title: Acute adverse events in cardiac MR imaging with gadolinium-based contrast agents: results from the European Society of Cardiovascular Radiology (ESCR) MRCT Registry in 72,839 patients.

text: OBJECTIVES To assess the incidence of acute adverse events (AAEs) in gadolinium-enhanced cardiac magnetic resonance (CMR) imaging. METHODS Gadolinium-based contrast agent (GBCA)-enhanced CMR data from the multinational, multicenter European Society of Cardiovascular Radiology MRCT Registry was included. AAE severity was classified according to the American College of Radiology Manual on Contrast Media (mild, moderate, severe). Multivariable generalized linear mixed effect models were used to assess the likelihood of AAEs in various GBCA, adjusting for pharmacological stressor, main indications (i.e., suspected or known coronary artery disease or myocarditis), age, sex, and submitting center as a random effect. RESULTS In the study population of 72,839 GBCA-enhanced CMRs, a total of 260 AAEs were reported (0.36%), with a minority of severe AAEs (n = 24, 0.033%). Allergic-like AAEs were less likely than physiologic AAEs (29% versus 71%). Patients without pharmacological stress imaging had a lower AAE rate (0.22%) compared to stress imaging (0.75%), with the highest AAE rates for regadenoson (2.95%). AAE rates also varied by GBCA subtype (overall p < 0.001). There was significant interaction between GBCA and pharmacological stressor (interaction p = 0.025), with AAE rates ranging between 0 and 10% for certain GBCA/stressor combinations. There was further marginal evidence that higher GBCA volume was associated with higher AAE incidence (OR = 1.02, p = 0.05). CONCLUSION GBCA-enhanced CMR imaging demonstrates low AAE rates comparable to those of other body regions. AAE likelihood correlates with GBCA subtype, pharmacological stressor, and imaging indication. Intravenous fluid administration in patients with cardiac impairment might contribute to these findings. KEY POINTS • Acute adverse event rates in cardiac magnetic resonance (CMR) imaging with gadolinium-based contrast agents (GBCAs) are low (0.36%), especially for severe adverse events (0.033%). • Mild and moderate adverse events are more frequent during stress CMR imaging. • Physiologic AAEs are more common than allergic AAEs in CMR imaging.


Possible treatment of Covid-19 with a therapeutic vaccine.


title: The Clinical Efficacy of ReCell® Autologous Cell Regeneration Techniques Combined with Dermabrasion Treatment in Acne Scars.

text: OBJECTIVE To evaluate the efficacy of ReCell® autologous cell regeneration techniques combined with dermabrasion treatment on the therapy of acne scars. METHODS We analyzed retrospectively 78 patients with acne scars who presented to the Department of Plastic Surgery at Peking Union Medical College Hospital from May 2015 to May 2017; 30 patients were treated with dermabrasion (Group 1), and the other 48 patients were treated with ReCell® autologous regeneration techniques combined with dermabrasion (Group 2). Efficacy was evaluated through self-evaluation of the patient, third-party evaluation and photographs taken before and after treatment. The wound healing time and postoperative complication rate were also recorded. RESULTS The study revealed a significant difference in healing time (P < 0.001) between patients treated with dermabrasion (Group 1) and patients treated with ReCell® autologous regeneration techniques combined with dermabrasion (Group 2). The average healing time of Group 1 was 12.30 ± 1.725 days, while the average healing time of Group 2 was 5.27 ± 1.086 days. In Group 2, patient self-evaluation and third-party evaluation were more satisfactory than those of Group 1 (P < 0.001). Moreover, there were no postoperative complications in Group 2 such as pigmentation and scar hyperplasia. CONCLUSION The ReCell® technique is simple, minimally invasive, biocompatible and effective in the treatment of acne scars. It can shorten healing time and reduce the occurrence of postoperative complications, thereby providing a safe and effective treatment approach for patients with facial acne scars. LEVEL OF EVIDENCE IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


What the law says about PPE responsibility.


title: Hemoadsorption of high-mobility group box chromosomal protein 1 using a column for large animals.

text: BACKGROUND High-mobility group box chromosomal protein 1 (HMGB1) has recently been identified as an important mediator of various kinds of acute and chronic inflammation. A method for efficiently removing HMGB1 from the systemic circulation could be a promising therapy for HMGB1-mediated inflammatory diseases. MATERIALS AND METHODS In this study, we produced a new adsorbent material by chemically treating polystyrene fiber. We first determined whether the adsorbent material efficiently adsorbed HMGB1 in vitro using a bovine HMGB1 solution and a plasma sample from a swine model of acute liver failure. We then constructed a column by embedding fabric sheets of the newly developed fibers into a cartridge and tested the ability of the column to reduce plasma HMGB1 levels during a 4-hour extracorporeal hemoperfusion in a swine model of acute liver failure. RESULTS The in vitro adsorption test of the new fiber showed high performance for HMGB1 adsorption (96% adsorption in the bovine HMGB1 solution and 94% in the acute liver failure swine plasma, 2 h incubation at 37°C; p < 0.05 vs. incubation with no adsorbent). In the in vivo study, the ratio of the HMGB1 concentration at the outlet versus the inlet of the column was significantly lower in swine hemoperfused with the newly developed column (53 and 61% at the beginning and end of perfusion, respectively) than in those animals hemoperfused with the control column (94 and 93% at the beginning and end of perfusion, respectively; p < 0.05). Moreover, the normalized plasma level of HMGB1 was significantly lower during perfusion with the new column than with the control column (p < 0.05 at 1, 2, and 3 h after initiation of perfusion). CONCLUSION These data suggest that the newly developed column has the potential to effectively adsorb HMGB1 during hemoperfusion in swine.


title: Multiplex Ventilation: A Simulation-based Study of Ventilating Two Patients with One Ventilator.

text: BACKGROUND The overwhelming demand for mechanical ventilators due to COVID-19 has stimulated interest in using one ventilator for multiple patients (multiplex ventilation). Despite a plethora of information on the Internet, there is little supporting evidence and no human studies. The risk of multiplex ventilation is that ventilation and PEEP effects are largely uncontrollable and depend on the difference between patient resistance, (R) and compliance (C). It is not clear whether volume control or pressure control is safer or more effective. We designed a simulation-based study to allow complete control over the relevant variables to determine the effects of various degrees of RC imbalance on tidal volume (VT), end-expiratory lung volume (VEE), and imputed pH. METHODS Two separate breathing simulators were ventilated with a ventilator using pressure control (PC) and volume control (VC) breaths. Evidence-based lung models simulated a range of differences in R and C (six pairs of simulated patients). Differences in VT, VEE, and imputed pH were recorded. RESULTS Depending on differences in R and C, differences in VT ranged from 1% (equal R and C) to 79%. Differences in VEE ranged from 2% to 109%. Differences in pH ranged from 0% to 5%. Failure due to excessive tidal volume (> 8 mL/kg) did not occur. Failure due to excessive VEE difference (> 10%) was evident in 50% of patient pairs. There was no difference in failure rate between VC and PC. CONCLUSIONS These experiments confirmed the potential for markedly different ventilation and oxygenation for patients with uneven respiratory system impedances during multiplex ventilation. Three critical problems must be solved to minimize risk: (1) partitioning of inspiratory flow from the ventilator individually between the two patients, (2) measurement of VT delivered to each patient, and (3) provision for individual PEEP. We provide suggestions for solving these problems.


ASGE guideline on screening and surveillance of Barrett's esophagus.


title: Flow Diversion for Intracranial Aneurysm Management: A New Standard of Care.

text: Endovascular treatment of intracranial aneurysms with complex morphologies such as giant, wide-necked, or fusiform aneurysms is challenging. Stent-assisted coiling and balloon-assisted coiling are alternative techniques to treat such complex aneurysms, but studies have shown less-than-expected efficacy, as suggested by their high rate of recanalization. The management of complex aneurysms via microsurgery or conventional neuroendovascular strategies has traditionally been poor. However, over the last few years, flow-diverting stents (FDS) have revolutionized the treatment of such aneurysms. FDS are implanted within the parent artery rather than the aneurysm sac. By modifying intra-aneurysmal and parent-vessel flow dynamics at the aneurysm/parent vessel interface, FDS trigger a cascade of gradual intra-aneurysmal thrombosis. As endothelialization of the FDS is complete, the parent vessel reconstructs while preserving the patency of normal perforators and side branch vessels. As with any intervention, the practice and application of flow-diversion technology is inherent, with risks that include vessel rupture or perforation, in-stent thrombosis, perforator occlusion, procedural and delayed hemorrhages, and perianeurysmal edema. Herein, we review the devices, their mechanisms of actions, clinical applications, complications, and ongoing studies.


Parainfluenza virus type 3 outbreak in a neonatal nursery.


title: Notch Signaling Promotes Development of Allergic Rhinitis by Suppressing Foxp3 Expression and Treg Cell Differentiation.

text: BACKGROUND The Notch signaling pathway plays an important role in regulating human immune function, but the relationship between allergic rhinitis (AR) and Notch signaling remains unclear. OBJECTIVE To investigate the role of Notch signaling in the pathogenesis of AR and its regulation on Foxp3-Treg cells. METHOD The sera of 100 patients with AR and 50 controls were collected to assess the differences in Notch1, Jagged1, and DLL1 (Delta-like 1) expression. Experimental mice were divided into normal control, AR, Notch inhibitor, and dexamethasone groups. Allergic symptoms, total IgE levels, and the proportion of Treg cells in the peripheral blood were detected. Notch1, Jagged1, NICD (Notch intracellular domain, also known as ICN), and Foxp3 expression and Th1/Th2/Th17-related cytokines in the spleen were detected and compared between each group of mice. RESULTS Compared with the control group, the expression of Notch1 and Jagged1 in patients with AR was significantly elevated (p < 0.05). The expression of Notch1 and Jagged1 in patients with severe AR was higher than that observed in the mild to moderate AR patients and positively correlated with the levels of allergen sIgE (p < 0.05). The animal experiments revealed that compared with the normal control group, the expression of Notch1, Jagged1, and NICD in the AR group was increased, Foxp3 expression was decreased, and the proportion of Treg cells was decreased (p < 0.05). Compared with the AR group, allergic symptoms and total serum IgE levels and the expression of Notch1, Jagged1, and NICD were significantly decreased in the Notch inhibited group, whereas the expression of Foxp3 and the proportion of Treg cells were increased significantly (p < 0.05). The Th2-type immune responses were also enhanced and Th1-type immune responses decreased in the AR group, but the Th1/Th2 imbalance was reversed in the Notch inhibited group. CONCLUSION Notch signaling downregulates Foxp3 expression and inhibits the differentiation of Treg cells to promote the development of AR. Blocking Notch signaling may be a potential treatment for AR.


