title: Next generation sequencing driven successful combined treatment with laparoscopic surgery and immunotherapy for relapsed stage IVB cervical and synchronous stage IV lung cancer.

text: BACKGROUND The treatment of patients with multiple synchronous tumors is challenging and complex. The use of next generation sequencing (NGS) may help in identification of germline mutations in genes involved in a common etiology for both tumors thus allowing a common effective therapeutic strategy. PATIENTS AND METHODS We describe the unexpected positive results obtained in a young woman with relapsed chemo-resistant stage IVB cervical and synchronous stage IV lung cancer, who underwent an interdisciplinary approach including palliative surgery with laparoscopic total pelvic exenteratio followed by a chemo-immunotherapy protocol with the anti-Programmed Death (PD)-1 antibody nivolumab plus metronomic cyclophosphamide. The treatment choice was based on tumor PD-Ligand 1 assessment and NGS analysis for the identification of potential treatment targets. Outcomes included tumor objective response and patient-centered outcomes (pain, performance status and overall quality of life). RESULTS Laparoscopic surgery obtained an immediate symptom control and allowed the early start of medical treatment. One month after combined therapy start the patient achieved a significant improvement in performance status, pain, overall Quality of life and after 3 months she resumed working. After 3 and 6 months of treatment we observed an objective dimensional and metabolic response. Currently, after 24 months (and 48 cycles of nivolumab) the patient is continuing to benefit from treatment: she is in complete remission, with good performance status and she is working and leading a self-dependent life. CONCLUSION Our study strongly affirms the efficacy of an interdisciplinary approach including surgical and innovative medical strategies based on immunotherapy in patients with advanced chemo-resistant synchronous cervical and lung cancer. The present findings support the use of NGS to drive a targeted rational treatment especially in heavily pre-treated patients.


Human bocavirus: increasing evidence for virulence.


title: Chloroquine in COVID-19: the evidence.

text: To the Editor The Coronavirus disease 2019 (COVID-19) has been declared as a pandemic by World Health Organisation (WHO). The global mortality has increased, especially in countries like Italy and Iran. With the increasing morbidity and mortality, search for a cure has been the global demand.


title: Comparison of outcomes for single-incision laparoscopic inguinal herniorrhaphy and traditional three-port laparoscopic herniorrhaphy at a single institution.

text: BACKGROUND Evidence in the literature regarding the potential of single-incision laparoscopic (SILS) inguinal herniorrhaphy currently is limited. A retrospective comparison of SILS and traditional multiport laparoscopic (MP) inguinal hernia repair was conducted to assess the safety and feasibility of the minimally invasive laparoscopic technique. METHODS All laparoscopic inguinal hernia repairs performed by three surgeons at a single institution during 4 years were reviewed. Statistical evaluation included descriptive analysis of demographics including age, gender, body mass index (BMI), and hernia location (uni- or bilateral), in addition to bivariate and multivariate analyses of surgical technique and outcomes including operative times, conversions, and complications. RESULTS The study compared 129 patients who underwent SILS inguinal hernia repair and 76 patients who underwent MP inguinal hernia repair. The cases included 190 men (92.68 %) with a mean age of 55.36 ± 18.01 years (range, 8-86 years) and a mean BMI of 26.49 ± 4.33 kg/m(2) (range, 17.3-41.7 kg/m(2)). These variables did not differ significantly between the SILS and MP cohorts. The average operative times for the SILS and MP unilateral cases were respectively 57.51 and 66.96 min. For the bilateral cases, the average operative times were 81.07 min for SILS and 81.38 min for MP. A multivariate analysis using surgical approach, BMI, case complexity, and laterality as the covariates demonstrated noninferiority of the SILS technique in terms of operative time (p = 0.031). No conversions from SILS to MP occurred, and the rates of conversion to open procedure did not differ significantly between the cohorts (p = 1.00, Fisher's exact test), nor did the complication rates (p = 0.65, χ (2)). CONCLUSIONS As shown by the findings, SILS inguinal herniorrhaphy is a safe and feasible alternative to traditional MP inguinal hernia repair and can be performed successfully with similar operative times, conversion rates, and complication rates. Prospective trials are essential to confirm equivalence in these areas and to detect differences in patient-centered outcomes.


Targeted degraders clear first safety hurdles.


title: Split-dose bowel preparation with polyethylene glycol for colonoscopy performed under propofol sedation. Is there an optimal timing?

text: OBJECTIVE Aspiration risk, especially with propofol sedation, remains a concern after split-dose bowel preparation of up to 1 L polyethylene glycol for the procedure. We aimed to identify the ideal timing of bowel preparation to achieve optimal colon cleansing with no increased risk of aspiration. METHODS A total of 892 consecutive patients undergoing simultaneous esophagogastroduodenoscopy (EGD) and colonoscopy were prospectively recruited. Residual gastric volume (RGV) and pH of gastric contents were measured at EGD, and patients' characteristics, runway time (duration between completion of the final liter of bowel preparation and colonoscopy commencement), and cleansing quality were recorded. RESULTS A shorter runway time resulted in better colon cleansing (r = -0.124, P < 0.001). No correlation between runway time and RGV or pH was found (r = -0.017, P = 0.62 and r = -0.030, P = 0.47, respectively). RGV and pH did not differ significantly with runway time of 4 or 5 h. RGV with runway time ≤3 h was 35.9 ± 11.8 mL and 17.4 ± 0.6 mL after runway time >3 h (P < 0.001). No aspiration pneumonia occurred. The only factors independently related to higher RGV were younger age and male sex. CONCLUSIONS The consumption of bowel preparation agent within 3-4 h before propofol sedation resulted in a similar RGV and pH as those achieved by more prolonged fasting, with no increased risk of aspiration even in patients perceived to be at high risk.


title: COVID-19: Generate and apply local modelled Transmission and Morbidity effects to provide an estimate of the variation in overall Relative Healthcare Resource Impact at General Practice Granularity.

text: INTRODUCTION Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the name given to the 2019 novel coronavirus. COVID-19 is the name given to the disease associated with the virus. SARS-CoV-2 is a new strain of coronavirus not been previously identified in humans. METHODS Two key factors, case incidence and case morbidity were analysed for England. When taken together they give an estimate of relative demand on healthcare utilisation. To analyse case incidence, the latest values for indicators that could be associated with infection transmission rates were collected from the Office of National Statistics (ONS) and Quality Outcome Framework (QOF) sources. These included population density, %age>16, at fulltime work/education, %age over 60, %BME ethnicity, social deprivation as IMD2019, location as latitude/longitude, and patient engagement as %self-confident in their own long-term condition management. Average case morbidity was calculated. To provide a comparative measure of overall healthcare resource impact, individual GP practice impact scores were compared against the median practice. RESULTS The case incidence regression is a dynamic situation but it currently shows that Urban, %Working and age>60 were the strongest determinants of case incidence. The local population comorbidity remains unchanged. The range of relative healthcare impact was wide with 80% of practices falling at 20%-250% of the national median. Once practice population numbers were included we found that the top 33% of GP practices supporting 45% of the patient population would require 68% of COVID-19 healthcare resources. The model provides useful information about the relative impact of Covid-19 on healthcare workload at GP practice granularity in all parts of England. CONCLUSION Covid-19 is impacting on the utilisation of health/social care resources across the world. This model provides a way of predicting relative local levels of disease burden based on defined criteria, thereby providing a method for targeting limited care resources to optimise national/regional/local responses to the COVID-19 outbreak.


title: Coronavirus nsp6 proteins generate autophagosomes from the endoplasmic reticulum via an omegasome intermediate.

text: Autophagy is a cellular response to starvation which generates autophagosomes to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy can provide an innate defence against virus infection, or conversely autophagosomes can promote infection by facilitating assembly of replicase proteins. We demonstrate that the avian coronavirus, Infectious Bronchitis Virus (IBV) activates autophagy. A screen of individual IBV non-structural proteins (nsps) showed that autophagy was activated by IBV nsp6. This property was shared with nsp6 of mammalian coronaviruses Mouse Hepatitis Virus, and Severe Acute Respiratory Syndrome Virus, and the equivalent nsp5-7 of the arterivirus Porcine Reproductive and Respiratory Syndrome Virus. These multiple-spanning transmembrane proteins located to the endoplasmic reticulum (ER) where they generated Atg5 and LC3II-positive vesicles, and vesicle formation was dependent on Atg5 and class III PI3 kinase. The vesicles recruited double FYVE-domain containing protein (DFCP) indicating localised concentration of phosphatidylinositol 3 phosphate, and therefore shared many features with omegasomes formed from the ER in response to starvation. Omegasomes induced by viral nsp6 matured into autophagosomes that delivered LC3 to lysosomes and therefore recruited and recycled the proteins needed for autophagosome nucleation, expansion, cellular trafficking and delivery of cargo to lysosomes. The coronavirus nsp6 proteins activated omegasome and autophagosome formation independently of starvation, but activation did not involve direct inhibition of mTOR signalling, activation of sirtuin1 or induction of ER stress.


