title: Closed-loop assisted versus manual goal-directed fluid therapy during high-risk abdominal surgery: a case-control study with propensity matching.

text: INTRODUCTION Goal-directed fluid therapy strategies have been shown to benefit moderate- to high-risk surgery patients. Despite this, these strategies are often not implemented. The aim of this study was to assess a closed-loop fluid administration system in a surgical cohort and compare the results with those for matched patients who received manual management. Our hypothesis was that the patients receiving closed-loop assistance would spend more time in a preload-independent state, defined as percentage of case time with stroke volume variation less than or equal to 12%. METHODS Patients eligible for the study were all those over 18 years of age scheduled for hepatobiliary, pancreatic or splenic surgery and expected to receive intravascular arterial blood pressure monitoring as part of their anesthetic care. The closed-loop resuscitation target was selected by the primary anesthesia team, and the system was responsible for implementation of goal-directed fluid therapy during surgery. Following completion of enrollment, each study patient was matched to a non-closed-loop assisted case performed during the same time period using a propensity match to reduce bias. RESULTS A total of 40 patients were enrolled, 5 were ultimately excluded and 25 matched pairs were selected from among the remaining 35 patients within the predefined caliper distance. There was no significant difference in fluid administration between groups. The closed-loop group spent a significantly higher portion of case time in a preload-independent state (95 ± 6% of case time versus 87 ± 14%, P =0.008). There was no difference in case mean or final stroke volume index (45 ± 10 versus 43 ± 9 and 45 ± 11 versus 42 ± 11, respectively) or mean arterial pressure (79 ± 8 versus 83 ± 9). Case end heart rate was significantly lower in the closed-loop assisted group (77 ± 10 versus 88 ± 13, P =0.003). CONCLUSION In this case-control study with propensity matching, clinician use of closed-loop assistance resulted in a greater portion of case time spent in a preload-independent state throughout surgery compared with manual delivery of goal-directed fluid therapy. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02020863. Registered 19 December 2013.


Good leadership will see vets through.


Racial and ethnic differences in breast cancer diagnosis and survival--reply.


title: Electroencephalographic variation during end maintenance and emergence from surgical anesthesia.

text: The re-establishment of conscious awareness after discontinuing general anesthesia has often been assumed to be the inverse of loss of consciousness. This is despite the obvious asymmetry in the initiation and termination of natural sleep. In order to characterize the restoration of consciousness after surgery, we recorded frontal electroencephalograph (EEG) from 100 patients in the operating room during maintenance and emergence from general anesthesia. We have defined, for the first time, 4 steady-state patterns of anesthetic maintenance based on the relative EEG power in the slow-wave (<14 Hz) frequency bands that dominate sleep and anesthesia. Unlike single-drug experiments performed in healthy volunteers, we found that surgical patients exhibited greater electroencephalographic heterogeneity while re-establishing conscious awareness after drug discontinuation. Moreover, these emergence patterns could be broadly grouped according to the duration and rapidity of transitions amongst these slow-wave dominated brain states that precede awakening. Most patients progressed gradually from a pattern characterized by strong peaks of delta (0.5-4 Hz) and alpha/spindle (8-14 Hz) power ('Slow-Wave Anesthesia') to a state marked by low delta-spindle power ('Non Slow-Wave Anesthesia') before awakening. However, 31% of patients transitioned abruptly from Slow-Wave Anesthesia to waking; they were also more likely to express pain in the post-operative period. Our results, based on sleep-staging classification, provide the first systematized nomenclature for tracking brain states under general anesthesia from maintenance to emergence, and suggest that these transitions may correlate with post-operative outcomes such as pain.


title: Infections as a risk factor for Parkinson's disease: a case-control study.

text: OBJECTIVES The etiology of Parkinson's disease (PD) is unknown. The aim of the study was to test the hypothesis that some infectious diseases are related to the occurrence of PD. METHODS The case-control study, conducted in Belgrade during the period 2001-2005, comprised 110 subjects diagnosed for the first time as PD cases, and 220 controls chosen among patients with degenerative joint disease and some diseases of the digestive tract. RESULTS According to logistic regression analysis, PD was significantly related to mumps [odds ratio adjusted on occupation and family history of PD (aOR) = 7.86, 95% confidence interval (CI) = 3.77-16.36], scarlet fever (aOR = 12.18, 95% CI = 1.97-75.19), influenza (aOR = 8.01, 95% CI = 4.61-13.92), whooping cough (aOR = 19.90, 95% CI = 2.07-190.66) and herpes simplex infections (aOR = 11.52, 95% CI = 2.25-58.89). Tuberculosis, measles and chicken pox were not associated with PD. Other infectious diseases we asked for were not reported (12 diseases), or were too rare (four diseases) to be analysed. CONCLUSION The results obtained are in line with the suggestion that some infectious diseases may play a role in the development of PD.


Management of healthcare areas for the prevention of COVID-19 emergency in an Italian teaching hospital (Pisa, Tuscany): A hospital renovation plan.


title: [The analysis of clinical characteristics of 34 novel coronavirus pneumonia cases in Ningxia Hui autonomous region].

text: Objective: To analyze the clinical characteristics of 34 COVID-19 cases and to provide the basis for the prevention and control of the epidemic disease. Methods: Thirty-four COVID-19 patients diagnosed with RT-PCR in the isolation ward of the Fourth People's Hospital of Ningxia Hui autonomous region (infectious diseases hospital) from the January 22 to February 4, 2020 were selected as the research subjects. The clinical data were collected. Excel was used to describe the relationship between clinical classification and age distribution, contact history and date of onset. SPSS 25.0 statistical software was used for analysis. The general information, clinical symptoms, blood test, virus nucleic acid test results, epidemiology, CT imaging, treatment and prognosis were analyzed. Results: There were 5 mild cases (5/34), 24 ordinary cases (24/34), 5 severe cases (5/34). The elderly was more common in severe patients. The main clinical symptoms were fever (27/34)and dry cough(26/34). The peripheral blood showed normal or decreased leukocyte count (33/34), decreased lymphocyte count (12/34). The increase of C-reactive protein (CRP) and D-dimer was related to the severity of the disease. Some patients had mild liver and kidney damage. Six patients were diagnosed through 3 or more times of nucleic acid tests. Sixteen cases had Wuhan related history,13 cases were close contacts, 5 cases had no confirmed route. The clustered infections were found in 6 families. In typical cases, CT showed single or multiple patchy ground glass shadow with thickening of interlobular septum. In severe cases, diffuse lesions of both lungs were found, with ground glass shadow, consolidation shadow and strip shadow coexisting. Thirty-four patients were treated with interferon-α and Lopinavir/Ritonavir with good prognosis. Conclusions: The clinical characteristics of COVID-19 were similar to that of general viral pneumonia but with strong infectivity. Close contact and family aggregation caused disease outbreaks. COVID-19 could not be excluded if two nucleic acid tests were negative and high-resolution CT was helpful for differential diagnosis. Early detection, early isolation, early diagnosis and early treatment are important for good prognosis. The effectiveness of antiviral drugs needs to be further verified.


Annexing AXL: Endothelial Cell Infection by the Zika Virus.


Virtual Cancer Care During and Beyond the COVID-19 Pandemic: We Need to Get It Right.


Reconstruction of active elbow flexion in patients with radial ray deficiency: report of two cases.


title: The learning curve in laparoscopic liver resection: improved feasibility and reproducibility.

text: OBJECTIVE To evaluate the "learning curve" effect on feasibility and reproducibility of laparoscopic liver resection (LLR). SUMMARY BACKGROUND DATA LLR is currently limited to few centers and to few procedures. Its reproducibility is still debated. METHODS : Patients undergoing LLR between 1996 and 2008 were included. Indications and type of hepatectomies were compared with those of open resections performed in the same period, considering 3 periods (1996-1999, 2000-2003, and 2004-2008). LLRs were divided into 3 equal groups of 58 cases and technical data and outcomes were compared. Risk-adjusted Cumulative Sum model was used for determining the learning curve based on the need for conversion. RESULTS Of 782, 174 (22.3%) patients underwent LLR. Proportion of LLR progressively increased (17.5%, 22.4%, and 24.2%), such as hepatocellular carcinoma (17.6%, 25.6%, and 39.4%, P < 0.05), colorectal metastases (0%, 6.5%, and 13.1%, P < 0.05), major hepatectomies (1.1%, 9.1%, 8.5%, P < 0.05), and right hepatectomies (0%, 13.2%, and 13.1%, P < 0.05). Comparing groups, results of LLR significantly improved in terms of conversion rate (15.5%, 10.3%, and 3.4%, P < 0.05), operative time (210, 180, and 150 minutes, P < 0.05), blood loss (300, 200, and 200 mL, P < 0.05), and morbidity (17.2%, 22.4%, and 3.4%, P < 0.05). Pedicle clamping was less used over time (77.6%, 62.1%, and 17.2%, P < 0.05) and for shorter durations (45, 30, and 20 minutes, P < 0.05). Having adjusted for case-mix, the Cumulative Sum analysis demonstrated a learning curve for laparoscopic hepatectomies of 60 cases. CONCLUSION A slow but constant evolution of LLR occurred: indications and magnitude of procedures increased and technical outcomes improved. The learning curve demonstrated in this study suggests that LLR is reproducible in liver units but specific training to advanced laparoscopy is required.


title: Differential regulation of hepatic physiology and injury by the TAM receptors Axl and Mer.

text: Genome-wide association studies have implicated the TAM receptor tyrosine kinase (RTK) Mer in liver disease, yet our understanding of the role that Mer and its related RTKs Tyro3 and Axl play in liver homeostasis and the response to acute injury is limited. We find that Mer and Axl are most prominently expressed in hepatic Kupffer and endothelial cells and that as mice lacking these RTKs age, they develop profound liver disease characterized by apoptotic cell accumulation and immune activation. We further find that Mer is critical to the phagocytosis of apoptotic hepatocytes generated in settings of acute hepatic injury, and that Mer and Axl act in concert to inhibit cytokine production in these settings. In contrast, we find that Axl is uniquely important in mitigating liver damage during acetaminophen intoxication. Although Mer and Axl are protective in acute injury models, we find that Axl exacerbates fibrosis in a model of chronic injury. These divergent effects have important implications for the design and implementation of TAM-directed therapeutics that might target these RTKs in the liver.


