title: Impact of CPAP on Forehead Near-infrared Spectroscopy Measurements in Patients With Acute Respiratory Failure: Truth or Illusion.

text: BACKGROUND Critically ill patients with acute respiratory failure admitted to an intensive care unit are at high risk for cerebral hypoxia. We investigated the impact of continuous positive airway pressure (CPAP) therapy on regional cerebral tissue oxygenation (rSO2). MATERIALS AND METHODS In total, 40 extubated surgical intensive care unit patients requiring classic oxygen therapy (COT) for acute respiratory failure were examined. Near-infrared spectroscopy (INVOS 5100C, Covidien) was used for 30 minutes to detect bilateral rSO2 during COT via facemask (6 L/min) and CPAP therapy (40% fraction of inspired oxygen, 8 cm H2O CPAP) using a randomized crossover study design. Patients served as their own control. Continuous hemodynamic routine monitoring and blood gas analysis were performed. The effect of CPAP therapy on rSO2 and influence of assessed covariables were investigated using a mixed linear model. RESULTS Median rSO2 increased from 57.9% (95% confidence interval [CI], 54.2-61.5) during COT to 62.8% (95% CI, 59.2-66.5) during CPAP therapy (P<0.0001). The estimated difference from the mixed model between COT and CPAP is -5.0 (95% CI, -6.3 to -3.7). Median arterial partial pressure of carbon dioxide decreased from 47.8±5.1 mm Hg during COT to 43.1±5 mm Hg during CPAP (P<0.001), whereas arterial partial pressure of oxygen remained unchanged (P=0.329). In total, 23% of patients had SO2 levels <50%, with a higher prevalence under COT. CONCLUSIONS Our results reveal that CPAP therapy compared with COT may influence rSO2 in patients with acute respiratory failure. However, the cause of the rSO2 increase following CPAP application remains to be elucidated, and the accuracy of cerebral oximetry during CPAP therapy in patients with acute respiratory failure remains questionable.


Refugees pose little health risk, says WHO.


title: Viral etiological causes of febrile seizures for respiratory pathogens (EFES Study).

text: BACKGROUND Febrile seizure is the most common childhood neurological disorder, is an important health problem with potential short- and long-term complications, also leading to economic burden and increased parental anxiety about fevers and seizures occurring in their children. There are no routine recommendation to detect etiological causes of FS for neurological perspective, further knowledge about the etiological causes of FS in children will support preventive measures and follow-up strategies. The aim of this study is to evaluate the percentage of respiratory viruses in children with FS. METHODS This prospective multicenter study, entitled "Viral etiological causes of febrile seizures for respiratory pathogens (EFES Study)" examined representative populations in eight different cities in Turkey between March 1, 2016 and April 1, 2017. Nasopharyngeal swabs were taken from all children at presentation. A respiratory multiplex array was performed to detect for influenza A and B; respiratory syncytial virus A and B; human parainfluenza virus 1-2-3 and 4; human coronavirus 229E and OC43; human rhinovirus; human enterovirus; human adenovirus; human bocavirus; human metapneumovirus. RESULTS During the study period, at least one virus was detected in 82.7% (144/174) of children with FS. The most frequently detected virus was adenovirus, followed by influenza A and influenza B. Detection of more than one virus was present in 58.3% of the children with FS, and the most common co-existence was the presence of adenovirus and influenza B. In children younger than 12 months, Coronavirus OC43 was the most common, while influenza A was most frequently observed in children older than 48 months (p < 0.05). Human bocavirus was common in children who experienced complex FS, while respiratory syncytial virus (RSV) A was more common in children who experienced simple FS. Influenza B virus was the most common virus identified in children who were experiencing their first incidence of FS (p < 0.05). CONCLUSIONS This study indicates that respiratory viruses are important in the etiology of FS in children. The results show that antibiotics must be prescribed carefully in children with FS since the majority of cases are related to viral causes. Widespread use of the existing quadrivalent influenza vaccine might be useful for the prevention of FS related to the flu. Further vaccine candidates for potential respiratory pathogens, including RSV, might be helpful for the prevention of FS.


title: [Diagnostic steps and estimation of disease prognosis in COVID-19-infected patients].

text: In December 2019, a new coronavirus outbreak hit his head in Wuhan, China. The identified pathogen is a new coronavirus named "severe acute respiratory syndrome coronavirus 2," or SARS-CoV-2, and the respiratory syndrome it elicits was named "coronavirus disease 2019," or COVID-19. The World Health Organization (WHO) classified the epidemic as a pandemic in March 2020. We reviewed the currently available international literature on the COVID-19 epidemic. In this paper, we summarize the relevant information for the diagnosis and prognosis of the new coronavirus. Details of the anamnestic factors and initial test results required to raise a clinical suspicion, the method of microbiological sampling, the basic information on the molecular diagnostic test - the 'gold-standard' real-time 'reverse transcriptase polymerase chain reaction (RT-PCR) - in particular the diagnostic current public health regulations for testing. We also place emphasis on the parameters of high-risk patients and how to identify them. The COVID-19 pandemic may also have significant epidemiological and health consequences in Hungary. In addition to epidemiological measures to slow down the epidemic, the timely identification and adequate hospital care of already infected individuals is also a key issue in terms of mortality. The chances of critically ill patients can only be improved with high-quality, careful intensive care, and to be able to provide the best, it is useful to use the experience of medical colleagues already working in endemic countries. Orv Hetil. 2020; 160 (17): 667-671.


title: Clopidogrel hyper-response and bleeding risk in neurointerventional procedures.

text: BACKGROUND AND PURPOSE Antiplatelet therapy is associated with decreased ischemic events after neurointerventional procedures. Antiplatelet resistance negates the protective effects of antiplatelet medication, leading to a higher incidence of ischemic events. A possible link between antiplatelet hyper-response and increased hemorrhagic complications has been inadequately investigated. We aimed to examine the correlation between antiplatelet hyper-response and the risk of hemorrhagic complications. MATERIALS AND METHODS Patients who were treated with antiplatelet medications and underwent neurointerventional procedures were prospectively recruited. We collected the following data: demographics, vascular risk factors, antiplatelet and anticoagulation treatment, antiplatelet responsiveness, coagulation profile, and hemorrhagic complications. P2Y12 receptor-mediated platelet inhibition was tested by using the VerifyNow assay device. The primary end points were postprocedural major and minor hemorrhagic complications. Receiver operator characteristic analysis was used to evaluate the percentage of platelet inhibition as a diagnostic tool for bleeding events. The association between hemorrhage and percentage of platelet inhibition was investigated by using logistic regression modeling. RESULTS Forty-seven patients were enrolled. The mean age was 56±12 years, and 28% were men. Ten patients (21.3%) developed hemorrhagic complications. Clopidogrel response was higher in patients with a major bleeding complication compared with those with minor or no bleeding (median, 94% versus 24% platelet inhibition; P=.0084). Of the 7 patients (14.9%) defined as hyper-responders with ≥72% platelet inhibition, 42.8% had a major bleeding complication. CONCLUSIONS Hyper-response to clopidogrel is associated with increased risk of hemorrhagic complications. Larger studies are urgently needed to validate a clinically useful threshold to define clopidogrel hyper-response and to examine the clinical effects of antiplatelet dosage adjustment.


title: Two alternative dural sealing techniques in posterior fossa surgery: (Polylactide-co-glycolide) self-adhesive resorbable membrane versus polyethylene glycol hydrogel.

text: BACKGROUND Post-operative cerebrospinal fluid (CSF) leak in posterior fossa surgery remains a significant source of morbidity. TissuePatchDural (TPD), a novel impermeable adhesive membrane, was used to reinforce dural closure. A comparison with one of the most commonly used dural sealing devices, DuraSeal, has been made. METHODS A retrospective, single-center study was conducted on 161 patients who underwent elective posterior fossa surgery. On surgeon's opinion, when a primary watertight closure was not possible, they received TPD or DuraSeal to reinforce dural closure. RESULTS Out of 161 patients analyzed, 115 were treated with TPD and 46 with DuraSeal. The post-operative leaks related purely to TPD or DuraSeal failure were recognized in 3 (2.6%) and 5 (10.86%) cases, respectively (P = 0.015). The presence of pre- and post-operative risk factors was associated with an increased incidence of CSF leak in both groups. TPD showed a better control in patients without these risk factors (P = 0.08). The incidence of CSF leak in patients who underwent posterior fossa surgery by craniectomy was statistically lower in TPD group compared to DuraSeal group (3.22% vs 17.8%, respectively; P = 0.008). CONCLUSIONS TPD seems to be a safe tool for use as an adjunct to standard dural closure in posterior fossa surgery, particularly in patients without pre- or post-oper ative risk factors, in those who did not develop hydrocephalus, and who underwent craniectomy. The CSF leak rate in TPD group was found to be lower or within the range of the more advanced alternative dural closure strategies, including polyethylene glycol (PEG)-based sealant.


title: Trends in childhood asthma hospitalisation in three Asia Pacific countries.

text: AIM The study aims to examine recent childhood asthma hospitalisation rates in the Asia Pacific countries of Australia, Hong Kong and Singapore. On the background of reported decline in many countries with high asthma prevalence during late 1990s. METHODS Annual asthma hospitalisation (ICD9-CM: 493 or ICD10-AM: J45-46)* and population data from 1994 to 2008, of children aged 0-14 years old, were obtained from the Australian National Hospital Morbidity Database, from the Hospital Authority in Hong Kong and from the Ministry of Health in Singapore. Data were stratified in two age groups: 0-4 and 5-14 years old, and also in different periods of calendar years. Time-series regression analyses were used to examine temporal trends. Diagnostic transfer was addressed by examining bronchitis hospitalisations. RESULTS Significant decreases of up to 6.5% per annum in childhood asthma hospitalisation rates were found over the study period. However, the latter half of the study period showed increases in hospitalisation rates in all countries studied. No evidence of diagnostic transfer was found. CONCLUSION Although there has been a decrease in childhood asthma hospitalisation rates since the 1990s, a modest increase was observed from 2003 to 2008. Ongoing monitoring is required.