title: Virus-induced translational arrest through 4EBP1/2-dependent decay of 5'-TOP mRNAs restricts viral infection.

text: The mosquito-transmitted bunyavirus, Rift Valley fever virus (RVFV), is a highly successful pathogen for which there are no vaccines or therapeutics. Translational arrest is a common antiviral strategy used by hosts. In response, RVFV inhibits two well-known antiviral pathways that attenuate translation during infection, PKR and type I IFN signaling. Despite this, translational arrest occurs during RVFV infection by unknown mechanisms. Here, we find that RVFV infection triggers the decay of core translation machinery mRNAs that possess a 5'-terminal oligopyrimidine (5'-TOP) motif in their 5'-UTR, including mRNAs encoding ribosomal proteins, which leads to a decrease in overall ribosomal protein levels. We find that the RNA decapping enzyme NUDT16 selectively degrades 5'-TOP mRNAs during RVFV infection and this decay is triggered in response to mTOR attenuation via the translational repressor 4EBP1/2 axis. Translational arrest of 5'-TOPs via 4EBP1/2 restricts RVFV replication, and this increased RNA decay results in the loss of visible RNA granules, including P bodies and stress granules. Because RVFV cap-snatches in RNA granules, the increased level of 5'-TOP mRNAs in this compartment leads to snatching of these targets, which are translationally suppressed during infection. Therefore, translation of RVFV mRNAs is compromised by multiple mechanisms during infection. Together, these data present a previously unknown mechanism for translational shutdown in response to viral infection and identify mTOR attenuation as a potential therapeutic avenue against bunyaviral infection.


Covid-19 in care homes: the many determinants of this perfect storm.


title: Rats susceptible to virus-induced asthma have a persistent virus-induced change in the predominant pulmonary form of the NF-κB inhibitor IκBα.

text: Weanling Brown Norway (BN) rats are susceptible to persistent steroid-responsive pulmonary abnormalities following resolution of an acute respiratory virus infection. In contrast, Fischer 344 (F344) rats recover without complications. Previous studies determined that NF-κB activation and subunit composition were markedly different between these 2 rat strains. This study examined whether viral infection also resulted in altered pulmonary expression of IκBα and IκBβ, 2 inhibitory regulators of NF-κB. Western blot analyses of total pulmonary protein extracted from BN and F344 rats at 7, 10, and 14 days after inoculation (n = 5 per group) did not reveal virus-induced differences in IκBβ expression. In contrast, a lower molecular weight form of IκBα appeared in the BN rats at 14 days postinfection, and it was still present at 21 days after infection (n = 5 per group). The change in IκBα expression observed in the susceptible BN but not the resistant F344 animals occurs when the epithelium is proliferating during the repair phase, and it correlates with the development of the persistent virus-induced airway inflammation and pulmonary functional abnormalities. These results further implicate differential regulation of NF-κB in the pathogenesis of virus-induced asthma.


title: Influenza virus polymerase: Functions on host range, inhibition of cellular response to infection and pathogenicity.

text: The viral polymerase is an essential complex for the influenza virus life cycle as it performs the viral RNA transcription and replication processes. To that end, the polymerase carries out a wide array of functions and associates to a large number of cellular proteins. Due to its importance, recent studies have found numerous mutations in all three polymerase protein subunits contributing to virus host range and pathogenicity. In this review, we will point out viral polymerase polymorphisms that have been associated with virus adaptation to mammalian hosts, increased viral polymerase activity and virulence. Furthermore, we will summarize the current knowledge regarding the new set of proteins expressed from the viral polymerase genes and their contribution to infection. In addition, the mechanisms used by the virus to counteract the cellular immune response in which the viral polymerase complex or its subunits are involved will be highlighted. Finally, the degradative process induced by the viral polymerase on the cellular transcription machinery and its repercussions on virus pathogenicity will be of particular interest.


title: Open versus minimally invasive esophagectomy: clinical outcomes for locally advanced esophageal adenocarcinoma.

text: BACKGROUND We compared oncologic and surgical outcome between minimally invasive esophagectomy (MIE) and the Ivor Lewis-type open approach (OE) in the treatment of locally advanced esophageal adenocarcinoma (EAC). MATERIALS AND METHODS Of 284 patients undergoing surgery for EAC between 2003 and 2013, the 153 selected with locally advanced EAC were 74 MIEs and 79 OEs [median age, 66 for MIE, 63 for OE (p = 0.009)]. Neoadjuvant therapy was given to 82% of MIEs and 78% of OEs. In the OE group, 86% was male, and in the MIE group, 78%. Data assessed were oncologic, intraoperative, and postoperative. RESULTS Mortality at 30 days was 3% for MIE and 1% for OE; and 90-day mortality was 4% for MIE and 5% for OE. The complication rate for MIE was 50%, and 60% for OE (p = 0.181). The pneumonia rate was 18% for MIE and 19% for OE; leak rate was 7% for MIE and 6% for OE; conduit necrosis was 0 for MIE and 3% for OE; and rate of airway-conduit fistula was 3% for MIE and 1 % for OE. Median blood loss (MIE 300 vs. OE 800, p < 0.0001), overall stay (MIE 13 vs. OE 14, p = 0.040), and harvested lymph nodes (MIE 20 vs. OE 22, p = 0.021) all were in favor of MIE. Median ICU stay and operative time did not differ. Neither did overall (OS) nor recurrence-free (RFS) 3-year survival differs significantly (MIE 64% vs. OS OE 49%, MIE 57% vs. RFS OE 53%). CONCLUSIONS In our institution, MIE appears to produce oncologic and survival results similar to those of OE. Shorter length of stay and less operative blood loss may reduce costs for MIE.


title: Statistical analysis plan for evaluating different intensities of blood pressure control in the ENhanced Control of Hypertension And Thrombolysis strokE stuDy.

text: BACKGROUND The ENhanced Control of Hypertension And Thrombolysis strokE study (ENCHANTED) trial was initiated as a 2 × 2 partial-factorial active-comparison, prospective, randomized, open, blinded endpoint clinical trial to evaluate in thrombolysis-eligible acute ischemic stroke (AIS) patients whether: (1) Arm A - low-dose (0.6 mg/kg body weight) intravenous (iv) alteplase has noninferior efficacy and lower risk of symptomatic intracerebral hemorrhage (sICH) compared with standard-dose (0.9 mg/kg body weight) iv alteplase; and (2) Arm B - early intensive blood pressure (BP) lowering (systolic target 130-140 mmHg) has superior efficacy and lower risk of ICH compared with guideline-recommended BP control (systolic target <180 mmHg). Arm A was completed in 2016; Arm B is now concluding. OBJECTIVE To outline in detail and make public the predetermined statistical analysis plan (SAP) for the 'BP control' arm of this study. METHODS All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be outlined, and for each item, statistically relevant descriptive elements will be described. For the trial outcomes, the most appropriate statistical comparisons to be made between groups are planned and described. RESULTS A SAP was developed for the results of the BP control arm of this study that is transparent, available to the public, verifiable, and predetermined before completion of data collection. CONCLUSIONS We have developed a predetermined SAP for the ENCHANTED BP control arm to be followed to avoid analysis bias arising from prior knowledge of the study findings. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov (NCT01422616); ISRCTN Register (ISRCTN82387104); Australian New Zealand Clinical Trial Registry (ACTRN12611000236998); EU Clinical Trials Register (2011-005545-12); and Clinical Trials Registry - India (REF/2017/05/014334).


title: New magnetic-resonance-imaging-visible poly(ε-caprolactone)-based polyester for biomedical applications.