title: Surveillance of Bat Coronaviruses in Kenya Identifies Relatives of Human Coronaviruses NL63 and 229E and Their Recombination History.

text: Bats harbor a large diversity of coronaviruses (CoVs), several of which are related to zoonotic pathogens that cause severe disease in humans. Our screening of bat samples collected in Kenya from 2007 to 2010 not only detected RNA from several novel CoVs but, more significantly, identified sequences that were closely related to human CoVs NL63 and 229E, suggesting that these two human viruses originate from bats. We also demonstrated that human CoV NL63 is a recombinant between NL63-like viruses circulating in Triaenops bats and 229E-like viruses circulating in Hipposideros bats, with the breakpoint located near 5' and 3' ends of the spike (S) protein gene. In addition, two further interspecies recombination events involving the S gene were identified, suggesting that this region may represent a recombination "hot spot" in CoV genomes. Finally, using a combination of phylogenetic and distance-based approaches, we showed that the genetic diversity of bat CoVs is primarily structured by host species and subsequently by geographic distances.IMPORTANCE Understanding the driving forces of cross-species virus transmission is central to understanding the nature of disease emergence. Previous studies have demonstrated that bats are the ultimate reservoir hosts for a number of coronaviruses (CoVs), including ancestors of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human CoV 229E (HCoV-229E). However, the evolutionary pathways of bat CoVs remain elusive. We provide evidence for natural recombination between distantly related African bat coronaviruses associated with Triaenops afer and Hipposideros sp. bats that resulted in a NL63-like virus, an ancestor of the human pathogen HCoV-NL63. These results suggest that interspecies recombination may play an important role in CoV evolution and the emergence of novel CoVs with zoonotic potential.


title: Outcome after stroke attributable to baseline factors-The PROSpective Cohort with Incident Stroke (PROSCIS).

text: BACKGROUND The impact of risk factors on poor outcome after ischemic stroke is well known, but estimating the amount of poor outcome attributable to single factors is challenging in presence of multimorbidity. We aim to compare population attributable risk estimates obtained from different statistical approaches regarding their consistency. We use a real-life data set from the PROSCIS study to identify predictors for mortality and functional impairment one year after first-ever ischemic stroke and quantify their contribution to poor outcome using population attributable risks. METHODS The PROSpective Cohort with Incident Stroke (PROSCIS) is a prospective observational hospital-based cohort study of patients after first-ever stroke conducted independently in Berlin (PROSCIS-B) and Munich (PROSCIS-M). The association of baseline factors with poor outcome one year after stroke in PROSCIS-B was analysed using multiple logistic regression analysis and population attributable risks were calculated, which were estimated using sequential population attributable risk based on a multiple generalized additive regression model, doubly robust estimation, as well as using average sequential population attributable risk. Findings were reproduced in an independent validation sample from PROSCIS-M. RESULTS Out of 507 patients with available outcome information after 12 months in PROSCIS-B, 20.5% suffered from poor outcome. Factors associated with poor outcome were age, pre-stroke physical disability, stroke severity (NIHSS), education, and diabetes mellitus. The order of risk factors ranked by magnitudes of population attributable risk was almost similar for all methods, but population attributable risk estimates varied markedly between the methods. In PROSCIS-M, incidence of poor outcome and distribution of baseline parameters were comparable. The multiple logistic regression model could be reproduced for all predictors, except pre-stroke physical disability. Similar to PROSCIS-B, the order of risk factors ranked by magnitudes of population attributable risk was almost similar for all methods, but magnitudes of population attributable risk differed markedly between the methods. CONCLUSIONS Ranking of risk factors by population impact is not affected by the different statistical approaches. Thus, for a rational decision on which risk factor to target in disease interventions, population attributable risk is a supportive tool. However, population attributable risk estimates are difficult to interpret and are not comparable when they origin from studies applying different methodology. The predictors for poor outcome identified in PROSCIS-B have a relevant impact on mortality and functional impairment one year after first-ever ischemic stroke.


title: Clinical evaluation of Miller class I and II recessions treatment with the use of modified coronally advanced tunnel technique with either collagen matrix or subepithelial connective tissue graft: A randomized clinical study.

text: AIM To compare outcomes of modified coronally advanced tunnel technique (MCAT) combined with either collagen matrix (CM) or subepithelial connective tissue graft (SCTG) in the treatment of Miller class I and II multiple gingival recessions in the mandible. MATERIALS AND METHODS The study encompassed 91 recessions in 29 patients for whom MCAT was combined with CM on one side of the mandible and SCTG on the contralateral one. The following clinical parameters were measured: gingival recession height (GR) and width (RW), probing depth (PD), clinical attachment level (CAL), width of keratinized tissue (KT), gingival thickness (GT), mean (MRC) and complete root coverage (CRC) and Root Coverage Esthetic Score (RES). RESULTS The MRC proportions on the CM- and SCTG-treated sides were 53.20% and 83.10%, respectively. CRC was achieved in 9 out of 45 (20%) gingival defects treated with CM and 31 out of 46 (67%) treated with SCTG. There were statistically significant differences in MRC, CRC, GR, RW, KT, GT and RES between CM- and CTG-treated sides. CONCLUSIONS Modified coronally advanced tunnel technique leads to reduction in gingival recession both when combined CM and SCTG, of which the latter is more efficient as far as root coverage and aesthetic parameters are concerned.


Open access epidemiologic data and an interactive dashboard to monitor the COVID-19 outbreak in Canada.


Preprints bring 'firehose' of outbreak data.


title: A systematic comparison of the properties of clinically used angiotensin II type 1 receptor antagonists.

text: Angiotensin II type 1 receptor antagonists (ARBs) have become an important drug class in the treatment of hypertension and heart failure and the protection from diabetic nephropathy. Eight ARBs are clinically available [azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan]. Azilsartan (in some countries), candesartan, and olmesartan are orally administered as prodrugs, whereas the blocking action of some is mediated through active metabolites. On the basis of their chemical structures, ARBs use different binding pockets in the receptor, which are associated with differences in dissociation times and, in most cases, apparently insurmountable antagonism. The physicochemical differences between ARBs also manifest in different tissue penetration, including passage through the blood-brain barrier. Differences in binding mode and tissue penetration are also associated with differences in pharmacokinetic profile, particularly duration of action. Although generally highly specific for angiotensin II type 1 receptors, some ARBs, particularly telmisartan, are partial agonists at peroxisome proliferator-activated receptor-γ. All of these properties are comprehensively reviewed in this article. Although there is general consensus that a continuous receptor blockade over a 24-hour period is desirable, the clinical relevance of other pharmacological differences between individual ARBs remains to be assessed.


title: Viral acute lower respiratory infections impair CD8+ T cells through PD-1.

text: Viruses are leading causes of severe acute lower respiratory infections (LRIs). These infections evoke incomplete immunity, as individuals can be repeatedly reinfected throughout life. We report that acute viral LRI causes rapid pulmonary CD8+ cytotoxic T lymphocyte (TCD8) functional impairment via programmed death-1/programmed death ligand-1 (PD-1/PD-L1) signaling, a pathway previously associated with prolonged antigenic stimulation during chronic infections and cancer. PD-1-mediated TCD8 impairment occurred acutely in mice following infection with human metapneumovirus or influenza virus. Viral antigen was sufficient for PD-1 upregulation, but induction of PD-L1 was required for impairment. During secondary viral infection or epitope-only challenge, memory TCD8 rapidly reexpressed PD-1 and exhibited severe functional impairment. Inhibition of PD-1 signaling using monoclonal antibody blockade prevented TCD8 impairment, reduced viral titers during primary infection, and enhanced protection of immunized mice against challenge infection. Additionally, PD-1 and PD-L1 were upregulated in the lungs of patients with 2009 H1N1 influenza virus, respiratory syncytial virus, or parainfluenza virus infection. These results indicate that PD-1 mediates TCD8 functional impairment during acute viral infection and may contribute to recurrent viral LRIs. Therefore, the PD-1/PD-L1 pathway may represent a therapeutic target in the treatment of respiratory viruses.


title: Successful Reperfusion With Mechanical Thrombectomy Is Associated With Reduced Disability and Mortality in Patients With Pretreatment Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score ≤6.

text: BACKGROUND AND PURPOSE In acute ischemic stroke patients, diffusion-weighted imaging (DWI)-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is correlated with infarct volume and is an independent factor of functional outcome. Patients with pretreatment DWI-ASPECTS ≤6 were excluded or under-represented in the recent randomized mechanical thrombectomy trials. Our aim was to assess the impact of reperfusion in pretreatment DWI-ASPECTS ≤6 patients treated with mechanical thrombectomy. METHODS We analyzed data collected between January 2012 and August 2015 in a bicentric prospective clinical registry of consecutive acute ischemic stroke patients treated with mechanical thrombectomy. Every patient with a documented internal carotid artery or middle cerebral artery occlusion with pretreatment DWI-ASPECTS ≤6 was eligible for this study. The primary end point was a favorable outcome defined by a modified Rankin Scale score ≤2 at 90 days. RESULTS Two hundred and eighteen patients with a DWI-ASPECTS ≤6 were included. Among them, 145 (66%) patients had successful reperfusion at the end of mechanical thrombectomy. Reperfused patients had an increased rate of favorable outcome (38.7% versus 17.4%; P=0.002) and a decreased rate of mortality at 3 months (22.5% versus 39.1%; P=0.013) compared with nonreperfused patients. The symptomatic intracranial hemorrhage rate was not different between the 2 groups (13.0% versus 14.1%; P=0.83). However, in patients with DWI-ASPECTS <5, favorable outcome was low (13.0% versus 9.5%; P=0.68) with a high mortality rate (45.7% versus 57.1%; P=0.38) with or without successful reperfusion. CONCLUSIONS Successful reperfusion is associated with reduced mortality and disability in patients with a pretreatment DWI-ASPECTS ≤6. Further data from randomized studies are needed, particularly in patients with DWI-ASPECTS <5.


title: Prevalence and impact of respiratory viral infections in young children with cystic fibrosis: prospective cohort study.

