title: Parkinson's disease case ascertainment in prospective cohort studies through combining multiple health information resources.

text: Epidemiological evidence from prospective cohort studies on risk factors of Parkinson's disease (PD) is limited as case ascertainment is challenging due to a lack of registries and the disease course of PD. The objective of this study was to create a case ascertainment method for PD within two prospective Dutch cohorts based on multiple sources of PD information. This method was validated using clinical records from the general practitioners (GPs). Face validity of the case ascertainment was tested for three etiological factors (smoking, sex and family history of PD). In total 54825 participants were included from the cohorts AMIGO and EPIC-NL. Sources of PD information included self-reported PD, self-reported PD medication, a 9 item screening questionnaire (Tanner), electronical medical records, hospital discharge data and mortality records. Based on these sources we developed a likelihood score with 4 categories (no PD, unlikely PD, possible PD, likely PD). For the different sources of PD information and for the likelihood score we present the agreement with GP-validated cases. Risk of PD for established factors was studied by logistic regression as exact diagnose dates were not always available. Based on the algorithm, we assigned 346 participants to the likely PD category. GP validation confirmed 67% of these participants in EPIC-NL, but only 12% in AMIGO. PD was confirmed in only 3% of the participants with a possible PD classification. PD case ascertainment by mortality records (91%), EMR ICPC (82%) and self-reported information (62-69%) had the highest confirmation rates. The Tanner PD screening questionnaire had a lower agreement (18%). Risk estimates for smoking, family history and sex using all likely PD cases were comparable to the literature for EPIC-NL, but not for smoking in AMIGO. Using multiple sources of PD evidence in cohorts remains important but challenging as performance of sources varied in validity.


COVID-19-associated ophthalmoparesis and hypothalamic involvement.


Measuring surgical skill: a rapidly evolving scientific methodology.


title: The Role of Emergency Radiology in COVID-19: From Preparedness to Diagnosis.

text: Emergency trauma radiology, although a relatively new subspecialty of radiology, plays a critical role in both the diagnosis/triage of acutely ill patients, but even more important in providing leadership and taking the lead in the preparedness of imaging departments in dealing with novel highly infectious communicable diseases and mass casualties. This has become even more apparent in dealing with COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, first emerged in late 2019. We review the symptoms, epidemiology, and testing for this disease. We discuss characteristic imaging findings of COVID-19 in relation to other modern coronavirus diseases including SARS and MERS. We discuss roles that community radiology clinics, outpatient radiology departments, and emergency radiology departments can play in the diagnosis of this disease. We review practical methods to reduce spread of infections within radiology departments.


title: Endoscopic management with multiple plastic stents of anastomotic biliary stricture following liver transplantation: long-term results.

text: BACKGROUND AND AIMS Anastomotic biliary stricture (ABS) is the most common biliary complication after orthotopic liver transplantation (OLT) and can be successfully managed endoscopically. The long-term results of a protocol using placement of multiple plastic stents to treat ABS following OLT were analyzed. METHODS All patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for OLT-related biliary complications at our Endoscopy Unit between July 1994 and March 2012 were retrospectively identified from the ERCP database. Patients with an ABS treated with an increasing number of plastic stents were included in the study. Follow-up after stent removal was obtained by telephone contact with the patient and/or referring physician and by liver function tests (LFTs) evaluation. RESULTS 56 patients, treated with an increasing number of plastic stents until resolution of the stricture, were included. Five patients were then excluded (unrelated death during treatment, n = 3; incomplete treatment because of poor compliance, n = 2), and 51/56 patients reached study end points and were included in the analysis. Resolution of ABS was obtained in 50/51 patients; 1 patient required hepaticojejunostomy because of failure to pass the stricture with the guidewire (per protocol resolution, 98 %). Mean duration of endoscopic treatment was 11.5 months, with a median 4 ERCPs per patient. Immediate ERCP-related adverse events occurred in 3/56 patients (5.4 %). After a median follow-up of 5.8 years from stent removal, 3/50 patients (6 %) had recurrence of ABS. These 3 patients were successfully treated again endoscopically and are asymptomatic after a further median follow-up of 5.6 years. CONCLUSIONS At long-term follow-up, endoscopic treatment with multiple plastic stents of ABS following OLT appeared to be effective in most patients. Stricture recurrence is rare and can be successfully treated again endoscopically.


title: MR susceptibility artefact associated with the use of Barricade coils for treatment of intracranial aneurysms.

text: Magnetic resonance angiography (MRA) is commonly used to follow up patients after endovascular treatment for intracranial aneurysms. Magnetic resonance artefacts from coil constructs may impair image quality and jeopardise the evaluation of the effectiveness of treatment and review of adjacent vasculature. We present here a technical note on the usage of Barricade coils recently introduced at our institution. The MRA artefacts associated with these coils may make it impossible to ascertain aneurysm closure and anatomy. Hence these patients would need to be recalled for digital subtraction angiograms for a complete neuroradiological follow-up.


Disinfection threatens aquatic ecosystems.


title: The effect of pre-operative gastric ultrasound examination on the choice of general anaesthetic induction technique for non-elective paediatric surgery. A prospective cohort study.

text: Ultrasound examination of the gastric antrum is a non-invasive tool that allows reliable estimation of gastric contents. We performed this prospective cohort study in non-elective paediatric surgery to assess whether gastric ultrasound may help to determine the best anaesthetic induction technique, whether rapid sequence or routine. The primary outcome was the reduction of inappropriate induction technique. A pre-operative clinical assessment was performed by the attending anaesthetist who made a provisional plan for induction. Gastric ultrasound was performed in the semirecumbent and right lateral decubitus positions for a qualitative assessment of gastric contents, using a 0-2 grading scale. A final induction plan was made based on this assessment. Immediately after tracheal intubation, gastric contents were suctioned through a multi-orifice nasogastric tube; these were defined as above risk threshold for regurgitation and aspiration if there was clear fluid > 0.8 ml.kg-1 , and/or the presence of thick fluid and/or solid particles. Gastric ultrasound was feasible in 130 out of 143 (90%) of children, and led to a change in the planned induction technique in 67 patients: 30 from routine to rapid sequence, and 37 from rapid sequence to routine. An appropriate induction technique was therefore performed in 85% of children, vs. 49% planned after pre-operative clinical assessment alone (p < 0.00001). Our results suggest that gastric ultrasound is a useful guide to the general anaesthetic induction technique with respect to the risk of pulmonary aspiration, in comparison with pre-operative clinical assessment alone.


title: Uniportal video-assisted thoracoscopic bronchoplastic and carinal sleeve procedures.

text: Despite of the recent advanced with the video-assisted thoracoscopic surgery (VATS), the most common approach for bronchial and carinal resection is still the open surgery. The technical difficulties, the steep learning curve and the concerns about performing an oncologic and safe reconstruction in advanced cases, are the main reasons for the low adoption of VATS for sleeve resections. Most of the authors use 3-4 incisions for thoracoscopic sleeve procedures. However these surgical techniques can be performed by a single incision approach by skilled uniportal VATS surgeons. The improvements of the surgical instruments, high definition cameras and recent 3D systems have greatly contributed to facilitate the adoption of uniportal VATS techniques for sleeve procedures. In this article we describe the technique of thoracoscopic bronchial sleeve, bronchovascular and carinal resections through a single incision approach.


docid: idzozzlh

title: Weaning from mechanical ventilation: why are we still looking for alternative methods?

text: Most patients who require mechanical ventilation for longer than 24 hours, and who improve the condition leading to the indication of ventilatory support, can be weaned after passing a first spontaneous breathing test. The challenge is to improve the weaning of patients who fail that first test. We have methods that can be referred to as traditional, such as the T-tube, pressure support or synchronized intermittent mandatory ventilation (SIMV). In recent years, however, new applications of usual techniques as noninvasive ventilation, new ventilation methods such as automatic tube compensation (ATC), mandatory minute ventilation (MMV), adaptive support ventilation or automatic weaning systems based on pressure support have been described. Their possible role in weaning from mechanical ventilation among patients with difficult or prolonged weaning remains to be established.


title: COVID-19 is catalyzing the adoption of teleneurology.

text: The novel coronavirus, COVID-19, changed the world within a matter of weeks. The primary action to constrain the spread of the virus is social isolation. Given this public health principle, and the shortage of personal protective equipment during the global pandemic, all health care stakeholders need to reconsider the indications for face-to-face health care encounters in providing patient care. Which encounters are imperative and which ones can be switched to non-face-to-face care? What changes in laws, regulations, payment policies and workflow are needed to enable this transition? (1,2,3).


title: Theoretical frameworks informing the relationship between parental death and suicidal behaviour: A scoping review.

text: Background Exposure to parental death in childhood has been strongly associated with offspring suicide although few studies have applied theoretical models to conceptualise this relationship. Methods Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Scoping Reviews guidelines, we conducted a scoping review of primary studies that identified a theory/framework explaining the aetiology of suicidal behaviour in adulthood, following childhood exposure to external-cause parental death, including suicide. Results The search yielded 1598 articles. Following full-text screening, 23 studies were identified as meeting inclusion criteria. Data extraction was then completed and found that the studies collectively referenced nine theories. The specific theories identified covered a range of biopsychosocial frameworks and included attachment theory, familial transmission of suicide, conservation of resources framework, diathesis-stress model, social integration theory, socio-ecological model, social learning theory, critical period hypothesis or life course approach and the developmental model of antisocial behaviour. Limitations It was beyond the scope of this review to conduct rigorous testing and evaluation of the theories identified. Future research could extend on this study by developing criteria to assess the range of theories and frameworks on suicide exposure, as well as the studies providing evidence for these theories, in order to guide more advanced theory development as well as policies, programs and interventions. Conclusions Based on these theories, the authors proposed that using an integrated biopsychosocial model will provide a more comprehensive understanding of the diverse risk and protective factors for suicidal behaviour following parental death.


docid: mehwufxd

title: Comparison of Permacol™ and Strattice™ for the repair of abdominal wall defects.