text: A great deal of effort has been made since the 1990s to enlarge the field of magnetic resonance imaging. Better tissue contrast, more biocompatible contrast agents and the absence of any radiation for the patient are some of the many advantages of using magnetic resonance imaging (MRI) rather than X-ray technology. But implantable medical devices cannot be visualized by conventional MRI and a tool therefore needs to be developed to rectify this. The synthesis of a new MRI-visible degradable polymer is described by grafting an MR contrast agent (DTPA-Gd) to a non-water-soluble, biocompatible and degradable poly(ε-caprolactone) (PCL). The substitution degree, calculated by (1)H nuclear magnetic resonance and inductively coupled plasma-mass spectrometry, is close to 0.5% and proves to be sufficient to provide a strong and clear T1 contrast enhancement. This new MRI-visible polymer was coated onto a commercial mesh for tissue reinforcement using an airbrush system and enabled in vitro MR visualization of the mesh for at least 1 year. A stability study of the DTPA-Gd-PCL chelate in phosphate-buffered saline showed that a very low amount of gadolinium was released into the medium over 52 weeks, guaranteeing the safety of the device. This study shows that this new MRI-visible polymer has great potential for the MR visualization of implantable medical devices and therefore the post-operative management of patients.


title: Zenker's diverticulum: flexible versus rigid repair.

text: Zenker's diverticula (ZDs) are a relatively common cause of cervical dysphagia. Diagnosis is best by a good upper GI exam though upper endoscopy should be performed as well. Treatment is either by open, transcervical approaches or trans-oral. Over the past 20 years, transoral approach has mostly replace transcervical approaches due to less pain, no scarring and a rapid recovery. Transoral approaches are either using rigid access or flexible endoscopy. Today, the most common approach is transoral stapling using a 12 mm laparoscopic linear cutting stapler. This has the drawbacks of requiring extreme neck extension, the massive size of the stapler making visualization mostly impossible and the current staple design that does not cut/staple all the way to the end of the blades-resulting in a residual pouch. Flexible endoscopy allows a more tailored approach under direct vision, the myotomy can even be extended beyond the diverticulum and onto the esophageal wall to minimize the risk of incomplete myotomy. Experienced endoscopists report high technical success and low complication. Success rates are similar but maybe slightly higher than with ridged transoral approaches or open surgery. Today, flexible endoscopic Zenkers is our preferred initial approach-with open or ridged being reserved for special indications.


Advanced hemodynamic monitoring in the critically ill patient: Nice to have or need to treat?


title: Structural and functional analysis of intra-articular interzone tissue in axolotl salamanders.

text: OBJECTIVE Knowledge of mechanisms directing diarthrodial joint development may be useful in understanding joint pathologies and identifying new therapies. We have previously established that axolotl salamanders can fully repair large articular cartilage lesions, which may be due to the presence of an interzone-like tissue in the intra-articular space. Study objectives were to further characterize axolotl diarthrodial joint structure and determine the differentiation potential of interzone-like tissue in a skeletal microenvironment. DESIGN Diarthrodial joint morphology and expression of aggrecan, brother of CDO (BOC), type I collagen, type II collagen, and growth/differentiation factor 5 (GDF5) were examined in femorotibial joints of sexually mature (>12 months) axolotls. Joint tissue cellularity was evaluated in individuals from 2 to 24 months of age. Chondrogenic potential of the interzone was evaluated by placing interzone-like tissue into 4 mm tibial defects. RESULTS Cavitation reached completion in the femoroacetabular and humeroradial joints, but an interzone-like tissue was retained in the intra-articular space of distal limb joints. Joint tissue cellularity decreased to 7 months of age and then remained stable. Gene expression patterns of joint markers are broadly similar in developing mammals and mature axolotls. When interzone-like tissue was transplanted into critical size skeletal defects, an accessory joint developed within the defect site. CONCLUSIONS These experiments indicate that mature axolotl diarthrodial joints are phenotypically similar to developing synovial joints in mammals. Generation of an accessory joint by interzone-like tissue suggests multipotent cellular differentiation potential similar to that of interzone cells in the mammalian fetus. The data support the axolotl as a novel vertebrate model for joint development and repair.


Can Covid Catalyze an Educational Transformation? Competency-Based Advancement in a Crisis.


title: Trainees' perspectives of assessment messages: a narrative systematic review.

text: OBJECTIVES This study was designed as a narrative systematic literature review of medical specialist trainees' perspectives of the assessment messages they receive in the context of clinical performance assessments. The aim of the study was to determine if trainees value the information they receive through the formats designed to promote their development and, if not, the reasons for this. METHODS The authors searched the ERIC, EMBASE, Ovid MEDLINE and PsycINFO databases for articles published up to 16 June 2018 that present original data on trainees' perspectives of the assessment messages they receive in the context of work-based assessments (WBAs) and in-training assessments (ITAs) used within their training programmes. All authors screened 938 abstracts and 139 full-text articles were assessed after this. Descriptions of quantitative data and thematic analysis of qualitative data were used to present the opinions of trainees. RESULTS Thirty-three articles met the inclusion criteria. Twenty-six articles (79%) described trainees' perspectives in the context of WBA and the remaining articles referred to ITA formats. Wide-ranging opinions were reported. The analysis categorised these into three themes: trainees value developmental assessment messages; trainees become disengaged when assessment messages are not developmental, and trainees' views depend on the environment, the assessor and themselves. Some trainees reported that the assessment messages were valuable and provided input on their performance to guide their development, but many disagreed. In particular, the trainee's own level of engagement with the assessments influenced his or her perspectives on the messages received. CONCLUSIONS Trainees do not universally perceive that clinical performance assessments provide them with the valuable developmental input on their performance they were designed to do. Factors related to the environment, the assessor and themselves influence their perspectives.


title: Severe COVID-19 in a pregnant patient admitted to hospital in Wuhan.

text: In December 2019, an outbreak of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, Hubei Province, China. This virus strain causes the respiratory illness coronavirus disease 2019 (COVID-19). Despite significant research efforts in this field, there is limited data on COVID-19 in pregnancy. This article presents a case of a pregnant woman from Wuhan infected with SARS-CoV-2, including her symptoms, pregnancy outcome, and treatment strategy.


title: Natural Orifice Trans-Luminal Endoscopic Surgery in the esophagus.

text: As limited as are the studies regarding peritoneal Natural Orifice Trans-Luminal Endoscopic Surgery, mediastinal transluminal experiments are certainly in their infancy. The authors evaluate the parallel development of minimally invasive thoracic surgery with regard to its counterpart in peritoneal laparoscopy to NOTES. Transesophageal interventions by both endosonographic and direct visualization are examined in the context of minimally invasive surgery and mediastinal NOTES. Techniques of viscerotomy creation, visualization, and closure are examined with particular emphasis on mediastinal structures. The state of current interventions is examined. Finally, current morbidity (including infectious complications) and survival outcomes are examined in those animals that have undergone transesophageal exploration.


title: Producing Independent, Systematic Review Evidence: Cochrane's Response to COVID-19.

text: Bad advice can lead to tragedy, such as death from taking an unproven medication.1 Now, more than ever, public health policies should be based on the best available evidence. Consumers, clinicians, and policymakers need balanced information that is free of commercial influence to make decisions about the best ways to prevent the spread and manage the symptoms and clinical consequences of COVID-19. The benefits and harms of each decision must be considered. Public health measures such as isolation, quarantine, and social distancing have fundamentally changed the way we live. (Am J Public Health. Published online ahead of print May 14, 2020: e1-e2. doi:10.2105/AJPH.2020.305734).


title: Bovine ephemeral fever rhabdovirus α1 protein has viroporin-like properties and binds importin β1 and importin 7.

