural protein 11 (nsp11). nsp11 is associated with multiple functions, such as RNA processing and suppression of the infected host innate immunity system. The three structures solved in this study provide new insight into the molecular mechanisms of this crucial protein family and will benefit the development of new treatments against these deadly viruses.


title: Closed reduction of distal radius fractures: a systematic review and meta-analysis.

text: Distal radius fractures (DRF) are a common injury, especially in the elderly.Displaced fractures can be reduced by closed reduction through several techniques, two of which are compared in this systematic review and meta-analysis.Closed reduction by finger-trap traction (FTT) seems to offer better correction of radial shortening. Additionally, there may be less pain and fewer complications associated with this technique.Closed reduction by manual traction seems to offer better correction of the dorsal tilt.Further research is needed to fully determine the optimal method of closed reduction. Cite this article: EFORT Open Rev 2018;3:114-120.DOI: 10.1302/2058-5241.3.170063.


Cancer care during and after the pandemic.


title: Laparoscopic assisted total gastrectomy for gastric cancer - operative technique.

text: For many years, open gastrectomy with lymphadenectomy was the gold standard treatment for gastric cancer. In recent years, however, laparoscopic assisted total gastrectomy with associated D2 lymphadenectomy has gained in popularity. It has a similar oncological outcome to open resection, but has all of the added advantages of a laparoscopic procedure, such as early mobilisation, less postoperative pain and shorter hospital stay. This article describes the operative techniques, including key procedure steps, as well as a guide for using the new OrVil device for the laparoscopic creation of the oesophago-jejunal anastomosis. A video of a laparoscopic assisted total gastrectomy is presented.


Development of a clinical decision rule for diagnosing sinus infections - to reduce unnecessary antibiotic prescribing.


title: Cosmesis and body image after single-port access surgery for gynaecologic disease.

text: BACKGROUND Little is known about patient satisfaction with single-port access (SPA) surgery for gynaecologic disease related to body image and cosmesis. AIMS This study aimed to determine cosmetic satisfaction with SPA surgery. METHODS Postal questionnaires, including the Body Image Questionnaire, were sent to 159 women who had undergone SPA surgery between May 2008 and April 2010. RESULTS Hundred and forty-six women participated in this study. Most of the women reported a relatively high body image and cosmetic score. The mean scores were 19.6 ± 1.1 and 21.9 ± 2.5, respectively. More than 67% of the women (N = 98) reported that the scar was invisible, and 97.3% of the women said that they would recommend SPA surgery to others. CONCLUSION Single-port access surgery is a good option for the management of gynaecologic disease with respect to patient satisfaction.


title: The Impact of Nutritional Interventions in Pregnant Women on DNA Methylation Patterns of the Offspring: A Systematic Review.

text: Epidemiological studies have consistently demonstrated that environmental exposures in early life are associated with later-life health status and disease susceptibility. Epigenetic modifications, such as DNA methylation, have been suggested as potential mechanisms linking the intrauterine environment with offspring health status. The present systematic review compiles peer-reviewed randomized controlled trials assessing the impact of maternal nutritional interventions on DNA methylation patterns of the offspring. The results of the included trials are consistent with micronutrient supplementation not significantly affecting offspring tissue DNA methylation patterns, yet subgrouping by sex, BMI, and smoking status increased the significance of nutritional supplementation on DNA methylation. Maternal BMI and smoking status as well as offspring sex were factors influencing offspring DNA methylation responsiveness to nutritional interventions during pregnancy. Future research should aim at assessing the impact of nutritional interventions on DNA methylation patterns of neonates comparing single versus multi-micronutrient supplementation, within populations having high versus low baseline nutritional statuses.


title: Radiological diagnosis in lung disease: factoring treatment options into the choice of diagnostic modality.

text: BACKGROUND Chest X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) each have characteristic advantages and disadvantages that need to be considered in clinical decision-making. This point is discussed in reference to the main types of lung disease that are encountered in practice. METHOD A selective literature search was performed in the PubMed and Google Scholar databases. Existing clinical guidelines on the main types of lung disease and studies concerning radiological diagnosis were also con - sidered in this review. RESULTS There have been no more than a few large-scale, controlled comparative trials of different radiological techniques. Chest X-ray provides general orientation as an initial diagnostic study and is especially useful in the diagnosis of pneumonia, cancer, and chronic obstructive pulmonary disease (COPD). Multi-detector CT affords nearly isotropic spatial resolution at a radiation dose of only 0.2-5 mSv, much lower than before. Its main indications, according to current guidelines, are tumors, acute pulmonary embolism, pulmonary hypertension, pulmonary fibrosis, advanced COPD, and pneumonia in a high-risk patient. MRI is used in the diagnosis of cystic fibrosis, pulmonary embolism, pulmonary hypertension, and bronchial carcinoma. The positive predictive value (PPV) of a chest X-ray in outpatients with pneumonia is only 27% (gold standard, CT); in contrast, an initial, non-randomized trial of MRI in nosocomial pneumonia revealed a PPV of 95%. For the staging of mediastinal lymph nodes in bronchial carcinoma, MRI has a PPV of 88% and positron emission tomography with CT (PET/CT) has a PPV of 79%, while CT alone has a PPV of 41% (gold standard, histology). CONCLUSION The choice of radiologicalal technique for the detection, staging, follow-up, and quantification of lung disease should be based on the individual clinical options, so that appropriate treatment can be provided without excessive use of diagnostic testing.