text: BACKGROUND Incisional hernias repaired with mesh can be expected have a lower recurrence rate than with primary repair. Biologic implants have replaced synthetic meshes in certain complex settings. We compared two porcine-dermis derived implants--cross-linked Permacol™ biologic implant and non-cross linked Strattice-firm™ tissue matrix--in a ventral hernia animal model. Our hypothesis is that cross-linked biologic implants are remodeled differently and thus behave differently than non-cross-linked biologic implants. METHODS Eighty-nine, female Sprague-Dawley rats had a 3 × 3 cm full-thickness segment of the abdominal wall excised. A 3 × 3 cm biologic mesh, either Permacol™ or Strattice™, was secured and the skin was closed. At 1-, 3-, 6- and 12-month time intervals, rats in each group were sacrificed and the mesh was excised. The number of adhesions, surface area, mesh thickness and tensile strength were determined, and immunohistochemical analysis performed. RESULTS Permacol™ biologic implant maintained thickness while Strattice™ thickness decreased significantly starting at 3 months. Adhesion area and tenacity were not significantly different between Permacol™ and Strattice™ at all time points. The tensile strength of the Permacol™ biologic implant was greater than that of Strattice™ at 3, 6 and 12 months. Migration of host cells and neo-vascularization was observed in both implant groups. CONCLUSIONS Cross-linked materials may prove more durable in the remodeling process as suggested by the increased thinning and weakening observed in non-cross-linked biomesh.


title: Reduction in Cerebral Oxygenation due to Patent Ductus Arteriosus Is Pronounced in Small-for-Gestational-Age Neonates.

text: BACKGROUND A haemodynamically significant patent ductus arteriosus (hsPDA) reduces cerebral oxygenation in appropriate-for-gestational-age (AGA) preterm neonates. Reduced cerebral oxygenation has been associated with brain injury. Preterm small-for-gestational-age (SGA) neonates show higher cerebral oxygenation than AGA peers throughout the first postnatal days. To date, no studies have investigated the effect of hsPDA on cerebral oxygenation in preterm SGA neonates. OBJECTIVE We aimed to assess the effect of hsPDA on cerebral oxygenation in preterm SGA neonates compared to AGA peers. We hypothesised that higher baseline cerebral oxygenation would reduce the impact of hsPDA on cerebral oxygenation in preterm SGA neonates. METHODS We monitored regional cerebral oxygen saturation (rScO2) with near-infrared spectroscopy and calculated the cerebral fractional tissue oxygen extraction (cFTOE) for 72 h after birth. Retrospective analysis compared 36 preterm SGA neonates (birth weight <10th percentile, 18 with hsPDA) to 36 preterm AGA neonates (birth weight 20th to 80th percentile, 18 with hsPDA). RESULTS In contrast to the other groups, SGA-hsPDA neonates demonstrated a significant fall in rScO2 [69% (SEM 2.5) at 4-8 h to 61% (2.7) at 68-72 h, p < 0.001] with a concurrent rise in cFTOE [0.26 (0.026) at 4-8 h to 0.34 (0.030) at 68-72 h, p < 0.001]. CONCLUSIONS Contrary to our hypothesis, hsPDA had a significant negative effect on cerebral oxygenation in preterm SGA neonates. Future studies should explore the potential benefits of early screening and treatment for hsPDA on long-term neurodevelopmental outcome in preterm SGA neonates.


Right upper quadrant pain? Think outside the liver: a case of diaphragmatic perihepatic endometriosis.


title: Conversion to open laparotomy during laparoscopic distal pancreatectomy: lessons from a single-center experience in 70 consecutive patients.

text: PURPOSE The purpose of this study was to determine the factors influencing conversion from laparoscopic distal pancreatectomy (LDP) to open surgery, and the effect of such conversion on the outcome. METHODS This retrospective single-center study included 70 consecutive patients undergoing LDP. The primary endpoint was the rate of conversion to open surgery during LDP. The secondary endpoints were determining the reasons for conversion to open surgery, with detailed analyses of these cases and a comparison of the surgical outcome with and without conversion. RESULTS Seven patients (10%) required conversion to open surgery during LDP. Pancreatic ductal adenocarcinoma (PDAC) was identified as a risk factor for conversion (p = 0.010). The reasons for conversion included technical difficulty (two bleeding, one severe adhesion) and pancreatic stump-related issues (two margin-positive, two stapling failures). Although the overall morbidity rate (29 vs. 11%, p = 0.48) and the rate of clinically relevant postoperative pancreatic fistula (14 vs. 5%, p = 0.82) were no different for the patients with or without open conversion, the postoperative hospital stay was significantly longer in the former (median 15 vs. 10 days, p = 0.03). CONCLUSIONS Careful preoperative assessment is required when planning LDP for PDAC. Although conversion to open surgery does not result in failure of LDP, efforts to reduce the duration of postoperative hospital stay and the occurrence of complications are desirable to improve the outcome of LDP.


title: Pregnancy affected by SARS-CoV-2 infection: a flash report from Michigan.

text: The world is currently affected by the invasion of a human to human highly transmissible novel corona virus classified as SARS-CoV-2. It causes a severe acute lower respiratory tract syndrome named corona virus disease (CoVid-19). The virus is detected primarily by RT-PCR. The reproduction number (Ro) has been reported between 2.28 and 5.27]. It is beyond our objective to provide an in-depth discussion of the virus characteristics and its distinct viral clades and pathogenic behavior. On 30 January 2020 the World Health Organization (WHO) declared this outbreak a Public Health Emergency of International Concern, (PHEIC) and on 11 March 2020 WHO declared it a pandemic. There is limited information on the effect of CoVid-19 in pregnancy and the new born. We describe the details of the hospital course of the first 16 cases involving pregnant women, admitted to an urban-suburban community general hospital in Wayne County Michigan, from 26 March to 10 April 2020. At the time of this writing the Covid-19 pandemic has affected 35,291 persons in the state of Michigan (0.37%) making it the third most affected state in the USA (MDHHS). Pregnant women are believed to be at higher risk of Covid-19 infection in association with the known physiologic changes of the immune, cardiorespiratory and metabolic systems during pregnancy.


title: Transanal minimally invasive surgery for total mesorectal excision (TAMIS-TME): results and experience with the first 20 patients undergoing curative-intent rectal cancer surgery at a single institution.

text: BACKGROUND Transanal TME is a new approach to performing minimally invasive rectal resection. It is particularly well suited for patients with locally advanced distal rectal cancer and obesity, where the abdominal approach is challenging. Transanal TME can be performed with either TAMIS or TEM. Here, we report our initial experience with transanal TME using TAMIS (TAMIS-TME). METHODS Patients were selected to undergo transanal TME using the TAMIS platform (TAMIS-TME) primarily for malignant disease, but also for select cases of benign disease. Transanal TME defines a "bottom-up" approach to en bloc rectal cancer resection. Transanal TME requires abdominal access for proximal colonic mobilization and is often done in conjunction with a laparoscopic approach. RESULTS During a 32-month period, 20 patients underwent TAMIS-TME with curative intent. The primary indication for transanal TME was distal, locally advanced rectal cancer. The median age of rectal cancer patients at the time of surgery was 57 years (range 36-73 years) with 30% (6) female and 70% (14) male. The median body mass index (BMI) measured was 24 kg/m(2) (range 18-41 kg/m(2)); this included six patients (30%) with obesity (BMI ≥ 30 kg/m(2)). Mean operating time was 243 min (range 140-495 min) with blood loss averaging 153 ml. Postoperative length of stay averaged 4.5 days (range 3-24 days). There was no 30-day postoperative mortality. Surgical complications included wound infection (n = 2), pelvic abscess (n = 4), and prolonged ileus (n = 4). The anastomotic leak rate was 6.7% (1/15). Of the 20 patients who underwent resection, 90% (18/20) had negative margins. Pathologic grading of the TME specimen revealed that 85% (17/20) of transanal TME specimens were found to have "completely" or "near-completely" intact mesorectal envelopes. Data collected during the 6-month median follow-up period revealed that only one patient had developed distant metastasis. There was no locoregional recurrence in any of the patients. CONCLUSIONS Transanal TME is a feasible method for oncologic resection of locally advanced mid- and distal-rectal cancer with curative intent. It has special application for patients with obesity and anatomic constraints such as a narrow male pelvis.


Remote digital monitoring in clinical trials in the time of COVID-19.


title: Associations Between Chronic Kidney Disease and Outcomes With Use of Prasugrel Versus Clopidogrel in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Report From the PROMETHEUS Study.

text: OBJECTIVES This study sought to compare clinical outcomes in a contemporary acute coronary syndrome (ACS) percutaneous coronary intervention (PCI) cohort stratified by chronic kidney disease (CKD) status. BACKGROUND Patients with CKD exhibit high risks for both thrombotic and bleeding events, thus complicating decision making regarding antiplatelet therapy in the setting of ACS. METHODS The PROMETHEUS study was a multicenter observational study comparing outcomes with prasugrel versus clopidogrel in ACS PCI patients. Major adverse cardiac events (MACE) at 90 days and at 1 year were defined as a composite of death, myocardial infarction, stroke, or unplanned revascularization. Clinically significant bleeding was defined as bleeding requiring transfusion or hospitalization. Cox regression multivariable analysis was performed for adjusted associations between CKD status and clinical outcomes. Hazard ratios for prasugrel versus clopidogrel treatment were generated using propensity score stratification. RESULTS The total cohort included 19,832 patients, 28.3% with and 71.7% without CKD. CKD patients were older with greater comorbidities including diabetes and multivessel disease. Prasugrel was less often prescribed to CKD versus non-CKD patients (11.0% vs. 24.0%, respectively; p < 0.001). At 1 year, CKD was associated with higher adjusted risk of MACE (1.27; 95% confidence interval: 1.18 to 1.37) and bleeding (1.46; 95% confidence interval: 1.24 to 1.73). Although unadjusted rates of 1-year MACE were lower with prasugrel versus clopidogrel in both CKD (18.3% vs. 26.5%; p < 0.001) and non-CKD (10.9% vs. 17.9%; p < 0.001) patients, associations were attenuated after propensity stratification. Similarly, unadjusted differences in 1-year bleeding with prasugrel versus clopidogrel (6.0% vs. 7.4%; p = 0.18 in CKD patients; 2.6% vs. 3.5%; p = 0.008 in non-CKD patients) were not significant after propensity score adjustment. CONCLUSIONS Although risks for 1-year MACE were significantly higher in ACS PCI patients with versus without CKD, prasugrel use was 50% lower in patients with renal impairment. Irrespective of CKD status, outcomes associated with prasugrel use were not significant after propensity adjustment. These data highlight the need for randomized studies evaluating the optimal antiplatelet therapy in CKD patients with ACS.


docid: qygcnaai

title: Ebola raises profile of blood-based therapy.


title: First clinical experience with intranasal cooling for hyperthermia in brain-injured patients.

text: INTRODUCTION Hyperthermia is common in brain-injured patients and associated with a worse outcome. As brain rather than body temperature reduction, theoretically, is the most important in cerebral protection, there is logic in targeting cooling at the brain. Selective brain cooling can, in theory, be obtained by cooling the skull or by heat loss from the upper airways. In this preliminary safety and efficacy study, we report clinical data from brain-injured patients who because of hyperthermia were treated with intranasal cooling. METHODS Nine intubated brain-injured patients with hyperthermia were treated using a prototype intranasal balloon system perfused with cold saline. Temperature in the cerebrum, esophagus, and bladder was monitored together with intracranial pressure. RESULTS In only two of nine patients, normothermia was reached in the esophagus and in only four of nine patients it was reached in the bladder. When normothermia was reached, the time to normothermia was delayed. In the brain, normothermia was reached in two of five patients after approximately 72 h. Median temperature curves from the first 72 h of cooling showed that normothermia was not reached in any of the three compartments. The temperature in the brain and bladder were on average 0.6 and 0.5 °C higher than in the esophagus. ICP increased with increasing brain temperature. We found no signs of clinical important injury to the nasal mucosa from the cold saline or pressure in the balloons. CONCLUSION In brain-injured patients with hyperthermia, cooling with a prototype intranasal balloon system was clinically inadequate as the effect was delayed and not brain selective.