title: Fatal disseminated toxoplasmosis in an immunocompetent cat.

text: A 10-year-old domestic short hair cat was referred for investigation of anorexia and polydipsia of 3 days' duration. Clinically the cat was obese, pyrexic (39.8 °C), had acute abdominal pain and severe bilirubinuria. Haematology and serum biochemistry revealed severe panleukopenia, thrombocytopenia, markedly elevated alanine aminotransferase (ALT) and five-fold increased pre-prandial bile acids. Ultrasonographic evaluation of the abdomen did not identify any abnormalities. Serum tests for feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) were negative. Broad-spectrum antibiotic treatment for infectious hepatitis was to no avail; the cat deteriorated and died 72 h after admission. Necropsy revealed mild icterus and anaemia, severe multifocal hepatic necrosis, serofibrinous hydrothorax, pulmonary oedema and interstitial pneumonia. Histopathology confirmed the macroscopic findings and revealed multifocal microgranulomata in the brain and myocardium, as well as areas of necrosis in lymph nodes and multifocally in splenic red pulp. Long bone shaft marrow was hyperplastic with a predominance of leukocyte precursors and megakaryocytes and splenic red pulp showed mild extramedullary haemopoiesis. Immunohistochemical staining for Toxoplasma gondii was strongly positive, with scattered cysts and tachyzoites in the liver, lymph nodes, spleen, lungs, brain, salivary glands and intracellularly in round cells in occasional blood vessels. Immunohistochemical staining for corona virus on the same tissues was negative, ruling out feline infectious peritonitis (FIP). Polymerase chain reaction (PCR) on formalin-fixed paraffin-wax embedded tissues was positive for Toxoplasma sp., but attempts at sequencing were unsuccessful. This was the first case report of fulminant disseminated toxoplasmosis in South Africa, in which detailed histopathology in an apparently immunocompetent cat was described.


title: Telemedicine from research to practice during the pandemic. "Instant paper from the field" on rehabilitation answers to the Covid-19 emergency.

text: Covid-19 pandemic is creating collateral damage to outpatients, whose rehabilitation services have been disrupted in most of the European countries. Telemedicine has been advocated as a possible solution. This paper reports the contents of the third Italian Society of Physical and Rehabilitation Medicine (SIMFER) webinar on "experiences from the field" Covid-19 impact on rehabilitation ("Covinars"). It provides readily available, first-hand information about the application of telemedicine in rehabilitation. The experiences reported were very different for population (number and health conditions), interventions, professionals, service payment, and technologies used. Commonalities included the pushing need due to the emergency, previous experiences, and a dynamic research and innovation environment. Lights included feasibility, results, reduction of isolation, cost decrease, stimulation to innovation, satisfaction of patients, families, and professionals beyond the starting diffidence. Shadows included that telemedicine can integrate but will never substitute face-to-face rehabilitation base on the encounter among human beings; age, and technology barriers (devices absence, bad connection and human diffidence) have also been reported. Possible issues included privacy and informed consent, payments, cultural difficulties in understanding that telemedicine is a real rehabilitation intervention. There was a final agreement that this experience will be incorporated by participants in their future services: technology is ready, but the real challenge is to change PRM physicians' and patients' habits, while better specific regulation is warranted.


title: Nonlytic viral spread enhanced by autophagy components.

text: The cell-to-cell spread of cytoplasmic constituents such as nonenveloped viruses and aggregated proteins is usually thought to require cell lysis. However, mechanisms of unconventional secretion have been described that bypass the secretory pathway for the extracellular delivery of cytoplasmic molecules. Components of the autophagy pathway, an intracellular recycling process, have been shown to play a role in the unconventional secretion of cytoplasmic signaling proteins. Poliovirus is a lytic virus, although a few examples of apparently nonlytic spread have been documented. Real demonstration of nonlytic spread for poliovirus or any other cytoplasmic constituent thought to exit cells via unconventional secretion requires demonstration that a small amount of cell lysis in the cellular population is not responsible for the release of cytosolic material. Here, we use quantitative time-lapse microscopy to show the spread of infectious cytoplasmic material between cells in the absence of lysis. siRNA-mediated depletion of autophagy protein LC3 reduced nonlytic intercellular viral transfer. Conversely, pharmacological stimulation of the autophagy pathway caused more rapid viral spread in tissue culture and greater pathogenicity in mice. Thus, the unconventional secretion of infectious material in the absence of cell lysis is enabled by components of the autophagy pathway. It is likely that other nonenveloped viruses also use this pathway for nonlytic intercellular spread to affect pathogenesis in infected hosts.


title: Predictors of the effects of treatment for shoulder pain: protocol of an individual participant data meta-analysis.

text: Background Shoulder pain is one of the most common presentations of musculoskeletal pain with a 1-month population prevalence of between 7 and 26%. The overall prognosis of shoulder pain is highly variable with 40% of patients reporting persistent pain 1 year after consulting their primary care clinician. Despite evidence for prognostic value of a range of patient and disease characteristics, it is not clear whether these factors also predict (moderate) the effect of specific treatments (such as corticosteroid injection, exercise, or surgery). Objectives This study aims to identify predictors of treatment effect (i.e. treatment moderators or effect modifiers) by investigating the association between a number of pre-defined individual-level factors and the effects of commonly used treatments on shoulder pain and disability outcomes. Methods This will be a meta-analysis using individual participant data (IPD). Eligible trials investigating the effectiveness of advice and analgesics, corticosteroid injection, physiotherapy-led exercise, psychological interventions, and/or surgical treatment in patients with shoulder conditions will be identified from systematic reviews and an updated systematic search for trials, and risk of bias will be assessed. Authors of all eligible trials will be approached for data sharing. Outcomes measured will be shoulder pain and disability, and our previous work has identified candidate predictors. The main analysis will be conducted using hierarchical one-stage IPD meta-analysis models, examining the effect of treatment-predictor interaction on outcome for each of the candidate predictors and describing relevant subgroup effects where significant interaction effects are detected. Random effects will be used to account for clustering and heterogeneity. Sensitivity analyses will be based on (i) exclusion of trials at high risk of bias, (ii) use of restricted cubic splines to model potential non-linear associations for candidate predictors measured on a continuous scale, and (iii) the use of a two-stage IPD meta-analysis framework. Discussion Our study will collate, appraise, and synthesise IPD from multiple studies to examine potential predictors of treatment effect in order to assess the potential for better and more efficient targeting of specific treatments for individuals with shoulder pain. Systematic review registration PROSPERO CRD42018088298.


[Peritoneal Dialysis in the Current Pandemic Crisis: An Opportunity for Reflection].


title: Arterivirus and nairovirus ovarian tumor domain-containing Deubiquitinases target activated RIG-I to control innate immune signaling.

text: The innate immune response constitutes the first line of defense against viral infection and is extensively regulated through ubiquitination. The removal of ubiquitin from innate immunity signaling factors by deubiquitinating enzymes (DUBs) therefore provides a potential opportunity for viruses to evade this host defense system. It was previously found that specific proteases encoded by the unrelated arteri- and nairoviruses resemble the ovarian tumor domain-containing (OTU) family of DUBs. In arteriviruses, this domain has been characterized before as a papain-like protease (PLP2) that is also involved in replicase polyprotein processing. In nairoviruses, the DUB resides in the polymerase protein but is not essential for RNA replication. Using both in vitro and cell-based assays, we now show that PLP2 DUB activity is conserved in all members of the arterivirus family and that both arteri- and nairovirus DUBs inhibit RIG-I-mediated innate immune signaling when overexpressed. The potential relevance of RIG-I-like receptor (RLR) signaling for the innate immune response against arterivirus infection is supported by our finding that in mouse embryonic fibroblasts, the production of beta interferon primarily depends on the recognition of arterivirus RNA by the pattern-recognition receptor MDA5. Interestingly, we also found that both arteri- and nairovirus DUBs inhibit RIG-I ubiquitination upon overexpression, suggesting that both MDA5 and RIG-I have a role in countering infection by arteriviruses. Taken together, our results support the hypothesis that arteri- and nairoviruses employ their deubiquitinating potential to inactivate cellular proteins involved in RLR-mediated innate immune signaling, as exemplified by the deubiquitination of RIG-I.


Expert consensus on management principles of orthopedic emergency in the epidemic of coronavirus disease 2019


title: Early results of single-incision laparoscopic cholecystectomy in comparison with the conventional: Does it have any impact on quality of life?

text: Background Laparoscopic cholecystectomy is the standard treatment for gallbladder diseases. In recent times, single-incision laparoscopic cholecystectomy(SILC) has developed as a less invasive alternative technique to conventional laparoscopy. In the literature, many studies have compared SILC and conventional laparoscopic cholecystectomy (CLC) procedures but a limited number of studies have compared the two techniques with regard to quality of life (QOL). The choice of surgical procedure was effected by QOL of the patients. The effects of SILC on QOL remain unclear. In this study, we aimed to compare the effects of conventional laparoscopic cholecystectomy (CLC) and single-incision laparoscopic cholecystectomy (SILC) procedures on the clinical outcomes and quality of life of patients by short-term follow-up evaluation. Material and methods In this study, 142 patients who underwent cholecystectomy operations with either technique underwent SILC and CLC were evaluated. The quality of life index in the patients was measured with short form 36 (SF 36) test. Results The results of mean operative time, length of stay and complication rate for SILC and CLC were similar. The postoperative health-related quality of life (HRQOL) scores were not significantly different between the SILC and CLC patients but only physical functioning score were higher in SILC patients. Conclusions SILC is a safe and effective alternative to CLC. To detect the effects of SILC on HRQOL, we need long-term prospective comparative studies.


title: Image-guided liver surgery: intraoperative projection of computed tomography images utilizing tracked ultrasound.