text: Bovine ephemeral fever virus (BEFV) is an arthropod-borne rhabdovirus that is classified as the type species of the genus Ephemerovirus. In addition to the five canonical rhabdovirus structural proteins (N, P, M, G, and L), the large and complex BEFV genome contains several open reading frames (ORFs) between the G and L genes (α1, α2/α3, β, and γ) encoding proteins of unknown function. We show that the 10.5-kDa BEFV α1 protein is expressed in infected cells and, consistent with previous predictions based on its structure, has the properties of a viroporin. Expression of a BEFV α1-maltose binding protein (MBP) fusion protein in Escherichia coli was observed to inhibit cell growth and increase membrane permeability to hygromycin B. Increased membrane permeability was also observed in BEFV-infected mammalian cells (but not cells infected with an α1-deficient BEFV strain) and in cells expressing a BEFV α1-green fluorescent protein (GFP) fusion protein, which was shown by confocal microscopy to localize to the Golgi complex. Furthermore, the predicted C-terminal cytoplasmic domain of α1, which contains a strong nuclear localization signal (NLS), was translocated to the nucleus when expressed independently, and in an affinity chromatography assay employing a GFP trap, the full-length α1 was observed to interact specifically with importin β1 and importin 7 but not with importin α3. These data suggest that, in addition to its function as a viroporin, BEFV α1 may modulate components of nuclear trafficking pathways, but the specific role thereof remains unclear. Although rhabdovirus accessory genes occur commonly among arthropod-borne rhabdoviruses, little is known of their functions. Here, we demonstrate that the BEFV α1 ORF encodes a protein which has the structural and functional characteristics of a viroporin. We show that α1 localizes in the Golgi complex and increases cellular permeability. We also show that BEFV α1 binds importin β1 and importin 7, suggesting that it may have a yet unknown role in modulating nuclear trafficking. This is the first functional analysis of an ephemerovirus accessory protein and of a rhabdovirus viroporin.


title: [Analysis of application of herd immunity as a control strategy for COVID-19].

text: Novel coronavirus spreads very fast and is not easy to control. It has spread over 200 countries or territories. China has taken action to implement containment strategies, including active COVID-19 case finding, tracing, and 14-day quarantine of close contacts, and home isolation of 1.39 billion of people countywide for at least 2 weeks, etc. The combination of these strategies has brought the epidemic under control in China. The United Kingdom had deliberately not implemented containment measures for a while, instead opting to allow herd immunity strategy to develop over time. This is a "do-nothing" strategy whereby the virus is allowed to move through communities naturally until certain proportion of people has been infected, and the epidemic ends without intervention. The author assesses containment strategies versus this herd immunity strategy in real-world application to the COVID-19 epidemic. The author suggests an innovative strategy to balance controlling the epidemic and preventing impediment to economic and social development.


title: Incidence, Patterns, and Associations Between Dual-Antiplatelet Therapy Cessation and Risk for Adverse Events Among Patients With and Without Diabetes Mellitus Receiving Drug-Eluting Stents: Results From the PARIS Registry.

text: OBJECTIVES The aim of this study was to examine the frequency and clinical impact of different cessation patterns of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents among patients with and those without diabetes mellitus (DM). BACKGROUND Early DAPT suspension after percutaneous coronary intervention increases the risk for major adverse cardiac events. However, temporal variability in risk and relation to DAPT cessation patterns among patients with DM remain unclear. METHODS Using data from the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients) registry, 1,430 patients with DM (34%) and 2,777 without DM (66%) treated with drug-eluting stents were identified. DAPT cessation modes were classified as temporary interruption (<14 days), disruption because of bleeding or poor compliance, and physician-recommended discontinuation. RESULTS During 2-year follow-up, DM was associated with an increased risk for thrombotic events but a similar risk for bleeding. The cumulative incidence of DAPT cessation was significantly lower in patients with versus those without DM (50.1% vs. 55.4%; p < 0.01), driven largely by less frequent physician-guided discontinuation beyond 1 year. In contrast, 2-year rates of interruption and disruption were similar between groups. When DAPT was interrupted or discontinued under physician guidance, the risk for major adverse cardiac events was unchanged compared with patients with DM on uninterrupted DAPT. Conversely, when DAPT was disrupted, the risk for major adverse cardiac events increased compared with uninterrupted DAPT, regardless of diabetic status, with no evidence of statistical interaction. CONCLUSIONS DAPT cessation patterns vary according to diabetic status, with less frequent physician-guided discontinuation among patients with DM. The presence of DM does not emerge as a modifier of cardiovascular risk after DAPT cessation.


title: Rapid generation of a mouse model for Middle East respiratory syndrome.

text: In this era of continued emergence of zoonotic virus infections, the rapid development of rodent models represents a critical barrier to public health preparedness, including the testing of antivirus therapy and vaccines. The Middle East respiratory syndrome coronavirus (MERS-CoV) was recently identified as the causative agent of a severe pneumonia. Given the ability of coronavirus to rapidly adapt to new hosts, a major public health concern is that MERS-CoV will further adapt to replication in humans, triggering a pandemic. No small-animal model for this infection is currently available, but studies suggest that virus entry factors can confer virus susceptibility. Here, we show that mice were sensitized to MERS-CoV infection by prior transduction with adenoviral vectors expressing the human host-cell receptor dipeptidyl peptidase 4. Mice developed a pneumonia characterized by extensive inflammatory-cell infiltration with virus clearance occurring 6-8 d after infection. Clinical disease and histopathological changes were more severe in the absence of type-I IFN signaling whereas the T-cell response was required for virus clearance. Using these mice, we demonstrated the efficacy of a therapeutic intervention (poly I:C) and a potential vaccine [Venezuelan equine encephalitis replicon particles expressing MERS-CoV spike protein]. We also found little protective cross-reactivity between MERS-CoV and the severe acute respiratory syndrome-CoV. Our results demonstrate that this system will be useful for MERS-CoV studies and for the rapid development of relevant animal models for emerging respiratory viral infections.


title: Advances in Detection of Infectious Agents by Aptamer-based Technologies.

text: Infectious diseases still remain one of the biggest challenges for human health. Accurate and early detection of infectious pathogens are crucial for transmission control, clinical diagnosis and therapy. For a traditional reason, most immunological and microbiological laboratories are equipped with instruments designated for antibody-based assays in detection of infectious pathogens or clinical diagnosis. Emerging aptamer-based technologies have pushed a shift from antibody-based to aptamer-based assays due to equal specificity, even better sensitivity, lower manufacturing cost and more flexibility in amending for chemiluminescent, electrochemical or fluorescent detection in a multifaceted and high throughput fashion in comparison of aptamer-based to antibody-based assays. The nature of aptamer-based technologies is particularly suitable for point-of-care testing in remote areas at warm or hot atmosphere, and mass screening for potential infection in pandemic of emerging infectious agents, such as SARS-CoV or SARS-CoV-2 in an epicenter or other regions. This review intends to summarize currently available aptamer-based technologies in detection of bacterial, viral and protozoan pathogens for research and clinical application. It is anticipated that potential technologies will be further optimized and validated for clinical translation in meeting increasing demands for prompt, precise and reliable detection of specific pathogens in various atmospheric conditions.


title: Safety and Efficacy of Laparoscopic Radiofrequency Ablation for Hepatic Hemangiomas: A Multicenter Retrospective Study.

text: INTRODUCTION Radiofrequency ablation (RFA) is an effective and minimally invasive technique for the management of hepatic hemangiomas (HHs). This study aims to assess the safety and efficacy of laparoscopic RFA for HHs. MATERIAL AND METHODS Forty-four patients with 50 hepatic hemangiomas (5-10 cm in diameter) undergoing laparoscopic RFA from January 2012 to May 2015 at three tertiary hospitals in China were retrospectively analyzed. RESULTS Thirty-three patients with subcapsular hemangiomas were treated with a laparoscopic approach, and 11 patients with lesions in the liver parenchyma were treated with a combined laparoscopy and an ultrasound-guided percutaneous approach. No conversion to open surgery or two-step surgery occurred during the study period. Patients with small hemangiomas (< 7 cm) required a significantly shorter operating time (71.1 ± 20.18 min vs. 106 ± 23.55 min, p = 0.000) and fewer punctures compared with patients with large hemangiomas (> 7 cm) (4.61 ± 1.09 vs. 6.73 ±1.01, P < 0.05). According to the Dindo-Clavien classification, 15 patients experienced 34 Grade 1 complications, and two had complications of Grade 3a. All complications were resolved by conservative treatment. Forty-three (86.0%) HHs in 38 patients were completely ablated after RFA, and 7 (14.0%) HHs in 6 patients were incompletely ablated. All patients were followed up for 6-24 months (mean 15 ± 6 months). CONCLUSION The data showed that laparoscopic RFA is an effective treatment for small (< 10 cm) HHs. While the incidence of postoperative complications remains high, the majority of complications are minor. Patients undergoing laparoscopic RFA for HHs, even for the small ones, should be carefully selected.