COVID-19, wet markets, and planetary health.


title: Pharmacotherapy for hypertension in Sub-Saharan Africa: a systematic review and network meta-analysis.

text: BACKGROUND The highest burden of hypertension is found in Sub-Saharan Africa (SSA) with a threefold greater mortality from stroke and other associated diseases. Ethnicity is known to influence the response to antihypertensives, especially in black populations living in North America and Europe. We sought to outline the impact of all commonly used pharmacological agents on both blood pressure reduction and cardiovascular morbidity and mortality in SSA. METHODS We used similar criteria to previous large meta-analyses of blood pressure agents but restricted results to populations in SSA. Quality of evidence was assessed using a risk of bias tool. Network meta-analysis with random effects was used to compare the effects across interventions and meta-regression to explore participant heterogeneity. RESULTS Thirty-two studies of 2860 participants were identified. Most were small studies from single, urban centres. Compared with placebo, any pharmacotherapy lowered SBP/DBP by 8.51/8.04 mmHg, and calcium channel blockers (CCBs) were the most efficacious first-line agent with 18.46/11.6 mmHg reduction. Fewer studies assessing combination therapy were available, but there was a trend towards superiority for CCBs plus ACE inhibitors or diuretics compared to other combinations. No studies examined the effect of antihypertensive therapy on morbidity or mortality outcomes. CONCLUSION Evidence broadly supports current guidelines and provides a clear rationale for promoting CCBs as first-line agents and early initiation of combination therapy. However, there is a clear requirement for more evidence to provide a nuanced understanding of stroke and other cardiovascular disease prevention amongst diverse populations on the continent. TRIAL REGISTRATION PROSPERO, CRD42019122490. This review was registered in January 2019.


docid: crbdcfqy

title: Fungicidal Potency and Mechanisms of θ-Defensins against Multidrug-Resistant Candida Species.

text: Systemic candidiasis is a growing health care concern that is becoming even more challenging due to the growing frequency of infections caused by multidrug-resistant (MDR) Candida species. Thus, there is an urgent need for new therapeutic approaches to candidiasis, including strategies bioinspired by insights into natural host defense against fungal pathogens. The antifungal properties of θ-defensins, macrocyclic peptides expressed in tissues of Old World monkeys, were investigated against a panel of drug-sensitive and drug-resistant clinical isolates of Candida albicans and non-albicans Candida species. Rhesus θ-defensin 1 (RTD-1), the prototype θ-defensin, was rapidly and potently fungicidal against drug-sensitive and MDR C. albicans strains. Fungal killing occurred by cell permeabilization that was temporally correlated with ATP release and intracellular accumulation of reactive oxygen species (ROS). Killing by RTD-1 was compared with that by histatin 5 (Hst 5), an extensively characterized anticandidal peptide expressed in human saliva. RTD-1 killed C. albicans much more rapidly and at a >200-fold lower concentration than that of Hst 5. Unlike Hst 5, the anticandidal activity of RTD-1 was independent of mitochondrial ATP production. Moreover, RTD-1 was completely resistant to Candida proteases for 2 h under conditions that rapidly and completely degraded Hst 5. MICs and minimum fungicidal concentrations (MFCs) of 14 natural θ-defensins isoforms against drug-resistant C. albicans isolates identified peptides that are more active than amphotericin B and/or caspofungin against fluconazole-resistant organisms, including MDR Candida auris. These results point to the potential of macrocyclic θ-defensins as structural templates for the design of antifungal therapeutics.


title: Identification of candidate protein markers of Bovine Parainfluenza Virus Type 3 infection using an in vitro model.

text: Bovine Parainfluenza Virus Type 3 (BPI3V) infections are often asymptomatic, causing respiratory tissue damage and immunosuppression, predisposing animals to severe bacterial pneumonia, the leading cause of Bovine Respiratory Disease (BRD) mortality. As with many pathogens, routine BPI3V serology does not indicate the presence of damaged respiratory tissue or active infection. In vitro proteomic marker screening using disease relevant cell models could help identify markers of infection and tissue damage that are also detectable during in vivo infections. This study utilised a proteomic approach to investigate in vitro cellular responses during BPI3V infection to enhance the current understanding of intracellular host-virus interactions and identify putative markers of in vivo infection. Through 2D gel electrophoresis proteomic analysis, BPI3V Phosphoprotein P and host T-complex Protein 1 subunit theta were found to be accumulated at the latter stages of infection within bovine fibroblasts. These proteins were subsequently detected using targeted multiple reaction monitoring (MRM) mass spectrometry in the plasma of animals challenged with BPI3V, with differential protein level profiles observed dependant on animal vaccination status. Potential mechanisms by which BPI3V overcomes host cellular immune response mechanisms allowing for replication and production of viral proteins were also revealed. Assessment of circulating protein marker levels identified through an in vitro approach as described may enable more effective diagnosis of active viral infection and diseased or damaged respiratory tissue in animals and allow for more effective utilisation of preventative therapeutic interventions prior to bacterial disease onset and significantly aid the management and control of BRD.


title: Single incision laparoscopic Nissen fundoplication: step by step.

text: INTRODUCTION Laparoscopic Nissen fundoplication has been shown to have many benefits for patients including shorter hospital stay and fewer operative complications. The traditional laparoscopic Nissen fundoplication has been performed by the use of 5 incisions. With the inception of single incision procedures, surgeons have been examining other procedures that may benefit from adoption of an even less invasive technique. MATERIALS A 36-year-old female underwent a single incision laparoscopic Nissen fundoplication using 3 trocars. The patient's body mass index was 29 kg/m. RESULTS The operative time was 52 minutes. There were no intraoperative or postoperative complications within the 30 days. The patient was discharged home on the first postoperative day on a full liquid diet. CONCLUSIONS Single incision laparoscopic Nissen fundoplication is feasible with comparable outcomes with the traditional 5 incision laparoscopic technique.


title: Economic optimization of a global strategy to address the pandemic threat.

text: Emerging pandemics threaten global health and economies and are increasing in frequency. Globally coordinated strategies to combat pandemics, similar to current strategies that address climate change, are largely adaptive, in that they attempt to reduce the impact of a pathogen after it has emerged. However, like climate change, mitigation strategies have been developed that include programs to reduce the underlying drivers of pandemics, particularly animal-to-human disease transmission. Here, we use real options economic modeling of current globally coordinated adaptation strategies for pandemic prevention. We show that they would be optimally implemented within 27 y to reduce the annual rise of emerging infectious disease events by 50% at an estimated one-time cost of approximately $343.7 billion. We then analyze World Bank data on multilateral "One Health" pandemic mitigation programs. We find that, because most pandemics have animal origins, mitigation is a more cost-effective policy than business-as-usual adaptation programs, saving between $344.0.7 billion and $360.3 billion over the next 100 y if implemented today. We conclude that globally coordinated pandemic prevention policies need to be enacted urgently to be optimally effective and that strategies to mitigate pandemics by reducing the impact of their underlying drivers are likely to be more effective than business as usual.


title: Analysis of COVID-19 infection spread in Japan based on stochastic transition model.

text: To assess the effectiveness of response strategies of avoiding large gatherings or crowded areas and to predict the spread of COVID-19 infections in Japan, we developed a stochastic transmission model by extending the Susceptible-Infected-Removed (SIR) epidemiological model with an additional modeling of the individual action on whether to stay away from the crowded areas. The population were divided into three compartments: Susceptible, Infected, Removed. Susceptible transitions to Infected every hour with a probability determined by the ratio of Infected and the congestion of area. The total area consists of three zones crowded zone, mid zone and uncrowded zone, with different infection probabilities characterized by the number of people gathered there. The time for each people to spend in the crowded zone is curtailed by 0, 2, 4, 6, 7, and 8 hours, and the time spent in mid zone is extended accordingly. This simulation showed that the number of Infected and Removed will increase rapidly if there is no reduction of the time spent in crowded zone. On the other hand, the stagnant growth of Infected can be observed when the time spent in the crowded zone is reduced to 4 hours, and the growth number of Infected will decrease and the spread of the infection will subside gradually if the time spent in the crowded zone is further cut to 2 hours. In conclusions The infection spread in Japan will be gradually contained by reducing the time spent in the crowded zone to less than 4 hours.