Don't forget chronic lung and immune conditions during covid-19, says WHO.


title: Activation of the carotid chemoreflex secondary to muscle metaboreflex stimulation in men.

text: Recent work has shown that the carotid chemoreceptor (CC) contributes to sympathetic control of cardiovascular function during exercise, despite no evidence of increased circulating CC stimuli, suggesting enhanced CC activity/sensitivity. As interactions between metaboreceptors and chemoreceptors have been previously observed, the purpose of this study was to isolate the metaboreflex while acutely stimulating or inhibiting the CC to determine whether the metaboreflex increased CC activity/sensitivity. Fourteen young healthy men (height: 177.0 ± 2.1 cm, weight: 85.8 ± 5.5 kg, age: 24.6 ± 1.1 yr) performed three trials of 40% maximal voluntary contraction handgrip for 2 min, followed by 3 min of postexercise circulatory occlusion (PECO) to stimulate the metaboreflex. In random order, subjects either breathed room air, hypoxia (target SPo2 = 85%), or hyperoxia (FiO2 = 1.0) during the PECO to modulate the chemoreflex. After these trials, a resting hypoxia trial was conducted without handgrip or PECO. Ventilation (Ve), heart rate (HR), blood pressure, and muscle sympathetic nervous activity (MSNA) data were continuously obtained. Relative to normoxic PECO, inhibition of the CC during hyperoxic PECO resulted in lower MSNA (P = 0.038) and HR (P = 0.021). Relative to normoxic PECO, stimulation of the CC during hypoxic PECO resulted in higher HR (P < 0.001) and Ve (P < 0.001). The ventilatory and MSNA responses to hypoxic PECO were not greater than the sum of the responses to hypoxia and PECO individually, indicating that the CC are not sensitized during metaboreflex activation. These results demonstrate that stimulation of the metaboreflex activates, but does not sensitize the CC, and help explain the enhanced CC activity with exercise.


title: Transanal single-port access microsurgery (TSPAM).

text: Transanal single-port access microsurgery (TSPAM) is an emerging and feasible minimally invasive method for the transanal excision of large sessile adenomas and early-stage carcinomas of the rectum. Here we present our TSPAM experience on rectal adenomas (high-grade rectal adenomas in 5 cases and carcinoma in situ in 1 case). TSPAM is an innovative method that can be an affordable and disseminated alternative to transanal endoscopic microsurgery for the local excision of the rectal lesions.


title: Regulation of endoplasmic reticulum turnover by selective autophagy.

text: The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein and lipid synthesis, ion homeostasis, quality control of newly synthesized proteins and organelle communication. Constant ER turnover and modulation is needed to meet different cellular requirements and autophagy has an important role in this process. However, its underlying regulatory mechanisms remain unexplained. Here we show that members of the FAM134 reticulon protein family are ER-resident receptors that bind to autophagy modifiers LC3 and GABARAP, and facilitate ER degradation by autophagy ('ER-phagy'). Downregulation of FAM134B protein in human cells causes an expansion of the ER, while FAM134B overexpression results in ER fragmentation and lysosomal degradation. Mutant FAM134B proteins that cause sensory neuropathy in humans are unable to act as ER-phagy receptors. Consistently, disruption of Fam134b in mice causes expansion of the ER, inhibits ER turnover, sensitizes cells to stress-induced apoptotic cell death and leads to degeneration of sensory neurons. Therefore, selective ER-phagy via FAM134 proteins is indispensable for mammalian cell homeostasis and controls ER morphology and turnover in mice and humans.


title: Adult colo-colonic intussusception caused by congenital bands: A case report and literature review.