Reflections on ethical challenges associated with the Ebola epidemic.


title: Radiofrequency ablation for hepatocellular carcinoma measuring 2 cm or smaller: results and risk factors for local recurrence.

text: OBJECTIVE The purpose of this study was to evaluate the risk factors for local recurrence with radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) measuring ≤2 cm. METHODS This study involved 234 patients with 274 HCCs measuring ≤2 cm who had undergone RFA as the initial treatment. The mean tumor diameter was 1.478 cm. The median follow-up period was 829 days. We evaluated the post-RFA cumulative local recurrence rate and analyzed the risk factors contributing to clinical outcomes. RESULTS Cumulative local recurrence rates were 9, 19 and 19% at 1, 2 and 3 years, respectively. Among the 145 cases with a complete safety margin (SM) after RFA, only 4 developed local tumor recurrence and the cumulative rates of local tumor recurrence at 1, 2 and 3 years were 2, 3 and 3%, respectively. Among the 129 cases with incomplete SM, local tumor recurrence developed in 34 and the cumulative rates of local tumor progression at 1, 2 and 3 years were 14, 36 and 36%, respectively. In multivariate analysis, significant risk factors were tumor location (liver surface), irregular gross type and SM <5 mm. CONCLUSION Even with HCC measuring ≤2 cm, location and gross type of tumor should be carefully evaluated before RFA is performed.


Coronavirus puts drug repurposing on the fast track.


title: A Naturally Occurring Recombinant Enterovirus Expresses a Torovirus Deubiquitinase.

text: Enteroviruses (EVs) are implicated in a wide range of diseases in humans and animals. In this study, a novel enterovirus (enterovirus species G [EVG]) (EVG 08/NC_USA/2015) was isolated from a diagnostic sample from a neonatal pig diarrhea case and identified by using metagenomics and complete genome sequencing. The viral genome shares 75.4% nucleotide identity with a prototypic EVG strain (PEV9 UKG/410/73). Remarkably, a 582-nucleotide insertion, flanked by 3Cpro cleavage sites at the 5' and 3' ends, was found in the 2C/3A junction region of the viral genome. This insertion encodes a predicted protease with 54 to 68% amino acid identity to torovirus (ToV) papain-like protease (PLP) (ToV-PLP). Structural homology modeling predicts that this protease adopts a fold and a catalytic site characteristic of minimal PLP catalytic domains. This structure is similar to those of core catalytic domains of the foot-and-mouth disease virus leader protease and coronavirus PLPs, which act as deubiquitinating and deISGylating (interferon [IFN]-stimulated gene 15 [ISG15]-removing) enzymes on host cell substrates. Importantly, the recombinant ToV-PLP protein derived from this novel enterovirus also showed strong deubiquitination and deISGylation activities and demonstrated the ability to suppress IFN-β expression. Using reverse genetics, we generated a ToV-PLP knockout recombinant virus. Compared to the wild-type virus, the ToV-PLP knockout mutant virus showed impaired growth and induced higher expression levels of innate immune genes in infected cells. These results suggest that ToV-PLP functions as an innate immune antagonist; enterovirus G may therefore gain fitness through the acquisition of ToV-PLP from a recombination event.IMPORTANCE Enteroviruses comprise a highly diversified group of viruses. Genetic recombination has been considered a driving force for viral evolution; however, recombination between viruses from two different orders is a rare event. In this study, we identified a special case of cross-order recombination between enterovirus G (order Picornavirales) and torovirus (order Nidovirales). This naturally occurring recombination event may have broad implications for other picornaviral and/or nidoviral species. Importantly, we demonstrated that the exogenous ToV-PLP gene that was inserted into the EVG genome encodes a deubiquitinase/deISGylase and potentially suppresses host cellular innate immune responses. Our results provide insights into how a gain of function through genetic recombination, in particular cross-order recombination, may improve the ability of a virus to evade host immunity.


title: Outcomes of laparoscopic Roux-en-Y gastric bypass versus laparoscopic adjustable gastric banding in adolescents.

text: BACKGROUND The goal of this study is to compare the outcomes of laparoscopic adjustable gastric banding (LAGB) and laparoscopic Roux-en-Y gastric bypass (LRYGB) in obese adolescents. METHODS We performed a retrospective review of all adolescents between the ages of 15 and 19 who underwent LAGB or LRYGB at our university affiliated Bariatric Center of Excellence from 2002 to 2011. Postsurgical weight loss at 1, 3, 6, 12, 18, and 24 months was noted and expressed as percentage of excess weight loss (% EWL). RESULTS Thirty-two patients underwent LRYGB and 23 underwent LAGB. The LAGB group was younger (18.6 ± 0.6 versus 17.2 ± 1.5) than the LRYGB group. Other preoperative demographic factors including body mass index, gender, ethnicity, and comorbidities were similar between the two groups. The average % EWL was superior in the LRYGB group compared to the LAGB group at all time points studied (p < 0.05), although at 2-year follow-up, only 16% (5/32) LRYGB and 30% (7/23) LAGB patients were available for follow-up. Three patients with type II diabetes mellitus underwent LRYGB and all experienced remission of their diabetes. The number of complications requiring interventions was similar between the two groups. CONCLUSIONS In our study, adolescents undergoing LRYGB achieved superior weight loss compared to LAGB in the short-term follow-up. The complication rate for LAGB was similar compared to LRYGB. More studies are needed to monitor the long-term effects of these operations on adolescents before definitive recommendations can be made.


title: Performance of portable ventilators at altitude.

text: BACKGROUND Aeromedical transport of critically ill patients requires continued, accurate performance of equipment at altitude. Changes in barometric pressure can affect the performance of mechanical ventilators calibrated for operation at sea level. Deploying ventilators that can maintain a consistent tidal volume (VT) delivery at various altitudes is imperative for lung protection when transporting wounded war fighters to each echelon of care. METHODS Three ventilators (Impact 731, Hamilton T1, and CareFusion Revel) were tested at pediatric (50 and 100 mL) and adult (250-750 mL) tidal VTs at 0 and 20 cm H₂O positive end expiratory pressure and at inspired oxygen of 0.21 and 1.0. Airway pressure, volume, and flow were measured at sea level as well as at 8,000, 16,000, and 22,000 ft (corresponding to barometric pressures of 760, 564, 412, and 321 mm Hg) using a calibrated pneumotachograph connected to a training test lung in an altitude chamber. Set VT and delivered VT as well as changes in VT at each altitude were compared by t test. RESULTS The T1 delivered VT within 10% of set VT at 8,000 ft. The mean VT was less than set VT at sea level as a result of circuit compressible volume with the Revel and the 731. Changes in VT varied widely among the devices at sea level and at altitude. Increasing altitudes resulted in larger VT than set for the Revel and the T1. The 731 compensated for changes in altitude delivered VT within 10% at the adult settings at all altitudes. CONCLUSION Altitude compensation is an active software algorithm. Only the 731 actively accounts for changes in barometric pressure to maintain the set VT at all tested altitudes.


title: Ablation for hepatocellular carcinoma: validating the 3-cm breakpoint.

text: BACKGROUND Although many previous studies on local ablation outcomes for hepatocellular carcinoma (HCC) have dichotomized tumor size with a 3-cm cutoff to determine prognostic significance, a growing number of reports describe excellent outcomes for larger tumors. To address the logic of this 3-cm cutoff beyond small single-center experiences, we stratified patients by 1-cm tumor size intervals and hypothesized that disease-specific survival (DSS) would not vary significantly between adjacent groups. METHODS Patients treated with local ablation for T1 HCC (≤8 cm) were identified from the surveillance, epidemiology, and end results database (2004-2008). Log-rank tests and multivariable Cox proportional hazards models were used to compare DSS curves of adjacent study groups. RESULTS There were 1,083 patients included in the study (26 % female, median age: 62 years). The 3-year DSS was significantly lower in patients with 3- to 4-cm tumors compared to 2- to 3-cm tumors (58 vs. 72 %, p = 0.002). In adjusted models, DSS did not vary significantly between any size intervals up to 3 cm. Patients with 3- to 4-cm tumors, however, had a poorer prognosis compared with patients with 2- to 3-cm tumors (hazard ratio: 1.6, 95 % confidence interval: 1.18-2.18, p = 0.002). DSS also fell when tumor size increased from 5-6 to 6-7 cm (53 vs. 21 %, 0.006). CONCLUSIONS This study emphasizes the 3-cm size, and possibly the 6-cm size, as informative predictive thresholds when ablating HCC, because variability of DSS occurred specifically at these tumor sizes. Future research in this field should either adopt a 3-cm breakpoint or provide evidence for alternative thresholds.