Nurses are always here, there, and everywhere.


title: A practice of anesthesia scenario design for emergency cesarean section in patients with COVID-19 infection based on the role of standard patient.

text: The new coronavirus (COVID-19) has been characterized as a world pandemic by WHO since March 11, 2020. Although it is likely that COVID-19 transmission is primarily via droplets and close contact, airborne transmission and fecal-oral route remains a possibility. The medical staff working in the operating room, such as anesthesiologists, surgeons and nurses, are at high risk of exposure to virus due to closely contacting patients. The perioperative management is under great challenge while performing surgeries for patients suffering COVID-19, including emergency cesarean section, which is one of the most common surgeries under such circumstances. How to prevent medical staff from cross-infection is an issue of great concern. In this article, we give a practice of anesthesia scenario design for emergency cesarean section in a supposed standard patient suffering COVID-19, aimed to optimize the work flow and implement the protective details through simulation of a real operation scenario, which may be useful for training and clinical practice of anesthesia management for patients suffering COVID-19 or other fulminating infectious diseases.


title: Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial.

text: BACKGROUND Ticagrelor is an effective antiplatelet therapy for patients with coronary atherosclerotic disease and might be more effective than aspirin in preventing recurrent stroke and cardiovascular events in patients with acute cerebral ischaemia of atherosclerotic origin. Our aim was to test for a treatment-by-ipsilateral atherosclerotic stenosis interaction in a subgroup analysis of patients in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial. METHODS SOCRATES was a randomised, double-blind, controlled trial of ticagrelor versus aspirin in patients aged 40 years or older with a non-cardioembolic, non-severe acute ischaemic stroke, or high-risk transient ischaemic attack from 674 hospitals in 33 countries. We randomly allocated patients (1:1) to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90, given orally) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90, given orally) within 24 h of symptom onset. Investigators classified all patients into atherosclerotic and non-atherosclerotic groups for the prespecified, exploratory analysis reported in this study. The primary endpoint was the time to occurrence of stroke, myocardial infarction, or death within 90 days. Efficacy analysis was by intention to treat. The SOCRATES trial is registered with ClinicalTrials.gov, number NCT01994720. FINDINGS Between Jan 7, 2014, and Oct 29, 2015, we randomly allocated 13 199 patients (6589 [50%] to ticagrelor and 6610 [50%] to aspirin). Potentially symptomatic ipsilateral atherosclerotic stenosis was reported in 3081 (23%) of 13 199 patients. We found a treatment-by-atherosclerotic stenosis interaction (p=0·017). 103 (6·7%) of 1542 patients with ipsilateral stenosis in the ticagrelor group and 147 (9·6%) of 1539 patients with ipsilateral stenosis in the aspirin group had an occurrence of stroke, myocardial infarction, or death within 90 days (hazard ratio 0·68 [95% CI 0·53-0·88]; p=0·003). In 10 118 patients with no ipsilateral stenosis, 339 (6·7%) of 5047 patients in the ticagrelor group had an occurrence of stroke, myocardial infarction, or death within 90 days compared with 350 (6·9%) of 5071 in the aspirin group (0·97 [0·84-1·13]; p=0·72). There were no significant differences in the proportion of life-threatening bleeding or major or minor bleeding events in patients with ipsilateral stenosis in the ticagrelor group compared with the aspirin group. INTERPRETATION In this prespecified exploratory analysis, ticagrelor was superior to aspirin at preventing stroke, myocardial infarction, or death at 90 days in patients with acute ischaemic stroke or transient ischaemic attack when associated with ipsilateral atherosclerotic stenosis. An understanding of stroke mechanisms and causes is important to deliver safe and efficacious treatments for early stroke prevention. FUNDING AstraZeneca.


title: Re-Sleeve Gastrectomy for Failed Primary Laparoscopic Sleeve Gastrectomy.

text: OBJECTIVE To investigate the effectiveness of re-sleeve gastrectomy (LRSG) in patients who had insufficient weight loss or weight regain after laparoscopic sleeve gastrectomy (LSG). STUDY DESIGN Descriptive study. PLACE AND DURATION OF STUDY Ortadogu Private Hospital, Turkey, between March 2013 and January 2017. METHODOLOGY Patients who underwent LRSG following LSG due to inadequate weight loss or weight regain retrospectively evaluated. Patients' demographics, comorbidities, and bariatric surgery outcomes, as well as hospitalisation rate, excess weight loss percentage (EWL%), and body mass index (BMI ) were recorded. Scheduled follow-up visits after surgery at 1, 3, 6, and 12 months post-surgery and every six months subsequently were done. RESULTS A total of 21 patients that underwent LRSG after LRG due to inadequate weight loss or a regain in weight. Of them, 7 (33.3%) were males, and 14 (66.7%) were females. The mean body weight index (BMI) before primary LSG was 52.3 ±4.7 Kg/m² and EWL% was 32.7 ±4.6. After an average follow-up of 24 months. BMI of patients before LRSG was 46.1 ±4.3 Kg/m². Following a 1-year observation, there was a substantial (p<0.001) improvement in BMI (21.6 ±3.1 Kg/m 2 ) and excess weight loss percentage (86.82% of EWL). CONCLUSION LRSG is an available and efficient method to correct the regain of weight or inadequate weight loss following LSG.


title: Transvaginal/transumbilical hybrid--NOTES--versus 3-trocar needlescopic cholecystectomy: short-term results of a randomized clinical trial.

text: OBJECTIVE For cholecystectomy, both the needlescopic cholecystectomy (NC) 3-trocar technique using 2 to 3 mm trocars and the umbilical-assisted transvaginal cholecystectomy (TVC) technique have found their way into clinical routine. This study compares these 2 techniques in female patients who are in need of an elective cholecystectomy. BACKGROUND Natural orifice transluminal endoscopic surgery (NOTES) is a surgical concept permitting scarless intra-abdominal operations through natural orifices, such as the vagina. Because of the lack of an adequately powered trial, we designed this first randomized controlled study for the comparison of TVC and NC. METHODS This prospective, randomized, nonblinded, single-center trial evaluates the safety and effectiveness of TVC (intervention), compared with NC (control) in female patients with symptomatic cholecystolithiasis. The primary endpoint was intensity of pain until the morning of postoperative day (POD) 2. Secondary outcomes were among others intra- and postoperative complications, procedural time, amount of analgesics used, pain intensity until POD 10, duration of hospital stay, satisfaction with the aesthetic result, and quality of life on POD 10 as quantified with the Eypasch Gastrointestinal Quality of Life Index (GIQLI). RESULTS Between February 2010 and June 2012, 40 patients were randomly assigned to the interventional or control group. All patients completed follow-up. Procedural time, length of postoperative hospital stay, and the rate of intra- and postoperative complications were similar in the 2 groups. However, significant advantages were found for the transvaginal access regarding pain until POD 2, but also until POD 10 (P = 0.043 vs P = 0.010) despite significantly less use of peripheral analgesics (P = 0.019). In the TVC group, patients were significantly more satisfied with the aesthetic result (P < 0.001) and had a significantly better GIQLI (P = 0.028). CONCLUSIONS Although comparable in terms of safety, TVC caused less pain, increased satisfaction with the aesthetic result, and improved postoperative quality of life in the short term.


COVID-19: time for WHO to reconsider its stance towards Taiwan.


title: First full-length sequences of the S gene of European isolates reveal further diversity among turkey coronaviruses.

text: An increasing incidence of enteric disorders clinically suggestive of the poult enteritis complex has been observed in turkeys in France since 2003. Using a newly designed real-time reverse transcriptase-polymerase chain reaction assay specific for the nucleocapsid (N) gene of infectious bronchitis virus (IBV) and turkey coronaviruses (TCoV), coronaviruses were identified in 37% of the intestinal samples collected from diseased turkey flocks. The full-length spike (S) gene of these viruses was amplified, cloned and sequenced from three samples. The French S sequences shared 98% identity at both the nucleotide and amino acid levels, whereas they were at most 65% and 60% identical with North American (NA) TCoV and at most 50% and 37% identical with IBV at the nucleotide and amino acid levels, respectively. Higher divergence with NA TCoV was observed in the S1-encoding domain. Phylogenetic analysis based on the S gene revealed that the newly detected viruses form a sublineage genetically related with, but significantly different from, NA TCoV. Additionally, the RNA-dependent RNA polymerase gene and the N gene, located on the 5' and 3' sides of the S gene in the coronavirus genome, were partially sequenced. Phylogenetic analysis revealed that both the NA TCoV and French TCoV (Fr TCoV) lineages included some IBV relatives, which were however different in the two lineages. This suggested that different recombination events could have played a role in the evolution of the NA and Fr TCoV. The present results provide the first S sequence for a European TCoV. They reveal extensive genetic variation in TCoV and suggest different evolutionary pathways in North America and Europe.


title: Clinical and Chest Radiography Features Determine Patient Outcomes In Young and Middle Age Adults with COVID-19.

text: Background Chest radiography (CXR) has not been validated for its prognostic utility in evaluating patients with coronavirus disease 2019 (COVID-19). Purpose The purpose of this study was to analyze the prognostic value of a CXR severity scoring system for younger (non-elderly) patients with COVID-19 upon initial presentation to the emergency department (ED). Outcomes of interest included hospitalization, intubation, prolonged stay, sepsis, and death. Materials & Methods In this retrospective study, patients between the ages of 21 and 50 years who presented to EDs of an urban multicenter health system from March 10 - 26, 2020 with COVID-19 confirmation on real-time reverse transcriptase polymerase chain reaction (RT-PCR) were identified. Each patient's ED CXR was divided into 6 zones and examined for opacities by two cardiothoracic radiologists with scores collated into a total concordant lung zone severity score. Clinical and laboratory variables were collected. Multivariable logistic regression was utilized to evaluate the relationship between clinical parameters, CXR scores, and patient outcomes. Results The study included 338 patients: 210 males (62%), median age 39 [31-45]. After adjustment for demographics and co-morbidities, independent predictors of hospital admission (n=145, 43%) were CXR severity score ≥ 2 (OR: 6.2, 95% CI 3.5-11, p<0.001) and obesity (OR 2.4 (1.1-5.4) or morbid obesity. Of patients who were admitted, a CXR score ≥3 was an independent predictor of intubation (n=28) (OR: 4.7, 95% CI 1.8-13, p=0.002) as was hospital site. We found no significant difference in primary outcomes across race/ethnicity, those with a history of tobacco use, asthma or diabetes mellitus type II. Conclusion For patients aged 21-50 with COVID-19 presenting to the emergency department, a chest x-ray severity score was predictive of risk for hospital admission and intubation.


title: Removal of the broken part of implantable cardioverter-defibrillator's electrode causing pulmonary embolism via femoral vein.

text: A 66-year-old patient with idiopathic dilated cardiomyopathy underwent transvenous extraction of an implantable cardioverter-defibrillator. The distal part of the electrode was broken during manual traction through the left subclavian vein. In the present case, we showed a rare complication of transvenous lead extraction and its management.


title: Long-term efficacy and safety of ustekinumab in 122 refractory Crohn's disease patients: a multicentre experience.

text: BACKGROUND Long-term outcome of ustekinumab in Crohn's disease (CD) has not been evaluated. AIM To evaluate the long-term efficacy and safety of ustekinumab and identify the predictive factors of ustekinumab failure-free persistence in a cohort of anti-TNF refractory CD patients. METHODS We performed a retrospective multicentre cohort study including all consecutive CD patients who began subcutaneous ustekinumab and presented a clinical response (defined as a significant improvement of CD-related clinical symptoms assessed by the patient's physician leading to continued ustekinumab) during the first year of treatment. Primary outcome was treatment failure defined as withdrawal of treatment due to loss of response, intolerance or need for surgery. RESULTS Eighty-eight of the 122 (72%) CD patients beginning ustekinumab from March 2011 to December 2014, responded to ustekinumab and were followed up until November 2016. Median time on ustekinumab was 26.6 (13.4-34.4) months. Forty-seven patients (54%) continued ustekinumab with a clinical response and 38 (43%) stopped treatment (32 for failure, five for remission and one for pregnancy). Endoscopic response was observed in 82% of patients with endoscopic evaluation and mucosal healing in 39%. Ustekinumab failure-free persistence rates were 78% at 12 months, 66% at 24 months and 55% at 36 months. No predictive factor of ustekinumab failure-free persistence was identified. One severe adverse event was observed (anal adenocarcinoma). CONCLUSION In this cohort of refractory CD patients receiving long-term ustekinumab therapy, more than 50% of patients continued ustekinumab treatment with no loss of response, intolerance or surgery and with a good safety profile.