text: OBJECTIVE We aimed to investigate differences in upper and lower respiratory tract symptoms in relation to respiratory viral infections detected with polymerase chain reaction assays in young children with cystic fibrosis and healthy control subjects. METHODS In a 6-month winter period, 20 young children with cystic fibrosis and 18 age-matched, healthy, control subjects were contacted twice per week for detection of symptoms of an acute respiratory illness. If any symptom was present, then a home visit was made for physical examination and collection of nasopharyngeal swabs for viral analysis. In addition, parents were instructed to collect nasopharyngeal swabs every 2 weeks. RESULTS Children with cystic fibrosis and healthy control subjects had similar frequencies of acute respiratory illnesses (3.8+/-1.0 and 4.2+/-1.7 episodes, respectively). Although there were no significant differences in upper respiratory tract symptoms, the children with cystic fibrosis had longer periods of lower respiratory tract symptoms (22.4+/-22.2 vs 12.8+/-13.8 days) and a higher mean severity score per episode (2.35+/-0.64 vs 1.92+/-0.46). In addition, similar increases in upper respiratory tract symptom scores were associated with significantly greater increases in lower respiratory tract symptom scores in children with cystic fibrosis. No differences in the seasonal occurrences and distributions of respiratory viruses were observed, with picornaviruses and coronaviruses being the most prevalent. CONCLUSIONS Although there were no differences in the seasonal occurrences and distributions of polymerase chain reaction-detected respiratory viruses, acute respiratory illnesses were frequently associated with increased lower respiratory tract morbidity in young children with cystic fibrosis.


title: PermacolTM collagen paste injection for the treatment of complex anal fistula - a video vignette.

text: Complex fistula treatment still possess a lot of difficulties and there is no gold standard treatment so far. Only a few small studies using PermacolTM collagen paste (Covidien plc, Gosport, Hampshire, UK) have been reported to date [1-5]. The success rate varies between 47.6% and 77.5%. Here we report a case of a complex transsphincteric fistula successfully treated with PermacolTM collagen paste. This article is protected by copyright. All rights reserved.


title: Deep learning for liver tumor diagnosis part I: development of a convolutional neural network classifier for multi-phasic MRI.

text: OBJECTIVES To develop and validate a proof-of-concept convolutional neural network (CNN)-based deep learning system (DLS) that classifies common hepatic lesions on multi-phasic MRI. METHODS A custom CNN was engineered by iteratively optimizing the network architecture and training cases, finally consisting of three convolutional layers with associated rectified linear units, two maximum pooling layers, and two fully connected layers. Four hundred ninety-four hepatic lesions with typical imaging features from six categories were utilized, divided into training (n = 434) and test (n = 60) sets. Established augmentation techniques were used to generate 43,400 training samples. An Adam optimizer was used for training. Monte Carlo cross-validation was performed. After model engineering was finalized, classification accuracy for the final CNN was compared with two board-certified radiologists on an identical unseen test set. RESULTS The DLS demonstrated a 92% accuracy, a 92% sensitivity (Sn), and a 98% specificity (Sp). Test set performance in a single run of random unseen cases showed an average 90% Sn and 98% Sp. The average Sn/Sp on these same cases for radiologists was 82.5%/96.5%. Results showed a 90% Sn for classifying hepatocellular carcinoma (HCC) compared to 60%/70% for radiologists. For HCC classification, the true positive and false positive rates were 93.5% and 1.6%, respectively, with a receiver operating characteristic area under the curve of 0.992. Computation time per lesion was 5.6 ms. CONCLUSION This preliminary deep learning study demonstrated feasibility for classifying lesions with typical imaging features from six common hepatic lesion types, motivating future studies with larger multi-institutional datasets and more complex imaging appearances. KEY POINTS • Deep learning demonstrates high performance in the classification of liver lesions on volumetric multi-phasic MRI, showing potential as an eventual decision-support tool for radiologists. • Demonstrating a classification runtime of a few milliseconds per lesion, a deep learning system could be incorporated into the clinical workflow in a time-efficient manner.


title: Treatment-focused Ebola trials, supportive care and future of filovirus care.

text: INTRODUCTION During the 2014-2016 Ebolavirus (EBOV) outbreak, several candidate therapeutics were used in EBOV-infected patients in clinical trials and under expanded access for emergency use. This review will focus briefly on medications used during the outbreak. We will discuss current therapeutic candidates and their status and will then turn to a related and essential topic: supportive care and the standard of care for filovirus infected patients. Potential benefits and pitfalls of combination therapies for filoviruses will be discussed. Areas covered: Clinical trials of therapeutics targeting EBOV; clinical usage of therapeutics during recent EBOV outbreak; potential need for combination therapy; role of supportive care in treatment of Ebola virus disease (EVD). Expert commentary: In the absence of another large scale EBOV outbreak, the path to therapeutic product licensure in the United States of America (USA) would need to be via the FDA Animal Rule. However, human data may be needed to supplement animal data. The future of filovirus therapeutics may therefore benefit by establishing the ability to implement clinical trials in an outbreak setting in a timely fashion. Supportive care guidelines for filovirus infection should be defined and established as standard of care for treatment of EVD.


title: The optimal number and location of sutures in conduit-assisted primary digital nerve repair.

text: We evaluated the strength of conduit-assisted primary digital nerve repairs, with varying suture location and number, in 56 digital nerves from cadavers. Maximum load to failure was tested for the following seven repairs, designated by the number of epineurial sutures followed by the number of sutures at each end of the conduit: 4 (epineurial sutures)/0 (sutures at each end of conduit), 4/4, 4/2, 2/2, 0/4, 0/2, 0/1. The 4/4 repair (3.0 N) was significantly stronger than 4/0 (1.5 N), 2/2 (1.6 N), 0/4 (2.0 N), 0/2 (1.4 N) and 0/1 (1.1 N). Considering all repair types, there was a significant correlation between suture number and failure load, with the strongest repair having a total of 12 sutures, which is impractical. Reasonable repair options, which have two sutures at each end of the conduit and either two or no epineurial sutures, are as strong as a four-suture epineurial repair but have less sutures at the coaptation site.


title: Restoration of gastrointestinal motility ameliorates nutritional deficiencies and body weight loss of patients who undergo laparoscopy-assisted proximal gastrectomy.

text: BACKGROUND Esophagogastrostomy after proximal gastrectomy (PG) is a simple and safe reconstruction, but it leads to a high incidence of reflux esophagitis and impairs postoperative quality of life. We have already reported gastric tube (GT) reconstruction after PG and performed it on more than 100 patients. No studies have reported long-term outcomes after PG-GT. The aim of this study was to investigate long-term outcomes, including nutrition indices, such as body weight, serum albumin, total protein, hemoglobin, and ferritin after PG, and observe recovery of upper gastrointestinal tract motility. METHODS We analyzed body weight loss and laboratory findings at our outpatient clinic at 1, 6, 12, 24, 36, 48, and 60 months postoperatively. Manometric recording was carried out at 1, 2, 3, 4, and 5 years after surgery. RESULTS The percentage change in body weight in the PG-GT group was significantly larger than that in the PG-JI and TG-RY groups at 2.5, 3, 4, and 5 years after surgery. The levels of hemoglobin and ferritin in the PG-GT and PG-JI groups were significantly higher than those in the TG-RY group at all time points except 6 months after surgery. In the fasted state, the phase III originated at the gastric tube was propagated to the duodenum 3 years after surgery. In the fed state, phasic contractions of the duodenum were in harmony with gastric tube contractions 3 years after surgery. CONCLUSIONS PG-GT is the least invasive procedure, and restoration of gastrointestinal motilities in the gastric tube and duodenum may ameliorate body weight loss and nutritional status, including anemia, in patients after PG.


title: GBF1, a guanine nucleotide exchange factor for Arf, is crucial for coxsackievirus B3 RNA replication.

text: The replication of enteroviruses is sensitive to brefeldin A (BFA), an inhibitor of endoplasmic reticulum-to-Golgi network transport that blocks activation of guanine exchange factors (GEFs) of the Arf GTPases. Mammalian cells contain three BFA-sensitive Arf GEFs: GBF1, BIG1, and BIG2. Here, we show that coxsackievirus B3 (CVB3) RNA replication is insensitive to BFA in MDCK cells, which contain a BFA-resistant GBF1 due to mutation M832L. Further evidence for a critical role of GBF1 stems from the observations that viral RNA replication is inhibited upon knockdown of GBF1 by RNA interference and that replication in the presence of BFA is rescued upon overexpression of active, but not inactive, GBF1. Overexpression of Arf proteins or Rab1B, a GTPase that induces GBF1 recruitment to membranes, failed to rescue RNA replication in the presence of BFA. Additionally, the importance of the interaction between enterovirus protein 3A and GBF1 for viral RNA replication was investigated. For this, the rescue from BFA inhibition of wild-type (wt) replicons and that of mutant replicons of both CVB3 and poliovirus (PV) carrying a 3A protein that is impaired in binding GBF1 were compared. The BFA-resistant GBF1-M832L protein efficiently rescued RNA replication of both wt and mutant CVB3 and PV replicons in the presence of BFA. However, another BFA-resistant GBF1 protein, GBF1-A795E, also efficiently rescued RNA replication of the wt replicons, but not that of mutant replicons, in the presence of BFA. In conclusion, this study identifies a critical role for GBF1 in CVB3 RNA replication, but the importance of the 3A-GBF1 interaction requires further study.


title: Effect of acellular human dermis buttress on laparoscopic hiatal hernia repair.