text: BACKGROUND Ultrasound (US) is the most commonly used form of image guidance during liver surgery. However, the use of navigation systems that incorporate instrument tracking and three-dimensional visualization of preoperative tomography is increasing. This report describes an initial experience using an image-guidance system with navigated US. METHODS An image-guidance system was used in a total of 50 open liver procedures to aid in localization and targeting of liver lesions. An optical tracking system was employed to localize surgical instruments. Customized hardware and calibration of the US transducer were required. The results of three procedures are highlighted in order to illustrate specific navigation techniques that proved useful in the broader patient cohort. RESULTS Over a 7-month span, the navigation system assisted in completing 21 (42%) of the procedures, and tracked US alone provided additional information required to perform resection or ablation in six procedures (12%). Average registration time during the three illustrative procedures was <1 min. Average set-up time was approximately 5 min per procedure. CONCLUSIONS The Explorer™ Liver guidance system represents novel technology that continues to evolve. This initial experience indicates that image guidance is valuable in certain procedures, specifically in cases in which difficult anatomy or tumour location or echogenicity limit the usefulness of traditional guidance methods.


title: Swimming Pool safety and prevention at the time of Covid-19: a consensus document from GSMS-SItI.

text: Public health measures to cope with the Covid-19 pandemic, imposed also a shutdown of sports facilities and swimming pools. Safety issues related to recreational waters were emerging during the lockdown, rising concerns on how and when reopening pools and on how improve their management while SARS-CoV-2 is circulating in the population. The GSMS-SItI, Working Group on Movement Sciences for Health of the Italian Society of Hygiene Preventive Medicine and Public Health, discussed and summarized some indications for a suitable preventive approach. Several measures are highlighted, including social distancing, optimized water management, airflow and microclimatic parameters in the pool as well in the annexed rooms, verification of sanitation procedures. The GSMS-SItI underlines that prevention should be based on monitoring of the local epidemiological situation and on the constant collaboration with the local health authority and the national health service.


title: Intracorporeal circular-stapled Billroth I anastomosis in single-incision laparoscopic distal gastrectomy.

text: PURPOSE The intracorporeal anastomotic procedure is one of the most difficult components in single-incision laparoscopic gastrectomy. We describe a simple surgical technique for intracorporeal circular-stapled Billroth I gastroduodenostomy with transumbilical introduction of the instrument. SURGICAL TECHNIQUE After standard laparoscopic mobilization of the distal stomach using a mini-loop retractor (diameter, 2 mm), a semi-circumference duodenotomy was made just distal to the pyloric ring. The anvil of a circular stapling device, secured with a Prolene suture with a needle, was introduced via the duodenotomy. The suture was advanced anteriorly such that an anvil shaft transfixed the anterior duodenal wall. The duodenum was staple-transected at this point, and the anvil shaft was removed from the duodenum by pulling the thread. The anvil shaft was advanced against the posterior wall of the stomach and tightly grasped by the mini-loop retractor to avoid slippage. After the cartridge-carrying instrument was introduced transumbilically with the pneumoperitoneum maintained using a surgical glove, the anvil shaft was connected with the center rod of the instrument under fine laparoscopic view. The instrument was fired to complete the circular-stapled gastroduodenostomy. RESULTS We employed this technique in 20 patients. Neither postoperative complications, including anastomotic leakage and stricture, nor postoperative mortality were observed. CONCLUSIONS Our modified technique for intracorporeal Billroth I reconstruction in single-incision laparoscopic distal gastrectomy is safe and feasible. This technique could be an attractive surgical option for all laparoscopic reconstructive procedures using circular stapling devices.


title: An update and systematic review on the treatment of primary dysmenorrhea.

text: OBJECTIVES Primary dysmenorrhea is a painful uterine contraction caused by endometrial laceration. Drug therapies and complementary medicine have been used to treat dysmenorrhea. The aim of this study was to investigate and offer an updated perspective on the treatments for dysmenorrhea. METHODS The present study was conducted in accordance with the PRISMA checklist for systematic reviews and meta-analyses. The required information was collected based on searches for the following keywords: treatment, primary dysmenorrhea, medicinal plants, chemical drugs, and herbs. Searches were performed on databases Pubmed, Web of Sciences, Scopus, Iran medex, and SID by March 2018 to find literature in the English and Persian languages on this subject without a time limit. RESULTS This review included 17 papers, 10 of which on complementary medicine, three on drug therapies, and four on acupuncture and acupressure. The largest and smallest samples had 303 and 24 patients, respectively. Length of treatment ranged from one to six months and the measures most commonly used in the studies were the visual analogue scale and clinical efficacy. Reported complications included gastrointestinal events, nausea, vomiting, diarrhea, abdominal pain, and liver and kidney disorders. CONCLUSION Medicinal plants, drugs, and acupressure seem to suppress pain by reducing the level of prostaglandins, mediating nitric oxide, increasing beta-endorphin levels, blocking the calcium channel, and enhancing circulatory flow through the uterine pathway. Further trials are required to confirm the benefits of the procedures described and ensure the absence of complications.


Rural and Remote Communities: Unique Ethical Issues in the COVID-19 Pandemic.


title: Surveillance for Avibacterium paragallinarum in autopsy cases of birds from small chicken flocks using a real-time PCR assay.

text: Infectious coryza is a severe respiratory disease of chickens associated with large economic losses in affected commercial flocks. The fastidious causative pathogen, Avibacterium paragallinarum, is difficult to recover and identify, resulting in delayed diagnosis and enhanced spread of the agent. Small poultry flocks are increasingly common in rural and suburban environments. We assessed the frequency of A. paragallinarum using real-time PCR and clinical conditions present in samples from such flocks submitted to the California Animal Health and Food Safety Laboratory System (Davis, CA) in 2018. From the 294 samples collected for our study, 86 (30%) were PCR-positive for A. paragallinarum. Juvenile birds (≤1 y) were significantly more likely to be PCR-positive ( p = 0.017), and birds diagnosed with respiratory disease had lower Ct values ( p = 0.001) than those without. Concurrent infections were also identified, including with Mycoplasma gallisepticum (18.6%), M. synoviae (18.6%), infectious bronchitis virus (12.8%), and infectious laryngotracheitis virus (7.0%). Only 46.5% of PCR-positive chickens had antemortem respiratory signs, making endemic infections in these flocks highly likely. Our study demonstrates that A. paragallinarum is present in small-flock operations including those without respiratory disease and may present a risk for airborne pathogen transmission to commercial poultry operations.


Modern techniques of fixing of meshes in surgical repair of inguinal and abdominal hernias.


title: Prospective comparative cohort study evaluating incompetent great saphenous vein closure using radiofrequency-powered segmental ablation or 1470-nm endovenous laser ablation with radial-tip fibers (Varico 2 study).

text: BACKGROUND Endovenous laser ablation (EVLA) and radiofrequency-powered segmental ablation (RPSA) of the incompetent great saphenous vein (GSV) are both known for their excellent technical and clinical outcomes for the treatment of varicose veins. RPSA has reduced postprocedural pain and morbidity with shorter recovery time for the patient compared with EVLA using bare-tip fibers. However, new-generation EVLA devices with less traumatic radial-tip fibers (RTFs) operating at longer wavelengths up to 1470 nm also reduce postprocedural pain. The objective of this study was to compare long-term effectiveness of GSV thermal ablation and postprocedural recovery using RPSA or 1470-nm EVLA with RTF (EVLA-RTF). METHODS In a comparative prospective monthly altering-treatment cohort study of 311 patients (346 treated legs), each leg with incompetence of the GSV was treated with either RPSA (158 patients, 175 legs) or EVLA-RTF (153 patients, 171 legs). The primary outcome was anatomic occlusion of the GSV, assessed at 12, 24, 36, 48, and 60 months using Kaplan-Meier statistics and compared using the log-rank test. Secondary outcomes included freedom of varicose vein recurrence, clinical success measured by Venous Clinical Severity Score (VCSS), disease-specific quality of life determined using the Aberdeen Varicose Vein Questionnaire (AVVQ), postoperative pain scores, and time to return to work. RESULTS The total primary obliteration rate after 36 and 60 months was 96.2% with RPSA and 96.7% with EVLA-RTF (P = .81). Freedom of symptomatic anterior accessory vein recurrence after 5 years was 85% after RPSA and 87% after EVLA-RTF (P = .50). VCSS and AVVQ score presented similar and durable improvements in both groups between 6 weeks and 60 months. There was no difference in postoperative pain scores after both treatments during the first 14 days (mean visual analog scale score, 0.54-2.19). The median time for return to work was 1 day after both treatments. No severe adverse events were observed. CONCLUSIONS RPSA and EVLA-RTF have similarly high GSV obliteration rates in the long term, and the treatments are equally effective clinically. Both treatments are associated with similar minimal postprocedural pain scores and short recovery times.


title: Renovascular reactivity measured by near-infrared spectroscopy.

text: Hypotension and shock are risk factors for death, renal insufficiency, and stroke in preterm neonates. Goal-directed neonatal hemodynamic management lacks end-organ monitoring strategies to assess the adequacy of perfusion. Our aim is to develop a clinically viable, continuous metric of renovascular reactivity to gauge renal perfusion during shock. We present the renovascular reactivity index (RVx), which quantifies passivity of renal blood volume to spontaneous changes in arterial blood pressure. We tested the ability of the RVx to detect reductions in renal blood flow. Hemorrhagic shock was induced in 10 piglets. The RVx was monitored as a correlation between slow waves of arterial blood pressure and relative total hemoglobin (rTHb) obtained with reflectance near-infrared spectroscopy (NIRS) over the kidney. The RVx was compared with laser-Doppler measurements of red blood cell flux, and renal laser-Doppler measurements were compared with cerebral laser-Doppler measurements. Renal blood flow decreased to 75%, 50%, and 25% of baseline at perfusion pressures of 60, 45, and 40 mmHg, respectively, whereas in the brain these decrements occurred at pressures of 30, 25, and 15 mmHg, respectively. The RVx compared favorably to the renal laser-Doppler data. Areas under the receiver operator characteristic curves using renal blood flow thresholds of 50% and 25% of baseline were 0.85 (95% CI, 0.83-0.87) and 0.90 (95% CI, 0.88-0.92). Renovascular autoregulation can be monitored and is impaired in advance of cerebrovascular autoregulation during hemorrhagic shock.