title: Cathepsin B Protease Facilitates Chikungunya Virus Envelope Protein-Mediated Infection via Endocytosis or Macropinocytosis.

text: Chikungunya virus (CHIKV) is an enveloped virus that enters host cells and transits within the endosomes before starting its replication cycle, the precise mechanism of which is yet to be elucidated. Endocytosis and endosome acidification inhibitors inhibit infection by CHIKV, murine leukemia virus (MLV), or SARS-coronavirus, indicating that these viral entries into host cells occur through endosomes and require endosome acidification. Although endosomal cathepsin B protease is necessary for MLV, Ebola virus, and SARS-CoV infections, its role in CHIKV infection is unknown. Our results revealed that endocytosis inhibitors attenuated CHIKV-pseudotyped MLV vector infection in 293T cells but not in TE671 cells. In contrast, macropinocytosis inhibitors attenuated CHIKV-pseudotyped MLV vector infection in TE671 cells but not in 293T cells, suggesting that CHIKV host cell entry occurs via endocytosis or macropinocytosis, depending on the cell lines used. Cathepsin B inhibitor and knockdown by an shRNA suppressed CHIKV-pseudotyped MLV vector infection both in 293T and TE671 cells. These results show that cathepsin B facilitates CHIKV infection regardless of the entry pathway.


SARS-CoV-2-induced Acute Respiratory Distress Syndrome: Pulmonary Mechanics and Gas Exchange Abnormalities.


title: Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly identified betacoronavirus causing high morbidity and mortality in humans. The coronavirus spike (S) protein is the main determinant of viral entry, and although it was previously shown that MERS-CoV S can be activated by various proteases, the details of the mechanisms of proteolytic activation of fusion are still incompletely characterized. Here, we have uncovered distinctive characteristics of MERS-CoV S. We identify, by bioinformatics and peptide cleavage assays, two cleavage sites for furin, a ubiquitously expressed protease, which are located at the S1/S2 interface and at the S2' position of the S protein. We show that although the S1/S2 site is proteolytically processed by furin during protein biosynthesis, the S2' site is cleaved upon viral entry. MERS-CoV pseudovirion infection was shown to be enhanced by elevated levels of furin expression, and entry could be decreased by furin siRNA silencing. Enhanced furin activity appeared to partially override the low pH-dependent nature of MERS-CoV entry. Inhibition of furin activity was shown to decrease MERS-CoV S-mediated entry, as well as infection by the virus. Overall, we show that MERS-CoV has evolved an unusual two-step furin activation for fusion, suggestive of a role during the process of emergence into the human population. The ability of MERS-CoV to use furin in this manner, along with other proteases, may explain the polytropic nature of the virus.


title: Radiofrequency Ablation Versus Endoscopic Submucosal Dissection in Treating Large Early Esophageal Squamous Cell Neoplasia.

text: Radiofrequency ablation (RFA) and endoscopic submucosal dissection (ESD) can potentially be applied for early esophageal squamous cell neoplasia (ESCN); however, no study has directly compared these 2 modalities.We retrospectively enrolled the patients with flat-type "large" (length ≥3 cm extending ≥1/2 of the circumference of esophagus) early ESCNs treated endoscopically. The main outcome measurements were complete response at 12 months, and adverse events.Of a total of 65 patients, 18 were treated with RFA and 47 with ESD. The procedure time of RFA was significantly shorter than that of ESD (126.6 vs 34.8 min; P < 0.001). The complete resection rate of ESD and complete response rate after primary RFA were 89.3% and 77.8%, respectively. Based on the histological evaluation of the post-ESD specimens showed 14 of 47 (29.8%) had histological upstaging compared with the pre-ESD biopsies, and 4 of them had lymphovascular invasion requiring chemoradiation or surgery. After additional therapy for residual lesions, 46 (97.9%) patients in the ESD group and 17 (94.4%) patients in the RFA group achieved a complete response at 12 months. Four patients (8.5%) developed major procedure-related adverse events in the ESD group, but none in the RFA group. In patients with lesions occupying more than 3/4 of the circumference, a significantly higher risk of esophageal stenosis was noted in the ESD group compared with RFA group (83% vs 27%, P = 0.01), which required more sessions of dilatation to resolve the symptoms (median, 13 vs 3, P = 0.04). There were no procedure-related mortality or neoplastic progression in either group; however, 1 patient who received ESD and 1 who received RFA developed local recurrence during a median follow-up period of 32.4 (range, 13-68) and 18.0 (range, 13-41) months, respectively.RFA and ESD are equally effective in the short-term treatment of early flat large ESCNs; however, more adverse events occur with ESD, especially in lesions extending more than 3/4 of the circumference. RFA does not allow for pathology to evaluate the curability after ablation, and thus currently the use for invasive ESCNs should be conservative until longer follow-up studies are available.


docid: doqsytyl

title: Calibrated response to emerging infections.


title: Effectiveness, safety, and long-term outcomes of non-powered mechanical sheaths for transvenous lead extraction.

text: Aims To analyse the effectiveness, safety and long-term outcomes of conventional non-powered mechanical systems for transvenous lead extraction (TLE) performed by experienced first operators. Outcomes were assessed according to lead location and type of operating room in which the procedure was performed. Methods and results Data from 2049 patients (mean age: 65 years), with infectious (40%) or non-infectious (60%) indications, were analysed over a mean of 3.37 (±2.29) years. A total of 3426 leads were extracted; and, overall, 95% full procedural, 4% partial procedural, and 98% clinical success were demonstrated. Within the patient cohort, 1.8% (37/2049) experienced major complications, with cardiac tamponade being predominant (30/37). Cardiac tamponade was identified as the main cause of mortality, as well as the cause of all procedure-related deaths (6/2049; 0.3%). Cardiac tamponade occurred in 1.8% of atrial and 0.3% of right ventricular lead extractions, with fatal tamponade reported in 9% of atrial, 40% of ventricular, and 67% of coronary sinus lead extractions. No association between lead location and cardiac tamponade-related mortality was observed; however, lead location did affect the success of pericardiocentesis. The cardiac tamponade-related mortality rate was 37% when TLE was performed in an electrophysiology laboratory. No deaths were reported when the procedure was performed in a cardiac surgery or hybrid operating room. Long-term survival was improved when TLE was performed due to non-infectious indications, rather than pocket infection or lead-related endocarditis (P < 0.001). Conclusion Using conventional non-powered mechanical sheaths, TLE was effective even in patients at high risk of complications.


Implementing the universal protocol.


title: Disconnections between medical education and medical practice: A neglected dilemma.

text: Medical practice has changed profoundly over the past 60 years. Many changes have also been made in medical education, often with a view to countering adverse aspects of highly specialised, commercialised and bureaucratised modern medical practice. Regardless of the state of the world today and of the variety of changes that may occur in the years ahead, excellence in the application of bedside skills and technological advances, accompanied by excellence in humanistic aspects of caring for patients as people, will remain preeminent goals at the heart of medical practice. Powerful social forces that negatively influence practice cannot be counteracted through changes in medical education alone and need to be addressed directly within health systems. Shifting healthcare towards a valued social service is arguably essential for improving both public and individual health through more widespread universal access to high quality and effectively integrated health care.


title: Patterned enzymatic degradation of poly(ε-caprolactone) by high-affinity microcontact printing and polymer pen lithography.

text: This paper reports deposition of Candida antarctica Lipase B (CALB) on relatively thick poly(ε-caprolactone) (PCL) films (300-500 nm) to create well-defined patterns using two different writing techniques: high-affinity microcontact (HA-μCL) and polymer pen (PPL) lithography. For both, an aqueous CALB ink is absorbed onto a polydimethylsiloxane (PDMS) writing implement (PDMS stamp or a PDMS pen tip), which is transferred to a spun-cast PCL film. HA-μCL experiments demonstrated the importance of applied pressure to obtain high-resolution patterns since uniform contact is needed between raised 20 μm parallel line regions of the PDMS stamp and the surface. AFM imaging shows pattern formation evolves gradually over incubation time only in areas stamped with CALB cutting through spherulites without apparent influence by grain boundaries. Strong binding of CALB to PCL is postulated as the mechanism by which lateral diffusion is limited. PPL enables formation of an arbitrary image by appropriate programming of the robot. The PDMS pen tips were coated with an aqueous CALB solution and then brought into contact with the PCL film to transfer CALB onto the surface. By repeating the ink transfer step multiple times where pen tips are brought into contact with the PCL film at a different locations, a pattern of dots is formed. After printing, patterns were developed at 37 °C and 95% RH. Over a 7-day period, CALB progressively etched the PCL down to the silicon wafer on which it was spun (350 nm) giving round holes with diameters about 10 μm. AFM images show the formation of steep PCL walls indicating CALB degraded the PCL film in areas to which it was applied. This work demonstrates that high-resolution patterns can be achieved without immobilizing the enzyme on the surface of polymeric stamps that limits the depth of features obtained as well as the throughput of the process.


title: Effects of weaning and finishing feeding treatment on fatty acids, especially cis and trans C18:1 isomers, in the Longissimus thoracis muscle of Galician Blond calves.