text: PURPOSE The objective of this study was to evaluate the performance of acellular human dermis reinforcement during laparoscopic hiatal hernia repair. METHODS A prospective non-randomized, single institution study enrolled patients undergoing laparoscopic hiatal hernia repair. Acellular human dermis, FlexHD (Musculoskeletal Transplant Foundation, Edison, NJ) or AlloDerm (LifeCell Inc., Branchburg, NJ) were used to buttress the repair after primary closure. A protocol barium swallow (BAS) was performed at 6 months and then as needed due to clinical indications. Primary outcome measure was recurrence. Patients completed preoperative and postoperative GERD symptom questionnaires and quality of life surveys (SF-36). Kruskal-Wallis ANOVA, Student's t test, Fisher's exact test, or Wilcoxon signed-rank test were utilized as appropriate (p < 0.05 considered statistically significant). RESULTS Fifty-four patients (10 men and 44 women) with a mean age of 62 ± 10 years underwent laparoscopic hiatal hernia repair using Flex HD (n = 37) or AlloDerm (n = 17). Both groups were similar with respect to gender, age, hiatus size, hernia type [sliding/Type I (n = 14) or paraesophageal/Type III/IV (n = 40)], esophageal motor function (manometry), preoperative SF-36 quality of life surveys, and GERD symptom questionnaires. Forty-seven patients (87 %) completed the BAS at 6 months; each group had two recurrences (p = 0.597). At median follow-up of 33 months, there were 3 recurrences (18 %) in the AlloDerm group and 5 recurrences (14 %) in the Flex HD group (p = 0.365). Minimal differences in GERD symptoms or SF-36 scores were detected between groups. However, anti-reflux medication usage, GERD symptoms, and quality of life significantly improved for both groups after laparoscopic hiatal hernia repair. CONCLUSIONS Laparoscopic hiatal hernia repair with acellular human dermis reinforcement results in improvement of GERD-related symptoms and quality of life without mesh-associated complications. The type of acellular human dermis did not influence recurrence rate.


title: Reorganization of a Northern Italy dermatology department during the COVID-19 pandemic: is it temporary or the beginning of a new era in dermatology?

text: COVID-19 outbreak, caused by the Coronavirus SARS-CoV2, started in December 2019 in Wuhan, Hubei, China and then has rapidly spread to the whole world becoming a pandemic. In February 2020, COVID-19 has reached Europe and, in particular, it has roughly hit Italy and, subsequently, other countries and continents. Consequently, hospitals have started to intensively reduce elective activities to face the high numbers of COVID-19 patients' admissions. In Italy, all the non-urgent clinical appointments (such as primary prevention visits and elective surgeries) have been postponed. We describe the reorganization of our Northern Italy dermatology department during COVID-19 pandemic, including teledermatology strategies. Considering the unknown duration of this emergency scenario we wonder if this is just a temporary measure or the beginning of a new era in dermatology departments' organization?


title: Neural versus pneumatic control of pressure support in patients with chronic obstructive pulmonary diseases at different levels of positive end expiratory pressure: a physiological study.

text: INTRODUCTION Intrinsic positive end-expiratory pressure (PEEPi) is a "threshold" load that must be overcome to trigger conventional pneumatically-controlled pressure support (PSP) in chronic obstructive pulmonary disease (COPD). Application of extrinsic PEEP (PEEPe) reduces trigger delays and mechanical inspiratory efforts. Using the diaphragm electrical activity (EAdi), neurally controlled pressure support (PSN) could hypothetically eliminate asynchrony and reduce mechanical inspiratory effort, hence substituting the need for PEEPe. The primary objective of this study was to show that PSN can reduce the need for PEEPe to improve patient-ventilator interaction and to reduce both the "pre-trigger" and "total inspiratory" neural and mechanical efforts in COPD patients with PEEPi. A secondary objective was to evaluate the impact of applying PSN on breathing pattern. METHODS Twelve intubated and mechanically ventilated COPD patients with PEEPi ≥ 5 cm H2O underwent comparisons of PSP and PSN at different levels of PEEPe (at 0 %, 40 %, 80 %, and 120 % of static PEEPi, for 12 minutes at each level on average), at matching peak airway pressure. We measured flow, airway pressure, esophageal pressure, and EAdi, and analyzed neural and mechanical efforts for triggering and total inspiration. Patient-ventilator interaction was analyzed with the NeuroSync index. RESULTS Mean airway pressure and PEEPe were comparable for PSP and PSN at same target levels. During PSP, the NeuroSync index was 29 % at zero PEEPe and improved to 21 % at optimal PEEPe (P < 0.05). During PSN, the NeuroSync index was lower (<7 %, P < 0.05) regardless of PEEPe. Both pre-trigger (P < 0.05) and total inspiratory mechanical efforts (P < 0.05) were consistently higher during PSP compared to PSN at same PEEPe. The change in total mechanical efforts between PSP at PEEPe0% and PSN at PEEPe0% was not different from the change between PSP at PEEPe0% and PSP at PEEPe80%. CONCLUSION PSN abolishes the need for PEEPe in COPD patients, improves patient-ventilator interaction, and reduces the inspiratory mechanical effort to breathe. TRIAL REGISTRATION Clinicaltrials.gov NCT02114567 . Registered 04 November 2013.


title: Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase.

text: The N7-methylguanosine (m7G) cap is the defining structural feature of eukaryotic mRNAs. Most eukaryotic viruses that replicate in the cytoplasm, including coronaviruses, have evolved strategies to cap their RNAs. In this report, we used a yeast genetic system to functionally screen for the cap-forming enzymes encoded by severe acute respiratory syndrome (SARS) coronavirus and identified the nonstructural protein (nsp) 14 of SARS coronavirus as a (guanine-N7)-methyltransferase (N7-MTase) in vivo in yeast cells and in vitro using purified enzymes and RNA substrates. Interestingly, coronavirus nsp14 was previously characterized as a 3'-to-5' exoribonuclease, and by mutational analysis, we mapped the N7-MTase domain to the carboxy-terminal part of nsp14 that shows features conserved with cellular N7-MTase in structure-based sequence alignment. The exoribonuclease active site was dispensable but the exoribonuclease domain was required for N7-MTase activity. Such combination of the 2 functional domains in coronavirus nsp14 suggests that it may represent a novel form of RNA-processing enzymes. Mutational analysis in a replicon system showed that the N7-MTase activity was important for SARS virus replication/transcription and can thus be used as an attractive drug target to develop antivirals for control of coronaviruses including the deadly SARS virus. Furthermore, the observation that the N7-MTase of RNA life could function in lieu of that in DNA life provides interesting evolutionary insight and practical possibilities in antiviral drug screening.


title: The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings.

text: Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms, which will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.


title: Brain oxygenation during laparoscopic correction of hypertrophic pyloric stenosis.

text: BACKGROUND Concern remains about the safety of carbon dioxide (CO2) pneumoperitoneum (PP) in young infants having surgery for pyloric stenosis via laparoscopy. Interests here mainly focus on possible jeopardized organ perfusion and in particular brain oxygenation with possible adverse neurodevelopmental outcomes. The aim of this study was to investigate the intraoperative effects of CO2 gas PP on cerebral oxygenation during laparoscopic surgery for hypertrophic pyloric stenosis in young infants. PATIENTS AND METHODS In this single-center prospective observational study, we investigated brain oxygenation in 12 young infants receiving laparoscopic pyloromyotomy with CO2 PP, with a pressure of 8 mm Hg and a flow rate of 5 L/minute. Intraoperative hemodynamic parameters and transcranial near-infrared spectroscopy to assess regional cerebral oxygen saturation (rScO2) were monitored continuously during the whole procedure. Parameters were analyzed in four intervals: before insufflation (T0), during (start [T1] and end [T2]), and after cessation (T3) of the CO2 PP. RESULTS Blood pressure and end-tidal CO2 (etCO2) increased during the procedure: mean arterial pressure, 35±5 mm Hg at T0 to 43±9 mm Hg at T2; etCO2, 35±4 mm Hg at T0 to 40±3 mm Hg at T3. The rScO2 remained stable throughout the whole anesthetic period. In none of the patients did the rScO2 drop below the safety threshold of 55% (rScO2, 68±14% at T0 to 71±9% at T3). CONCLUSIONS Our results indicate that a laparoscopic procedure with a CO2 PP of 8 mm Hg can be performed under safe anesthetic conditions in the presence of gradually increasing blood pressure and etCO2 without altering regional brain oxygenation levels.


title: Laser-supported partial laparoscopic nephrectomy for renal cell carcinoma without ischaemia time.

text: BACKGROUND To date, elective nephron-sparing surgery is an established method for the exstirpation of renal tumors. While open partial nephrectomy remains the reference standard of the management of renal masses, laparoscopic partial nephrectomy (LPN) continues to evolve. Conventional techniques include clamping the renal vessels risking ischaemic damage of the clamped organ. Thus, new techniques are needed that combine a sufficient tissue incision for exstirpation of the tumor with an efficient coagulation to assure haemostasis and abandon renal vessel clamping in LPN. Laser-excision of renal tumors during laparoscopic surgery seems to be a logical solution. METHODS We performed nephron-sparing surgery without clamping of the renal vessels in 11 patients with a renal tumor in exophytic position (mean size 32 mm, ranging 8-45 mm) by laser-supported LPN. RESULTS Regular ultrasound monitoring and insertion of a temporary drainage showed no evidence of postoperative hemorrhage. All tumors were removed with a histopathologically confirmed surrounding margin of normal renal tissue (R0 resection). Serum creatinine, hemoglobin, and hematocrit were nearly unaltered before and after surgery. CONCLUSIONS The experience won in these patients have confirmed that laser-assisted LPN without clamping of the renal vessels could be a safe and gentle alternative to classic partial nephrectomy in patients with exophytic position of renal tumors.


title: Early Intervention of Tongxinluo () on Right Ventricular Function Assessed by Echocardiography in Rats with Pulmonary Arterial Hypertension Induced by Monocrotaline.