docid: sydcbalt

title: Modeling bimodal vessel effects on radio and microwave frequency ablation zones.

text: A bench liver model is presented that separates the thermal and electrical effects of large blood vessels within radio and microwave frequency ablation boundaries. The model includes a cylindrical tissue environment with a 5 mm vessel placed parallel to and 15 mm way from either a Covidien Energy-based Devices Evident MW Ablation Percutaneous Antenna or a CoolTip RF Ablation Single Electrode Kit. An array of fiber optic thermal probes is used to monitor radial temperature profile on the vessel and non-vessel sides of the ablation zone. Circulating blood exhibits higher electrical conductivity than surrounding liver tissue and provides a significant means for transport of thermal energy. Data from the thermal probes indicate key performance differentiators between MW and RF ablation modalities when they are used next to large blood vessels clarifying the difference between thermal and electrical energy sink. The results suggest RFA is susceptible to both the thermal and electrical energy sink effects of large vasculature while MWA is only susceptible to thermal sink. Ablation zone boundaries were distorted on both the vessel and non-vessel sides with RFA whereas with MWA only the vessel side is affected.


title: Laparoscopic treatment of duodenal injury caused by gunshot.

text: Duodenal injury in most cases, presents as a complex trauma of all adjacent organs which it is generally treated with a midline laparotomy though laparoscopic treatment in selected cases might be beneficial. We present a case of haemodynamically stable patient who suffered abdominal gunshot injury causing grade II trauma of the liver and penetrating wound of the first part of the duodenum and was treated laparoscopically. We believe that laparoscopic primary or assisted repair of injured duodenum is an appropriate surgical option in haemodynamically stable patients who sustain focal abdominal trauma.


title: Care of newborns born to mothers with COVID-19 infection; a review of existing evidence.

text: Background: The novel Coronavirus disease 2019 (COVID-19) pandemic is already wreaking havoc on families and communities' welfare. It is critical to discuss newborn care of infected mothers with COVID-19 based on the latest international guidelines and national guidelines of countries with the highest incidence of COVID-19 cases.Objective: We discuss how to care for a newborn of a suspected or infected mother with COVID-19 using existing evidence.Method: As of 16 April 2020, we reviewed articles and guidelines related to COVID-19 in the reproductive health field, mother, and newborn health. Our review yielded in 10 categories (i) the risk of diagnostic procedures in suspected mothers on fetus/infant health, (ii) the risk of intrauterine or postpartum transmission to the fetus/infant, (iii) appropriate method and delivery time in women with confirmed COVID-19, (iv) umbilical cord clamping and skin to skin contact, (v) clinical manifestations of infected infants, (vi) confirmation of infection in a suspected neonate/infant, (vii) instructions for infant's care and how to feed her/him, (viii) bathing the baby, (ix) the criteria of discharging baby from the hospital, (x) the impact of isolation on the maternal mental health.Results: Our findings showed that the possibility of intrauterine or perinatal transmission of COVID-19 is still questionable and ambiguous. However, what has been agreed upon in the existing texts and guidelines is that the close contact of mother and infant after birth can transmit the virus to the baby through droplets or micro-droplets.Conclusions: Based on our findings, it is recommended to separate the baby from the mother with confirmed (or suspected) COVID-19 infection for at least 2 weeks. Since the motivation and stable situation of mothers allow breastfeeding during the isolation, infected mothers should be taught about breast expression skills, common breast problems, the symptoms of their baby's infection, and the principles of personal hygiene to protect the infant against COVID-19 infection.


title: Avoiding airway obstruction after pediatric adenotonsillectomy.

text: OBJECTIVE To evaluate the efficacy of a protocol designed to prevent post-adenotonsillectomy airway obstruction in small children with obstructive sleep apnea. DESIGN Computerized retrospective review of single surgeon case series. SETTING Tertiary children's medical center. METHODS Children with sleep study proven obstructive sleep apnea or children under the age of 3 years with clinically suspected obstructive sleep apnea were treated according to a protocol that included: (1) rapid bloodless tonsillectomy; (2) repeated release of the tonsillar retractor; (3) avoidance of uvular edema; (4) routine intra-operative intranasal oxymetazoline, and placement of nasal airway; (5) extended recovery room observation. Primary outcome measures were (1) avoidance of unexpected intensive care unit admission; (2) post-extubation pulmonary edema; (3) aspiration pneumonia. RESULTS During the period March 2004-August 2007, 864 children underwent adenotonsillectomy by a single surgeon-604 for the indication of obstructive sleep apnea or adenotonsillar hypertrophy with obstruction. Two hundred and ten were under the age of 3 years or had sleep study proven obstructive sleep apnea. There were two unexpected admissions to the pediatric intensive care unit for persistent upper airway obstruction-none required intubation. No child developed post-obstructive pulmonary edema. Three children were treated for infiltrates consistent with aspiration pneumonitis. CONCLUSION Most cases of post-extubation pulmonary edema and pneumonia can be avoided in young children and those with mild-to-moderate obstructive sleep apnea following a protocol that anticipates and avoids precipitating causes of upper airway obstruction.


Surgery in the COVID-19 Phase 2 Italian scenario: lessons learned in Northern Italy spoke hospitals.


title: Quantitative reverse transcriptase real-time polymerase chain reaction (qRT-PCR) in translational oncology: lung cancer perspective.

text: Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) is rapidly becoming a basic method in lung cancer research. Analysis of transcriptional activity of tumor cells or detection of tumor markers by this technique has the potential to change lung cancer diagnosis and treatment. Quantitative RT-PCR is characterized by unparalleled sensitivity and specificity, with very reliable reproducibility. Its prime advantage for gene expression analysis is its broad dynamic range of 10(7)-fold. Moreover, it is cost-effective, feasible in every day laboratory routine and efficient in terms of biological material consumption. Still, there are a number of methodological aspects that need to be carefully considered before it can sensibly be implemented into clinical practice. Three major technical issues: the choice of chemistries, gene expression data normalization and statistical processing of the results will be specifically highlighted in this review. Further, clinical applications of qRT-PCR will be thoroughly discussed: detection and staging of lung cancer and construction and validation of prognostic and predictive gene expression signatures.


title: The Anesthetic Challenges of Lung Biopsy-Associated Intrathoracic Hemorrhage in a Child With Suprasystemic Pulmonary Hypertension.

text: Children with suspected pulmonary hypertension must undergo extensive and invasive evaluations to establish a definitive diagnosis. A previously healthy 4-year old girl, newly diagnosed with suprasystemic pulmonary hypertension required multiple lung biopsies. Each procedure was associated with significant bleeding. The challenging anesthetic management of lung biopsy in the presence of suprasystemic pulmonary hypertension is described.


title: Energy Status and Body Composition Across a Collegiate Women's Lacrosse Season.

text: Little data is available regarding the energy and nutritional status of female collegiate team sport athletes. Twenty female NCAA Division II lacrosse athletes (mean ± SD: 20.4 ± 1.8 years; 68.8 ± 8.9 kg; 168.4 ± 6.6 cm; 27.9 ± 3% body fat) recorded dietary intake and wore a physical activity monitor over four consecutive days at five different time points (20 days total) during one academic year. Body composition, bone health, and resting metabolic rate were assessed in conjunction with wearing the monitor during off-season, pre-season, and season-play. Body fat percentage decreased slightly during the course of this study (p = 0.037). Total daily energy expenditure (TDEE) (p < 0.001) and activity energy expenditure (AEE) (p = 0.001) energy were found to change significantly over the course of the year, with pre-season training resulting in the highest energy expenditures (TDEE: 2789 ± 391 kcal/day; AEE: 1001 ± 267 kcal/day). Caloric (2124 ± 448 kcal/day), carbohydrate (3.6 ± 1.1 g/kg), and protein (1.2 ± 0.3 g/kg) intake did not change over the course of the year (p > 0.05). Athletes self-reported a moderate negative energy balance (366⁻719 kcal/day) and low energy availability (22.9⁻30.4 kcal/kg FFM) at each measurement period throughout the study. Reported caloric and macronutrient intake was low given the recorded energy expenditure and macronutrient intake recommendations for athletes. Athletic support staff should provide athletes with appropriate fueling strategies, particularly during pre-season training, to adequately meet energy demands.