text: Seven- to 10-month-old calves are the typical production of Galician Blond (GB), the most important bovine local beef breed in Spain. As meat lipid repercussions on human health depend on their fatty acid (FA) profile, this study aimed at analysing the individual FA at weaning and at the end of the feeding finishing period, especially trans and cis 18:1 isomers in total lipids of the Longissimus thoracis muscle in GB male calves. Distribution of main FA in veal lipids was characterized by gas-liquid chromatography (GLC) analysis on a high polar glass capillary column. Total trans and cis 18:1 isomers were purified, from total FA (TFA) methyl esters, by preparative reversed-phase high-performance liquid chromatography, to allow subsequent specific analysis of their different isomers by GLC. Calves stayed with their mothers at pasture for 2 or 5 months in intensive or semi-extensive systems, followed by an indoor feeding period. The weaned (W) group was finished on concentrate and hay, whereas the non-weaned (NW) group was finished on concentrate and hay and it continued suckling until slaughter. The studied effects did not present interactions. The duration of the indoor finishing period hardly had a significant influence on the parameters analysed. Compared to W calves, NW calves had higher proportions (% TFA) of 18:3n-3 (+38%, P < 0.0001), 20:5n-3 (+22%, P = 0.005), 22:5n-3 (+13%, P = 0.042), cis monounsaturated FA (MUFA; +8%, P = 0.032), total MUFA (+8%, P = 0.013), n-3 polyunsaturated FA (PUFA; +25%, P = 0.0001) and conjugated linoleic acid (CLA; +48%, P < 0.0001) to the detriment of 18:0 (-10%, P = 0.002), 18:2n-6 (-25%, P = 0.004) and n-6 PUFA (-20%, P = 0.011). With regard to cis and trans 18:1 isomers, NW calves had higher proportions (% total cis or trans 18:1) of Δ11trans and Δ16trans (+25% and +22%, respectively, P < 0.01) and Δ13 + 14trans (+13%, P < 0.05) and lower proportions of Δ6 to 8 and Δ10trans (-28% and 58%, respectively, P < 0.001). NW calves' meat might be more suitable for human health than W calves' meat due to the increase of anti-atherogenous FA such as n-3 PUFA, CLA and 18:1 Δ11trans.


title: Intraprocedural contrast-enhanced ultrasound-CT/MR fusion imaging assessment in HCC thermal ablation to reduce local tumor progression: compared with routine contrast-enhanced ultrasound.

text: Purpose: To evaluate whether local tumor progression (LTP) would be further reduced when contrast-enhanced ultrasound (CEUS)-CT/MR fusion imaging was used as intraprocedural assessment method in hepatocellular carcinoma (HCC) thermal ablation compared with routine CEUS. Materials and methods: This prospective non-randomized study was conducted from December 2010 to July 2012. CEUS-CT/MR fusion imaging and routine CEUS were used for treatment response assessment in the ablation procedure of 146 HCCs and 122 HCCs, respectively. Supplementary ablations were performed immediately if necessary. The primary technique efficacy rate, LTP rate and overall survival (OS) rate were calculated. Results: For CEUS-CT/MR fusion imaging and routine CEUS, the technical success rate, technique efficacy rate and supplementary ablation rate were 86.3% (126/146) and 98.4% (120/122) (p = .000), 99.2% (125/126) and 94.2% (113/120) (p = .032), and 14.3% (18/126) and 4.2% (5/120) (p = .006), respectively. The cumulative LTP rate and OS rate were not significantly different between fusion imaging group and routine CEUS group. However, for lesions that were larger than 3 cm or close to major vessels (41 lesions in fusion imaging group and 44 lesions in routine CEUS group, who received transcatheter arterial chemoembolization before ablation), the cumulative LTP rate was significantly lower in fusion imaging group than in routine CEUS group (p = .032). Conclusion: Although intraprocedural CEUS-CT/MR fusion imaging has certain limitations in application, it might provide a potential more efficient method compared with routine CEUS in reducing LTP in HCC thermal ablation, especially for difficult ablation lesions.


Ritonavir/Lopinavir and Its Potential Interactions With Psychiatric Medications: A COVID-19 Perspective.


title: Ultrasound Responsive Macrophase-Segregated Microcomposite Films for in Vivo Biosensing.

text: Ultrasound imaging is a safe, low-cost, and in situ method for detecting in vivo medical devices. A poly(methyl-2-cyanoacrylate) film containing 2 μm boron-doped, calcined, porous silica microshells was developed as an ultrasound imaging marker for multiple medical devices. A macrophase separation drove the gas-filled porous silica microshells to the top surface of the polymer film by controlled curing of the cyanoacrylate glue and the amount of microshell loading. A thin film of polymer blocked the wall pores of the microshells to seal air in their hollow core, which served as an ultrasound contrast agent. The ultrasound activity disappeared when curing conditions were modified to prevent the macrophase segregation. Phase segregated films were attached to multiple surgical tools and needles and gave strong color Doppler signals in vitro and in vivo with the use of a clinical ultrasound imaging instrument. Postprocessing of the simultaneous color Doppler and B-mode images can be used for autonomous identification of implanted surgical items by correlating the two images. The thin films were also hydrophobic, thereby extending the lifetime of ultrasound signals to hours of imaging in tissues by preventing liquid penetration. This technology can be used as a coating to guide the placement of implantable medical devices or used to image and help remove retained surgical items.


title: Health economics of use fluoroquinolones to treat patients with community-acquired pneumonia.

text: Respiratory diseases account for approximately 10% of all hospital admissions in the United States. Pneumonia constitutes 35% of these cases, with an average length of stay (LOS) of 5.1 days. It is estimated that $8.4 billion to $10 billion of all annual US hospital expenditures are attributable to community-acquired pneumonia (CAP). As such, medical decisions, including empiric antibiotic choice, potentially exert an impact on hospital LOS and associated costs. In this review, we focus on the empiric antibiotic choices and associated costs of treatment for hospitalized patients with CAP, focusing on the use of fluoroquinolone therapy as recommended by the CAP guidelines.


title: Can electromyographic arousal be detected visually on the Datex-Ohmeda S/5™ anesthesia monitor?

text: BACKGROUND Electroencephalogram (EEG)-based depth of anaesthesia monitoring is susceptible to contaminating electromyographic (EMG) activity. Many authorities have suggested that anaesthesiologists using these monitors should interpret the raw EEG waveform seen on the anaesthesia monitor. METHODS In 34 patients anaesthetized with propofol using two doses of rocuronium (0.6 and 1.2 mg/kg), we studied whether the EMG arousal can be detected visually on the anaesthesia monitor. The Bispectral Index (BIS) and Entropy biosignals on the monitor were recorded with a video camera, and the one-channel EEG recorded by the Entropy strip was collected on a laptop computer. The recordings and the one-channel EEG were analyzed offline by two experts (anaesthesiologist and neurophysiologist), both with a long experience on anaesthesia-related EEG. RESULTS EMG arousal existed in 14/34 and 13/33 patients in the BIS and Entropy biosignals, respectively. The anaesthesiologist detected EMG on the monitor in 7/14 patients with BIS (sensitivity 50%) and in 4/13 patients with Entropy (31%). The clinical neurophysiologist detected EMG in 6/14 (43%) patients with BIS and in 5/13 (38%) with Entropy. The specificity of the EMG analyses was 55 and 65% with BIS, and 85 and 90% with Entropy. EMG arousal was detected in BIS biosignal in 10/17 and 4/17 patients with 0.6 and 1.2 mg/kg doses of rocuronium (P = 0.04). CONCLUSIONS In contrast to many EEG phenomena, EMG activity cannot be accurately detected visually from the raw EEG on the anaesthesia monitor. Further development in the quality of the anaesthesia monitors is warranted.


docid: iwhfvdir

title: Nuclear magnetic resonance structure of the nucleic acid-binding domain of severe acute respiratory syndrome coronavirus nonstructural protein 3.

text: The nuclear magnetic resonance (NMR) structure of a globular domain of residues 1071 to 1178 within the previously annotated nucleic acid-binding region (NAB) of severe acute respiratory syndrome coronavirus nonstructural protein 3 (nsp3) has been determined, and N- and C-terminally adjoining polypeptide segments of 37 and 25 residues, respectively, have been shown to form flexibly extended linkers to the preceding globular domain and to the following, as yet uncharacterized domain. This extension of the structural coverage of nsp3 was obtained from NMR studies with an nsp3 construct comprising residues 1066 to 1181 [nsp3(1066-1181)] and the constructs nsp3(1066-1203) and nsp3(1035-1181). A search of the protein structure database indicates that the globular domain of the NAB represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. Two antiparallel two-strand beta-sheets and two 3(10)-helices are anchored against the surface of this barrel-like molecular core. Chemical shift changes upon the addition of single-stranded RNAs (ssRNAs) identified a group of residues that form a positively charged patch on the protein surface as the binding site responsible for the previously reported affinity for nucleic acids. This binding site is similar to the ssRNA-binding site of the sterile alpha motif domain of the Saccharomyces cerevisiae Vts1p protein, although the two proteins do not share a common globular fold.


title: Laparoscopic sphincter-saving surgery for low rectal cancer through marker meeting approach.

text: Laparoscopic low anterior resection (LAR) with sphincter preservation for ultra-low rectal cancer is always a challenging operation in colorectal surgery. To achieve negative margins, reducing the difficulty and risks of the procedure are major goals for us. The marker meeting approach we reported can help to accomplish this goal. The key technique for the marker meeting approach is to ensure a clear distal margin in a low resection of the rectum by transanal dissection. This procedure allows access to the space around the distal rectum and mesorectum and to pack the gauzes in the distal part of the space as a landmark. Routine laparoscopic LAR was performed to dissect the space until reaching the gauzes packed above and achieve complete mobilization of the rectum and mesorectum. This surgical procedure is simpler and reduces the difficulty of the operation. Therefore, it is expected to reduce the risk of surgery-related complications and positive margins and is suitable to be widely applied and extended in clinical practice. The short-term and long-term clinical outcomes of the marker meeting approach need more research in large samples.


title: Comparison of the effects of platelet-rich or growth factor-rich plasma on intestinal anastomosis healing in pigs.

text: BACKGROUND The use of autologous platelet-rich plasma (PRP) and plasma rich in growth factors (PRGF) has been proposed for the treatment of several acute and chronic syndromes, such as corneal epithelial defects and dry eye syndrome, gum bleeding during oral surgery, and in orthopaedic surgery. We hypothesized that PRGF, rather than PRP, could be more effective because of its intrinsic characteristics in promoting the healing of intestinal anastomosis. The purpose of the present study was to evaluate and compare the effects of PRP and PRGF on various parameters of anastomotic healing in a swine model. METHODS Eight female pigs were randomly assigned to two groups and subjected to hand sewn jeujuno-jejunal appositional extramucosal anastomoses. For each animal, a total of six anastomoses were performed: two were considered controls and received no treatment, while the remaining four anastomoses were treated with PRP or PRGF of which both were prepared at a platelet concentration that was respectively 3.4-fold and 2.81-fold higher than the original platelet count. In each animal, either PRP or PRGF was used as a treatment, to avoid interference among products. Animals were euthanized after 8 days and the anastomoses were evaluated and compared for the presence of adhesions, anastomotic leakage, bursting pressure, and histological appearance. RESULTS The concentration of platelets in PRP was 3.41-fold higher (range, 3.20-4.24) that the concentration in whole blood, while the concentration in PRGF was 2.81-fold higher (range, 2.89-4.88). The results obtained from the present study highlighted that there are no differences between anastomotic samples treated with either PRP or PRGF preparations, except for a significant increase in epithelization of the intestinal mucosa at the anastomotic site in the PRGF group. CONCLUSIONS Both PRP and PRGF suspensions should be considered a safe strategy and represent a relatively low-cost technology that is flexible enough to be applied in several therapeutic fields. No true benefit could be proven in our study compared to the no treatment following anastomoses formation, with the exception of enhanced epithelization of the mucosa in the PRGF group.