title: Clinical Relevance and Role of Neuronal AT1 Receptors in ADAM17-Mediated ACE2 Shedding in Neurogenic Hypertension.

text: RATIONALE Neurogenic hypertension is characterized by an increase in sympathetic activity and often resistance to drug treatments. We previously reported that it is also associated with a reduction of angiotensin-converting enzyme type 2 (ACE2) and an increase in a disintegrin and metalloprotease 17 (ADAM17) activity in experimental hypertension. In addition, while multiple cells within the central nervous system have been involved in the development of neurogenic hypertension, the contribution of ADAM17 has not been investigated. OBJECTIVE To assess the clinical relevance of this ADAM17-mediated ACE2 shedding in hypertensive patients and further identify the cell types and signaling pathways involved in this process. METHODS AND RESULTS Using a mass spectrometry-based assay, we identified ACE2 as the main enzyme converting angiotensin II into angiotensin-(1-7) in human cerebrospinal fluid. We also observed an increase in ACE2 activity in the cerebrospinal fluid of hypertensive patients, which was correlated with systolic blood pressure. Moreover, the increased level of tumor necrosis factor-α in those cerebrospinal fluid samples confirmed that ADAM17 was upregulated in the brain of hypertensive patients. To further assess the interaction between brain renin-angiotensin system and ADAM17, we generated mice lacking angiotensin II type 1 receptors specifically on neurons. Our data reveal that despite expression on astrocytes and other cells types in the brain, ADAM17 upregulation during deoxycorticosterone acetate-salt hypertension occurs selectively on neurons, and neuronal angiotensin II type 1 receptors are indispensable to this process. Mechanistically, reactive oxygen species and extracellular signal-regulated kinase were found to mediate ADAM17 activation. CONCLUSIONS Our data demonstrate that angiotensin II type 1 receptors promote ADAM17-mediated ACE2 shedding in the brain of hypertensive patients, leading to a loss in compensatory activity during neurogenic hypertension.


Sequencing Treatments for Cancer During the COVID-19 Pandemic.


title: Ivor Lewis minimally invasive esophagectomy for esophageal cancer: An excellent operation that improves with experience.

text: OBJECTIVE Esophagectomy is associated with major morbidity. In this study we sought to assess the learning curve of minimally invasive Ivor Lewis esophagectomy (MIILE) and to evaluate perioperative outcomes, including anastomotic leak and hospital readmission, as a function of graduated surgeon experience. METHODS Data were extracted from the electronic medical records of patients who underwent MIILE, performed by a single surgeon over an 8-year period (2009-2017). Primary outcomes were 5-year overall survival, postoperative complications, and 90-day readmission rates. Surgeon experience was divided into 4 quartiles, representing graduated experience. Statistical analysis was performed using univariate and multivariate logistic regression, whereas Kaplan-Meier estimators were used to assess survival outcomes. RESULTS A total of 170 patients underwent MIILE and were analyzed after exclusion criteria were applied. Five-year overall survival was 50.1% (95% confidence interval, 39.7%-63.2%). Mortality at 90 days was 3.9% (95% confidence interval, 0.8%-6.9%). Major complications occurred in 25.3% (n = 43) and 25.9% (n = 44) were readmitted to the hospital within 90 days after surgery. Conversion to open surgery, anastomotic leaks, and readmissions decreased over time. CONCLUSIONS MIILE can be performed safely and effectively with improving results as the surgeon's experience evolves.


docid: leatazuy

title: Antagonism of type I interferon responses by new world hantaviruses.

text: Evasion of interferon (IFN)-mediated antiviral signaling is a common defense strategy for pathogenic RNA viruses. To date, research on IFN antagonism by hantaviruses is limited and has focused on only a subset of the numerous recognized hantavirus species. The host IFN response has two phases, an initiation phase, resulting in the induction of alpha/beta IFN (IFN-α/β), and an amplification phase, whereby IFN-α/β signals through the Jak/STAT pathway, resulting in the establishment of the cellular antiviral state. We examined interactions between these critical host responses and the New World hantaviruses. We observed delayed cellular responses in both Andes virus (ANDV)- and Sin Nombre virus (SNV)-infected A549 and Huh7-TLR3 cells. We found that IFN-β induction is inhibited by coexpression of ANDV nucleocapsid protein (NP) and glycoprotein precursor (GPC) and is robustly inhibited by SNV GPC alone. Downstream amplification by Jak/STAT signaling is also inhibited by SNV GPC and by either NP or GPC of ANDV. Therefore, ANDV- and SNV-encoded proteins have the potential for inhibiting both IFN-β induction and signaling, with SNV exhibiting the more potent antagonism ability. Herein we identify ANDV NP, a previously unrecognized inhibitor of Jak/STAT signaling, and show that IFN antagonism by ANDV relies on expression of both the glycoproteins and NP, whereas the glycoproteins appear to be sufficient for antagonism by SNV. These data suggest that IFN antagonism strategies by hantaviruses are quite variable, even between species with similar disease phenotypes, and may help to better elucidate species-specific pathogenesis.


title: RNase-resistant virus-like particles containing long chimeric RNA sequences produced by two-plasmid coexpression system.

text: RNase-resistant, noninfectious virus-like particles containing exogenous RNA sequences (armored RNA) are good candidates as RNA controls and standards in RNA virus detection. However, the length of RNA packaged in the virus-like particles with high efficiency is usually less than 500 bases. In this study, we describe a method for producing armored L-RNA. Armored L-RNA is a complex of MS2 bacteriophage coat protein and RNA produced in Escherichia coli by the induction of a two-plasmid coexpression system in which the coat protein and maturase are expressed from one plasmid and the target RNA sequence with modified MS2 stem-loop (pac site) is transcribed from another plasmid. A 3V armored L-RNA of 2,248 bases containing six gene fragments-hepatitis C virus, severe acute respiratory syndrome coronavirus (SARS-CoV1, SARS-CoV2, and SARS-CoV3), avian influenza virus matrix gene (M300), and H5N1 avian influenza virus (HA300)-was successfully expressed by the two-plasmid coexpression system and was demonstrated to have all of the characteristics of armored RNA. We evaluated the 3V armored L-RNA as a calibrator for multiple virus assays. We used the WHO International Standard for HCV RNA (NIBSC 96/790) to calibrate the chimeric armored L-RNA, which was diluted by 10-fold serial dilutions to obtain samples containing 10(6) to 10(2) copies. In conclusion, the approach we used for armored L-RNA preparation is practical and could reduce the labor and cost of quality control in multiplex RNA virus assays. Furthermore, we can assign the chimeric armored RNA with an international unit for quantitative detection.


title: A simple prediction rule for all-cause mortality in a cohort eligible for bariatric surgery.

text: IMPORTANCE Current eligibility criteria for bariatric surgery use arbitrarily chosen body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) thresholds, an approach that has been criticized as arbitrary and lacking evidence. OBJECTIVES To verify the importance of BMI as a mortality predictor, to identify other important mortality predictors, and to construct a mortality prediction rule in a population eligible for bariatric surgery. DESIGN We studied individuals from a population-representative register who met contemporary eligibility criteria for bariatric surgery (BMI, ≥35.0 alone or 30.0-34.9 with an obesity-related comorbidity) from January 1, 1988, through December 31, 1998. We used binary logistic regression to construct a parsimonious model and a clinical prediction rule for 10-year all-cause mortality. SETTING The United Kingdom General Practice Research Database, a population-representative primary care registry. PARTICIPANTS Fifteen thousand three hundred ninety-four patients aged 18 to 65 years. EXPOSURE Bariatric surgery. MAIN OUTCOME AND MEASURE Ten-year all-cause mortality. RESULTS Mean (SD) age was 46.9 (11.9) years, BMI was 36.2 (5.5), and 63.2% of the patients were women. All-cause mortality was 2.1%, and mean follow-up duration was 9.9 years. The final model, which included age (odds ratio, 1.09 per year [95% CI, 1.07-1.10]), type 2 diabetes mellitus (2.25 [1.76-2.87]), current smoking (1.62 [1.28-2.06]), and male sex (1.50 [1.20-1.87]), had a C statistic of 0.768. Although BMI significantly predicted mortality (odds ratio, 1.03 per unit [95% CI, 1.01-1.05]), it did not improve model discrimination or calibration. We divided clinical prediction rule scoring into 4 tiers. All-cause mortality was 0.2% in tier 1, 0.9% in tier 2, 2.0% in tier 3, and 5.2% in tier 4. CONCLUSIONS AND RELEVANCE All-cause 10-year mortality in obese individuals eligible for bariatric surgery can be estimated using a simple 4-variable prediction rule based on age, sex, smoking, and diabetes mellitus. Body mass index was not an important mortality predictor. Further work is needed to define low, moderate, and high absolute risk thresholds and to provide external validation.


title: "Top down no-touch" technique in robotic complete mesocolic excision for extended right hemicolectomy with intracorporeal anastomosis.

text: BACKGROUND Proper identification of the mesocolic vessels is essential for achieving complete mesocolic excision (CME) in cases of colon cancer requiring an extended right hemicolectomy. In robotic procedures, we employed a "top down technique" to allow early identification of the gastrocolic trunk and middle colic vessels. The aim of our study was to illustrate the details of this technique in a series of 12 patients. METHODS The top down technique consists of two steps. First, the omental bursa was entered to identify the right gastroepiploic vein. Tracing down this vein as a landmark, the gastrocolic trunk was exposed, branches of this trunk and the middle colic vessels were divided. Second, dissection was directed to the ileocolic region and proceeded in an inferior-to-superior direction along the superior mesenteric vein to divide the ileocolic and right colic vessels consecutively. The ileotranverse anastomosis was created intracorporeally. RESULTS There were 8 males and 4 females with a mean age of 64.8 ± 16.9 years and a mean body mass index of 25.6 ± 3.7 kg/m2. All the procedures were completed successfully. No conversions occurred. The mean operative time and blood loss were 312.1 ± 93.9 min and 110.0 ± 89.9 ml, respectively. The mean number of harvested lymph nodes was 45.2 ± 11.1. The mean length of hospital stay was 7.6 ± 4.7 days. Two patients had intraoperative complications and two had postoperative complications. There was no disease recurrence at a mean follow-up period of 10.4 ± 7.1 months. CONCLUSIONS The top down technique appears to be useful in robotic CME for an extended right hemicolectomy. Early identification of the gastrocolic trunk and middle colic vessels via this technique may prevent inadvertent vascular injury at the mesenteric root of the transverse colon.