text: OBJECTIVE To investigate the effect of early intervention of Tongxinluo (, TXL) on right ventricular function (RVF) of rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). METHODS A total of 30 adult male Sprague-Dawley rats were assigned to 5 groups with complete random experiment design: Sham group (Sham), MCT group, TXL group, sildenafil (SIL) group and combination group (TXL+SIL), 6 rats in each group. Rats were injected with 50 mg/kg MCT solution for inducing PAH model except for those in the sham group. From the day of modeling, rats of TXL, SIL and TXL+SIL groups were given TXL (1.2 g/kg), SIL (10 mg/kg) and combination solution (TXL:1.2 g/kg, SIL: 10 mg/kg) respectively, and rats in Sham and MCT groups were given normal saline (5 mL/kg). The samples were collected and tested after 21 consecutive days of intragastric administration. Echocardiography was used to measure the related indices of RVF, including pulmonary arterial flow spectrum, pulmonary artery diameter (PAD), right ventricular wall thickness (RVWT), right ventricular diameter (RVD), tricuspidannular plane systolic excursion (TAPSE), right atrium transverse diameter (RAT), and inferior vena cava diameter (IVCD). Elastic Verhoeff-Van Gieson staining was adopted to measure the percentage of wall thickness (WT%) of pulmonary arteriols. Hematoxylin-eosin staining was used to measure the cross-sectional area (CSA) of right ventricular cardiomyocytes. RESULTS MCT-induced PAH rat model was successfully established. In MCT group the wall of pulmonary arterioles exhibited a prominent-increase thickness, PAD, RVWT, RVD, RAT, IVCD, WT%, right ventricular hypertrophy index (RVHI) as well as CSA of RV cardiomyocyte significantly increased (all P<0.01), and TAPSE markedly decreased (P<0.01). At the same time, TXL prominently improved all of the above indices (all P<0.01). In comparison with SIL, TXL significantly reduced RVD (P<0.05) and decreased CAS of RV cardiomyocytes (P<0.01), but TAPSE in SIL group was much larger than in TXL group (P<0.01). Moreover, TAPSE in TXL+SIL group was larger than that in TXL group (P<0.01), while the two groups performed equally well in terms of the other indices. CONCLUSION Early intervention of TXL could inhibit pulmonary arterioles remodeling, and improve RVF by attenuating right ventricular hypertrophy, and TXL has a stronger effect on inhibiting right ventricular remodeling than SIL.


title: Laparoscopic type 7 total hysterectomy and adnexectomy with or without Burch colposuspension: operative technique with the LigaSure device and results.

text: INTRODUCTION The purpose of the present study was to investigate the use of an operative technique incorporating the LigaSure vessel sealing system in patients undergoing type 7 total laparoscopic hysterectomy (TLH) and adnexectomy with or without Burch colposuspension. METHODS Data were collected for 68 patients who underwent type 7 TLH with adnexectomy. Analyzed variables included patient characteristics (age, body mass index (BMI), parity, medical and surgical history, indications for hysterectomy, weight of the removed uterus), operative data (operative time, procedures performed in addition to TLH, intraoperative blood loss), complications, difference between preoperative and postoperative hemoglobin levels, and length of hospital stay. RESULTS Mean age was 53.7 ± 6.9 years (range 46-74) and mean body mass index was 27.9 ± 6.1 kg/m(2) (range 19.4-45.7). Overall mean operative time was 100.4 ± 31.7 min (range 60-180), mean intraoperative blood loss was 98.1 ± 96.9 ml (range 0-700), and the mean difference between preoperative and postoperative hemoglobin levels was 1.39 ± 0.6 g/dl (range 0-3.4). Mean weight of the removed uteruses was 229.4 ± 174.8 g (range 60-750). Mean hospital stay was 1.12 ± 0.7 days (range 1-7). Additional operative procedures included Burch colposuspension (15; 22.1%), adhesiolysis (9; 13.2%), cholecystectomy (2; 2.9%), transabdominal preperitoneal hernia repair (1; 1.5%) and repair of intraoperative bladder injury (1; 1.5%). Major intraoperative complications were encountered in two patients. In one, the left ureter was injured and in the other the bladder was injured. Conversion to open surgery was not needed in any of the patients. CONCLUSION The procedure we describe here for type 7 TLH with adnexectomy, performed alone or with additional Burch colposuspension, appears to be safe and effective.


title: Clinical and immunologic features in severe and moderate Coronavirus Disease 2019.

text: BACKGROUND Since December 2019, an outbreak of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunologic features of severe and moderate COVID-19. METHODS In this retrospective study, the clinical and immunologic characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the Guidelines released by the National Health Commission of China. RESULTS The median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough and fatigue. Compared to moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute number of T lymphocytes, CD4+T and CD8+T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5 and 89.0 × 106/L) than moderate cases (640.5, 381.5 and 254.0 × 106/L). The expressions of IFN-γ by CD4+T cells tended to be lower in severe cases (14.1%) than moderate cases (22.8%). CONCLUSION The SARS-CoV-2 infection may affect primarily T lymphocytes particularly CD4+T and CD8+ T cells, resulting in decrease in numbers as well as IFN-γ production. These potential immunological markers may be of importance due to their correlation with disease severity in COVID-19.


title: Impact of valve-less vs. standard insufflation on pneumoperitoneum volume, inflammation, and peritoneal physiology in a laparoscopic sigmoid resection experimental model.

text: BACKGROUND Standard insufflators compensate for intra-abdominal pressure variations with pressure spikes. Our aim was to evaluate the impact of a stable, low-pressure pneumoperitoneum induced by a valve-less insufflator, on working space, hemodynamics, inflammation, and peritoneal physiology, in a model of laparoscopic sigmoid resection. MATERIALS AND METHODS Twelve pigs (47 ± 3.3 kg) were equipped for invasive hemodynamic monitoring and randomly assigned to Standard (n = 6) vs. valve-less (n = 6) insufflation. Animals were positioned in a 30° Trendelenburg on a CT scan bed. A low-pressure pneumoperitoneum (8 mmHg) was started and duration was set for 180 min. Abdominal CT scans were performed, under neuromuscular blockade, before, immediately after, and 1 and 3 h after insufflation. Pneumoperitoneum volumes were calculated on 3D reconstructed CT scans. After creation of a mesenteric window, capillary blood was obtained by puncturing the sigmoid serosa and local lactatemia (mmol/L) was measured using a handheld analyzer. Surgical resection was performed according to the level of lactates, in order to standardize bowel stump perfusion. IL-1 and IL-6 (ng/mL) were measured repeatedly. The peritoneum was sampled close to the surgical site and distantly for the oxygraphic assessment of mitochondrial respiration. A pathologist applied a semi-quantitative score to evaluate the anastomosis. RESULTS Mean arterial pressure, pulse, body temperature, oximetry, systemic lactatemia, and local lactates were similar. IL-6 was lower in the valve-less group, reaching a statistically significant difference after 3 h of insufflation (64.85 ± 32.5 vs. 133.95 ± 59.73; p = 0.038) and 48 h (77.53 ± 68.4 vs. 190.74 ± 140.79; p = 0.029). Peritoneal mitochondrial respiration was significantly increased after the survival period, with no difference among the groups. The anastomoses in the valve-less group demonstrated a lower acute (p = 0.04) inflammatory infiltration. The mean anterior posterior thickness was slightly, yet significantly higher in the valve-less group, on all post-insufflation CT scans. CONCLUSIONS Valve-less insufflation achieved a slightly higher working space and a lower systemic and localized inflammatory response in this experimental setting.


Tele-rounding in a university hospital pulmonary ward during the COVID-19 pandemic: a pilot study.


title: Complete Uniportal Thoracoscopic Anatomic Lung Resection With Systematic Mediastinal Lymphadenectomy for Non-Small Cell Lung Cancer: Personal Experience of 326 Cases.

text: BACKGROUND With its growing popularity and potential outcome, complete uniportal thoracoscopic (CUT) surgery has been used in the treatment of thoracic diseases. This study aimed to summarize a personal experience of CUT anatomic lung resection with systematic mediastinal lymphadenectomy (CUT-ALR-SML) for non-small cell lung cancer (NSCLC) and to evaluate the feasibility and safety of CUT-ALR-SML in our institute. MATERIALS AND METHODS A total of 326 patients with NSCLC were chosen to undergo CUT-ALR-SML in our institute from August 2013 to July 2018. Data such as clinicopathologic characteristics and perioperative outcomes were reviewed in this article. RESULTS For the 326 cases of ALR, the specific procedures and the corresponding number of cases were as follows: segmentectomy, 90; lobectomy, 218; sleeve lobectomy, 9; ipsilateral lobe combined with segment resected synchronously (i-L+S), 6; and pneumonectomy, 3. A total of 31 cases required conversion to open surgery, and 4 cases were converted to multiportal thoracoscopic surgery. All patients underwent SML. The average mediastinal lymph node stations and mediastinal lymph nodes dissected under CUT-ALR-SML were 3.3±1.4 and 9.6±8.4, respectively. Approximately 99.7% of the patients acquired free resection margins. A total of 42 (12.9%) patients suffered from postoperative complications, and 1 patient died of pneumonia during the perioperative period. CONCLUSIONS Complete uniportal ALR, particularly for segmentectomy and lobectomy is safe and feasible with low complication rates and excellent free resection margin rates. SML during complete uniportal thoracoscopic surgery adequately assesses the N2 lymph node. However, further studies need to be conducted to evaluate the role of CUT-ALR-SML in the treatment of NSCLC.


Innovation in a post-Covid 'new normal'.


title: MMM-QSAR recognition of ribonucleases without alignment: comparison with an HMM model and isolation from Schizosaccharomyces pombe, prediction, and experimental assay of a new sequence.

text: The study of type III RNases constitutes an important area in molecular biology. It is known that the pac1+ gene encodes a particular RNase III that shares low amino acid similarity with other genes despite having a double-stranded ribonuclease activity. Bioinformatics methods based on sequence alignment may fail when there is a low amino acidic identity percentage between a query sequence and others with similar functions (remote homologues) or a similar sequence is not recorded in the database. Quantitative structure-activity relationships (QSAR) applied to protein sequences may allow an alignment-independent prediction of protein function. These sequences of QSAR-like methods often use 1D sequence numerical parameters as the input to seek sequence-function relationships. However, previous 2D representation of sequences may uncover useful higher-order information. In the work described here we calculated for the first time the spectral moments of a Markov matrix (MMM) associated with a 2D-HP-map of a protein sequence. We used MMMs values to characterize numerically 81 sequences of type III RNases and 133 proteins of a control group. We subsequently developed one MMM-QSAR and one classic hidden Markov model (HMM) based on the same data. The MMM-QSAR showed a discrimination power of RNAses from other proteins of 97.35% without using alignment, which is a result as good as for the known HMM techniques. We also report for the first time the isolation of a new Pac1 protein (DQ647826) from Schizosaccharomyces pombe strain 428-4-1. The MMM-QSAR model predicts the new RNase III with the same accuracy as other classical alignment methods. Experimental assay of this protein confirms the predicted activity. The present results suggest that MMM-QSAR models may be used for protein function annotation avoiding sequence alignment with the same accuracy of classic HMM models.