Cryptococcus gattii VGIIb-like Variant in White-Tailed Deer, Nova Scotia, Canada.


title: New insights into the molecular profile of lung adenocarcinoma and implications for therapy.

text: Lung cancer is a molecularly heterogeneous disease. The advent of next-generation sequencing techniques has significantly advanced our understanding of the complex molecular underpinnings of lung cancer. Furthermore, the development of targeted therapies has significantly altered the landscape of lung cancer therapy over the past decade. There is hence an increasing interest in developing a classification system that guides clinical management and also incorporates relevant genomic information. Here, we highlight the molecular features of lung adenocarcinoma as highlighted by several independent groups, and more recently The Cancer Genome Atlas and discuss their potential clinical significance.


title: Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.

text: Optical biosensor technology continues to be the method of choice for label-free, real-time interaction analysis. But when it comes to improving the quality of the biosensor literature, education should be fundamental. Of the 1413 articles published in 2008, less than 30% would pass the requirements for high-school chemistry. To teach by example, we spotlight 10 papers that illustrate how to implement the technology properly. Then we grade every paper published in 2008 on a scale from A to F and outline what features make a biosensor article fabulous, middling or abysmal. To help improve the quality of published data, we focus on a few experimental, analysis and presentation mistakes that are alarmingly common. With the literature as a guide, we want to ensure that no user is left behind.


title: Measurement issues when assessing quality of life outcomes for different types of hernia mesh repair.

text: INTRODUCTION The NHS is required to collect data from patient reported outcome measures (PROMs) for inguinal hernia surgery. We explored the use of one such measure, the Carolinas Comfort Scale(®) (CCS), to compare long-term outcomes for patients who received two different types of mesh. The CCS questionnaire asks about mesh sensation, pain and movement limitations, and combines the answers into a total score. PATIENTS AND METHODS A total of 684 patients were treated between January 2007 and August 2008 and were followed up in November 2009. RESULTS Data on 215 patients who met the inclusion criteria were available (96 patients who received Surgipro™ mesh and 119 who received Parietene™ Progrip™ mesh). Recurrence rates were similar in the Surgipro™ group (2/96, 2.1%) and Progrip™ group (3/118, 2.5%) (Fisher's exact test = 1.0). Chronic pain occurred less frequently in the Surgipro™ group (11/95, 11.6%) than in the Progrip™ group (22/118, 18.6%) (p<0.157). Overall, 90% of CCS total scores indicated a good outcome (scores of 10 or less out of 115). A principal component analysis of the CCS found that responses clustered into two subscales: 'mesh sensation' and 'pain+movement limitations'. The Progrip™ group had a slightly higher mesh sensation score (p<0.051) and similar pain+movement limitations scores (p<0.120). CONCLUSIONS In this study of quality of life outcomes related to different mesh types, the CCS subscales were more sensitive to differences in outcome than the total CCS score for the whole questionnaire. Future research should consider using the CCS subscales rather than the CCS total score.


title: Spectrum of Neurological Manifestations in Covid-19: A Review.

text: COVID-19, in most patients, presents with mild flu-like illness. Elderly patients with comorbidities, like hypertension, diabetes, or lung and cardiac disease, are more likely to have severe disease and deaths. Neurological complications are frequently reported in severely or critically ill patients with comorbidities. In COVID-19, both central and peripheral nervous systems can be affected. The SARS-CoV-2 virus causes the disease COVID-19 and has the potential to invade the brain. The SARS-CoV-2 virus enters the brain either via a hematogenous route or olfactory system. Angiotensin-converting enzyme two receptors, present on endothelial cells of cerebral vessels, are a possible viral entry point. The most severe neurological manifestations, altered sensorium (agitation, delirium, and coma), are because of hypoxic and metabolic abnormalities. Characteristic cytokine storm incites severe metabolic changes and multiple organ failure. Profound coagulopathies may manifest with ischemic or hemorrhagic stroke. Rarely, SARS-CoV-2 virus encephalitis or pictures like acute disseminated encephalomyelitis or acute necrotizing encephalopathy have been reported. Nonspecific headache is a commonly experienced neurological symptom. A new type of headache "personal protection equipment-related headache" has been described. Complete or partial anosmia and ageusia are common peripheral nervous system manifestations. Recently, many cases of Guillain-Barré syndrome in COVID-19 patients have been observed, and a postinfectious immune-mediated inflammatory process was held responsible for this. Guillain-Barré syndrome does respond to intravenous immunoglobulin. Myalgia/fatigue is also common, and elevated creatine kinase levels indicate muscle injury. Most of the reports about neurological complications are currently from China. COVID-19 pandemic is spreading to other parts of the world; the spectrum of neurological complications is likely to widen further.


title: Robot-Assisted Sacrocolporectopexy for Multicompartment Prolapse of the Pelvic Floor: A Prospective Cohort Study Evaluating Functional and Sexual Outcome.

text: BACKGROUND Pelvic floor disorders are a major public health issue. For female genital prolapse, sacrocolpopexy is the gold standard. Laparoscopic ventral mesh rectopexy is a relatively new and promising technique correcting rectal prolapse. There is no literature combining the 2 robotically assisted techniques. OBJECTIVE This study was designed to evaluate the safety, quality of life, and functional and sexual outcomes of robot-assisted sacrocolporectopexy for multicompartment prolapse of the pelvic floor. DESIGN This was a prospective, observational cohort study. SETTINGS The study was conducted in a tertiary care setting. PATIENTS All sexually active patients undergoing robot-assisted sacrocolporectopexy at our institution between 2012 and 2014 were included. INTERVENTION Robot-assisted sacrocolporectopexy was the study intervention. MAIN OUTCOME MEASURES Preoperative and postoperative (12 months) questionnaires using the Urinary Distress Inventory, Pescatori Incontinence Scale, Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, and Pelvic Floor Impact Questionnaire were completed. In addition Wexner and Vaizey incontinence scores and the Wexner constipation score were recorded postoperatively. RESULTS Fifty-one patients underwent robot-assisted sacrocolporectopexy (median follow-up, 12.5 months). The simplified Pelvic Organ Prolapse Quantification improved significantly (p < 0.0005) for all 4 of the anatomic landmarks. Both median fecal (preoperative and postoperative Pescatori 4 vs 3, p = 0.002) and urinary incontinence scores (Urinary Distress Inventory, 27.8 vs 22.2; p < 0.0005) improved significantly at 12 months. Postoperatively median Wexner (3) and Vaizey incontinence (6) and Wexner Constipation (7) scores were noted. A positive effect on sexual function (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire score 31.8 vs 35.9; p = 0.002) and quality of life for each compartment (p < 0.0005) was observed. One patient (2%) developed mesh erosion. No multicompartment recurrences were detected. LIMITATIONS This was a observational study with a limited follow-up, no control group, and no preoperatively validated constipation score. CONCLUSIONS Robot-assisted sacrocolporectopexy is a safe and effective technique for multicompartment prolapse in terms of functional outcome, quality of life, and sexual function.


title: Live attenuated Salmonella enterica serovar Typhimurium expressing swine interferon-alpha has antiviral activity and alleviates clinical signs induced by infection with transmissible gastroenteritis virus in piglets.

text: Enhancing innate and acquired immunity by cytokines such as IFN-alpha appears to be useful as a first line of defense against viral infection. However, the practical use of cytokines in livestock is not evident due to cost and production issues associated with mass administration. In this study, we tested the efficacy of live attenuated Salmonella enterica serovar Typhimurium designed to secrete swine IFN-alpha (swIFN-alpha) protein for preventing the clinical signs caused by infection with transmissible gastroenteritis virus (TGEV), one of the diarrhea-causing viruses in the swine industry. Attenuated Salmonella vaccine (chi8501) containing swIFN-alpha-encoding pYA3560 vector (chi8501/swIFN-alpha) successfully induced the secretion of swIFN-alpha protein into the culture supernatants, as confirmed by SDS-PAGE and Western blot. The culture supernatants of chi8501/swIFN-alpha had antiviral activity against TGEV with 50% effective dose (ED(50)) of 320 per mg of supernatant protein. In addition, oral administration of chi8501/swIFN-alpha reduced the severity of clinical signs caused by TGEV infection with the effect more apparent at 6-8 days post-infection, and reduced excretion of TGEV in feces. Similarly, the amount of TGEV in intestinal tissues and mesenteric lymph node of chi8501/swIFN-alpha-administered piglets was lower than in piglets that were treated with control bacteria. These results indicate the value of attenuated Salmonella vaccines as delivery systems of cytokines that can be used for mass administration, thereby overcoming cost and production issues.


title: Head position and cerebral blood flow in acute ischemic stroke patients: Protocol for the pilot phase, cluster randomized, Head Position in Acute Ischemic Stroke Trial (HeadPoST pilot).

text: RATIONALE Few proven interventions exist for acute ischemic stroke (AIS), and most are expensive and restricted in applicability. Lying flat 'head down' positioning of AIS patients has been shown to increase by as much as 20%, mean cerebral blood flow velocities (CBFV) measured by transcranial Doppler (TCD) but whether this translates into clinical improvement is uncertain. AIM To determine if the lying flat position increases mean CBFV in the affected territory as compared to the sitting up position in AIS patients. METHODS AND DESIGN Head Position in Acute Ischemic Stroke Trial (HeadPoST pilot) is a cluster randomized (clusters being months), assessor-blinded end-point, phase IIb trial, where consecutive adults with anterior circulation AIS within 12 h of symptom onset are positioned to a randomized position for 48 h with TCD performed serially. STUDY OUTCOMES Primary outcome is mean CBFV on TCD at 1 and 24 h after positioning. Secondary outcomes include: serious adverse events, neurological impairment at seven days, and death and disability at 90 days. SAMPLE SIZE ESTIMATES Assuming an increase of 8.3 (SD 11.4) cm/s in average of mean CBFV when tilted from 30° to 0°, 46 clusters are required (92 patients in total) to detect a 20% increase of mean CBFV with 90% power and 5% level of significance. CONCLUSION HeadPoST pilot is a cluster randomized multicenter clinical trial investigating the effect of head positioning on mean CBFV in anterior circulation AIS.


title: Endovascular treatment of fusiform cerebral aneurysms with the Pipeline Embolization Device.