title: [2019 Novel coronavirus, renin-angiotension system imbalance and coronavirus disease 2019].

text: 2019 Novel coronavirus (2019-nCoV) destroys angiotensin converting enzyme 2 (ACE2) and breaks the balance of renin-angiotension system (RAS) by interacting with ACE2. The imbalance of RAS takes part in the development of organ injury of different systems through pro-inflammation, oxidative stress, cell proliferation and so on. 2019-nCoV not only attacks the lung, but also influences many other systems. It is speculated that RAS imbalance plays an important role in the development of multi-organ dysfunction caused by 2019-nCoV, and the usage of angiotensin converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) may become a new treatment of 2019-nCoV-related organ injury. Further studies are need to confirm the relationship between coronavirus infection, multi-organ injury and RAS imbalance.


title: Genetic and antigenic characterization of newly isolated bovine toroviruses from Japanese cattle.

text: Torovirus, a member of the Coronaviridae family, is a gastrointestinal infectious agent that has been identified in humans, cattle, pigs, and equines. Toroviruses, except equine torovirus, are difficult to propagate in cell culture; indeed, to date, only the Aichi/2004 strain of bovine torovirus (BToV) has been isolated among the human, bovine, and porcine toroviruses. In the present study, four cytopathogenic BToVs were isolated from diarrheal feces of the cattle using the HRT-18 cell line, and their genetic and antigenic properties were compared. The cytopathogenic features of BToV isolates in HRT-18 cells were similar to those of the Aichi/2004 strain. However, none of the isolates showed cytopathogenic effects in the HRT-18 cells of different origin, suggesting that one significant factor contributing to the cytopathogenicity of BToV depends on properties of the HRT-18 cells themselves. All BToVs isolated were able to agglutinate mouse, but not chicken, erythrocytes, while they lacked receptor-destroying enzyme activity. Analysis of the N terminus of the spike gene showed that three isolates, but not the Gifu-2007TI/E strain, were phylogenetically located in cluster 1 and its analogs and revealed high cross-reactivity with each other, as demonstrated by neutralization (NT) and hemagglutination inhibition (HI) assays. The Gifu-2007TI/E strain was classified close to cluster 2 and exhibited relatively low cross-reactivity with these viruses; however, the difference was not sufficient to classify BToVs into serotypes, suggesting that at least two subtypes distinguishable by the structure of the N terminus of the spike gene and that both NT and HI tests may be exist.


title: Autophagy and SARS-CoV-2 infection: Apossible smart targeting of the autophagy pathway.

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak resulted in 5,993,317 confirmed cases worldwide with 365,394 confirmed deaths (as of May 29th, 2020, WHO). The molecular mechanism of virus infection and spread in the body is not yet disclosed, but studies on other betacoronaviruses show that, upon cell infection, these viruses inhibit macroautophagy/autophagy flux and cause the accumulation of autophagosomes. No drug has yet been approved for the treatment of SARS-CoV-2 infection; however, preclinical investigations suggested repurposing of several FDA-approved drugs for clinical trials. Half of these drugs are modulators of the autophagy pathway. Unexpectedly, instead of acting by directly antagonizing the effects of viruses, these drugs appear to function by suppressing autophagy flux. Based on the established cross-talk between autophagy and apoptosis, we speculate that over-accumulation of autophagosomes activates an apoptotic pathway that results in apoptotic death of the infected cells and disrupts the virus replication cycle. However, administration of the suggested drugs are associated with severe adverse effects due to their off-target accumulation. Nanoparticle targeting of autophagy at the sites of interest could be a powerful tool to efficiently overcome SARS-CoV-2 infection while avoiding the common adverse effects of these drugs.


title: Rectovaginal fistula: a new technique and preliminary results using collagen matrix biomesh.

text: BACKGROUND A rectovaginal fistula (RVF) is a debilitating condition that is difficult to treat. Many available techniques are invasive and involve extensive surgery. A local procedure with good closure rates would be preferable as a first step in the treatment of RVF. The aim of this study was the development of a local technique for the closure of RVF with good closure rates to prevent the use of more invasive procedures. METHODS This was a pilot study. Patients with RVF who had undergone multiple operations in the pelvic area, local radiotherapy, chemotherapy or had been diagnosed with Crohn's disease were included in the study. All had a history of surgery for RVF. A cross-linked collagen matrix biomesh was placed in the rectovaginal septum using a transperineal or a transvaginal approach. The main outcome measure in this study was the closure rate reported as absence of the fistula at 1 year. RESULTS Twelve patients were included in the study. Absence of fistula at 1 year was 0.64 (95 % confidence interval 0.30-0.85). Three patients (25.0 %) developed a recurrence, two were reoperated on with a gracilis flap transposition, and one was treated with laparoscopic ligation. In one patient (8.3 %), the fistula failed to close within 3 months after the mesh placement. CONCLUSIONS Our technique shows promising results. A local and simple technique with acceptable closure and morbidity rates, like our local repair with biomesh, would be ideal as a first step in treating RVFs. Long-term results are needed.


title: Robotic Gastrotomy With Intracorporeal Suture for Patients With Gastric Gastrointestinal Stromal Tumors Located at Cardia and Subcardiac Region.

text: PURPOSE Few studies of robotic gastric gastrointestinal stromal tumors (GISTs) resection have been conducted. This study was aimed to evaluate the robotic gastrotomy with intracorporeal suture for patients with GISTs located at cardia and subcardiac region. MATERIALS AND METHODS From January 2014 to August 2016, 11 patients with GISTs located at cardia and subcardiac region underwent robotic gastrotomy with intracorporeal suture. Data of these patients were collected. RESULTS The mean operative time was 82.7 minutes and the mean blood loss was 30.0 mL. No complication was reported. The postoperative length of stay was 3.3 days. On postoperative day 14, inflammation recovered to preoperative level. On postoperative month 6, the nutritional status was similar to that before the surgery. After 25.5 months follow-up, all patients survived with no recurrence or metastasis. CONCLUSIONS Robotic gastrotomy with intracorporeal suture for patients with GISTs located at cardia and subcardiac region is safe and feasible.


title: Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease.

text: SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.


title: Herbal medicines: challenges in the modern world. Part 3. China and Japan.

text: INTRODUCTION Medicinal plants, and formulations prepared from them, have been used in China and Japan for thousands of years. Nowadays, ancient formulations of Traditional Chinese and Kampo (Japanese) Medicines coexist with Western herbal medicines (HMs) and complement each other. HMs are used for the treatment of mild and chronic diseases, as an adjunct therapy, to improve wellbeing and delay aging, or as healthy (functional) foods. AREAS COVERED This article, a third part in a series of reviews, is focusing on history, use and regulation of the traditional and modern HMs in Japan and China. Materials available from legislative and governmental websites, PubMed and news media were used. Expert commentary: HMs are heavily regulated in both countries, often in a similar manner as conventional pharmaceutical drugs. The majority of herbal formulations are sold as over-the-counter medications supplied with leaflets describing indications and appropriate dosages for patients of different ages. Medical practitioners prescribe herbal formulations that are tailored to the needs of particular patients. Both countries had problems with adverse drug reactions and toxicity of single herbs and herbal formulations that have been investigated by authorities, and some drugs have been removed from the market.


title: Bispectral index to monitor propofol sedation in trauma patients.

text: BACKGROUND This study tested the hypothesis that the bispectral index (BIS) is reliable relative to clinical judgment for estimating sedation level during daily propofol spontaneous awakening trials (SATs) in trauma patients. METHODS This was a prospective observational trial with waiver of consent conducted in the intensive care unit of Level I trauma center in 94 mechanically ventilated trauma patients sedated with propofol alone or in combination with midazolam. BIS, Richmond Agitation Sedation Scale (RASS), electromyography, and heart rate variability, as a test of autonomic function, were measured for 45 minutes during daily SATs. Data were evaluated with analysis of variance, linear regression, and nonparametric tests. RESULTS The BIS wave form coincided almost exactly with propofol on/off. Steady-state BIS correlated with RASS (p < 0.0001) and with propofol dose (p < 0.0001), but the strengths of association were relatively low (all r(2) < 0.5). BIS wave form was not altered by age, heart rate, or heart rate variability and was similar with propofol alone or propofol plus midazolam, but the presence of brain injury or the use of paralytics shifted the curve downward (both p < 0.001). The overall test characteristics for BIS versus RASS without neuromuscular blockade were sensitivity: 90% versus 77% (p = 0.034); specificity: 90% versus 75% (p = 0.021); positive predictive value: 90% versus 76% (p = 0.021), and negative predictive value: 90% versus 76% (p = 0.021). CONCLUSIONS In the first trial in trauma patients and largest trial in any surgical population, the (1) BIS was reliable and has advantages over RASS of being continuous and objective, at least during a propofol SAT; (2) BIS interpretation remains somewhat subjective in patients receiving paralytic agents or with traumatic brain injury.


title: Mannitol and Outcome in Intracerebral Hemorrhage: Propensity Score and Multivariable Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 Results.

text: BACKGROUND AND PURPOSE Mannitol is often used to reduce cerebral edema in acute intracerebral hemorrhage but without strong supporting evidence of benefit. We aimed to determine the impact of mannitol on outcome among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). METHODS INTERACT2 was an international, open, blinded end point, randomized controlled trial of 2839 patients with spontaneous intracerebral hemorrhage (<6 hours) and elevated systolic blood pressure allocated to intensive (target systolic blood pressure, <140 mm Hg within 1 hour) or guideline-recommended (target systolic blood pressure, <180 mm Hg) blood pressure-lowering treatment. Propensity score and multivariable analyses were performed to investigate the relationship between mannitol treatment (within 7 days) and poor outcome, defined by death or major disability on the modified Rankin Scale score (3-6) at 90 days. RESULTS There was no significant difference in poor outcome between mannitol (n=1533) and nonmannitol (n=993) groups: propensity score-matched odds ratio of 0.90 (95% confidence interval, 0.75-1.09; P=0.30) and multivariable odds ratio of 0.87 (95% confidence interval, 0.71-1.07; P=0.18). Although a better outcome was suggested in patients with larger (≥15 mL) than those with smaller (<15 mL) baseline hematomas who received mannitol (odds ratio, 0.52 [95% confidence interval, 0.35-0.78] versus odds ratio, 0.91 [95% confidence interval, 0.72-1.15]; P homogeneity<0.03 in propensity score analyses), the association was not consistent in analyses across other cutoff points (≥10 and ≥20 mL) and for differing grades of neurological severity. Mannitol was not associated with excess serious adverse events. CONCLUSIONS Mannitol seems safe but might not improve outcome in patients with acute intracerebral hemorrhage. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079.