docid: gkdtxjee

title: The race to unravel the United States' biggest coronavirus outbreak.


title: Experience with Hydroxychloroquine and Azithromycin in the COVID-19 Pandemic: Implications for QT Interval Monitoring.

text: Background Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected COVID-19. Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods and Results We performed a case series of COVID-19 positive/suspected patients admitted between 2/1/2020 and 4/4/2020 who were treated with azithromycin, hydroxychloroquine, or a combination. We evaluated baseline and post-medication QT interval (QTc, Bazett's) using 12-lead ECGs. Critical QTc prolongation was defined as: a) maximum QTc ≥500 ms (if QRS <120 ms) or QTc ≥550 ms (if QRS ≥120 ms) and b) increased QTc of ≥60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Of 490 COVID-19 positive/suspected patients, 314 (64%) received either/both drugs, and 98 (73 COVID-19 positive, 25 suspected) met study criteria (age 62±17 yrs, 61% male). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448±29 ms and increased to 459±36 ms (p=0.005) with medications. Significant prolongation was observed only in men (18±43 ms vs -0.2±28 ms in women, p=0.02). 12% of patients reached critical QTc prolongation. Changes in QTc were highest with the combination compared to either drug, with much greater prolongation with combination vs. azithromycin (17±39 vs. 0.5±40 ms, p=0.07). No patients manifested torsades de pointes. Conclusions Overall 12% of patients manifested critical QTc prolongation, and the combination caused greater prolongation than either drug alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients should be carefully assessed.


title: Role of embolization in the treatment of renal masses.

text: Renal arterial embolization (RAE) performed for the treatment of renal masses has been proven to be a safe and effective technique, with several decades of experience. RAE is well tolerated with few complications, particularly if the time interval from embolization to surgery is reduced to less than 48 hours. Review of the literature suggests that RAE is also extremely effective for palliation of symptoms in the setting of nonoperative advanced stage renal cell carcinoma. In addition, this technique plays a large role in the management of angiomyolipomas that are symptomatic or at risk of spontaneous rupture. To date, RAE has not been evaluated in a randomized controlled setting, which has contributed to its underutilization. All of these potential benefits warrant the need for prospective studies for further validation.


title: Indications for use and cost-effectiveness of pathogen-reduced ABO-universal plasma.

text: PURPOSE OF REVIEW Donor selection and viral screening methods combined with pathogen reduction have increased the safety of pooled plasma to a level which makes reintroduction of ABO-universal plasma an important option. RECENT FINDINGS Solvent detergent-treated pooled plasma has proved to be well suited for the production of pathogen-reduced ABO-universal plasma. One such product, Bioplasma FDP, was licensed in South Africa in 1994 and has since 1996 been in successful clinical use. A clinical study with this product and two studies with the European product, Uniplas, have confirmed the efficacy and safety of pathogen-reduced ABO-universal plasma. SUMMARY Pooling of plasma enables the production of ABO-universal plasma. Pathogen reduction with solvent detergent eliminates lipid-enveloped viruses, whereas neutralizing antibodies in the plasma pool and nucleic acid amplification testing ensures the safety for recognized nonlipid-enveloped viruses. Pooling also eliminates transfusion-associated acute lung injury (the leading cause of plasma transfusion-related death), reduces immunologic/allergic adverse events by 60-80% and standardizes plasma protein content. Thus, in addition to ABO compatibility, pathogen-reduced ABO-universal plasma has important supplementary benefits that improve the product's cost-effectiveness.


title: Simulation with standardized patients to prepare undergraduate nursing students for mental health clinical practice: An integrative literature review.

text: OBJECTIVE To evaluate the available evidence supporting the efficacy of using simulation with standardized patients to prepare nursing students for mental health clinical practice. DESIGN Integrative literature review. DATA SOURCES A systematic search of the electronic databases CINAHL (EBSCOhost), Embase, MEDLINE, PsycINFO, and SveMed+ was conducted to identify empirical studies published until November 2016. Multiple search terms were used. Original empirical studies published in English and exploring undergraduate nursing students' experiences of simulation with standardized patients as preparation for mental health nursing practice were included. A search of reference lists and gray literature was also conducted. In total, 1677 studies were retrieved; the full texts of 78 were screened by 2 of the authors, and 6 studies reminded in the review. REVIEW METHODS The authors independently reviewed the studies in three stages by screening the titles, abstracts, and full texts, and the quality of the included studies was assessed in the final stage. Design-specific checklists were used for quality appraisal. The thematic synthesizing method was used to summarize the findings of the included studies. RESULTS The studies used four different research designs, both qualitative and quantitative. All studies scored fairly low in the quality appraisal. The five themes identified were enhanced confidence, clinical skills, anxiety regarding the unknown, demystification, and self-awareness. CONCLUSIONS The findings of this study indicate that simulation with standardized patients could decrease students' anxiety level, shatter pre-assumptions, and increase self-confidence and self-awareness before entering clinical practice in mental health. More high-quality studies with larger sample sizes are required because of the limited evidence provided by the six studies in the present review.


title: Antibody fragments, expressed by a fowl adenovirus vector, are able to neutralize infectious bursal disease virus.

text: Single-chain variable fragments (scFv) contain the heavy and light chain variable domains of immunoglobulin, joined by a short peptide linker. Previously, our laboratory has produced neutralizing scFv to epitopes of infectious bursal disease virus (IBDV). The in vitro delivery and expression of one of these scFv with and without the C(H)2-C(H)4 Fc domain of chicken IgY attached (scFv-Fc) by a serotype 8 fowl adenovirus (FAdV-8) vector was investigated in the present study. A panel of FAdV-8 vectors was constructed, each containing a different transgene (scFv or scFv-Fc), a different promoter to drive scFv and scFv-Fc transcription (CMVie or the fowl adenovirus major late promoter), and a different sized, right-hand end genomic deletion (52 bp or 2.3 kb). This panel was used to establish what effect these variables had on protein production, viral replication and scFv transcription, as measured by enzyme-linked imunosorbent assay and real-time polymerase chain reaction. Our results showed that, using a FAdV-8 vector containing the optimal CMVie promoter/2.3 kb deletion combination, we successfully expressed a secreted form of both scFv and scFv-Fc that were able to neutralize IBDV both in vitro and in ovo. These studies indicate that the FAdV-8 vector may be a promising candidate to deliver and express therapeutic molecules such as scFv and scFv-Fc in vivo in poultry.


docid: mrcfsspn

title: Cerebral arteriovenous malformations in the era of embolization for angiographic cure: a single-center experience in Egypt.

text: Background Embolization for cerebral arteriovenous malformations (AVMs) has evolved in the last decade with evolution in both equipment and material. Embolization targets have expanded to include angiographic cure. Methods To discuss the technical and management outcomes of our first cerebral AVM case series treated with embolization. The clinical, angiographic, treatment, and outcome variables of consecutive cerebral arteriovenous malformation cases, treated with curative embolization, between January 2011 and June 2017 in one regional center, were retrospectively analyzed. Results In 21 patients, 21 AVMs were identified, and 13 patients (61.9%) were males. The mean of the age was 34.24 ± 12.99. Fifteen patients (71.4%) had a history of intracranial hemorrhage, and 10 (47.6%) patients had seizures. Sixteen patients (76.2%) were at grade 1 of modified Rankin Scale (mRS) at admission. The median for modal Spetzler-Martin grade was 2. The average number of arterial feeders was 3. Direct arteriovenous fistulas were found in 4 cases (19.0%). Venous aneurysms were found in 4 cases (19.0%). Seventeen AVMs (80.9%) were considered high bleeding risk lesions. Forty-three embolization sessions were done. Early hemorrhage occurred in 3 sessions (7.0%). Vessel perforation occurred 1 session (2.3%). Poor outcome occurred in 1 patient that was discharged at grade 3 mRS. Angiographic cure was achieved in 9 patients (42.9%). The average size reduction was 65%. Conclusions Onyx embolization could serve as a curative option for AVM treatment with accepted morbidity and mortality.


title: Identification of in vivo-interacting domains of the murine coronavirus nucleocapsid protein.