title: Low-dose single acquisition rest (99m)Tc/stress (201)Tl myocardial perfusion SPECT protocol: phantom studies and clinical validation.

text: PURPOSE We developed and tested a single acquisition rest (99m)Tc-sestamibi/stress (201)Tl dual isotope protocol (SDI) with the intention of improving the clinical workflow and patient comfort of myocardial perfusion single photon emission computed tomography (SPECT). METHODS The technical feasibility of SDI was evaluated by a series of anthropomorphic phantom studies on a standard SPECT camera. The attenuation map was created by a moving transmission line source. Iterative reconstruction including attenuation correction, resolution recovery and Monte Carlo simulation of scatter was used for simultaneous reconstruction of dual tracer distribution. For clinical evaluation, patient studies were compared to stress (99m)Tc and rest (99m)Tc reference images acquired in a 2-day protocol. Clinical follow-up examinations like coronary angiography (CAG) and fractional flow reserve (FFR) were included in the assessment if available. RESULTS Phantom studies demonstrated the technical feasibility of SDI. Artificial lesions inserted in the phantom mimicking ischaemia could be clearly identified. In 51/53 patients, the image quality was adequate for clinical evaluation. For the remaining two obese patients with body mass index > 32 the injected (201)Tl dose of 74 MBq was insufficient for clinical assessment. In answer to this the (201)Tl dose was adapted for obese patients in the rest of the study. In 31 patients, SDI and (99m)Tc reference images resulted in equivalent clinical assessment. Significant differences were found in 20 patients. In 18 of these 20 patients additional examinations were available. In 15 patients the diagnosis based on the SDI images was confirmed by the results of CAG or FFR. In these patients the SDI images were more accurate than the (99m)Tc reference study. In three patients minor ischaemic lesions were detected by SDI but were not confirmed by CAG. In one of these cases this was probably caused by pronounced apical thinning. For two patients no relevant clinical follow-up information was available for evaluation. CONCLUSION The proposed SDI protocol has the potential to improve clinical workflow and patient comfort and suggests improved accuracy as demonstrated in the clinical feasibility study.


title: Laparoscopic pancreaticoduodenectomy in Brisbane, Australia: an initial experience.

text: BACKGROUND The role of minimally invasive approach for pancreaticoduodenectomy has not yet been well defined in Australia. We present our early experience with laparoscopic pancreaticoduodenectomy (LPD) from Brisbane, Australia. METHODS Retrospective review in a prospectively collected database of patients undergoing LPD between 2006 and 2016 was performed. Patients who underwent a hybrid LPD (HLPD) mobilization approach and resection followed by open reconstruction and totally LPD (TLPD) approach were included in this study. Operative characteristics, perioperative outcomes, pathological and survival data were collected. RESULTS Twenty-seven patients underwent LPD including 17 HLPD (63%) and 10 TLPD (37%) patients. HLPD patients were mostly converted to open for planned reconstruction or vascular resection. With increasing experience, more TLPDs were performed, including laparoscopic anastomoses. Median operating time was 462 min (504 min for TLPD). Median length of hospital stay was 10 days. Histology showed 21 invasive malignancies, two neuroendocrine tumours, two intraductal papillary mucinous neoplasms and two benign lesions. Median nodal harvest was 22. Margin negative resection was achieved in 84% of patients. Twenty-two percent of patients developed a Grade 3/4 complication, including 19% clinically significant pancreatic fistula. There was one perioperative mortality (4%) due to pancreatic fistula, post-operative haemorrhage and sepsis. CONCLUSIONS LPD is a technically challenging operation with a steep learning curve. The early oncological outcomes appear satisfactory. It remains to be determined whether the minimally invasive approach to pancreaticoduodenectomy offers benefits to patients.


title: The education and training of future hip preservation surgeons: aggregate recommendations of high-volume surgeons.

text: Hip preservation is one of the fastest growing subspecialties in orthopaedic surgery. Surgical training recommendations and guidelines in this field are lacking. To survey high volume hip preservation surgeons regarding their perspectives on the current and future training of surgeons entering their field, a cross-sectional survey of 16 high-volume hip preservation surgeons was conducted to gather perspectives and opinions on the most appropriate education of future hip preservation surgeons. All participants completed the survey in person and anonymously. Of the surveyed surgeons, the mean career hip preservation volume was 1031.25 cases (250 to >3000) with an average annual volume of 162.08 cases (75-400). The average number of hip arthroscopy cases necessary to competently perform joint access is 19, labral repair is 34, acetabuloplasty/femoroplasty are 54, labral reconstruction is 101 and capsular closure/plication is 53. Fifty-six percent of the surgeons believe mid-career surgeons who have never performed hip preservation surgery should not adopt it as part of their practice. The mean optimal number of cases recommended was 128 hip arthroscopies during a dedicated hip preservation fellowship and 67 hip arthroscopies during a sports medicine fellowship. Surgeons with an interest in hip preservation careers, should strongly consider a 12-month dedicated hip preservation fellowship that provides exposure to at least 128 cases, including open and arthroscopic techniques, hip arthroplasty, and research opportunities. Mid-career surgeons should be cautious about adopting hip preservation into their practice if they have not had prior adequate training.


title: Symptomatic marginal ulcer disease after Roux-en-Y gastric bypass: incidence, risk factors and management.

text: BACKGROUND One of the long-term complications of laparoscopic Roux-and-Y gastric bypass (LRYGB) is the development of marginal ulcers (MU). The aim of the present study is to assess the incidence, risk factors, symptomatology and management of patients with symptomatic MU after LRYGB surgery. METHODS A consecutive series of patients who underwent a LRYGB from 2006 until 2011 were evaluated in this study. Signs of abdominal pain, pyrosis, nausea or other symptoms of ulcer disease were analysed. Acute symptoms of (perforated) MU such as severe abdominal pain, vomiting, melena and haematemesis were also collected. Patient baseline characteristics, medication and intoxications were recorded. Statistical analysis was performed to identify risk factors associated with MU. RESULTS A total of 350 patients underwent a LRYGB. Minimal follow-up was 24 months. Twenty-three patients (6.6%) developed a symptomatic MU of which four (1.1%) presented with perforation. Smoking, the use of corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) was significantly associated with the development of MU. Five out of 23 patients (22%) underwent surgery. All other patients could be treated conservatively. CONCLUSIONS Marginal ulcers occurred in 6.6% of the patients after a LRYGB. Smoking, the use of corticosteroids and the use of NSAIDs were associated with an increased risk of MU. Most patients were managed conservatively.


title: Sex-dependent differences in plasma cytokine responses to hantavirus infection.

text: There are often sex differences in susceptibility to infectious diseases and in level of mortality after infection. These differences probably stem from sex-related abilities to mount proper or unwanted immune responses against an infectious agent. We report that hantavirus-infected female patients show significantly higher plasma levels of interleukin-9 (IL-9), fibroblast growth factor 2, and granulocyte-macrophage colony-stimulating factor and lower levels of IL-8 and gamma interferon-induced protein 10 than male patients. The results demonstrate that a virus infection can induce sex-dependent differences in acute immune responses in humans. This finding may, at least partly, explain the observed sex differences in susceptibility to infectious diseases and in mortality following infection.


title: Telemedicine in Orthopaedic Surgery: Challenges and Opportunities.

text: Improvements in technology and a push toward value-based health care have poised the telemedicine industry for growth; however, despite the benefits of virtual care, widespread implementation had not occurred until the coronavirus 2019 (COVID-19) pandemic. Powerful barriers have hindered the widespread adoption of telemedicine, including lack of awareness, implementation costs, inefficiencies introduced, difficulty performing physical examinations, overall lack of perceived benefit of virtual care, negative financial implications, concern for medicolegal liability, and regulatory restrictions. Some of these challenges have been addressed with temporary state and federal mandates in response to the COVID-19 pandemic; however, continued investment in systems and technology as well as refinement of regulations around telemedicine are needed to sustain widespread adoption by patients and providers.


title: [Otorhinolaryngological aspects of the disease course in children infected with SARS-CoV-2 virus].

text: Recently, almost all over the world attention of doctors and scientists is focused on a new coronavirus infection, the source of which was the causative agent SARS-CoV-2. In this regard, early diagnosis, including on the basis of symptoms from ENT organs, is crucial. A brief analysis of the available literature on the peculiarities of ENT organs manifestations in patients with SARS-CoV-2 is given. It was found out that to date there is very little data on the state of loro organs in patients with SARS-CoV-2 and no data on anosmia in the pediatric population. However, it is in children in the epidemic aspect that early diagnosis of infection and understanding of its key symptoms is of utmost importance.


title: A Matched Cohort Analysis of Sleeve Gastrectomy With and Without 300 cm Loop Duodenal Switch With 18-Month Follow-Up.

text: BACKGROUND In bariatric surgery, a significant question remains unanswered-What proportion of weight loss comes from each component and does this differ with time? Single anastomosis duodenal switch (LDS) combines a vertical sleeve gastrectomy (VSG) with a loop attachment of the duodenal stump. There are two major variables the sleeve, and the intestine that processes ingested food. A comparison of patients that had a VSG with those that have had a LDS approximates the contribution of each component. METHODS A retrospective matched cohort analysis of VSG and LDS patients was obtained by matching every LDS patient to a VSG patient of the same sex and BMI. Excess weight lost percentage (%EWL) and the total weight loss percentage (%TWL) was analyzed. The data was compared through descriptive statistics and non-linear regression analysis. RESULTS Over 18 months, patients who received the LDS lost more %TWL and %EWL and the difference was statistically significant (p < 0.05). Additionally, with time, the difference became more profound. Weight loss stabilized at approximately 9-12 months and 15 to 18 for VSG and LDS patients', respectively. At 6 months post op, there was approximately 13 % difference in weight loss. This increased to 29 % difference at 18 months. CONCLUSION LDS patients lose more weight than VSG. Preserving 3 m of intestinal length adds 30 % greater weight loss at 18 months. Early weight loss is similar between the two operations, while the intestinal component becomes more important with weight loss differentials increasing as time since surgery lengthens.