Thoracoscopic basilar segmentectomy.


title: Thrombus remnant despite intra-arterial thrombolysis for thrombus formation during endovascular treatment of ruptured cerebral aneurysms: Does it harm?

text: BACKGROUND The fate and safety of thrombus remnant despite intra-arterial thrombolysis for unexpected thrombus formation has rarely been reported. METHODS From January 2010 to May 2015, 131 consecutive patients with ruptured intracranial aneurysms were treated by endovascular methods at our institution. Among the 21 patients (16%) treated by intra-arterial thrombolysis for the thrombus formation during the procedure, nine patients (nine aneurysms) suffered from thrombus remnant. We reviewed the clinical and radiologic outcomes of patients with thrombus remnant as well as intraoperative and postoperative management of thrombus formation. RESULTS Thrombus formation occurred near the coiled aneurysm in eight patients, and distal embolic occlusion was observed in one patient. All nine patients were initially managed by intra-arterial thrombolysis with tirofiban. One patient with persistent distal embolic occlusion and two patients with distal migration of the thrombus after intra-arterial thrombolysis were additionally treated with stent retriever. One patient with occlusion of the parent artery near the coiled aneurysm despite intra-arterial thrombolysis was partially recanalized by permanent deployment of a stent retriever. Delayed cerebral angiography showed no increase in size of thrombus remnant in any patients. After the procedure, thrombus remnant was managed by intravenous tirofiban. Follow-up CT angiography on the first postoperative day showed patent arterial flow, and ischemic complication related with thromboembolism did not occur in any patients. One patient suffered from hemorrhagic complication. CONCLUSION If the patency of parent artery is maintained and the size of the thrombus remnant does not increase on delayed angiography after intra-arterial thrombolysis, postoperative thromboembolic events rarely occur.


Public Health Approach of Ayurveda and Yoga for COVID-19 Prophylaxis.


title: [Facing the pandemic of 2019 novel coronavirus infections: the pediatric perspectives].

text: 自2019年12月中旬以来，武汉市暴发新型冠状病毒感染的肺炎流行，疫情很快扩散到全国各地以及境外国家，形势严峻。在本次重大突发疫情中，儿童确诊病例数占比很小，但随着疫情高峰及更多地区开展病原检测，儿童感染例数有较明显增多趋势，应予以高度重视。本文将从儿科医生的角度，重点就儿童病例的流行病学特征与防控措施、临床疾病特点与转归、诊断标准及治疗等方面进行讨论，并提出相应建议。.


COVID-19 lockdown in India triggers a rapid rise in suicides due to the alcohol withdrawal symptoms: Evidence from media reports.


COVID-19: children on the front line.


title: Combined lysis of thrombus with ultrasound and systemic tissue plasminogen activator for emergent revascularization in acute ischemic stroke (CLOTBUST-ER): design and methodology of a multinational phase 3 trial.

text: BACKGROUND We designed a Phase 3 clinical trial to determine the safety and efficacy of adding transcranial ultrasound using an operator-independent headframe to recombinant tissue-plasminogen-activator for the treatment of acute ischemic stroke. METHODS Combined lysis of thrombus with ultrasound and systemic tissue-plasminogen-activator for emergent revascularization in acute ischemic stroke is a randomized, double-blind, placebo-controlled clinical trial that will enroll subjects with the following main inclusion criteria: less than 4·5 hours from symptom onset (three-hours in US and Canada), age 18-80 years, baseline National Institutes of Health Stroke Scale score ≥ 10, and premorbid modified-Rankin-score of 0-1, eligibility for full dose recombinant tissue-plasminogen-activator. Subjects will receive two-hours of 2-MHz pulsed wave transcranial ultrasound (target group) or sham ultrasound (control group). The projected sample size is approximately 824 subjects. RESULTS The primary endpoint, based on intention-to-treat criteria of patients enrolled within three-hours of symptom onset is the comparison between target and control groups of modified-Rankin-score scores at day 90 poststroke assessed using the proportional odds method. The study will have two planned interim analyses after approximately one-third and two-thirds of subjects have reached the 90-day modified-Rankin-score evaluation. Safety outcomes are symptomatic intracranial hemorrhage within 24 h and an overall analysis of adverse events. CONCLUSIONS Since intravenous recombinant tissue-plasminogen-activator remains the only medical therapy to reverse ischemic stroke applicable in the emergency department, our trial will determine if the additional use of transcranial ultrasound improves functional outcomes in patients with severe acute ischemic stroke (NCT#01098981).


title: Reducing rectal injury in men receiving prostate cancer radiation therapy: current perspectives.

text: Dose escalation is now the standard of care for the treatment of prostate cancer with radiation therapy. However, the rectum tends to be the dose-limiting structure when treating prostate cancer, given its close proximity. Early and late toxicities can occur when the rectum receives large doses of radiation therapy. New technologies allow for prevention of these toxicities. In this review, we examine the evidence that supports various dose constraints employed to prevent these rectal injuries from occurring. We also examine the use of intensity-modulated radiation therapy and how this compares to older radiation therapy techniques that allow for further sparing of the rectum during a radiation therapy course. We then review the literature on endorectal balloons and the effects of their daily use throughout a radiation therapy course. Tissue spacers are now being investigated in greater detail; these devices are injected into the rectoprostatic fascia to physically increase the distance between the prostate and the anterior rectal wall. Last, we review the use of systemic drugs, specifically statin medications and antihypertensives, as well as their impact on rectal toxicity.


title: Intragastric Balloons: An Emerging Therapy for Nonalcoholic Steatohepatitis and Fibrosis?

text: Weight loss through lifestyle intervention remains the mainstay treatment for nonalcoholic steatohepatitis (NASH). Nevertheless, only a minority of patients undergoing lifestyle intervention are able to achieve the weight loss threshold that reverses NASH histologic features. This case report demonstrates a minimally invasive method of treating NASH using an intragastric balloon. With endoscopic ultrasound-guided liver biopsy at the time of intragastric balloon removal, we demonstrate a significant improvement in NASH histologic features including steatosis, ballooning, lobular inflammation, and fibrosis. This endoscopic method may offer an alternative solution to patients with NASH who fail lifestyle intervention.


docid: krklvuxg

title: Covid-19: face masks could foster distrust and blame.


title: Therapeutic occlusion of the vertebral artery using a new penumbra occlusion device system and ruby coils (penumbra): A technical note.

text: There are several methods to achieve the therapeutic sacrifice of the vessel, coiling brings the most commonly used. Penumbra occlusion device (POD) system is a newer modality for therapeutic large vessel occlusion, and it is the Food and Drug Administration approved only for peripheral vessels. We report a case where therapeutic vertebral artery (VA) occlusion was achieved with the POD system and Ruby coils for the first time. A patient was diagnosed with a new malignant-appearing tumor of the cervical spine. A conventional angiogram showed multiple tiny arterial feeders from the VA beyond scope of coil/onyx embolization, so we performed a balloon occlusion test followed by therapeutic sacrifice of the VA. A successful VA occlusion was achieved with significant reduction in the tumor blush, followed by open resection of the tumor. The patient had favorable postoperative course and without any neurological symptoms attributed to the VA occlusion.


title: The effect of ice slurry ingestion on body temperature and cycling performance in competitive athletes.

text: The effects of pre cooling on endurance performance are widely known. In contrast, the approach of cooling during endurance exercise in combination with pre-exercise cooling has been poorly understood. The purpose of the present study was to determine whether the effects of precooling and cooling during exercise enhance exercise performance compared to the ingestion of a thermo-neutral beverage (20 °C) or precooling alone in cycling performance. This was an experimental study using a randomised crossover design in which 7 cyclists underwent three trials comprising of 45 min steady state cycling (SS) at 70% VO2 max and a subsequent 10 km time trial (TT) in hot conditions (32 °C, 50% relative humidity). Rectal temperature (Tre), heat storage (HS), heart rate (HR), blood lactate concentration (BLA) and thermal sensation (TS) were measured. The intervention consisted of: (1) ingestion of thermo-neutral beverage before and during SS cycling (TN), (2) ingestion of ice slurry beverage and application of iced towels (precooling) prior to exercise, and then ingestion of thermo-neutral beverage during SS (PRE) and (3) precooling strategy as above plus ice slurry ingestion during SS cycling (PRE + MID). The intake of thermo-neutral or ice slurry beverage (14 g/kg) occurred over 30 min before and every 15 min during SS cycling. There was no significant difference in TT performance between all the conditions (P =0.72). However, PRE and PRE + MID caused a significant decrease in Tre (P < 0.05) from TN during exercise. Accordingly, both precooling and a combination of precooling and mid-cooling during exercise in hot conditions may be a practical and effective way of reducing core temperature. Future studies should investigate longer distance events and timing of ice slurry ingestion.