[Analysis of the threat perceived by the COVID-19 in the Spanish population].


title: Incidental Parathyroidectomy during Total Thyroidectomy: Risk Factors and Consequences.

text: Objective. To evaluate the incidence of accidental parathyroidectomy in our series of total thyroidectomies, to investigate its clinical and biochemical consequences, and to identify potential risk factors. Methods. Patients who underwent total thyroidectomy between January 2006 and December 2015 were retrospectively analyzed. Pathology reports were reviewed to identify those cases who had an incidental parathyroidectomy and these were compared to patients with no parathyroidectomy, in terms of clinical (age, sex, and symptoms of hypocalcemia), pathological (thyroid specimen weight, Hashimoto thyroiditis, and malignancy), and biochemical (serum calcium and phosphate levels) factors. Results. 281 patients underwent total thyroidectomy during the study period. Incidental parathyroidectomy was noticed in 24.9% of cases, with 44.3% of parathyroid glands found in an intrathyroidal location. Evidence of postoperative biochemical hypocalcemia was noticed in 28.6% of patients with parathyroidectomy, compared with 13.3% in the no-parathyroidectomy group (p = 0.003). Symptomatic hypocalcemia was observed in 5.7% and 3.8%, respectively (p = 0.49). Age, sex, thyroid specimen weight, Hashimoto thyroiditis, and malignancy did not differ significantly between the two groups. Conclusions. Our study found an association of incidental parathyroidectomy with transient postoperative biochemical hypocalcemia, but not with clinically symptomatic disease. Age, sex, thyroid gland weight, Hashimoto thyroiditis, and malignancy were not identified as risk factors.


title: Outcomes of a single-port laparoscopic appendectomy using a glove port with a percutaneous organ-holding device and commercially-available multichannel single-port device.

text: PURPOSE A laparoscopic appendectomy is now commonly performed. The push in recent years toward reducing the number of ports required to perform this surgery has led to the development of a single-port laparoscopic appendectomy (SPA). We compared postoperative pain after an SPA using a glove port with a percutaneous organ-holding device (group 1) with that of an SPA using a commercially-available multichannel single-port device (group 2). METHODS Between March 2010 and July 2011, a retrospective study was conducted of a total of 77 patients who underwent an SPA by three surgeons at department of surgery, Kangbuk Samsung Medical Center. Thirty-eight patients received an SPA using a glove port with a percutaneous organ-holding device. The other 39 patients received an SPA using a commercially-available multichannel single port (Octo-Port or SILS Port). Operative details and postoperative outcomes were collected and evaluated. RESULTS There were no differences in the mean operative times, times to pass gas, postoperative hospital stays, or cosmetic satisfaction scores between the two groups. The pain score in the first 24 hours after surgery was higher in group 2 than group 1 patients (P < 0.001). Furthermore, the trocar used in group 2 was more expensive than that used in group 1. CONCLUSION An SPA using a glove port with a percutaneous organ-holding device was associated with a lower pain score during the first 24 hours after surgery because of the shorter fascia incision length and a cheaper cost than an SPA using a commercially-available multichannel single-port device.


title: Successful Repair of Acute Type A Aortic Dissection 15 Years Following Bilateral Lung Transplantation.

text: This report describes a patient treated for acute type A aortic dissection 15 years after undergoing bilateral lung transplantation by a clamshell thoracotomy.


title: A decrease in blood pressure is associated with unfavorable outcome in patients undergoing thrombectomy under general anesthesia.

text: BACKGROUND Up to two-thirds of patients are either dependent or dead 3 months after thrombectomy for acute ischemic stroke (AIS). Loss of cerebral autoregulation may render patients with AIS vulnerable to decreases in mean arterial pressure (MAP). OBJECTIVE To determine whether a fall in MAP during intervention under general anesthesia (GA) affects functional outcome. METHODS This subgroup analysis included patients from the MR CLEAN trial treated with thrombectomy under GA. The investigated variables were the difference between MAP at baseline and average MAP during GA (ΔMAP) as well as the difference between baseline MAP and the lowest MAP during GA (ΔLMAP). Their association with a shift towards better outcome on the modified Rankin Scale (mRS) after 90 days was determined using ordinal logistic regression with adjustment for prognostic baseline variables. RESULTS Sixty of the 85 patients treated under GA in MR CLEAN had sufficient anesthetic information available for the analysis. A greater ΔMAP was associated with worse outcome (adjusted common OR (acOR) 0.95 per point mm Hg, 95% CI 0.92 to 0.99). An average MAP during GA 10 mm Hg lower than baseline MAP constituted a 1.67 times lower odds of a shift towards good outcome on the mRS. For ΔLMAP this association was not significant (acOR 0.97 per mm Hg, 95% CI 0.94 to 1.00, p=0.09). CONCLUSIONS A decrease in MAP during intervention under GA compared with baseline is associated with worse outcome. TRIAL REGISTRATION NUMBER NTR1804; ISRCTN10888758; post-results.


title: Outcomes of laparoscopic sleeve gastrectomy in Crohn's disease patients: an initial Australian experience.

text: BACKGROUND Crohn's disease (CD) in association with obesity is becoming an increasing issue in Australia and worldwide. This report looks at outcomes for patients with CD undergoing laparoscopic sleeve gastrectomy. METHODS This is a retrospective analysis of our database of patients undergoing laparoscopic sleeve gastrectomy from 2007 to 2016. Patients with concurrent CD were included. RESULTS Eight patients with CD underwent laparoscopic sleeve gastrectomy with a mean preoperative body mass index of 43.8. There were no identified intraoperative or post-operative complications. The mean excess weight loss was 55.7% and 56.5% at 6 months and 1 year, respectively. CONCLUSION Laparoscopic sleeve gastrectomy can be achieved in CD patients. No complications and effective weight loss was observed in the eight reported patients.


NHS should develop bioinformatics to make best use of whole genome sequencing, expert group says.


COVID-19 and myocardial injury: is there a role for interleukin-1 inhibition?


Obesity Is a Risk Factor for Greater COVID-19 Severity.


title: Randomized Clinical Trial of 24% Oral Sucrose to Decrease Pain Associated With Peripheral Intravenous Catheter Insertion in Preterm and Term Newborns.

text: PURPOSE To determine whether 24% sucrose solution given orally before insertion of a peripheral intravenous (PIV) catheter decreases neonatal pain. BACKGROUND Prior studies of pain caused by heel and arterial needlesticks found oral administration of 24% sucrose to significantly blunt pain during these painful procedures. No studies have evaluated this treatment with needlestick pain associated with PIV catheter insertion. METHODS Oral 24% sucrose or placebo solution was administered 2 minutes prior to PIV catheter insertion. Outcome measures were obtained prior to, during, and for 5 minutes after PIV catheter insertion. Investigators and caregivers were blinded to group assignment. Data were analyzed with longitudinal analysis of repeated measures, with P < .05 for significance. RESULTS A total of 40 neonates (24% sucrose: N = 20; placebo: N = 20) were studied. Pain scores significantly increased from 3.2 ± 1.6 to a maximum of 7.6 ± 3.8 at the time of catheter insertion, returning to baseline levels 8 minutes after PIV catheter insertion (P < .001). No significant differences were found in pain, heart rate, or noninvasive oxygen saturation (SpO2) between the sucrose and placebo groups (P > 0.05). IMPLICATIONS FOR PRACTICE Results from this study did not find that 24% sucrose administered prior to PIV catheter insertion altered the infant's pain response. IMPLICATIONS FOR RESEARCH Since this is the first study to evaluate the pain-blunting effects of 24% sucrose administration before PIV catheter insertion, replication of this study is needed before widespread application of findings.


Ten work-life balance tips for researchers based at home during the pandemic.


title: Hepatic resection using a liver-hanging maneuver and Glissonean pedicle transection for hepatocellular carcinoma in a patient with situs inversus totalis: report of a case.

text: Situs inversus totalis is a rare congenital anomaly in which the major abdominal organs are located as a mirror image of their normal positions. This poses much difficulty for surgeons. We describe how we performed the liver-hanging maneuver (LHM) for hepatocellular carcinoma (HCC) in a 59-year-old man with situs inversus totalis, to resolve the difficulty of the mirror-image location of his liver. The HCC was located in the right lateral sector. Although segmentectomy of segment 7 would normally be considered minimal for a curative treatment of HCC, this was relatively complicated in this patient. Thus, we performed an extended right lateral sectionectomy using the LHM to achieve a simple transection. The hepatic hilum was dissected using the Glissonean pedicle transection method. The operation time and intraoperative blood loss were 6 h 45 min and 471 ml, respectively. No blood product transfusion was required. The LHM and the hilar Glissonean pedicle approach proved effective for resolving the difficulties of performing surgery in a mirror image for HCC in a patient with situs inversus totalis.


title: Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review.

text: Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing human coronavirus disease 2019 (COVID-19), which has now spread into a worldwide pandemic. The pulmonary manifestations of COVID-19 have been well described in the literature. Two similar human coronaviruses that cause Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV-1) are known to cause disease in the central and peripheral nervous systems. Emerging evidence suggests COVID-19 has neurologic consequences as well. Observations This review serves to summarize available information regarding coronaviruses in the nervous system, identify the potential tissue targets and routes of entry of SARS-CoV-2 into the central nervous system, and describe the range of clinical neurological complications that have been reported thus far in COVID-19 and their potential pathogenesis. Viral neuroinvasion may be achieved by several routes, including transsynaptic transfer across infected neurons, entry via the olfactory nerve, infection of vascular endothelium, or leukocyte migration across the blood-brain barrier. The most common neurologic complaints in COVID-19 are anosmia, ageusia, and headache, but other diseases, such as stroke, impairment of consciousness, seizure, and encephalopathy, have also been reported. Conclusions and Relevance Recognition and understanding of the range of neurological disorders associated with COVID-19 may lead to improved clinical outcomes and better treatment algorithms. Further neuropathological studies will be crucial to understanding the pathogenesis of the disease in the central nervous system, and longitudinal neurologic and cognitive assessment of individuals after recovery from COVID-19 will be crucial to understand the natural history of COVID-19 in the central nervous system and monitor for any long-term neurologic sequelae.


title: The Effectiveness of Crisis Line Services: A Systematic Review.