title: Comparison of two different barbed suture materials for end-to-end jejuno-jejunal anastomosis in pigs.

text: BACKGROUND Hand-sewn intestinal anastomoses are a fundamental procedure in both open and laparoscopic intestinal surgery. Self-retaining barbed suture devices have been tested for a variety of surgical applications. With the exception of clinical reports and various experimental studies on enterotomy, little has been published so far on the use of barbed suture for end-to-end intestinal anastomoses. The aim of the study was to compare two different barbed suture materials for end-to-end jejuno-jejunal anastomosis in pigs. End-to-end jejuno-jejunal anastomosis were performed with unidirectional barbed (A group), bidirectional barbed (B group) or normal (C group) sutures in each animal. A comparison was then made between the groups based on adhesions scoring, suturing time, bursting pressure and histopathology. RESULTS Mean construction times in the A group (518 ± 40 s) and in the B group (487 ± 45 s) were significantly lower than in the C group (587 ± 63 s) but were not different between A and B group (P = 0.10). Mean bursting pressures were significantly higher in the intact intestine (197 ± 13 mmHg) than in any other group (group A 150 ± 16 mmHg, group B 145 ± 22 mmHg, group C 145 ± 24 mmHg). Among anastomotic techniques, the bursting pressures were not significantly different. Histologically no difference could be detected in the grade of inflammation, collagen deposition and neovascularization at the anastomotic sites. CONCLUSIONS Barbed sutures can be effectively used for handsewn end-to-end jejunojejunal anastomosis in pigs. They are comparable to normal suture but could provide a shorter surgical time.


title: Embedded cervical esophagogastrostomy: a simple and convenient method using a circular stapler after esophagectomy for esophageal carcinomas.

text: BACKGROUND Cervical esophagogastrostomy is currently the most common method for esophageal reconstruction after esophagectomy. The advantages and disadvantages of hand-sewn, linear-stapled, or circular-stapled anastomoses have been subject to debate in recent years. We explored a new method of end-to-side anastomosis using a circular stapler that embeds the anastomosis and the remaining esophageal tissue into the gastric cavity to reduce the occurrence of anastomotic leakage and to prevent gastroesophageal reflux. METHODS In 127 patients with esophageal carcinomas, end-to-side anastomoses with esophageal embedding were performed by connecting the anvil and body of the circular stapler inside the stomach before firing and embedding the anastomosis and remaining esophagus into the stomach after esophagectomy. Retrospective investigations on postoperative complications such as leakage, stricture, and gastroesophageal reflux were conducted. RESULTS A total of 123 patients (96.9%) had successful surgery, and 4 patients (3.3%) developed anastomotic leakage, with the total morbidity of 20 of 123 (16.3%) and in-hospital mortality of 1 of 123 (0.8%). The incidence of stricture (<1 cm) affected 14 of 123 patients (11.4%). Eight patients underwent dilatation treatment as a result of severe dysphagia (6.5%). Half of the patients [62 of 123 (50.4%)] experienced postoperative heartburn, 11 of 123 patients (8.9%) experienced acid regurgitation, and 16 of 123 patients (13.0%) experienced nocturnal cough. CONCLUSIONS Embedded cervical esophagogastrostomy with circular stapler is a simple and convenient method, with low incidence of anastomotic leakage and a good antireflux effect.


title: Facile synthesis of mPEG-luteolin-capped silver nanoparticles with antimicrobial activity and cytotoxicity to neuroblastoma SK-N-SH cells.

text: We firstly report a facile route for the green synthesis of mPEG-luteolin-capped silver nanoparticles (mPEG-luteolin-AgNPs) using mPEG-luteolin as both the reducer and stabilizer. The reaction was carried out in a stirred aqueous solution at 50°C without additional poisonous reagents. The prepared mPEG-luteolin-AgNPs was characterized by scanning electron microscope (SEM), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), zeta potential and UV-vis (UV-vis) spectrum, respectively. The proportions of mPEG-luteolin capped silver nanoparticles is about 89.9%, and the content of silver is 6.65%. The mPEG-luteolin-AgNPs was evaluated the antimicrobial effects on Staphlococcus aureus, Extended spectrum β-Lactamases Staphlococcus aureus, Escherichia Coli and Extended spectrum β-Lactamases Escherichia Coli using drilling hole method. The results showed that both gram-positive and gram-negative bacteria were killed by the mPEG-luteolin-AgNPs at low concentration. Meanwhile, the cell viability assay demonstrated that mPEG-luteolin-AgNPs had toxic effects on human neuroblastoma SK-N-SH cells.


Guest Editorial: Global Health Governance of Public Health Emergencies.


title: A Conserved Inhibitory Mechanism of a Lycorine Derivative against Enterovirus and Hepatitis C Virus.

text: Enterovirus 71 (EV71) (Picornaviridae family) and hepatitis C virus (HCV) (Flaviviridae family) are the causative agents of human hand, foot, and mouth disease (HFMD) and hepatitis C, resulting in a severe pandemic involving millions of infections in the Asia-Pacific region and worldwide. The great impact of EV71 and HCV on public health highlights the need to further our understanding of the biology of these two viruses and develop effective therapeutic antivirals. Here, we evaluated a total of 32 lycorine derivatives and demonstrated that 1-acetyllycorine suppressed the proliferation of multiple strains of EV71 in various cells. The results of the drug resistance analysis revealed that 1-acetyllycorine targeted a phenylalanine (F76) in EV71 2A protease (2A(pro)) to stabilize the conformation of a unique zinc finger. Most interestingly, the zinc binding site in EV71 2A(pro) is the exclusive homolog of HCV NS3 among all viruses. Further analysis revealed that 1-acetyllycorine also inhibits HCV with high efficacy, and the mutation on R118 in HCV NS3, which corresponds to F76 in EV71 2A(pro), confers the resistance of HCV to 1-acetyllycorine. These results revealed a conserved mechanism of 1-acetyllycorine against EV71 and HCV through targeting viral proteases. We also documented the significant synergistic anti-EV71 and anti-HCV effects of 1-acetyllycorine with reported inhibitors, supporting potential combination therapy for the treatment of EV71 and HCV infections.


title: Anaesthetic management of extra-pleural pneumonectomy and hyperthermic intrathoracic chemotherapy procedure.

text: Malignant pleural mesothelioma is a rare tumour with survival of 9-17 months after diagnosis. Radical surgical resection by extra-pleural pneumonectomy combined with hyperthermic intrathoracic chemotherapy has shown to improve patient survival and better microscopic tumour control. Anaesthetic management of this procedure is challenging due to the complex pathophysiological changes associated with prolonged duration of surgery, one- lung ventilation, haemodynamic instability due to major blood loss, temperature variations including heat loss during pneumonectomy and rapid rise in temperature during hyperthermic chemotherapy, cardiac arrhythmias due to exposure to heated chemotherapeutics, cisplatin toxicity and acid-base changes. Intra-operative management involves protective ventilation, regulation of temperature and haemodynamics along with prevention of complications associated with 'heated chemotherapeutics'. Thorough pre-operative assessment and preparation, advanced intra-operative monitoring with prompt corrective interventions, will help in improved patient outcome in the immediate post-operative period. We present one such case done for the 1(st) time in India.


title: Value of CT application in the screening,diagnosis,and treatment of COVID-19.

text: The coronavirus disease 2019 (COVID-19) has attracted extensive attention all around the world recently. Early screening, early diagnosis, early isolation, and early treatment remain the most effective prevention and control measures. Computed tomography (CT) plays a vital role in the screening, diagnosis, treatment, and follow-up of COVID-19, especially in the early screening, with a higher sensitivity than that of real-time fluorescence RT-PCR. The combination of CT and artificial intelligence has the potential to help clinicians in improving the diagnostic accuracy and working efficiency.


title: Plasma membrane wounding and repair in pulmonary diseases.

text: Various pathophysiological conditions such as surfactant dysfunction, mechanical ventilation, inflammation, pathogen products, environmental exposures, and gastric acid aspiration stress lung cells, and the compromise of plasma membranes occurs as a result. The mechanisms necessary for cells to repair plasma membrane defects have been extensively investigated in the last two decades, and some of these key repair mechanisms are also shown to occur following lung cell injury. Because it was theorized that lung wounding and repair are involved in the pathogenesis of acute respiratory distress syndrome (ARDS) and idiopathic pulmonary fibrosis (IPF), in this review, we summarized the experimental evidence of lung cell injury in these two devastating syndromes and discuss relevant genetic, physical, and biological injury mechanisms, as well as mechanisms used by lung cells for cell survival and membrane repair. Finally, we discuss relevant signaling pathways that may be activated by chronic or repeated lung cell injury as an extension of our cell injury and repair focus in this review. We hope that a holistic view of injurious stimuli relevant for ARDS and IPF could lead to updated experimental models. In addition, parallel discussion of membrane repair mechanisms in lung cells and injury-activated signaling pathways would encourage research to bridge gaps in current knowledge. Indeed, deep understanding of lung cell wounding and repair, and discovery of relevant repair moieties for lung cells, should inspire the development of new therapies that are likely preventive and broadly effective for targeting injurious pulmonary diseases.


title: Permeability measures predict haemorrhagic transformation after ischemic stroke.

text: OBJECTIVE We sought to examine the diagnostic utility of existing predictors of any haemorrhagic transformation (HT) and compare them to novel perfusion imaging permeability measures in ischemic stroke patients receiving alteplase only. METHODS A pixel-based analysis of pre-treatment CT perfusion (CTP) was undertaken to define the optimum CTP permeability thresholds to predict the likelihood of HT. We then compared previously proposed predictors of HT using regression analyses and receiver operator characteristic curve analysis to produce an Area Under the Cure (AUC), and compared AUCs using Chi Square analysis. RESULTS From 5 centres, 1407 patients were included in this study, 282 had HT. The cohort was split into a derivation (1025, 70% patients) and validation cohort (382 patients or 30%). The E permeability map at a threshold of 30% relative to contralateral had the highest AUC at predicting any HT (derivation AUC 0.85, 95% CI, 0.79-0.91, validation AUC 0.84, 95% CI, 0.77-0.91). The AUC improved when permeability was assessed within the acute perfusion lesion for the E maps at a threshold of 30% (derivation AUC 0.91, 95% CI, 0.86-0.95, validation AUC 0.89, 95% CI, 0.86-0.95). Previously proposed associations with HT and PH showed lower AUC values than the permeability measure. INTERPRETATION In this large multi-centre study, we have validated a highly accurate measure of HT prediction. This measure may be useful in clinical practice to predict haemorrhagic transformation in ischemic stroke patients before receiving alteplase alone. This article is protected by copyright. All rights reserved.