title: Endoscopic therapy for Barrett's oesophagus.

text: Barrett's oesophagus (BO) is thought to progress through the development of dysplasia (low grade and high grade) to oesophageal adenocarcinoma, a lethal cancer with poor survival. The overall goal of endoscopic therapy of BO is to eliminate metaplastic and dysplastic epithelium, to prevent and/or reduce the risk of progression to OAC. Endoscopic therapy techniques can be divided into two broad complementary techniques: tissue acquiring (endoscopic mucosal resection and endoscopic submucosal dissection) and ablative. Endoscopic therapy has been established as safe and effective for the subjects with intra-mucosal cancer (IMC), high-grade dysplasia (HGD) and more recently in treating low-grade dysplasia (LGD). Challenges to endoscopic therapy are being recognized, such as incomplete response and recurrence. While eradication of intestinal metaplasia is the immediate goal of endoscopic therapy, surveillance must continue after complete elimination of intestinal metaplasia, to detect and treat recurrences.


title: The EEG signal: a window on the cortical brain activity.

text: The accurate assessment of the depth of anesthesia, allowing a more accurate adaptation of the doses of hypnotics, is an important end point for the anesthesiologist. It is a particularly crucial issue in pediatric anesthesia, in the context of the recent controversies about the potential neurological consequences of the main anesthetic drugs on the developing brain. The electroencephalogram signal reflects the electrical activity of the neurons in the cerebral cortex. It is thus the key to assessment of the level of hypnosis. Beyond visual analysis, several monitoring devices allow an automated treatment of the electroencephalographic (EEG) signal, combining time and frequency domain analysis. Each of these monitors focuses on a specific combination of characteristics of the signal and provides the clinician with useful information that remains, however, partial. For a comprehensive approach of the EEG-derived indices, the main features of the normal EEG, in adults and children, will be presented in the awake state and during sleep. Age-related modifications accompanying cerebral maturation during infancy and childhood will be detailed. Then, this review will provide an update on how anesthetic drugs, particularly hypnotics, influence the EEG signal, and how the main available monitors analyze these drug-induced modifications. The relationships between pain, memory, and the EEG will be discussed. Finally, this review will focus on some specific EEG features such as the electrical epileptoid activity observed under sevoflurane anesthesia. The EEG signal is the best window we have on cortical brain activity and provides a fair pharmacodynamic feedback of the effects of hypnotics. However, the cortex is only one of several targets of anesthesia. Hypnotics and opiates, have also subcortical primary targets, and the EEG performances in the evaluation or prediction of nociception are poor. Monitoring subcortical structures in combination with the EEG might in the future allow a better evaluation and a more precise adaptation of balanced anesthesia.


title: A point prevalence cross-sectional study of healthcare-associated urinary tract infections in six Australian hospitals.

text: OBJECTIVES Urinary tract infections (UTIs) account for over 30% of healthcare-associated infections. The aim of this study was to determine healthcare-associated UTI (HAUTI) and catheter-associated UTI (CAUTI) point prevalence in six Australian hospitals to inform a national point prevalence process and compare two internationally accepted HAUTI definitions. We also described the level and comprehensiveness of clinical record documentation, microbiology laboratory and coding data at identifying HAUTIs and CAUTIs. SETTING Data were collected from three public and three private Australian hospitals over the first 6 months of 2013. PARTICIPANTS A total of 1109 patients were surveyed. Records of patients of all ages, hospitalised on the day of the point prevalence at the study sites, were eligible for inclusion. Outpatients, patients in adult mental health units, patients categorised as maintenance care type (ie, patients waiting to be transferred to a long-term care facility) and those in the emergency department during the duration of the survey were excluded. OUTCOME MEASURES The primary outcome measures were the HAUTI and CAUTI point prevalence. RESULTS Overall HAUTI and CAUTI prevalence was 1.4% (15/1109) and 0.9% (10/1109), respectively. Staphylococcus aureus and Candida species were the most common pathogens. One-quarter (26.3%) of patients had a urinary catheter and fewer than half had appropriate documentation. Eight of the 15 patients ascertained to have a HAUTI based on clinical records (6 being CAUTI) were coded by the medical records department with an International Classification of Diseases (ICD)-10 code for UTI diagnosis. The Health Protection Agency Surveillance definition had a positive predictive value of 91.67% (CI 64.61 to 98.51) compared against the Centers for Disease Control and Prevention definition. CONCLUSIONS These study results provide a foundation for a national Australian point prevalence study and inform the development and implementation of targeted healthcare-associated infection surveillance more broadly.


title: Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial.

text: BACKGROUND Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life. METHODS In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18-80 years, had active Crohn's disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150). FINDINGS Between May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1-185·0) in the resection group versus 172·0 (164·3-179·6) in the infliximab group (mean difference 6·1 points, 95% CI -4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0-116·2) in the resection group versus 106·5 (102·1-110·9) in the infliximab group (mean difference 5·6, 95% CI -0·4 to 11·6), the mean physical component score was 47·7 (45·7-49·7) versus 44·6 (42·5-46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0-52·1) versus 46·1 (43·3-48·9; mean difference 3·5, -0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p<0·0001), days not able to take part in social life were 1·8 days (6·3) versus 1·1 days (4·5; p=0·20), days of scheduled hospital admission were 6·5 days (3·8) versus 6·8 days (3·2; p=0·84), and the number of patients who had unscheduled hospital admissions were 13 (18%) of 73 versus 15 (21%) of 70 (p=0·68). Body-image scale mean scores in the patients who had resection were 16·0 (95% CI 15·2-16·8) at baseline versus 17·8 (17·1-18·4) at 12 months, and cosmetic scale mean scores were 17·6 (16·6-18·6) versus 18·6 (17·6-19·6). Surgical intervention-related complications classified as IIIa or worse on the Clavien-Dindo scale occurred in four patients in the resection group. Treatment-related serious adverse events occurred in two patients in the infliximab group. During a median follow-up of 4 years (IQR 2-6), 26 (37%) of 70 patients in the infliximab group had resection, and 19 (26%) of 73 patients in the resection group received anti-TNF. INTERPRETATION Laparoscopic resection in patients with limited (diseased terminal ileum <40 cm), non-stricturing, ileocaecal Crohn's disease in whom conventional therapy has failed could be considered a reasonable alternative to infliximab therapy. FUNDING Netherlands Organisation for Health Research and Development.


title: Heat transfer within hydrodissection fluids: An analysis of thermal conduction and convection using liquid and gel materials.

text: Interventional oncology procedures such as thermal ablation are becoming widely used for many tumours in the liver, kidney and lung. Thermal ablation refers to the focal destruction of tissue by generating cytotoxic temperatures in the treatment zone. Hydrodissection - separating tissues with fluids - protects healthy tissues adjacent to the ablation treatment zone to improve procedural safety, and facilitate more aggressive power application or applicator placement. However, fluids such as normal saline and 5% dextrose in water (D5W) can migrate into the peritoneum, reducing their protective efficacy. As an alternative, a thermo-gelable poloxamer 407 (P407) solution has been recently developed to facilitate hydrodissection procedures. We hypothesise that the P407 gel material does not provide convective heat dissipation from the ablation site, and therefore may alter the heat transfer dynamics compared to liquid materials during hydrodissection-assisted thermal ablation. The purpose of this study was to investigate the heat dissipation mechanics within D5W, liquid P407 and gel P407 hydrodissection barriers. Overall it was shown that the gel P407 dissipated heat primarily through conduction, whereas the liquid P407 and D5W dissipated heat through convection. Furthermore, the rate of temperature change within the gel P407 was greater than liquid P407 and D5W. Testing to evaluate the in vivo efficacy of the fluids with different modes of heat dissipation seems warranted for further study.


title: A new approach to determine the results of minimally invasive pulmonary vein isolation using a continuous loop monitor: preliminary results.

text: OBJECTIVES Surgical ablation is a well-known treatment for atrial fibrillation (AF); however, little is known about the absolute success rate. The aim of this study is to compare the absolute pre- and postoperative incidence of AF after minimally invasive surgical ablation for paroxysmal AF. METHODS Twenty consecutive patients (mean age 55 ± 8; 55% male) received a continuous loop monitor (CLM) 4 weeks prior to a minimally invasive pulmonary vein isolation (MIPVI). The mean preoperative AF burden was compared with the mean AF burden during follow-up. Follow-up was achieved for a period of 12 months. RESULTS Seventeen patients underwent an MIPVI successfully. Two patients did not reach the threshold for surgery. In 1 patient, surgery was discontinued because of a perioperative bleeding due to adhesions after a previous percutaneous AF ablation. Mean AF burden preoperatively was 66%. After 12 months, there was an absolute reduction in AF burden of 65% (95% CI 42-88, P < 0.001) and 12 of 15 patients in follow-up (80%) were free of AF without antiarrhythmic drugs (AADs). CONCLUSIONS The use of a CLM in the follow-up of surgical ablation is a very accurate way to confirm absolute surgical results. Furthermore, with the use of a CLM, preoperative evaluation can be done more accurately, and the surgical procedure can be adjusted to the patients' needs.


title: Prioritizing "psychological" consequences for disaster preparedness and response: a framework for addressing the emotional, behavioral, and cognitive effects of patient surge in large-scale disasters.

text: While information for the medical aspects of disaster surge is increasingly available, there is little guidance for health care facilities on how to manage the psychological aspects of large-scale disasters that might involve a surge of psychological casualties. In addition, no models are available to guide the development of training curricula to address these needs. This article describes 2 conceptual frameworks to guide hospitals and clinics in managing such consequences. One framework was developed to understand the antecedents of psychological effects or "psychological triggers" (restricted movement, limited resources, limited information, trauma exposure, and perceived personal or family risk) that cause the emotional, behavioral, and cognitive reactions following large-scale disasters. Another framework, adapted from the Donabedian quality of care model, was developed to guide appropriate disaster response by health care facilities in addressing the consequences of reactions to psychological triggers. This framework specifies structural components (internal organizational structure and chain of command, resources and infrastructure, and knowledge and skills) that should be in place before an event to minimize consequences. The framework also specifies process components (coordination with external organizations, risk assessment and monitoring, psychological support, and communication and information sharing) to support evidence-informed interventions.