text: Background: Crisis lines are a standard component of a public health approach to suicide prevention. Clinical aims include reducing individuals' crisis states, psychological distress, and risk of suicide. Efforts may also include enhancing access and facilitating connections to behavioral health care. This review examines models of crisis line services for demonstrated effectiveness. Methods: Literature searches of Medline, EMBASE, PsycINFO, Web of Science, CINAHL, Cochrane Library, and Google Scholar were conducted from January 1, 1990, to May 7, 2018. Experts were contacted, and references were mined for additional studies. Eligible studies provided health- or utilization-related effectiveness outcome(s). Results were graded according to the Oxford Centre for Evidence-Based Medicine and evaluated for risk of bias using the Effective Public Health Practice Project quality assessment tool for quantitative studies. Results: Thirty-three studies yielded effectiveness outcomes. In most cases findings regarding crisis calls vs. other modalities were presented. Evaluation approaches included user- and helper-reported data, silent monitoring, and analyses of administrative records. About half of studies reported immediate proximal outcomes (during the crisis service), and the remaining reported distal outcomes (up to four years post-contact). Most studies were rated at Oxford level four evidence and 80% were assessed at high risk of bias. Conclusions: High quality evidence demonstrating crisis line effectiveness is lacking. Moreover, most approaches to demonstrating impact only measured proximal outcomes. Research should focus on innovative strategies to assess proximal and distal outcomes, with a specific focus on behavioral health treatment engagement and future self-directed violence.


title: Intraindividual Comparison of 99mTc-Methylene Diphosphonate and Prostate-Specific Membrane Antigen Ligand 99mTc-MIP-1427 in Patients with Osseous Metastasized Prostate Cancer.

text: The objective of this study was to evaluate the rate of detection of bone metastases obtained with the prostate-specific membrane antigen (PSMA)-targeting tracer 99mTc-MIP-1427, as opposed to conventional bone scanning with 99mTc-methylene diphosphonate (99mTc-MDP), in a collective of patients with known advanced-stage osseous metastasized prostate cancer. Methods: Twenty-one patients with known metastatic disease were staged with both conventional bone scanning and PSMA ligand scintigraphy within a time frame of less than 10 d. Imaging included planar whole-body scanning and SPECT or SPECT/CT with 2 bed positions 3 h after injection of either 500-750 MBq of 99mTc-MIP-1427 or 600-750 MBq of 99mTc-MDP. Lesions were scored as typical tumor, equivocal (benign/malignant), or normal within a standard reporting schema divided into defined anatomic regions. Masked and consensus readings were performed with sequential unmasking: planar scans first, then SPECT/CT, the best evaluable comparator (including MRI), PET/CT, and follow-up examinations. Results: Eleven patients had PSMA-positive visceral metastases that were predictably not diagnosed with conventional bone scanning. However, SPECT/CT was required to distinguish between soft-tissue uptake and overlapping bone. Four patients had extensive 99mTc-MDP-negative bone marrow lesions. Seven patients had superscan characteristics on bone scans; in contrast, the extent of red marrow involvement was more evident on PSMA scans. Only 3 patients had equivalent results on bone scans and PSMA scans. In 16 patients, more suspect lesions were detected with PSMA scanning than with bone scanning. In 2 patients (10%), a PSMA-negative tumor phenotype was present. Conclusion: PSMA scanning provided a clear advantage over bone scanning by reducing the number of equivocal findings in most patients. SPECT/CT was pivotal for differentiating bone metastases from extraosseous tumor lesions.


title: Adaptation of tobacco etch potyvirus to a susceptible ecotype of Arabidopsis thaliana capacitates it for systemic infection of resistant ecotypes.

text: Viral pathogens continue to emerge among humans, domesticated animals and cultivated crops. The existence of genetic variance for resistance in the host population is crucial to the spread of an emerging virus. Models predict that rapid spread decreases with the frequency and diversity of resistance alleles in the host population. However, empirical tests of this hypothesis are scarce. Arabiodpsis thaliana--tobacco etch potyvirus (TEV) provides an experimentally suitable pathosystem to explore the interplay between genetic variation in host's susceptibility and virus diversity. Systemic infection of A. thaliana with TEV is controlled by three dominant loci, with different ecotypes varying in susceptibility depending on the genetic constitution at these three loci. Here, we show that the TEV adaptation to a susceptible ecotype allowed the virus to successfully infect, replicate and induce symptoms in ecotypes that were fully resistant to the ancestral virus. The value of these results is twofold. First, we showed that the existence of partially susceptible individuals allows for the emerging virus to bypass resistance alleles that the virus has never encountered. Second, the concept of resistance genes may only be valid for a well-defined viral genotype but not for polymorphic viral populations.


title: Randomized controlled trial of uncut Roux-en-Y vs Billroth II reconstruction after distal gastrectomy for gastric cancer: Which technique is better for avoiding biliary reflux and gastritis?

text: AIM To identify which technique is better for avoiding biliary reflux and gastritis between uncut Roux-en-Y and Billroth II reconstruction. METHODS A total of 158 patients who underwent laparoscopy-assisted distal gastrectomy for gastric cancer at the First Hospital of Jilin University (Changchun, China) between February 2015 and February 2016 were randomized into two groups: uncut Roux-en-Y (group U) and Billroth II group (group B). Postoperative complications and relevant clinical data were compared between the two groups. RESULTS According to the randomization table, each group included 79 patients. There was no significant difference in postoperative complications between groups U and B (7.6% vs 10.1%, P = 0.576). During the postoperative period, group U stomach pH values were lower than 7 and group B pH values were higher than 7. After 1 year of follow-up, group B presented a higher incidence of biliary reflux and alkaline gastritis. However, histopathology did not show a significant difference in gastritis diagnosis (P = 0.278), and the amount of residual food and gain of weight between the groups were also not significantly different. At 3 mo there was no evidence of partial recanalization of uncut staple line, but at 1 year the incidence was 13%. CONCLUSION Compared with Billroth II reconstruction, uncut Roux-en-Y reconstruction is secure and feasible, and can effectively reduce the incidence of alkaline reflux, residual gastritis, and heartburn. Despite the incidence of recanalization, uncut Roux-en-Y should be widely applied.


title: Laparoscopic treatment for inguinal hernia combined with cryptorchidism: Totally extraperitoneal repair with orchiectomy under the same operative view.

text: INTRODUCTION Approximately 7% of child patients with inguinal hernias also present with cryptorchidism. On the other hand, combined adult cases are uncommon. Here we report two adult cases of inguinal hernia combined with intra-canalicular cryptorchidism who underwent totally extraperitoneal (TEP) repair with orchiectomy under the same operative view. PRESENTATION OF CASES We treated two patients (49- and 38-year-old men) with right indirect inguinal hernias and cryptorchidism. Both patients underwent TEP repair with orchiectomy. In operative findings, an atrophic testis was drawn out with a hernia sac from the internal inguinal ring. After the testis was separated from the sac and cord structure was sheared, it was removed. The procedure did not require special techniques and devices. In both patients, the postoperative courses were satisfactory. DISCUSSION To our knowledge, there has been only one such reported case till date which demonstrated the feasibility of TEP repair accompanied by orchiectomy. CONCLUSIONS TEP repair with orchiectomy under the same operative view could be safely performed in adults with an inguinal hernia combined with extra-abdominal cryptorchidism. This procedure could be an option for the treatment of such adult patients.


title: Robotic radical cystectomy with intracorporeal urinary diversion: beyond the initial experience.

text: Robotic assisted radical cystectomy (RARC) has gained popularity within minimally-invasive urologic surgery, and has been shown to be a safe procedure with similar oncologic outcomes when compared to the conventional open standard. While initial RARC feasibility and outcomes studies were performed with extracorporeal urinary diversion, intracorporeal urinary diversion (ICUD) is becoming increasingly utilized. Reported benefits of an intracorporeal approach include decreased blood loss and a lower incidence of ureteral strictures. While ICUD is technically challenging, many have overcome the learning curve associated with this procedure via a mentorship model and a dedicated operative team. Techniques vary between institutions, and ileal conduit, continent cutaneous and orthotopic continent (neobladder) diversions have all been performed. Herein, we describe the learning curve, technical points, and unique complications associated with ICUD.


title: The versatile heparin in COVID-19.

text: Coagulopathy in corona virus infection has been shown to be associated with high mortality with high D-dimers being a particularly important marker for the coagulopathy.1 In the latest paper from the same group, the use of anticoagulant therapy with heparin was shown to decrease mortality as well. 2 This is especially so in patients i) who have met the sepsis induced coagulopathy (SIC) criteria ≥4 (40.0% vs 64.2%, P=0.029) compared to those with SIC score <4 (29.0% vs 22.6%, P=0.419).or ii) with markedly elevated D-dimer (greater than six-fold at the upper limit of normal).


2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.


Viral pneumonia in severe respiratory failure.


title: Stent-Assisted Coil Embolization of a Transverse-Sigmoid Sinus Diverticulum Presenting with Pulsatile Tinnitus.

text: When tinnitus is pulse-synchronous, a vascular etiology is suggested. We present a case of persistent and troublesome pulsatile tinnitus caused by a transverse-sigmoid sinus diverticulum that was endovascularly treated with stent-assisted coiling. A 39-yearold woman presented with a 4-year history of progressive pulsatile tinnitus involving the right ear. Slight pulsatile bruit was heard on the right mastoid bone by auscultation. Cerebral angiography demonstrated a diverticulum of the transverse-sigmoid sinus. The procedure was performed with an 8F guiding catheter (Cordis, USA) catheterized into the right sigmoid sinus. The diverticulum was completely coiled following deployment of a 5.5 mm-50 mm Leo stent. This patient awakened without any neurological deficit and with immediate resolution of her tinnitus. This case report describes a stent-assisted coil embolization of venous sinus diverticulum, which provides immediate resolution of pulsatile tinnitus.


title: Social media use for nutrition outcomes in young adults: a mixed-methods systematic review.