text: INTRODUCTION Intussusception refers to the telescoping of a segment of bowel into the lumen of an adjacent segment. While pediatric intussusception is common and generally idiopathic, adult intussusception is exceedingly rare and is usually attributable to a pathologic lead point. PRESENTATION OF CASE 37-year-old man who presented with abdominal pain, and was preoperatively diagnosed with a colo-colonic intussusception. Intraoperatively, the lead point was found to be congenital bands, and there was no evidence of underlying malignancy. He underwent a laparoscopic-assisted extended right hemicolectomy with side-to-side ileo-colic anastomosis. DISCUSSION Colo-colonic intussusception is a rare cause of intestinal obstruction in adults. Patients generally present with subacute abdominal pain and obstructive symptoms, rendering the clinical diagnosis challenging. Computed tomography has been shown to be the most accurate diagnostic imaging modality. Due to the high incidence of underlying malignancy in adult colo-colonic intussusception, en-bloc resection of the involved bowel segment remains the standard of care. CONCLUSION Congenital bands can serve as a lead point in colo-colonic intussusception, particularly in younger adults. Prompt surgical intervention remains paramount to limit morbidity.


title: Ethics of Outbreaks Position Statement. Part 1: Therapies, Treatment Limitations, and Duty to Treat.

text: OBJECTIVES Outbreaks of disease, especially those that are declared a Public Health Emergency of International Concern, present substantial ethical challenges. Here we start a discourse (with a continuation of the dialogue in Ethics of Outbreaks Position Statement. Part 2: Family-Centered Care) concerning the ethics of the provision of medical care, research challenges and behaviors during a Public Health Emergency of International Concern with a focus on the proper conduct of clinical or epidemiologic research, clinical trial designs, unregistered medical interventions (including vaccine introduction, devices, pharmaceuticals, who gets treated, vulnerable populations, and methods of data collection), economic losses, and whether there is a duty of health care providers to provide care in such emergencies, and highlighting the need to understand cultural diversity and local communities in these efforts. DESIGN Development of a Society of Critical Care Medicine position statement using literature review and expert consensus from the Society of Critical Care Medicine Ethics committee. The committee had representation from ethics, medical philosophy, critical care, nursing, internal medicine, emergency medicine, pediatrics, anesthesiology, surgery, and members with international health and military experience. SETTING Provision of therapies for patients who are critically ill or who have the potential of becoming critically ill, and their families, regarding medical therapies and the extent of treatments. POPULATION Critically ill patients and their families affected by a Public Health Emergency of International Concern that need provision of medical therapies. INTERVENTIONS Not applicable. MAIN RESULTS Interventions by high income countries in a Public Health Emergency of International Concern must always be cognizant of avoiding a paternalistic stance and must understand how families and communities are structured and the regional/local traditions that affect public discourse. Additionally, the obligations, or the lack of obligations, of healthcare providers regarding the treatment of affected individuals and communities must also be acknowledged. Herein, we review such matters and suggest recommendations regarding the ethics of engagement in an outbreak that is a Public Health Emergency of International Concern.


title: Generation of human neutralizing monoclonal antibodies against the 2009 pandemic H1N1 virus from peripheral blood memory B lymphocytes.

text: The 2009 H1N1 influenza pandemic demonstrated the significance of a global health threat to human beings. Although pandemic H1N1 vaccines have been rapidly developed, passive serotherapy may offer superior immediate protection against infections in children, the elderly and immune-compromised patients during an influenza pandemic. Here, we applied a novel strategy based on Epstein-Barr virus (EBV)-immortalized peripheral blood memory B cells to screen high viral neutralizing monoclonal antibodies (MAbs) from individuals vaccinated with the 2009 pandemic H1N1 vaccine PANFLU.1. Through a massive screen of 13 090 immortalized memory B-cell clones from three selected vaccinees, seven MAbs were identified with both high viral neutralizing capacities and hemagglutination inhibition (HAI) activities against the 2009 pandemic H1N1 viruses. These MAbs may have important clinical implications for passive serotherapy treatments of infected patients with severe respiratory syndrome, especially children, the elderly and immunodeficient individuals. Our successful strategy for generating high-affinity MAbs from EBV-immortalized peripheral blood memory B cells may also be applicable to other infectious or autoimmune diseases.


docid: onefogsj

title: Laparoscopic versus open repair of parastomal hernias: an ACS-NSQIP analysis of short-term outcomes.