title: Semi-free forearm flap for pharyngeal-esophageal reconstruction after radiation therapy.

text: Reconstruction of the pharynx and upper esophagus uses various procedures, including pedicled or free flap. Pharyngoplasty with free forearm flap provides excellent functional results. In radiation-related pharyngeal stenosis, recipient vascularization is often poor, especially in the venous system. The authors describe pharyngeal reconstruction with semi-free forearm flap, pedicled on the cephalic vein, to minimize the risk of venous thrombosis, which is the main factor of free forearm flap necrosis. Taking the case of a laryngectomy with complete pharyngeal stenosis after radiation therapy and iterative neck surgery, the technique of pharyngeal-esophageal reconstruction by semi-free forearm flap is described in a context of impaired vascularization.


title: One thousand single anastomosis (omega loop) gastric bypasses to treat morbid obesity in a 7-year period: outcomes show few complications and good efficacy.

text: BACKGROUND A short-term randomized controlled trial shows that the one anastomosis gastric bypass (OAGB) is a safe and effective alternative to the Roux-en-Y gastric bypass (RYGB). OBJECTIVE The aim of this study is to evaluate the OAGB at our University Hospital between 2006 and 2013. PATIENTS One thousand patients have undergone an OAGB. Data were collected on all consecutive patients. The mean follow-up period was 31 months (SD, 26.3; range, 12-82.9), and complete follow-up was available in 126 of 175 patients (72 %) at 5 years after surgery. RESULTS Mortality rate was 0.2 %. Overall morbidity was 5.5 %; 34 required reoperations: i.e., 6 leaks, 5 obstructions, 5 incisional hernias, 7 biliary refluxes, 2 perforated ulcers, 2 bleeds, 2 abscesses, and 1 anastomotic stricture. Four patients were reoperated for weight regain. Overall rate of marginal ulcers was 2 % (n = 20), all in heavy smokers. Conversion from an OAGB to a RYGB was required in nine cases (0.9 %): seven for intractable biliary reflux, two for a marginal ulcer. At 5 years, percent excess body mass index loss was 71.6 ± 27 %. One hundred patients with type-2 diabetes, with a mean preoperative HbA1C of 7.7 ± 1.9 %, were followed for >2 years; the total resolution rate was 85.7 %. CONCLUSION This study confirms that the OAGB is an effective procedure for morbid obesity with comparable outcomes to RYGB; in addition, it seems to be safer with lower morbidity. Its technical simplicity represents a real advantage and makes it an option that should be considered by all bariatric surgeons.


COVID-19 and Home Positive Airway Pressure (PAP) Therapy.


Covid-19: GPs call for same personal protective equipment as hospital doctors.


title: Prevalence of upper respiratory pathogens in four management models for unowned cats in the Southeast United States.

text: Upper respiratory infection (URI) is a pervasive problem in cats and impacts the capacity and cost of sheltering programs. This study determined the pattern of respiratory pathogens in cats with and without clinical signs of URI in four different models for managing unowned cats, namely, (1) short-term animal shelters (STS), (2) long-term sanctuaries (LTS), (3) home-based foster care programs (FCP), and (4) trap-neuter-return programs for community cats (TNR). Conjunctival and oropharyngeal swabs from 543 cats, approximately half of which showed clinical signs of URI, were tested for feline herpes virus-1 (FHV), feline calicivirus (FCV), Chlamydia felis, Bordetella bronchiseptica, Mycoplasma felis, and canine influenza virus by real-time PCR. FHV (59%, 41%) and B. bronchiseptica (33%, 24%) were more prevalent in both clinically affected and nonclinical cats, respectively, in STS than other management models. FCV (67%, 51%) and M. felis (84%, 86%) were more prevalent in LTS than any other management model. Clinically affected cats in FCP were more likely to carry FHV (23%, 6%), C. felis (24%, 10%), or M. felis (58%, 38%) than were nonclinical cats. Clinically affected cats in TNR were more likely to carry FCV (55%, 36%) or C. felis (23%, 4%) than were nonclinical cats. The prevalence of individual pathogens varied between different management models, but the majority of the cats in each model carried one or more respiratory pathogens regardless of clinical signs. Both confined and free-roaming cats are at risk of developing infectious respiratory disease and their health should be protected by strategic vaccination, appropriate antibiotic therapy, effective biosecurity, feline stress mitigation, and alternatives to high-density confinement.


title: Overcoming Barriers: The Endothelium As a Linchpin of Coronavirus Disease 2019 Pathogenesis?

text: OBJECTIVE Coronavirus disease 2019 (COVID-19) is a global pandemic involving >5 500 000 cases worldwide as of May 26, 2020. The culprit is the severe acute respiratory syndrome coronavirus-2, which invades cells by binding to angiotensin-converting enzyme 2. While the majority of patients mount an appropriate antiviral response and recover at home, others progress to respiratory distress requiring hospital admission for supplemental oxygen. In severe cases, deterioration to acute respiratory distress syndrome necessitating mechanical ventilation, development of severe thrombotic events, or cardiac injury and dysfunction occurs. In this review, we highlight what is known to date about coronavirus disease 2019 and cardiovascular risk, focusing in on the putative role of the endothelium in disease susceptibility and pathogenesis. Approach and Results: Cytokine-driven vascular leak in the lung alveolar-endothelial interface facilitates acute lung injury in the setting of viral infection. Given that the virus affects multiple organs, including the heart, it likely gains access into systemic circulation by infecting or passing from the respiratory epithelium to the endothelium for viral dissemination. Indeed, cardiovascular complications of coronavirus disease 2019 are highly prevalent and include acute cardiac injury, myocarditis, and a hypercoagulable state, all of which may be influenced by altered endothelial function. Notably, the disease course is worse in individuals with preexisting comorbidities that involve endothelial dysfunction and may be linked to elevated ACE2 (angiotensin-converting enzyme 2) expression, such as diabetes mellitus, hypertension, and cardiovascular disease. CONCLUSIONS Rapidly emerging data on coronavirus disease 2019, together with results from studies on severe acute respiratory syndrome coronavirus-1, are providing insight into how endothelial dysfunction may contribute to the pandemic that is paralyzing the globe. This may, in turn, inform the design of biomarkers predictive of disease course, as well as therapeutics targeting pathogenic endothelial responses.


title: Quantification of regional aortic stiffness using MR elastography: A phantom and ex-vivo porcine aorta study.

text: MR Elastography (MRE) is a noninvasive technique for measuring tissue stiffness that has been used to assess the average stiffness of the abdominal aorta. The utility of aortic MRE would be improved if it could provide information about local variations in aortic stiffness. We hypothesize that regional variations in aortic stiffness can also be measured with MRE and the purpose of this work was to demonstrate that MRE can measure regional stiffness variations in a vascular phantom and in ex vivo porcine aortas. A vascular phantom was fabricated, containing two silicone tubes embedded in gel. A segment of one of the tubes was modified to increase its stiffness. MRE was performed on the phantom with a continuous flow of water through the tubes. The stiffness distribution along the modified tube was measured and compared to the reference tube. MRE was also performed in porcine aortas embedded in gel with segments treated with saline or formalin for 4 days. The stiffness difference between saline- and formalin-treated aortic segments was measured by MRE and mechanical tests. A positive correlation was found between the regional stiffnesses measured by MRE and mechanical tests. The results indicate that MRE can be used to evaluate the local stiffness distribution in silicone tubes and ex vivo porcine aortas. It may therefore be possible to apply MRE to measure regional stiffness variations of the aorta in vivo.


title: Invasive Mechanical Ventilation and Mortality in Pediatric Hematopoietic Stem Cell Transplantation: A Multicenter Study.

text: OBJECTIVE To establish the current respiratory practice patterns in pediatric hematopoietic stem cell transplant patients and investigate their associations with mortality across multiple centers. DESIGN Retrospective cohort between 2009 and 2014. SETTING Twelve children's hospitals in the United States. PATIENTS Two hundred twenty-two pediatric allogeneic hematopoietic stem cell transplant recipients with acute respiratory failure using invasive mechanical ventilation. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS PICU mortality of our cohort was 60.4%. Mortality at 180 days post PICU discharge was 74%. Length of PICU stay prior to initiation of invasive mechanical ventilation was significantly lower in survivors, and the odds of mortality increased for longer length of PICU stay prior to intubation. A total of 91 patients (41%) received noninvasive ventilation at some point during their PICU stay prior to intubation. Noninvasive ventilation use preintubation was associated with increased mortality (odds ratio, 2.1; 95% CI, 1.2-3.6; p = 0.010). Patients ventilated longer than 15 days had higher odds of death (odds ratio, 2.4; 95% CI, 1.3-4.2; p = 0.004). Almost 40% of patients (n = 85) were placed on high-frequency oscillatory ventilation with a mortality of 76.5% (odds ratio, 3.3; 95% CI, 1.7-6.5; p = 0.0004). Of the 20 patients who survived high-frequency oscillatory ventilation, 18 were placed on high-frequency oscillatory ventilation no later than the third day of invasive mechanical ventilation. In this subset of 85 patients, transition to high-frequency oscillatory ventilation within 2 days of the start of invasive mechanical ventilation resulted in a 76% decrease in the odds of death compared with those who transitioned to high-frequency oscillatory ventilation later in the invasive mechanical ventilation course. CONCLUSIONS This study suggests that perhaps earlier more aggressive critical care interventions in the pediatric hematopoietic stem cell transplant patient with respiratory failure requiring invasive mechanical ventilation may offer an opportunity to improve outcomes.


title: Homology-Based Identification of a Mutation in the Coronavirus RNA-Dependent RNA Polymerase That Confers Resistance to Multiple Mutagens.