text: OBJECT Despite advances in surgical and endovascular techniques, fusiform aneurysms remain a therapeutic challenge. Introduction of flow-diverting stents has revolutionized the treatment of aneurysms with wide necks and of complex morphology. The authors report their experience with the endovascular treatment of fusiform aneurysms using the Pipeline Embolization Device. METHODS A retrospective review of 146 patients with cerebral aneurysms treated with the Pipeline Embolization Device between June 2011 and January 2013 was performed. Twenty-four patients were identified as having fusiform aneurysms. Twenty-four aneurysms in these 24 patients were treated. The mean patient age was 59 years. There were 9 men and 15 women. Angiographic and clinical data (including the modified Rankin Scale [mRS] score) were recorded at the time of treatment and at follow-up. The aneurysms were located in the internal carotid artery in 8 patients (33.3%), middle cerebral artery in 8 patients (33.3%), anterior cerebral artery in 1 patient (4%), and vertebrobasilar circulation in 7 patients (29%). The aneurysms were smaller than 10 mm in 3 patients, 10-25 mm in 16 patients, and larger than 25 mm in 5 patients. The mean largest dimension diameter was 18 mm. RESULTS Stent deployment was successful in all cases. The minor procedural morbidity was 4% (1 case). Morbidity and mortality related to aneurysm treatment were 4.2% and 4.2%, respectively. The mean mRS scores preoperatively and at clinical follow-up (median 6.0 months, mean 6.9 months) were 0.71 and 1.2, respectively (91.7% presented with an mRS score of 2 or better, and 79.2% had an mRS score of 2 or better at the 6.0-month follow-up). At clinical follow-up, 82.6% of patients were stable or had improved, 13.0% worsened, and 4.2% had died. Twenty-two (91.7%) of 24 patients had follow-up angiography available (mean follow-up time 6.3 months); 59% had excellent angiographic results (> 95% or complete occlusion), 31.8% had complete aneurysm occlusion, 27.3% had greater than 95% aneurysm occlusion, 18.2% had a moderate decrease in size (50%-95%), 4.5% had a minimal decrease in size (< 50%), 13.6% had not changed, and 4.5% had an increase in size. CONCLUSIONS This series demonstrates that endovascular treatment of fusiform cerebral aneurysms with flow diversion was a safe and effective treatment. Procedural complications were low. Long-term morbidity and mortality rates were acceptable given the complex nature of these lesions.


title: Transpapillary drainage has no added benefit on treatment outcomes in patients undergoing EUS-guided transmural drainage of pancreatic pseudocysts: a large multicenter study.

text: BACKGROUND AND AIMS The need for transpapillary drainage (TPD) in patients undergoing transmural drainage (TMD) of pancreatic fluid collections (PFCs) remains unclear. The aims of this study were to compare treatment outcomes between patients with pancreatic pseudocysts undergoing TMD versus combined (TMD and TPD) drainage (CD) and to identify predictors of symptomatic and radiologic resolution. METHODS This is a retrospective review of 375 consecutive patients with PFCs who underwent EUS-guided TMD from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TMD and CD technical success, treatment outcomes (symptomatic and radiologic resolution) at follow-up, and predictors of treatment outcomes on logistic regression. RESULTS A total of 375 patients underwent EUS-guided TMD of PFCs, of which 174 were pseudocysts. TMD alone was performed in 95 (55%) and CD in 79 (45%) pseudocysts. Technical success was as follows: TMD, 92 (97%) versus CD, 35 (44%) (P = .0001). There was no difference in adverse events between the TMD (15%) and CD (14%) cohorts (P = .23). Median long-term (LT) follow-up after transmural stent removal was 324 days (interquartile range, 72-493 days) for TMD and 201 days (interquartile range, 150-493 days) (P = .37). There was no difference in LT symptomatic resolution (TMD, 69% vs CD, 62%; P = .61) or LT radiologic resolution (TMD, 71% vs CD, 67%; P = .79). TPD attempt was negatively associated with LT radiologic resolution of pseudocyst (odds ratio, 0.11; 95% confidence interval, 0.02-0.8; P = .03). CONCLUSIONS TPD has no benefit on treatment outcomes in patients undergoing EUS-guided TMD of pancreatic pseudocysts and negatively affects LT resolution of PFCs.


Throat and ear infections in children: URTI in the time of COVID-19.


title: Deubiquitinating and interferon antagonism activities of coronavirus papain-like proteases.

text: Coronaviruses encode multifunctional proteins that are critical for viral replication and for blocking the innate immune response to viral infection. One such multifunctional domain is the coronavirus papain-like protease (PLP), which processes the viral replicase polyprotein, has deubiquitinating (DUB) activity, and antagonizes the induction of type I interferon (IFN). Here we characterized the DUB and IFN antagonism activities of the PLP domains of human coronavirus NL63 and severe acute respiratory syndrome (SARS) coronavirus to determine if DUB activity mediates interferon antagonism. We found that NL63 PLP2 deconjugated ubiquitin (Ub) and the Ub-line molecule ISG15 from cellular substrates and processed both lysine-48- and lysine-63- linked polyubiquitin chains. This PLP2 DUB activity was dependent on an intact catalytic cysteine residue. We demonstrated that in contrast to PLP2 DUB activity, PLP2-mediated interferon antagonism did not require enzymatic activity. Furthermore, addition of an inhibitor that blocks coronavirus protease/DUB activity did not abrogate interferon antagonism. These results indicated that a component of coronavirus PLP-mediated interferon antagonism was independent of protease and DUB activity. Overall, these results demonstrate the multifunctional nature of the coronavirus PLP domain as a viral protease, DUB, and IFN antagonist and suggest that these independent activities may provide multiple targets for antiviral therapies.


title: Analysis of social networks supporting the self-management of type 2 diabetes for people with mental illness.

text: BACKGROUND People with mental illness have been identified as being more likely to experience type 2 diabetes and the complications arising from this, necessitating more complex chronic illness self-management. Social support has been identified as a significant factor in the successful adoption of lifestyle change for people with type 2 diabetes, however people with mental illness often have impoverished social networks leading to greater reliance upon professional care givers. This study maps the support provided by formal (paid and professional carers) and informal networks to people with mental illness and type 2 diabetes, comparing the experiences of people with a spouse with those without one. METHODS Interviews were conducted with 29 clients of a community nursing service with mental health problems who receive professional support to self-manage type 2 diabetes. Participants were asked to complete an egocentric social network map which involved mapping the people and services who support them to manage their health. Demographic data was collected as was data about co-morbidities and service use within the last 6 months. Network maps were supplemented by a series of open-ended questions about self-management practices, who supports these practices and what support they provide. RESULTS Participants identified small social networks with few friendship ties. These networks had diminished due to illness. For people with a spouse, this person provided significant support for chronic illness self-management performing a range of daily care and illness management tasks. People without a spouse were more reliant on professional and paid care givers for daily care and illness management. People without a spouse also demonstrated greater reliance upon weak social ties for emotional support and social connection and often developed friendships with formal caregivers. CONCLUSIONS Spousal support reduces the need for professional services. In the absence of a spouse, participants were more reliant upon paid and professional carers and weaker social ties for chronic illness support and social connection leading to greater vulnerability of loss of support.


title: Usefulness of the Pipeline Embolic Device for Large and Giant Carotid Cavernous Aneurysms.

text: PURPOSE Conventional coil embolization for large carotid cavernous aneurysms (CCAs) has limited utility due to its inability to prevent recurrences and reduce mass effect. Trapping of the parent artery may have a risk of ischemic complications due to intracranial perfusion disorders. We successfully treated 24 patients with large CCAs using a flow diverter (Pipeline™ embolic device: PED), and this report discusses the safety and efficacy of this method. MATERIALS AND METHODS Twenty four patients (23 females, mean age 71.5 years old) with large CCAs, including 6 giant CCAs, were treated with a PED over three years. Under sufficient dual anti-platelet management, the PED was deployed over the orifice of the aneurysm. Two patients required multiple telescoping stents. Clinical and radiological states were checked with MRI at 1, 3 and 6 months post-surgically. Angiographic follow-up was performed at 6 months. RESULTS In all patients, PED was appropriately deployed. Stagnation of contrast with eclipse signs was observed post-angiogram in 21 cases. One patient requiring 5 telescoping stents experienced temporary ischemic symptoms. Fourteen patients experienced improvement of ocular motor impairment deficiency, including 6 patients who recovered. Angiograms at 6 months follow-up showed complete occlusion in 63% (12/19) of patients, and MRI showed reduction of aneurysm volume in 89% (17/19) of patients. CONCLUSION Flow diverters for large CCAs showed promising clinical and radiological efficacy. They can shrink the aneurysm and improve symptoms without sacrificing the parent artery. It will be necessary to summarize the cases and to verify the long-term results.


docid: eajdwnjt

title: Laparoscopic Surgical Skills programme: preliminary evaluation of Grade I Level 1 courses by trainees.

text: INTRODUCTION New training models are needed to maintain safety and quality of surgical performance. A simulated setting using virtual reality, synthetic, and/or organic models should precede traditional supervised training in the operating room. AIM The aim of the paper is to describe the Laparoscopic Surgical Skills (LSS) programme and to provide information about preliminary evaluation of Grade I Level 1 courses, including overall quality, applicability of the course content in practice and the balance between theory and hands-on training modules, by participating trainees. MATERIAL AND METHODS During 5 accredited LSS Grade I Level 1 courses held in Eindhoven (the Netherlands), Kosice (Slovak Republic), and Lisbon (Portugal) between April 2011 and January 2012, demographic data and pre-course surgical experience in laparoscopic surgery of the participants were recorded. The final course evaluation form was completed by each participant after the course (anonymous) to evaluate course progress, course materials, assessment, staff, location and overall impression of the course on a 1-10 scale to obtain feedback information. RESULTS Forty-seven surgeons of 5 different nationalities were enrolled in an LSS Grade I Level 1 programme. Most participants were first or second year residents (n = 25), but also already established surgeons took part (n = 6). The mean age of the participants was 31.2 years (SD = 2.86), the male/female ratio was 32/15, and previous experience with laparoscopic surgery was limited. Overall impression of the course was rated with 8.7 points (SD = 0.78). The applicability of the course content in practice and the balance between theory and hands-on training were also rated very well - mean 8.8 (SD = 1.01) and 8.1 points (SD = 0.80) respectively. CONCLUSIONS Laparoscopic Surgical Skills Grade I Level 1 courses are evaluated as well balanced, with content applicable in clinical practice, meeting the expectations of individual participants. International interest in the programme suggests that LSS might become the future European standard in surgical education in laparoscopic surgery. Further conclusions concerning success of the programme may be drawn after the completion of clinical assessment of enrolled participants.