text: BACKGROUND Parastomal hernia (PSH) is a frequent complication following the creation of a stoma. While a significant number of cases require operative management, data comparing short-term outcomes of laparoscopic versus open repair of parastomal hernias are limited. METHODS The ACS-NSQIP was retrospectively reviewed from 2005 to 2011 for all PSH cases that underwent open or laparoscopic repair. Patients characteristics, operative details, and outcomes were listed for both procedure types. Selected end points were compared on multivariate regression analysis. RESULTS Among the 2,167 identified parastomal hernia cases, only 222 (10.24 %) were treated laparoscopically. The open and laparoscopic groups were similar with respect to mean patient age (63 vs. 63 years; p = 1) and gender distribution as the majority of patients were females (56.8 %). However, open repair was more likely to be performed in patients with a higher ASA class (III and IV) (p < 0.001). Also, the open approach was more likely to be used emergently (8.64 vs. 3.60 %; p = 0.01) and for recurrent hernias (6.99 vs. 3.15 %; p < 0.05). After adjusting for all potential confounders including age, gender, ASA, emergency designation of the operation, hernia type, and wound class, laparoscopy was associated with shorter operative time (137.5 vs. 153.4 min; p < 0.05), shorter length of hospital stay by 3.32 days (p < 0.001), lower risk of overall morbidity (OR = 0.42; p < 0.001), and a lower risk of surgical site infections (OR = 0.35; p < 0.01) compared to open repair. Mortality rates were similar in the laparoscopic and open groups (0.45 vs. 1.59 %, respectively; p = 0.29). CONCLUSIONS Laparoscopic parastomal hernia repair is safe and appears to be associated with better short-term outcomes compared to open repair in selected cases. Large prospective randomized trials are needed to confirm those results and to assess long-term recurrence rates.


title: Prolonged intralymphatic delivery of dendritic cells through implantable lymphatic ports in patients with advanced cancer.

text: BACKGROUND The currently-used modes of administration of immunotherapeutic agents result in their limited delivery to the lymph nodes and/or require repetitive ultrasound-guided nodal injections or microsurgical lymphatic injections, limiting their feasibility. Here, we report on the feasibility and safety of a new method of long-term repetitive intralymphatic (IL) infusion of immune cells, using implantable delivery ports. METHODS Nine patients with stage IV recurrent colorectal cancer underwent complete resection and received autologous dendritic cells (DCs) loaded with killed autologous tumor cells, KLH and PADRE, for up to four monthly cycles. Leg lymphatic vessels were cannulated, connected to 6.6Fr low-profile implantable subcutaneous delivery ports, and used to infuse 12 doses of DC over each 72 h-long cycle (every 6 h), followed by heparin flushes of the cannula-port system (one 72 h-long cycle per month). The patients who opted for alternative route of vaccine administration (2 patients) or whose ports became non-functional between cycles, continued treatment via intranodal (one injection/cycle) or intradermal (four injections/cycle) routes. RESULTS A total of nine lymphatic cannulations and implantations of subcutaneous delivery ports were attempted in seven patients, with a success rate of eight out of nine (89 %). The average patency of the IL delivery system was 7.5 (±3.2) weeks. All six patients with IL ports successfully completed at least one complete 72 h-long DC infusion cycle (12 injections). Five patients (56 %) completed two full IL cycles (24 IL injections). No patients received more than two IL cycles without replacement of the IL port, due to catheter occlusion and/or local side effects: cellulitis and hematoma. Intranodal and intradermal backup options were used in, respectively, one and two patients. Overall cohort survival was >28 (±25) months. One patient with aggressive recurrent carcinomatosis, who received DC vaccines by intranodal route is alive at > 90 months, without evidence of disease. CONCLUSIONS We conclude that an intermediate-duration IL delivery of multiple doses of immunotherapeutic factors using implantable delivery ports is feasible, highly-tolerable and can be reproducibly performed in cancer patients to administer immune cells, or potentially, other immune factors. However, long-term IL port placement (>7.5 weeks), is not a currently-feasible option. TRIAL REGISTRATION NCT00558051, registered Nov. 13, 2007.


title: Harmonic scalpel compared to conventional hemostasis in thyroid surgery: a meta-analysis of randomized clinical trials.

text: Background. The study's aim was to determine whether conventional hemostasis (CH) or the Harmonic Scalpel (HS) results in shorter operative times for thyroidectomy and to evaluate the incidence of postoperative complications with each approach. Methods. A literature search was conducted from study inception to September 30, 2008. Included studies randomized thyroidectomy patients to either CH or HS and reported the incidence of postoperative transient recurrent laryngeal nerve dysfunction (RLND) and hypocalcemia. Results. Nine RCTs were included. Use of the HS reduced operative time by 23.1 minutes (95% CI = 13.8, 32.33). There was no difference in the incidence of transient RLND (RR = 1.25, 95% CI = .56, 2.76), but a lower rate of transient hypocalcemia with the use of the HS (RR = .69, 95% CI = .51, .92). Conclusions. The use of HS in thyroidectomy significantly reduces operative time and is associated with a reduction in postoperative hypocalcemia compared to CH.