text: UNLABELLED Positive-sense RNA viruses encode RNA-dependent RNA polymerases (RdRps) essential for genomic replication. With the exception of the large nidoviruses, such as coronaviruses (CoVs), RNA viruses lack proofreading and thus are dependent on RdRps to control nucleotide selectivity and fidelity. CoVs encode a proofreading exonuclease in nonstructural protein 14 (nsp14-ExoN), which confers a greater-than-10-fold increase in fidelity compared to other RNA viruses. It is unknown to what extent the CoV polymerase (nsp12-RdRp) participates in replication fidelity. We sought to determine whether homology modeling could identify putative determinants of nucleotide selectivity and fidelity in CoV RdRps. We modeled the CoV murine hepatitis virus (MHV) nsp12-RdRp structure and superimposed it on solved picornaviral RdRp structures. Fidelity-altering mutations previously identified in coxsackie virus B3 (CVB3) were mapped onto the nsp12-RdRp model structure and then engineered into the MHV genome with [nsp14-ExoN(+)] or without [nsp14-ExoN(-)] ExoN activity. Using this method, we identified two mutations conferring resistance to the mutagen 5-fluorouracil (5-FU): nsp12-M611F and nsp12-V553I. For nsp12-V553I, we also demonstrate resistance to the mutagen 5-azacytidine (5-AZC) and decreased accumulation of mutations. Resistance to 5-FU, and a decreased number of genomic mutations, was effectively masked by nsp14-ExoN proofreading activity. These results indicate that nsp12-RdRp likely functions in fidelity regulation and that, despite low sequence conservation, some determinants of RdRp nucleotide selectivity are conserved across RNA viruses. The results also indicate that, with regard to nucleotide selectivity, nsp14-ExoN is epistatic to nsp12-RdRp, consistent with its proposed role in a multiprotein replicase-proofreading complex. IMPORTANCE RNA viruses have evolutionarily fine-tuned replication fidelity to balance requirements for genetic stability and diversity. Responsibility for replication fidelity in RNA viruses has been attributed to the RNA-dependent RNA polymerases, with mutations in RdRps for multiple RNA viruses shown to alter fidelity and attenuate virus replication and virulence. Coronaviruses (CoVs) are the only known RNA viruses to encode a proofreading exonuclease (nsp14-ExoN), as well as other replicase proteins involved in regulation of fidelity. This report shows that the CoV RdRp (nsp12) likely functions in replication fidelity; that residue determinants of CoV RdRp nucleotide selectivity map to similar structural regions of other, unrelated RNA viral polymerases; and that for CoVs, the proofreading activity of the nsp14-ExoN is epistatic to the function of the RdRp in fidelity.


title: Urinary bladder matrix scaffolds strengthen esophageal hiatus repair.

text: BACKGROUND Laparoscopic repair of the hiatal hernia is associated with a recurrence rate between 12% and 42% depending on the defect size. Although the impact of hiatal reinforcement on long-term recurrence remains controversial, the main limitation of this approach has been the risk of adverse events related with the use of synthetic materials in the vicinity of the esophagus. METHODS A total of 14 female domestic pigs underwent laparoscopic primary hiatal hernia repair of a simulated defect in the esophageal hiatus. Seven of the hiatal repairs were reinforced with an extracellular matrix (ECM) scaffold, whereas the remaining seven served as primary repair controls. Animals were survived for 8 wk. At necropsy, after gross morphologic evaluation, samples were sent for mechanical testing and histology. RESULTS The repaired defect site reinforced with ECM scaffolds showed a robust closure of the crura in all cases with a smooth peritoneal-like structure covering the entire repair. Average load at failure of the treated group was found to be significantly stronger than that of the controls (185.8 ± 149.7 g versus 57.5 ± 57.5 g, P < 0.05). Similarly, the stiffness was significantly higher in the treated animals (57.5 ± 26.9 g/mm versus 19.1 ± 17.5 g/mm; P < 0.01). Interestingly, there was no difference in elongation at failure (7.62 ± 2.02 mm versus 7.87 ± 3.28 mm; P = 0.44). CONCLUSIONS In our animal survival model, we have provided evidence that the addition of an ECM to augment a primary hiatal repair leads to tissue characteristics that may decrease the possibility of early failure of the repair. This may translate to decreased recurrence rates. Further study is necessary.


title: Direct Mechanical Intervention Versus Combined Intravenous and Mechanical Intervention in Large Artery Anterior Circulation Stroke: A Matched-Pairs Analysis.

text: BACKGROUND AND PURPOSE Five randomized controlled trials have consistently shown that mechanical thrombectomy (MT) in addition to best medical treatment (±intravenous tissue-type plasminogen activator) improves outcome after acute ischemic stroke in patients with large artery anterior circulation stroke. Whether direct MT is equally effective as combined intravenous thrombolysis with MT (ie, bridging thrombolysis) remains unclear. METHODS We retrospectively compared clinical and radiological outcomes in 167 bridging patients with 255 patients receiving direct MT because of large artery anterior circulation stroke. We matched all patients from the direct MT group who would have qualified for intravenous tissue-type plasminogen activator with controls from the bridging group, using multivariate and propensity score analyses. Functional independence was defined as modified Rankin Scale score of 0 to 2. RESULTS From February 2009 to August 2014, 40 patients from the direct MT group would have qualified for bridging thrombolysis but were treated with MT only. Clinical and radiological characteristics did not differ from the bridging cohort, except for higher rates of hypercholesterolemia (P=0.019), coronary heart disease (P=0.039), and shorter intervals from symptom onset to endovascular intervention (P=0.01) in the direct MT group. Functional independence, mortality, and intracerebral hemorrhage rates did not differ (P>0.1). After multivariate matching analysis outcome in both groups did not differ, except for lower rates of asymptomatic intracerebral hemorrhage (P=0.023) and lower mortality (P=0.007) in the direct MT group. CONCLUSIONS In patients with large anterior circulation stroke, direct mechanical intervention seems to be equally effective as bridging thrombolysis. A randomized trial comparing direct MT with bridging therapy is warranted.


title: Controlled Hypercapnia Enhances Cerebral Blood Flow and Brain Tissue Oxygenation After Aneurysmal Subarachnoid Hemorrhage: Results of a Phase 1 Study.

text: BACKGROUND This study investigated if cerebral blood flow (CBF) regulation by changes of the arterial partial pressure of carbon dioxide (PaCO2) can be used therapeutically to increase CBF and improve neurological outcome after subarachnoid hemorrhage (SAH). METHODS In 12 mechanically ventilated poor-grade SAH-patients, a daily trial intervention was performed between day 4 and 14. During this intervention, PaCO2 was decreased to 30 mmHg and then gradually increased to 40, 50, and 60 mmHg in 15-min intervals by modifications of the respiratory minute volume. CBF and brain tissue oxygen saturation (StiO2) were the primary and secondary endpoints. Intracranial pressure was controlled by an external ventricular drainage. RESULTS CBF reproducibly decreased during hyperventilation and increased to a maximum of 141 ± 53 % of baseline during hypercapnia (PaCO2 60 mmHg) on all days between day 4 and 14 after SAH. Similarly, StiO2 increased during hypercapnia. CBF remained elevated within the first hour after resetting ventilation to baseline parameters and no rebound effect was observed within this time-span. PaCO2-reactivities of CBF and StiO2 were highest between 30 and 50 mmHg and slightly decreased at higher levels. CONCLUSION CBF and StiO2 reproducibly increased by controlled hypercapnia of up to 60 mmHg even during the period of the maximum expected vasospasm. The absence of a rebound effect within the first hour after hypercapnia indicates that an improvement of the protocol is possible. The intervention may yield a therapeutic potential to prevent ischemic deficits after aneurysmal SAH.


title: Changes in major depressive and generalized anxiety disorders in the national French working population between 2006 and 2010.

text: BACKGROUND This study aimed at assessing the changes in mental disorders in the French working population between 2006 and 2010, using nationally representative prospective data and a structured diagnostic interview for major depressive episode (MDE) and generalized anxiety disorder (GAD), and also at exploring the differential changes in mental disorders according to age, origin, occupation, public/private sector, self-employed/employee status and work contract. METHODS The data came from the prospective national representative Santé et Itinéraire Professionnel (SIP) survey, including a sample of 5600 French workers interviewed in 2006 and 2010. The Mini International Neuropsychiatric Interview (MINI) was used to measure MDE and GAD. Analyses were performed using weighted generalized estimation equations, and were stratified by gender. RESULTS No changes in MDE and GAD were observed for both genders among the working population. No differential changes were observed, except one: the prevalence of GAD increased among women working in the public sector while there was no change among women in the private sector. LIMITATIONS Two data collections over a 4-year period may not capture the effects of the crisis on mental disorders properly. CONCLUSION No changes in mental disorders between 2006 and 2010 were found but the increase in the prevalence of anxiety among women in the public sector may be of particular interest for prevention policies. High levels of social protection in France might contribute to explain these non-significant results.


title: The intensive use of the internet by children and adolescents in the context of COVID-19 and the risks for self-inflicted violence.

text: This essay aimed to discuss the implications of social isolation due to the COVID-19 pandemic for the intensive use of the internet among children and adolescents and its possible consequences for the practice of self-inflicted violence. We briefly discussed the anxiogenic potential and the reproduction of a "global fear" that are consolidated with the massive and unmediated exposure of the content consumed, which can increase the vulnerabilities to stress and suicidal ideas. We centered our debate on "recreational" practices, called "challenges" with self-harm power, carried out by teenagers on the YouTube website. This practice has been shown to increase with the social isolation measures. Our reflection on these risks builds on the theoretical perspective of digital sociability, and its implications for the internet-mediated interactions of adolescents.


title: Antiplatelet and anticoagulant agents for secondary prevention of stroke and other thromboembolic events in people with antiphospholipid syndrome.

text: BACKGROUND Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. OBJECTIVES To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. SEARCH METHODS We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. SELECTION CRITERIA We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. DATA COLLECTION AND ANALYSIS Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. MAIN RESULTS We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ-5D-5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains.The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low-quality evidence). Investigators reported similar rates of clinically relevant non-major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate-quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ-5D-5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low-quality evidence) but not measured as health utility (MD 0.04, 95% CI -0.02 to 0.10 [on a scale from 0 to 1]).Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low-quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high-intensity warfarin treatment compared to the standard-intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low-quality evidence).In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). AUTHORS' CONCLUSIONS There is not enough evidence for or against NOACs or for high-intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high-intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future.


title: Galectin-9 binding to cell surface protein disulfide isomerase regulates the redox environment to enhance T-cell migration and HIV entry.