title: Detection of COVID-19 in a Vulvar Lesion.

text: As new information about coronavirus disease 2019 (COVID-19) is rapidly discovered, clinicians are better equipped to make informed decisions for their patients. While current research suggests COVID-19 viral antigen is not found in vaginal secretions, its detectability in the female lower genital tract may have clinical implications for obstetric and gynecologic care for women. We present a case of a woman at 31 weeks' gestation with simultaneous upper respiratory symptoms and vulvovaginitis. She was found to have a vulvar lesion positive for severe acute respiratory syndrome-COVID by viral swab. This case shows that COVID-19 is detectable in the vulva. This may have implications for health care workers' exposure and personal protective equipment needs. While vertical transmission has largely not been reported, the presence of detectable virus in the female lower genital tract makes this a continued possibility and area of study. KEY POINTS: · COVID-19 is detectable in the female lower genital tract.. · The detection of COVID-19 in the vulva may have implications for personal protective equipment use.. · The detection of COVID-19 in vulvovaginal lesions makes vertical transmission a continued possibility..


title: Protective effects of purple grape juice on carbon tetrachloride-induced oxidative stress in brains of adult Wistar rats.

text: The antioxidant properties of purple grape juice, organic and conventional, in brain tissues are not well known. In this study our objective was to evaluate the antioxidant activity in substantia nigra and striatum of rats chronically treated with organic or conventional purple grape juice and to correlate the results obtained with the polyphenol content (total polyphenolic content, resveratrol, and anthocyanins [malvidin, delphinidin, peonidin, and cyanidin]). We observed that CCl(4) damage decreased significantly in the grape juice-treated groups when compared with the control group. In the grape juice-treated groups we further observed a decrease of lipid (thiobarbituric acid-reactive substances assay) and protein (carbonyl) peroxidation, as well as a significant antioxidant protection through the increase of enzyme activity. Antioxidant activities were significantly correlated with polyphenol content. These findings demonstrated that both grape juices have potent antioxidant properties and these activities could be at least attributed to the high phenolic content present in these juices.


title: Viruses and non-allergen environmental triggers in asthma.

text: Asthma is a complex inflammatory disease with many triggers. The best understood asthma inflammatory pathways involve signals characterized by peripheral eosinophilia and elevated immunoglobulin E levels (called T2-high or allergic asthma), though other asthma phenotypes exist (eg, T2-low or non-allergic asthma, eosinophilic or neutrophilic-predominant). Common triggers that lead to poor asthma control and exacerbations include respiratory viruses, aeroallergens, house dust, molds, and other organic and inorganic substances. Increasingly recognized non-allergen triggers include tobacco smoke, small particulate matter (eg, PM2.5), and volatile organic compounds. The interaction between respiratory viruses and non-allergen asthma triggers is not well understood, though it is likely a connection exists which may lead to asthma development and/or exacerbations. In this paper we describe common respiratory viruses and non-allergen triggers associated with asthma. In addition, we aim to show the possible interactions, and potential synergy, between viruses and non-allergen triggers. Finally, we introduce a new clinical approach that collects exhaled breath condensates to identify metabolomics associated with viruses and non-allergen triggers that may promote the early management of asthma symptoms.


title: Detection of respiratory viruses and the associated chemokine responses in serious acute respiratory illness.

text: BACKGROUND A specific diagnosis of a lower respiratory viral infection is often difficult despite frequent clinical suspicion. This low diagnostic yield may be improved by use of sensitive detection methods and biomarkers. METHODS The prevalence, clinical predictors and inflammatory mediator profile of respiratory viral infection in serious acute respiratory illness were investigated. Sequential bronchoalveolar lavage (BAL) fluids from all patients hospitalised with acute respiratory illness over 12 months (n=283) were tested for the presence of 17 respiratory viruses by multiplex PCR assay and for newly discovered respiratory viruses (bocavirus, WU and KI polyomaviruses) by single-target PCR. BAL samples also underwent conventional testing (direct immunoflorescence and viral culture) for respiratory virus at the clinician's discretion. 27 inflammatory mediators were measured in a subset of the patients (n=64) using a multiplex immunoassay. RESULTS 39 respiratory viruses were detected in 37 (13.1% of total) patients by molecular testing, including rhinovirus (n=13), influenza virus (n=8), respiratory syncytial virus (n=6), human metapneumovirus (n=3), coronavirus NL63 (n=2), parainfluenza virus (n=2), adenovirus (n=1) and newly discovered viruses (n=4). Molecular methods were 3.8-fold more sensitive than conventional methods. Clinical characteristics alone were insufficient to separate patients with and without respiratory virus. The presence of respiratory virus was associated with increased levels of interferon gamma-inducible protein 10 (IP-10) (p<0.001) and eotaxin-1 (p=0.017) in BAL. CONCLUSIONS Respiratory viruses can be found in patients with serious acute respiratory illness by use of PCR assays more frequently than previously appreciated. IP-10 may be a useful biomarker for respiratory viral infection.


title: Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques.

text: The 2019 novel coronavirus (SARS-CoV-2) outbreak is a major challenge for public health. SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases, with a mortality rate of ~6.4% worldwide (based on World Health Organization daily situation report). However, the dynamics of viral infection, replication and shedding are poorly understood. Here, we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2. After intratracheal inoculation, the first peak of viral RNA was observed in oropharyngeal swabs one day post infection (1 d.p.i.), mainly from the input of the inoculation, while the second peak occurred at 5 d.p.i., which reflected on-site replication in the respiratory tract. Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals, characterized by hyperemia and edema, and infiltration of monocytes and lymphocytes in alveoli. We also identified SARS-CoV-2 RNA in respiratory tract tissues, including trachea, bronchus and lung; and viruses were also re-isolated from oropharyngeal swabs, bronchus and lung, respectively. Furthermore, we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2. The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics.


title: Morphological changes and clinical impact of unstable plaques within untreated segments of acute myocardial infarction patients during a 3-year follow-up: an analysis from the HORIZONS-AMI trial.

text: OBJECTIVES Plaque ruptures and attenuated plaques are considered to be unstable and have been identified in both culprit and nonculprit lesions of patients with ST-segment elevation myocardial infarction (STEMI). However, there are limited data available on the natural evolution of these plaques and their long-term clinical outcome. We investigated the natural evolution and long-term impact of plaque ruptures and attenuated plaques in untreated segments of infarct-related arteries in patients with STEMI. METHODS In the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial, 389 patients with 429 lesions underwent intravascular ultrasound (IVUS) at baseline. Follow-up IVUS at 13 months was conducted in 245 patients. Three-year follow-up data were available for all patients. RESULTS Segments not treated between baseline and follow-up were compared. Baseline IVUS identified 29 plaque ruptures in 27 patients (7%). Of 11 plaque ruptures with follow-up IVUS, four healed and seven persisted. Conversely, through follow-up IVUS, nine new plaque ruptures in nine patients (4%) were identified. Attenuated plaques were identified in 31 of 38 plaque ruptures (81.5%), of which 24 were in the same circumferential segment as the ruptured cavity and seven were within 5 mm proximal or distal to the plaque rupture. Morphologic changes during follow-up, including new plaque ruptures and changes in the attenuated plaque frequency and distribution, were not accompanied by either serious lumen compromise or clinical events. CONCLUSION Serial IVUS analysis demonstrated that the morphology of unstable plaques within untreated segments in STEMI patients treated with optimal systemic therapies markedly changed during the 13-month follow-up period, without lumen compromise or clinical events at the 3-year follow-up.


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title: Risk of bias and methodological appraisal practices in systematic reviews published in anaesthetic journals: a meta-epidemiological study.

text: The validity of primary study results included in systematic reviews plays an important role in drawing conclusions about intervention effectiveness and carries implications for clinical decision-making. We evaluated the prevalence of methodological quality and risk of bias assessments in systematic reviews published in the five highest-ranked anaesthesia journals since 2007. The initial PubMed search yielded 315 citations, and our final sample after screening consisted of 207 systematic reviews. One hundred and seventy-four reviews conducted methodological quality/risk of bias analyses. The Jadad scale was most frequently used. Forty-four of the 83 reviews that included high risk of bias studies re-analysed their data omitting these trials: 20 showed differences in pooled effect estimates. Reviews containing a greater number of primary studies evaluated quality less frequently than smaller reviews. Overall, the majority of reviews evaluated bias; however, many applied questionable methods. Given the potential effects of bias on summary outcomes, greater attention is warranted.


title: TRIM30 alpha negatively regulates TLR-mediated NF-kappa B activation by targeting TAB2 and TAB3 for degradation.

text: Toll-like receptor (TLR) signaling is pivotal to innate and adaptive immune responses and must be tightly controlled. The mechanisms of TLR signaling have been the focus of extensive studies. Here we report that the tripartite-motif protein TRIM30alpha, a RING protein, was induced by TLR agonists and interacted with the TAB2-TAB3-TAK1 adaptor-kinase complex involved in the activation of transcription factor NF-kappaB. TRIM30alpha promoted the degradation of TAB2 and TAB3 and inhibited NF-kappaB activation induced by TLR signaling. In vivo studies showed that transfected or transgenic mice overexpressing TRIM30alpha were more resistant to endotoxic shock. Consistent with that, in vivo 'knockdown' of TRIM30alpha mRNA by small interfering RNA impaired lipopolysaccharide-induced tolerance. Finally, expression of TRIM30alpha depended on NF-kappaB activation. Our results collectively indicate that TRIM30alpha negatively regulates TLR-mediated NF-kappaB activation by targeting degradation of TAB2 and TAB3 by a 'feedback' mechanism.