text: BACKGROUND Social media has been widely adopted by young adults, consequently health researchers are looking for ways to leverage this engagement with social media for the delivery of interventions and health promotion campaigns. Weight gain and sub-optimal dietary choices are common in young adults, and social media may be a potential tool to facilitate and support healthier choices. METHODS We conducted a mixed-methods systematic review of studies examining social media use for nutrition-related outcomes in young adults. Seven databases [EBscohost, ERIC, ProQuest Central, PubMed, Ovid, Scopus, and Emerald] were systematically searched; 1225 abstracts were screened, and 47 full-text articles were assessed for eligibility. Study designs included both quantitative, such as experimental and observational studies, and qualitative, such as focus groups and interviews, approaches. Quality was assessed using the Mixed Methods Appraisal Tool. Quantitative and qualitative results were examined separately, and then synthesized. RESULTS Twenty-one studies were included although their use of social media was highly variable. The main purpose of social media was to provide information and social support to participants. In the nine randomized controlled trials, social media was used as one aspect of a multi-faceted intervention. Interventions had a positive statistically significant impact on nutritional outcomes in 1/9 trials. Engagement with the social media component of interventions varied, from 3 to 69%. Young adults appear to be open to receiving healthy eating and recipe tips through social media, however, they are reluctant to share personal weight-related information on their online social networks. CONCLUSIONS Information-dissemination is now an acceptable use of social media by young adults. Using social media effectively for social support, either via private groups or public pages, requires careful evaluation as its effectiveness is yet to be demonstrated in experimental designs. Concerns about public social media use may be a contributing factor to poor engagement with social media in research intervention studies aimed at influencing weight. Future research should consider how to best engage with young adults using social media, how to more effectively use social media to support young adults and to facilitate social and peer-to-peer support in making healthier choices.


title: A systematic review of therapeutic ketamine use in children and adolescents with treatment-resistant mood disorders.

text: Suicide is the second leading cause of death in the United States among individuals aged 10-24, and severe youth depression is often refractory to the current standards of care. Many studies have demonstrated the efficacy of ketamine in reducing depressive symptoms in adults with treatment-resistant mood disorders, though few studies utilizing ketamine in youth populations exist. This systematic review examines the current state of evidence for ketamine use in children with treatment-resistant mood disorders. We conducted a search utilizing two electronic databases for English-language studies investigating the therapeutic effects and side effect profile of ketamine in youth ≤ 19 years of age with a diagnosis of a treatment-resistant mood disorder. Analysis included subjects with treatment-resistant depression with and without psychotic features and with bipolar disorder. Primary outcome measures included the following scales: Montgomery-Asberg Depression Rating Scale, Children's Depression Rating Scale, Children's Depression Rating Scale Revised, Child Bipolar Questionnaire, Overt Aggression Scale, Yale-Brown Obsessive-Compulsive Scale, and Scale for Suicidal Ideation. Four published studies were identified that investigated therapeutic ketamine use in youth for the primary purpose of treating a treatment-resistant psychiatric disorder. Three additional studies that did not meet eligibility criteria were identified and discussed. Ketamine was shown in youth to generally improve depressive symptoms, decrease acute suicidality, and reduce mood lability, though a number of subjects remained resistant to its treatment. These findings substantiate the need for further longitudinal studies investigating ketamine's long-term safety, its efficacy, and abuse potential in the youth.


title: Recombinant protein subunit vaccine synthesis in microbes: a role for yeast?

text: OBJECTIVES Recombinant protein subunit vaccines are formulated using protein antigens that have been synthesized in heterologous host cells. Several host cells are available for this purpose, ranging from Escherichia coli to mammalian cell lines. This article highlights the benefits of using yeast as the recombinant host. KEY FINDINGS The yeast species, Saccharomyces cerevisiae and Pichia pastoris, have been used to optimize the functional yields of potential antigens for the development of subunit vaccines against a wide range of diseases caused by bacteria and viruses. Saccharomyces cerevisiae has also been used in the manufacture of 11 approved vaccines against hepatitis B virus and one against human papillomavirus; in both cases, the recombinant protein forms highly immunogenic virus-like particles. SUMMARY Advances in our understanding of how a yeast cell responds to the metabolic load of producing recombinant proteins will allow us to identify host strains that have improved yield properties and enable the synthesis of more challenging antigens that cannot be produced in other systems. Yeasts therefore have the potential to become important host organisms for the production of recombinant antigens that can be used in the manufacture of subunit vaccines or in new vaccine development.


Controlling Worms Needs Traditional Public Health Programs.


title: Difficult-to-Treat Resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-line Agents.

text: Background Resistance to all first-line antibiotics necessitates the use of less effective or more toxic "reserve" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic. Methods The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ≥1 first-line agent, and graded loss of active categories. Results Between 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0. Conclusion Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance.


title: Lymph node evaluation in video-assisted thoracoscopic lobectomy versus lobectomy by thoracotomy.

text: BACKGROUND With the emergence of video-assisted thoracic surgery (VATS) lobectomy, concern remains regarding the adequacy of nodal assessment versus thoracotomy. METHODS All clinical stage I non-small cell lung cancer patients treated with VATS or open lobectomy were retrospectively evaluated. Total nodes, N2 nodes, and nodes at each station were evaluated for associations with surgery type and location of involved lobe. RESULTS There were 79 VATS and 464 open lobectomy or segmental resections for stage I tumors. Overall, fewer lymph nodes were sampled with VATS compared with thoracotomy (7.4 +/- 0.6 vs 8.9 +/- 0.2, respectively; p = 0.029), and fewer N2 nodes were sampled with VATS versus thoracotomy as well (2.5 +/- 3.0 vs 3.7 +/- 3.3, p = 0.004). There were no differences in N1 node sampling between the two groups (5.2 +/- 3.6 vs 4.9 +/- 4.2, p = 0.592). Furthermore, there were more station 7 nodes with thoracotomy versus VATS (1.2 +/- 0.1 vs 0.6 +/- 0.1, p = 0.002). Among right-sided lesions, there was no difference in 4R nodes between groups (1.4 +/- 0.4 vs 1.6 +/- 0.2, p = 0.7) although there was a trend toward more level 7 nodes with thoracotomy (1.0 +/- 0.2 vs 1.4 +/- 0.2, p < 0.08). Among left-sided resections there were more station 7 nodes with thoracotomy versus VATS (1.0 +/- 0.1 vs 0.4 +/- 0.1, p < 0.001) and more station 5/6 nodes (1.1 +/- 0.1 vs 0.5 +/- 0.1, p < 0.04). For upper lobe resections, the total nodes (8.9 +/- 0.3 vs 7.4 +/- 0.7, p = 0.05) and station 7 nodes (1.0 +/- 0.1 vs 0.6 +/- 0.1, p < 0.01) were higher with thoracotomy than VATS. There was no difference in 2-year survival between groups (81% vs 83%, p = 0.4). CONCLUSIONS Our early experience with VATS has been associated with fewer lymph nodes sampled compared with open lobectomy although there was no survival difference. Analysis of these differences has directed us toward a more focused lymph node sampling with VATS lobectomy.


title: COVID-19: animals, veterinary and zoonotic links.

text: Coronavirus disease 2019 (COVID-19), has spread over 210 countries and territories beyond China shortly. On February 29, 2020, the World Health Organization (WHO) denoted it in a high-risk category, and on March 11, 2020, this virus was designated pandemic, after its declaration being a Public Health International Emergency on January 30, 2020. World over high efforts are being made to counter and contain this virus. The COVID-19 outbreak once again proves the potential of the animal-human interface to act as the primary source of emerging zoonotic diseases. Even though the circumstantial evidence suggests the possibility of an initial zoonotic emergence, it is too early to confirm the role of intermediate hosts such as snakes, pangolins, turtles, and other wild animals in the origin of SARS-CoV-2, in addition to bats, the natural hosts of multiple coronaviruses such as SARS-CoV and MERS-CoV. The lessons learned from past episodes of MERS-CoV and SARS-CoV are being exploited to retort this virus. Best efforts are being taken up by worldwide nations to implement effective diagnosis, strict vigilance, heightened surveillance, and monitoring, along with adopting appropriate preventive and control strategies. Identifying the possible zoonotic emergence and the exact mechanism responsible for its initial transmission will help us to design and implement appropriate preventive barriers against the further transmission of SARS-CoV-2. This review discusses in brief about the COVID-19/SARS-CoV-2 with a particular focus on the role of animals, the veterinary and associated zoonotic links along with prevention and control strategies based on One-health approaches.


title: Rotavirus entry: a deep journey into the cell with several exits.

text: Rotaviruses are the leading etiological agents of acute gastroenteritis in infants and young children worldwide. These nonenveloped viruses enter cells using different types of endocytosis and, depending on the virus strain, travel to different endosomal compartments before exiting to the cytosolic space. In this Gem, we review the viral and cellular factors involved in the different stages of a productive virus cell entry and share with the readers the journey that we have taken into the cell to learn about virus entry.


title: Evolution of Flow-Diverter Endothelialization and Thrombus Organization in Giant Fusiform Aneurysms after Flow Diversion: A Histopathologic Study.

text: BACKGROUND AND PURPOSE Treatment of giant fusiform aneurysms with flow diverters has been associated with a relatively high rate of complications. Our goal was to study the evolution of flow-diverter endothelialization and thrombus organization at different time points after flow-diverter treatment in giant fusiform aneurysms to better understand reasons for flow-diverter thrombosis and delayed aneurysm ruptures. MATERIALS AND METHODS Two giant anterior and 2 posterior circulation aneurysms, all of which had partially thrombosed before treatment, were studied. An unruptured, untreated posterior circulation aneurysm was used as a control. Each specimen was removed at 7 days or at 6, 9, or 13 months after flow-diverter treatment. The 3 patients who survived longer than 7 days were followed up by angiography and MR imaging. Formaldehyde-fixed paraffin-embedded sections were stained by using H&E, Van Gieson elastic, CD34, h-Caldesmon, and Picrosirius stains and studied by light microscopy. RESULTS According to angiography, aneurysms were found to be obliterated partially at 6 and 9 months and completely at 13 months. MR imaging revealed that mass effect remained unchanged in each case. Sections of the flow diverter within the normal parent artery were covered by an endothelialized fibrous layer as early as 6 months, but there was no tissue coverage or endothelialization seen even at 13 months inside the aneurysm itself. Each treated aneurysm had a thin wall with complete lack of smooth muscle cells. No signs of thrombus organization were found at any of the time points studied. CONCLUSIONS Endothelialization of the flow diverter in giant fusiform aneurysms may not occur and thrombus organization may not be initiated inside these aneurysms for as long as 1 year, which explains delayed flow-diverter thrombosis and the possibility of delayed ruptures.