text: Interaction of cell surface glycoproteins with endogenous lectins on the cell surface regulates formation and maintenance of plasma membrane domains, clusters signaling complexes, and controls the residency time of glycoproteins on the plasma membrane. Galectin-9 is a soluble, secreted lectin that binds to glycoprotein receptors to form galectin-glycoprotein lattices on the cell surface. Whereas galectin-9 binding to specific glycoprotein receptors induces death of CD4 Th1 cells, CD4 Th2 cells are resistant to galectin-9 death due to alternative glycosylation. On Th2 cells, galectin-9 binds cell surface protein disulfide isomerase (PDI), increasing retention of PDI on the cell surface and altering the redox status at the plasma membrane. Cell surface PDI regulates integrin function on platelets and also enhances susceptibility of T cells to infection with HIV. We find that galectin-9 binding to PDI on Th2 cells results in increased cell migration through extracellular matrix via β3 integrins, identifying a unique mechanism to regulate T-cell migration. In addition, galectin-9 binding to PDI on T cells potentiates infection with HIV. We identify a mechanism for regulating cell surface redox status via a galectin-glycoprotein lattice, to regulate distinct T-cell functions.


title: Topology and membrane anchoring of the coronavirus replication complex: not all hydrophobic domains of nsp3 and nsp6 are membrane spanning.

text: Coronaviruses express two very large replicase polyproteins, the 16 autoproteolytic cleavage products of which collectively form the membrane-anchored replication complexes. How these structures are assembled is still largely unknown, but it is likely that the membrane-spanning members of these nonstructural proteins (nsps) are responsible for the induction of the double-membrane vesicles and for anchoring the replication complexes to these membranes. For 3 of the 16 coronavirus nsps-nsp3, nsp4, and nsp6-multiple transmembrane domains are predicted. Previously we showed that, consistent with predictions, nsp4 occurs in membranes with both of its termini exposed in the cytoplasm (M. Oostra et al., J. Virol. 81:12323-12336, 2007). Strikingly, however, for both nsp3 and nsp6, predictions based on a multiple alignment of 27 coronavirus genome sequences indicate an uneven number of transmembrane domains. As a consequence, the proteinase domains present in nsp3 and nsp5 would be separated from their target sequences by the lipid bilayer. To look into this incongruity, we studied the membrane disposition of nsp3 and nsp6 of the severe acute respiratory syndrome coronavirus and murine hepatitis virus by analyzing tagged forms of the proteins expressed in cultured cells. Contrary to the predictions, in both viruses, both proteins had their amino terminus, as well as their carboxy terminus, exposed in the cytoplasm. We established that two of the three hydrophobic domains in nsp3 and six of the seven in nsp6 are membrane spanning. Subsequently, we verified that in nsp4, all four hydrophobic domains span the lipid bilayer. The occurrence of conserved non-membrane-spanning hydrophobic domains in nsp3 and nsp6 suggests an important function for these domains in coronavirus replication.


title: Observational study of two oxygen saturation targets for discharge in bronchiolitis.

text: OBJECTIVES To assess the potential effect of two guideline discharge oxygen saturation (SpO(2)) recommendations (≥90% and ≥94%) in recovering bronchiolitis. METHODS AND PATIENTS Infants aged up to 18 months requiring therapeutic oxygen for SpO(2) (≤93%) had SpO(2) assessed in air every 2 h. Time from admission to re-establish feeding (>75% normal) and for SpO(2) to become stable for at least 4 h at ≥90% and ≥94% were noted. RESULTS 68 infants, median age 14 weeks, were included. Feeding problems resolved at a median of 11 h (inter-quartile range, IQR 0-47). SpO(2) became stable for at least 4 h at 17 h (IQR 0-49) for ≥90% and 63 h (IQR 34-105) for ≥94%. Time for infants to achieve a stable SpO(2)≥90% and resolve feeding difficulties was a median of 22 h (IQR 7-39 h) sooner than the equivalent for stable SpO(2)≥94%. CONCLUSIONS Accepting lower SpO(2) at discharge could significantly reduce length of stay, but require the clinical and safety effects to be studied.


Incidence of severe COVID-19 in a Spanish cohort of 1037 patients with rheumatic diseases treated with biologics and JAK-inhibitors.


title: Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels.

text: Corneal injuries are common causes of visual impairment worldwide. Accordingly, there is an unmet need for transparent biomaterials that have high adhesion, cohesion, and regenerative properties. Herein, we engineer a highly biocompatible and transparent bioadhesive for corneal reconstruction using a visible light cross-linkable, naturally derived polymer, GelCORE (gel for corneal regeneration). The physical properties of GelCORE could be finely tuned by changing prepolymer concentration and photocrosslinking time. GelCORE revealed higher tissue adhesion compared to commercial adhesives. Furthermore, in situ photopolymerization of GelCORE facilitated easy delivery to the cornea, allowing for bioadhesive curing precisely according to the required geometry of the defect. In vivo experiments, using a rabbit stromal defect model, showed that bioadhesive could effectively seal corneal defects and induce stromal regeneration and re-epithelialization. Overall, GelCORE has many advantages including low cost and ease of production and use. This makes GelCORE a promising bioadhesive for corneal repair.


Obesity surgery and eating and weight disorders: a new topical collection of EWD.


title: Blame the signaling: role of cAMP for the resolution of inflammation.

text: A complex intracellular signaling governs different cellular responses in inflammation. Extracellular stimuli are sensed, amplified, and transduced through a dynamic cellular network of messengers converting the first signal into a proper response: production of specific mediators, cell activation, survival, or death. Several overlapping pathways are coordinated to ensure specific and timely induction of inflammation to neutralize potential harms to the tissue. Ideally, the inflammatory response must be controlled and self-limited. Resolution of inflammation is an active process that culminates with termination of inflammation and restoration of tissue homeostasis. Comparably to the onset of inflammation, resolution responses are triggered by coordinated intracellular signaling pathways that transduce the message to the nucleus. However, the key messengers and pathways involved in signaling transduction for resolution are still poorly understood in comparison to the inflammatory network. cAMP has long been recognized as an inducer of anti-inflammatory responses and cAMP-dependent pathways have been extensively exploited pharmacologically to treat inflammatory diseases. Recently, cAMP has been pointed out as coordinator of key steps of resolution of inflammation. Here, we summarize the evidence for the role of cAMP at inducing important features of resolution of inflammation.


title: Video-assisted thoracoscopic lobectomy: an unavoidable trend? A retrospective single-institution series of 410 cases.

text: OBJECTIVES Evaluation of the feasibility, safety and oncological validity of video-assisted thoracic lobectomy (VATS). The VATS study exclusion criteria included T3 or T4 tumours, central hilar tumours, tumours visible on bronchoscopy requiring sleeve resection, hilar lymphadenopathy, N2 disease, history of neoadjuvant chemotherapy or radiation, previous thoracic surgery or pleurodesis. METHODS A retrospective study of 410 patients (143 women, mean age 61.5 ± 13.1 years (84-15) treated by VATS lobectomy between 1996 and 2011 was performed at our institution. VATS lobectomy was performed for lung cancer (n = 364, 88.9%), pulmonary metastasis (n = 25, 5.8%) and non-neoplastic diseases (n = 21, 5.1%). In lung cancer, a systematic radical lymph node dissection was performed. RESULTS There was no intraoperative death. The conversion rate was 6.1% (n = 25): bleeding (n = 4), extended pleural adhesion (n = 6, 1.4%), technical difficulty (n = 6, 1.4%), tumour extension to the fissure or mediastinum or adenopathy (n = 7, 1.7%) and intolerance to one-lung ventilation (n = 2, 0.4%). The postoperative mortality rate was 1.2% (n = 5). Major complications occurred in 21 patients (5.1%). The mean number of mediastinal nodes removed was 14.6 (5-44) and 42 patients (10.2%) presented N2 disease at the definitive staging. The mean operating time was 152 (85-315) min. The mean drainage duration was 3.2 days (1-15). Mean postoperative length of hospital stay before return at home was 6.8 days (3-75) and 5.5 days in patients without major complications. There was no port site recurrence. Kaplan-Meier 3-year survival rates were 76.5% for Stage I and 87.3% for Stage IA, 58% for Stage II and 61% for Stage III. CONCLUSIONS VATS lobectomy is an acceptable alternative and seems equivalent to open lobectomy in terms of complications and oncological value. Our experience prompts us to consider VATS lobectomy for early stage NSCLC as the first surgical approach in view of the improvement in outcome, provided that the procedure is performed by a surgeon with adequate experience with this approach.


title: Comparison of 3 suture closure techniques for pelvic flexure enterotomy in equine cadaveric large colon.

text: OBJECTIVE To compare a 2-layer closure with suture line reversal for a pelvic flexure enterotomy to 1-layer and traditional 2-layer hand sewn closures. STUDY DESIGN Ex vivo, simple randomized study. SAMPLE POPULATION Large colon segments from adult horses (n = 18). METHODS Pelvic flexures were harvested from 18 horses and randomly assigned to 1 of 3 closure techniques (n = 6 per technique). A 10-cm enterotomy was made in each pelvic flexure and closed with the assigned technique. Closure time, luminal diameter via contrast radiographs, and bursting pressure were recorded for each specimen and compared between techniques using 1-way ANOVA with Duncan post hoc test at P < .05. RESULTS There was a significant difference in closure time (P = .034) with 1-layer closure faster than both the traditional 2-layer closure (P=.024) and the 2-layer closure with suture line reversal (P = .030). There was no significant difference in luminal diameter or bursting pressure between the 3 closure techniques. CONCLUSIONS Two-layer closure with suture line reversal may be an alternative to traditional 2-layer closure for closure of the pelvic flexure based on ex vivo bursting pressure testing and closure time. A 1-layer simple continuous closure resisted bursting pressure not different to both 2-layer closure techniques. Further in vivo evaluation may be indicated.


title: Closing the loop on plastic packaging materials: What is quality and how does it affect their circularity?

text: While attention on the importance of closing materials loops for achieving circular economy (CE) is raging, the technicalities of doing so are often neglected or difficult to overcome. These technicalities determine the ability of materials, components and products (MCPs) to be properly recovered and redistributed for reuse, recycling or recovery, given their remaining functionality, described here as the remaining properties and characteristics of MCPs. The different properties of MCPs make them useful for various functions and purposes. A transition, therefore, towards a CE would require the utmost exploitation of the remaining functionality of MCPs; ideally, enabling recirculation of them back in the economy. At present, this is difficult to succeed. This short communication article explains how the remaining functionality of MCPs, defined here as quality, is perceived at different stages of the supply chain, focusing specifically on plastic packaging, and how this affects their potential recycling. It then outlines the opportunities and constraints posed by some of the interventions that are currently introduced into the plastic packaging system, aimed at improving plastic materials circularity. Finally, the article underpins the need for research that integrates systemic thinking, with technological innovations and policy reforms at all stages of the supply chain, to promote sustainable practices become established.


title: Real-world data of the association between quality of life using the EuroQol 5 Dimension 5 Level utility value and adverse events for outpatient cancer chemotherapy.

text: BACKGROUND Outpatient cancer chemotherapy may lead to improved quality of life (QOL) by allowing treatment to continue without impairing the social lives of patients compared with hospitalization. However, the occurrence of serious adverse events may cause a decline in QOL. We investigated the relationship between outpatient chemotherapy-induced adverse events and QOL. METHODS A single-center retrospective descriptive study was conducted in patients who received outpatient chemotherapy at Gifu University Hospital (Gifu, Japan) between September 2017 and December 2018. The utility values of QOL, type and severity of adverse events, type of cancer, chemotherapy regimen, and other patient demographics were analyzed. Adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. QOL was evaluated using the Japanese version of the EuroQol 5 Dimension 5 Level (EQ-5D-5L). Associations between the EQ-5D-5L utility value and serious adverse events were assessed using adjusted (age and sex) odds ratios obtained with a proportional odds logistic regression model. RESULTS Data from 1008 patients who received 4695 chemotherapy cycles were analyzed. According to proportional odds logistic regression, the adverse events that significantly correlated with a decreased EQ-5D-5L utility value were malaise, edema of the limbs, peripheral neuropathy, pruritus, and dry skin. Based on the proportional odds logistic analysis, neither cancer type nor anticancer drugs were significantly correlated with the EQ-5D-5L utility value in patients who received chemotherapy. Pharmaceutical care for peripheral neuropathy significantly improved patients' EQ-5D-5L utility value from 0.747 to 0.776 (P < 0.01). CONCLUSIONS Adverse events (i.e., peripheral neuropathy, malaise, and edema of the limbs) are significantly correlated with a decrease in QOL, regardless of the type of cancer or anticancer drugs used. Pharmaceutical care provided by pharmacists in collaboration with physicians may improve QOL.


COVID-19: protect great apes during human pandemics.


title: Laparoscopic versus open nephroureterectomy for the treatment of upper urinary tract urothelial carcinoma: a systematic review and cumulative analysis of comparative studies.

text: CONTEXT Laparoscopic nephroureterectomy (LNU) has increasingly been used as a minimally invasive alternative to open nephroureterectomy (ONU), but studies comparing the efficacy and safety of the two surgical procedures are still limited. OBJECTIVE Evaluate the oncologic and perioperative outcomes of LNU versus ONU in the treatment of upper urinary tract urothelial carcinoma. EVIDENCE ACQUISITION A systematic review and cumulative analysis of comparative studies reporting both oncologic and perioperative outcomes of LNU and ONU was performed through a comprehensive search of the Medline, Embase, and the Cochrane Library electronic databases. All analyses were performed using the Review Manager (RevMan) v.5 (Nordic Cochrane Centre, Copenhagen, Denmark) and Meta-analysis In eXcel (MIX) 2.0 Pro (BiostatXL) software packages. EVIDENCE SYNTHESIS Twenty-one eligible studies (1235 cases and 3093 controls) were identified. A significantly higher proportion of pTa/Tis was observed in LNU compared to ONU (27.52% vs 22.59%; p = 0.047), but there were no significant differences in other stages and pathologic grades (all p>0.05). For patients who underwent LNU, the 5-yr cancer-specific survival (CSS) rate was significantly higher, at 9% (p = 0.03), compared to those who underwent ONU, while the overall recurrence rate and bladder recurrence rate were notably lower, at 15% (p = 0.01) and 17% (p = 0.02), respectively. However, there were no statistically significant differences in 2-yr CSS, 5-yr recurrence-free survival (RFS), 5-yr overall survival (OS), 2-yr OS, and metastasis rates between LNU and ONU (all p>0.05). Moreover, there were no significant differences between LNU and ONU in terms of intraoperative complications, postoperative complications, and perioperative mortality (all p>0.05). The results of our study were mainly limited by the retrospective design of most of the individual studies included as well as selection biases based on different management of regional lymph nodes and pathologic characteristics. CONCLUSIONS Our data suggest that LNU offers reliable perioperative safety and comparable oncologic efficacy when compared to ONU. Given that some limitations cannot be overcome, well-designed prospective trials are needed to confirm our findings.


title: Current readings: Redefining minimally invasive: uniportal video-assisted thoracic surgery.

text: Minimally invasive surgery is clearly dominating the modern surgical era across multiple surgical subspecialties and thoracic surgery is no exception. Video-assisted thoracic surgery (VATS) is a well-established method of performing various interventions, and it continues to gain momentum. Though small differences in VATS methods exist, it is commonly accepted as a non-rib-spreading approach into the thoracic cavity via 2-4 incisions and allows for a wide range of anatomical and nonanatomical pulmonary resections. As more experience is gained with VATS, more complex surgeries take place and greater refinement of the technique occurs. A newer single-incision or uniportal VATS has been described to minimize surgical trauma, to decrease the number and size of thoracic incisions, to reduce the number of complications, and to enable faster recovery. It allows performing a full spectrum of thoracic operations through a single incision adhering to surgical and oncological principles without compromise.


title: Modeling the Novel Coronavirus (SARS-CoV-2) Outbreak in Sicily, Italy.

text: Italy was the first country in Europe which imposed control measures of travel restrictions, quarantine and contact precautions to tackle the epidemic spread of the novel coronavirus (SARS-CoV-2) in all its regions. While such efforts are still ongoing, uncertainties regarding SARS-CoV-2 transmissibility and ascertainment of cases make it difficult to evaluate the effectiveness of restrictions. Here, we employed a Susceptible-Exposed-Infectious-Recovered-Dead (SEIRD) model to assess SARS-CoV-2 transmission dynamics, working on the number of reported patients in intensive care unit (ICU) and deaths in Sicily (Italy), from 24 February to 13 April. Overall, we obtained a good fit between estimated and reported data, with a fraction of unreported SARS-CoV-2 cases (18.4%; 95%CI = 0-34.0%) before 10 March lockdown. Interestingly, we estimated that transmission rate in the community was reduced by 32% (95%CI = 23-42%) after the first set of restrictions, and by 80% (95%CI = 70-89%) after those adopted on 23 March. Thus, our estimates delineated the characteristics of SARS-CoV2 epidemic before restrictions taking into account unreported data. Moreover, our findings suggested that transmission rates were reduced after the adoption of control measures. However, we cannot evaluate whether part of this reduction might be attributable to other unmeasured factors, and hence further research and more accurate data are needed to understand the extent to which restrictions contributed to the epidemic control.


title: [Prevention and control of novel coronavirus infection in department of stomatology].

text: During a short period of time, the COVID-19, a respiratory disease caused by a novel coronavirus and first reported by the end of the year 2019 in China, has spread rapidly to many countries and regions outside China. The number of confirmed cases and deaths continued to rise. World Health Organization announced that the outbreaks of the novel coronavirus infection have constituted a Public Health Emergency of International Concern. Efficient infection control can prevent the virus from further spreading, which may make the pandemic situation under control. Due to the specialty of oral healthcare settings, the risk of cross infection is severe among patients and oral healthcare workers. It's urgent to implement more strict and efficient infection control protocols. This article, based on existing guidelines and published researches pertinent to dental infection-control principles and practices, mainly discusses epidemiological characteristics of COVID-19 and the features of nosocomial infection in oral healthcare settings, and furthermore provides recommendations on patient's evaluation, and infection control protocols in departments of stomatology under current circumstance.


title: Risk-adjusted procedure tailoring leads to uniformly low complication rates in ventral and incisional hernia repair: a propensity score analysis and internal validation of classification criteria.

text: BACKGROUND The usual approach in hernia surgery is to select the ideal repair method independent of the patient's characteristics. In the present study, we change the approach to ask which technique is best for the individual patient`s risk profile. For this, two criteria are important: does the patient need reconstruction of the abdominal wall? or does he or she need treatment of symptoms without being exposed to unnecessarily high perioperative risks? METHODS In a heuristic selection procedure, 486 consecutive patients were classified according to their characteristics as low-risk or high-risk for postoperative complications. Low-risk patients preferentially underwent open abdominal wall reconstruction with mesh (MFR + mesh), high-risk patients mainly a bridging-mesh procedure, either by laparoscopic (Lap.-IPOM) or open approach (Open-IPOM). Primary outcome was the incidence of postoperative complications. Secondary outcome was the recurrence-free interval. The propensity score was used for covariate adjustment analyzing recurrence rate as well as postoperative complications using Cox regression and logistic regression, respectively. RESULTS Comparison of all surgical procedures showed risk factors had no independent influence on occurrence of complications (p = 0.110). Hernial gap width was an independent factor for occurrence of complications (p = 0.002). Propensity score adjustment revealed Lap.-IPOM to have a significantly higher recurrence rate than MFR + mesh (HR 2.367, 95% CI 1.123-4.957, p = 0.024). Three or more risk factors were protective against recurrence (HR 0.454, 95% CI 0.221-0.924, p = 0.030). In the univariate Cox regression analysis for recurrence, age >50 years was a protective prognostic factor (HR 0.412, 95% CI 0.245-0.702, p = 0.002). CONCLUSIONS The classification criteria applied were internally validated. The heuristic algorithm ensured that patients at high-risk of complications did not have a higher perioperative complication rate than patients at low-risk.


Emerging infectious diseases.


title: Differentiating Carotid Terminus Occlusions into Two Distinct Populations Based on Willisian Collateral Status.

text: BACKGROUND AND PURPOSE The outcomes of acute internal carotid artery (ICA) terminus occlusions are poor. We classified ICA terminus occlusions into 2 groups according to the occlusion pattern of the circle of Willis and hypothesized that clinical outcomes would significantly differ between them. METHODS Consecutive patients with acute ICA terminus occlusions evaluated by baseline computed tomographic angiography were enrolled. We investigated the occlusion patterns in the circle of Willis, retrospectively classified patients into simple ICA terminus occlusion (STO; with good Willisian collaterals from neighboring cerebral circulation) and complex ICA terminus occlusion (CTO; with one or more of A2 anterior cerebral artery, fetal posterior cerebral artery occlusion, or hypoplastic/absent contralateral A1; or with poor collaterals from anterior communicating artery) groups, and compared their baseline characteristics and outcomes. RESULTS The STO group (n=58) showed smaller infarct volumes at 72 hours than the CTO group (n=34) (median, 81 mL [interquartile range, 38-192] vs. 414 mL [193-540], P<0.001) and more favorable outcomes (3-month modified Rankin Scale 0-3, 44.8% vs. 8.8%, P<0.001; 3-month mortality, 24.1% vs. 67.6%, P<0.001). In multivariable analyses, STO remained an independent predictor for favorable outcomes (odds ratio 6.1, P=0.010). CONCLUSIONS Favorable outcomes in STO group suggested that the outcomes of acute ICA terminus occlusions depend on Willisian collateral status. Documenting the subtypes on computed tomographic angiography would help predict patient outcome.


title: Evaluation of the Cunningham Panel™ in pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS): Changes in antineuronal antibody titers parallel changes in patient symptoms.

text: OBJECTIVE This retrospective study examined whether changes in patient pre- and post-treatment symptoms correlated with changes in anti-neuronal autoantibody titers and the neuronal cell stimulation assay in the Cunningham Panel in patients with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS), and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). METHODS In an analysis of all tests consecutively performed in Moleculera Labs' clinical laboratory from April 22, 2013 to December 31, 2016, we identified 206 patients who were prescribed at least one panel prior to and following treatment, and who met the PANDAS/PANS diagnostic criteria. Patient follow-up was performed to collect symptoms and treatment or medical intervention. Of the 206 patients, 58 met the inclusion criteria of providing informed consent/assent and documented pre- and post-treatment symptoms. Clinician and parent-reported symptoms after treatment or medical intervention were categorized as "Improved/Resolved" (n = 34) or "Not-Improved/Worsened" (n = 24). These were analyzed for any association between changes in clinical status and changes in Cunningham panel test results. Clinical assay performance was also evaluated for reproducibility and reliability. RESULTS Comparison of pre- and post-treatment status revealed that the Cunningham Panel results correlated with changes in patient's neuropsychiatric symptoms. Based upon the change in the number of positive tests, the overall accuracy was 86%, the sensitivity and specificity were 88% and 83% respectively, and the Area Under the Curve (AUC) was 93.4%. When evaluated by changes in autoantibody levels, we observed an overall accuracy of 90%, a sensitivity of 88%, a specificity of 92% and an AUC of 95.7%. Assay reproducibility for the calcium/calmodulin-dependent protein kinase II (CaMKII) revealed a correlation coefficient of 0.90 (p < 1.67 × 10-6) and the ELISA assays demonstrated test-retest reproducibility comparable with other ELISA assays. CONCLUSION This study revealed a strong positive association between changes in neuropsychiatric symptoms and changes in the level of anti-neuronal antibodies and antibody-mediated CaMKII human neuronal cell activation. These results suggest there may be clinical utility in monitoring autoantibody levels and stimulatory activity against these five neuronal antigen targets as an aid in the diagnosis and treatment of infection-triggered autoimmune neuropsychiatric disorders. Future prospective studies should examine the feasibility of predicting antimicrobial and immunotherapy responses with the Cunningham Panel.


Renin-angiotensin-aldosterone system inhibitors to treat COVID-19?


Surgeons, Surgical Research, and the COVID-19 Pandemic.


title: Luteolin ameliorates experimental lung fibrosis both in vivo and in vitro: implications for therapy of lung fibrosis.

text: Lonicera japonica (Caprifoliaceae) has been known as an anti-inflammatory herb in traditional Chinese medicine for thousands of years and is used constantly for upper respiratory tract infections. Luteolin, an active flavonoid compound isolated from Lonicera japonica, has a spectrum of biological activities, especially with antioxidative and anti-inflammatory properties. However, whether luteolin has a direct inhibitory effect on lung fibrosis has not been established. In this study, we examined the effects of luteolin on lung fibrosis both in vivo and in vitro. We found that oral administration of luteolin (10 mg/kg) efficiently suppressed the neutrophil infiltration as well as TNF-α and IL-6 elevation in the bronchoalveolar lavage fluid in bleomycin-instilled C57BL/6J mice. Luteolin also alleviated collagen deposition, TGF-β1 expression, and lung fibrosis upon bleomycin instillation. A similar tendency was observed in both early and delayed luteolin-treated groups. Next, our in vitro studies showed that luteolin inhibited TGF-β1-induced α-SMA, type I collagen, and vimentin expression in primary cultured mouse lung fibroblasts. Moreover, luteolin significantly blocked TGF-β1-mediated epithelial marker (E-cadherin) downregulation and mesenchymal cell markers (fibronectin and vimentin) upregulation, as well as retaining epithelial morphology in human alveolar epithelial-derived A549 cells. Additionally, luteolin could attenuate TGF-β1-induced Smad3 phosphorylation in both lung fibroblasts and A549 cells. These findings suggest that luteolin has a potent antifibrotic activity; this effect was mediated, at least in part, by inhibition of lung inflammation and suppression of myofibroblast differentiation as well as epithelial-to-mesenchymal transition.


title: Ischemic Stroke After Treatment of Intraprocedural Thrombosis During Stent-Assisted Coiling and Flow Diversion.

text: BACKGROUND AND PURPOSE Intraprocedural thrombosis poses a formidable challenge during neuroendovascular procedures because the risks of aggressive thromboembolic treatment must be balanced against the risk of postprocedural hemorrhage. The aim of this study was to identify predictors of ischemic stroke after intraprocedural thrombosis after stent-assisted coiling and pipeline embolization device placement. METHODS A retrospective analysis of intracranial aneurysms treated with stent-assisted coiling or pipeline embolization device placement between 2007 and 2016 at 4 major academic institutions was performed to identify procedures that were complicated by intraprocedural thrombosis. RESULTS Intraprocedural thrombosis occurred in 34 (4.6%) procedures. Postprocedural ischemic stroke and hemorrhage occurred in 20.6% (7/34) and 11.8% (4/34) of procedures complicated by intraprocedural thrombosis, respectively. Current smoking was an independent predictor of ischemic stroke. There was no statistically significant difference in the rate of ischemic stroke or postprocedural hemorrhage with the use of abciximab compared with the use of eptifibatide in treatment of intraprocedural thrombosis. CONCLUSIONS Current protocols for treatment of intraprocedural thrombosis associated with placement of intra-arterial devices were effective in preventing ischemic stroke in ≈80% of cases. Current smoking was the only independent predictor of ischemic stroke.


title: Histological findings in equine testes one year after standing laparoscopic peritoneal flap hernioplasty.

text: In order to know reproduction-related complications due to standing laparoscopic peritoneal flap hernioplasty, histological characteristics of the testicles from five stallions one year after surgery were compared with seven testicles from four healthy stallions. Moreover, the daily sperm output (DSO) was determined before (T0) and one year after surgery (T12). DSO did not show significant differences between T0 and T12. The diameter of the seminiferous tubules was significantly decreased in the samples from the hernioplasty group. The percentage of tubules with full spermatogenesis was smaller in the hernioplasty group, but the difference was not significant. It can be concluded that standing laparoscopic peritoneal flap hernioplasty produced mild histological changes in the testicular parenchyma, epididymis and pampiniform plexus after one year follow-up.


We Can Choose NOT to Fail.


title: Corona Virus Disease 2019 and Paediatric Inflammatory Bowel Diseases: Global Experience and Provisional Guidance (March 2020) from the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology, and Nutrition

text: INTRODUCTION: With the current coronavirus disease 2019 (COVID-19) pandemic, concerns have been raised about the risk to children with inflammatory bowel diseases (IBD). We aimed to collate global experience and provide provisional guidance for managing paediatric IBD (PIBD) in the era of COVID-19. METHODS: An electronic reporting system of children with IBD infected with SARS-CoV-2 has been circulated among 102 PIBD centres affiliated with the Porto and Interest-group of ESPGHAN. A survey has been completed by major PIBD centres in China and South-Korea to explore management during the pandemic. A third survey collected current practice of PIBD treatment. Finally, guidance points for practice have been formulated and voted upon by 37 PIBD authors and Porto group members. RESULTS: Eight PIBD children had COVID-19 globally, all with mild infection without needing hospitalization despite treatment with immunomodulators and/or biologics. No cases have been reported in China and South Korea but biologic treatment has been delayed in 79 children, of whom 17 (22%) had exacerbation of their IBD. Among the Porto group members, face-to-face appointments were often replaced by remote consultations but almost all did not change current IBD treatment. Ten guidance points for clinicians caring for PIBD patients in epidemic areas have been endorsed with consensus rate of 92% to 100%. CONCLUSIONS: Preliminary data for PIBD patients during COVID-19 outbreak are reassuring. Standard IBD treatments including biologics should continue at present through the pandemic, especially in children who generally have more severe IBD course on one hand, and milder SARS-CoV-2 infection on the other. SUPPLEMENTAL DIGITAL CONTENT: An infographic accompanying this article can be found at.


title: Sequential activation of the three protomers in the Moloney murine leukemia virus Env.

text: Viral membrane fusion proteins of class I are trimers in which the protomeric unit is a complex of a surface subunit (SU) and a fusion active transmembrane subunit (TM). Here we have studied how the protomeric units of Moloney murine leukemia virus envelope protein (Env) are activated in relation to each other, sequentially or simultaneously. We followed the isomerization of the SU-TM disulfide and subsequent SU release from Env with biochemical methods and found that this early activation step occurred sequentially in the three protomers, generating two asymmetric oligomer intermediates according to the scheme (SU-TM)3 → (SU-TM)2TM → (SU-TM)TM2 → TM3 This was the case both when activation was triggered in vitro by depleting stabilizing Ca2+ from solubilized Env and when viral Env was receptor triggered on rat XC cells. In the latter case, the activation reaction was too fast for direct observation of the intermediates, but they could be caught by alkylation of the isomerization active thiol.


COVID-19 and non-communicable diseases.