text: The coronavirus nucleocapsid protein (N), together with the large, positive-strand RNA viral genome, forms a helically symmetric nucleocapsid. This ribonucleoprotein structure becomes packaged into virions through association with the carboxy-terminal endodomain of the membrane protein (M), which is the principal constituent of the virion envelope. Previous work with the prototype coronavirus mouse hepatitis virus (MHV) has shown that a major determinant of the N-M interaction maps to the carboxy-terminal domain 3 of the N protein. To explore other domain interactions of the MHV N protein, we expressed a series of segments of the MHV N protein as fusions with green fluorescent protein (GFP) during the course of viral infection. We found that two of these GFP-N-domain fusion proteins were selectively packaged into virions as the result of tight binding to the N protein in the viral nucleocapsid, in a manner that did not involve association with either M protein or RNA. The nature of each type of binding was further explored through genetic analysis. Our results defined two strongly interacting regions of the N protein. One is the same domain 3 that is critical for M protein recognition during assembly. The other is domain N1b, which corresponds to the N-terminal domain that has been structurally characterized in detail for two other coronaviruses, infectious bronchitis virus and the severe acute respiratory syndrome coronavirus.


title: Factors Influencing Physician Practices' Adoption of Behavioral Health Integration in the United States: A Qualitative Study.

text: BACKGROUND Behavioral health integration is uncommon among U.S. physician practices despite recent policy changes that may encourage its adoption. OBJECTIVE To describe factors influencing physician practices' implementation of behavioral health integration. DESIGN Semistructured interviews with leaders and clinicians from physician practices that adopted behavioral health integration, supplemented by contextual interviews with experts and vendors in behavioral health integration. SETTING 30 physician practices, sampled for diversity on specialty, size, affiliation with parent organizations, geographic location, and behavioral health integration model (collaborative or co-located). PARTICIPANTS 47 physician practice leaders and clinicians, 20 experts, and 5 vendors. MEASUREMENTS Qualitative analysis (cyclical coding) of interview transcripts. RESULTS Four overarching factors affecting physician practices' implementation of behavioral health integration were identified. First, practices' motivations for integrating behavioral health care included expanding access to behavioral health services, improving other clinicians' abilities to respond to patients' behavioral health needs, and enhancing practice reputation. Second, practices tailored their implementation of behavioral health integration to local resources, financial incentives, and patient populations. Third, barriers to behavioral health integration included cultural differences and incomplete information flow between behavioral and nonbehavioral health clinicians and billing difficulties. Fourth, practices described the advantages and disadvantages of both fee-for-service and alternative payment models, and few reported positive financial returns. LIMITATION The practice sample was not nationally representative and excluded practices that did not implement or sustain behavioral health integration, potentially limiting generalizability. CONCLUSION Practices currently using behavioral health integration face cultural, informational, and financial barriers to implementing and sustaining behavioral health integration. Tailored, context-specific technical support to guide practices' implementation and payment models that improve the business case for practices may enhance the dissemination and long-term sustainability of behavioral health integration. PRIMARY FUNDING SOURCE American Medical Association and The Commonwealth Fund.


docid: kjtdrndf

title: Managing Complications in Abdominoplasty: A Literature Review.

text: BACKGROUND Abdominoplasty, with or without liposuction, is among the most frequently performed aesthetic procedures. Its main objective is to improve the body contour by means of excising redundant skin and fat tissue. Although abdominoplasty is considered a safe procedure with high satisfaction rates, intraoperative and postoperative complications can become a challenge for the surgical team. The aim of this article is to offer a synopsis of the most common complications arising after abdominoplasty, along with evidence-based guidelines about how to prevent and treat them. METHODS A systematic MEDLINE search strategy was designed using appropriate Medical Subject Headings (MeSH) terms, and references were scanned for further relevant articles. RESULTS According to the published case series, local complications are considerably more common than complications with systemic repercussions. Approximately 10% to 20% of patients suffer a local complication following abdominoplasty, while fewer than 1% suffer a systemic complication. Prevention and management strategies are critically discussed for complications including seroma, haematoma, infection, skin necrosis, suture extrusions, hypertrophic scars, neurological symptoms, umbilical anomalies, deep venous thrombosis and pulmonary thromboembolism, respiratory distress, and death. CONCLUSIONS The complications of abdominoplasty vary in severity and in the impact they have on the aesthetic outcomes. Recommendations for prevention and management are based on various levels of evidence, with a risk of observer bias. However, most complications can be treated appropriately following the current standards, with satisfactory results.


title: Utility of Flexible Bronchoscopic Cryobiopsy for Diagnosis of Diffuse Parenchymal Lung Diseases.

text: BACKGROUND Initial reports of transbronchial cryobiopsy for diffuse parenchymal lung disease (DPLD) suggest the diagnostic yield approaches that of surgical lung biopsy (SLB) with an excellent safety profile. Centers performing cryobiopsy differ significantly in procedure technique; an optimal technique minimizing complications but still capable of diagnosing a wide range of DPLDs has not been established. We evaluated our practice of flexible bronchoscopic cryobiopsy in a primarily outpatient setting for patients who required a tissue diagnosis for DPLD of uncertain etiology. METHODS Consecutive patients with indeterminate DPLD who underwent bronchoscopic cryobiopsy at a large academic medical center from January 2012 to August 2015 were retrospectively analyzed. Rates of confident histopathologic diagnosis, confident multidisciplinary consensus diagnosis, management change, and complications were determined. RESULTS One hundred four cases were identified. Confident histopathologic diagnoses were established in 44% (46/104) and confident multidisciplinary consensus diagnoses in 68% (71/104). Usual interstitial pneumonia (19/104) and idiopathic pulmonary fibrosis (22/104) were the most common histopathologic and consensus diagnoses, respectively. Five subjects proceeded to SLB after cryobiopsy which was diagnostic in 3. Results of cryobiopsies changed management in 70% (73/104). Complications occurred in 8 cases with no death. CONCLUSIONS Cryobiopsy during outpatient flexible bronchoscopy facilitated confident multidisciplinary consensus diagnosis of DPLD in more than two thirds of cases, and appears sufficient to establish the histopathologic diagnosis of usual interstitial pneumonia, with a complication rate that compares favorably to that reported for SLB.


title: CANDO and the infinite drug discovery frontier.

text: The Computational Analysis of Novel Drug Opportunities (CANDO) platform (http://protinfo.org/cando) uses similarity of compound-proteome interaction signatures to infer homology of compound/drug behavior. We constructed interaction signatures for 3733 human ingestible compounds covering 48,278 protein structures mapping to 2030 indications based on basic science methodologies to predict and analyze protein structure, function, and interactions developed by us and others. Our signature comparison and ranking approach yielded benchmarking accuracies of 12-25% for 1439 indications with at least two approved compounds. We prospectively validated 49/82 'high value' predictions from nine studies covering seven indications, with comparable or better activity to existing drugs, which serve as novel repurposed therapeutics. Our approach may be generalized to compounds beyond those approved by the FDA, and can also consider mutations in protein structures to enable personalization. Our platform provides a holistic multiscale modeling framework of complex atomic, molecular, and physiological systems with broader applications in medicine and engineering.


title: Alginate dressings for healing diabetic foot ulcers.

text: BACKGROUND Foot ulcers in people with diabetes mellitus are a common and serious global health issue. Dressings form a key part of ulcer treatment, with clinicians and patients having many different types to choose from including alginate dressings. A clear and current overview of current evidence is required to facilitate decision-making regarding dressing use. OBJECTIVES To compare the effects of alginate wound dressings with no wound dressing or alternative dressings on the healing of foot ulcers in people with diabetes mellitus. SEARCH METHODS We searched The Cochrane Wounds Group Specialised Register (searched 4 January 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4); Ovid MEDLINE (1950 to December Week 3 2011); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, January 03, 2012); Ovid EMBASE (1980 to 2011 Week 52); and EBSCO CINAHL (1982 to 30 December 2011). There were no restrictions based on language or date of publication. SELECTION CRITERIA Published or unpublished randomised controlled trials (RCTs) that have compared the effects on ulcer healing of alginate dressings with alternative wound dressings or no dressing in the treatment of foot ulcers in people with diabetes. DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection, risk of bias assessment and data extraction. MAIN RESULTS We included six studies (375 participants) in this review; these compared alginate dressings with basic wound contact dressings, foam dressings and a silver-containing, fibrous-hydrocolloid dressing. Meta analysis of two studies found no statistically significant difference between alginate dressings and basic wound contact dressings: risk ratio (RR) 1.09 (95% CI 0.66 to 1.80). Pooled data from two studies comparing alginate dressings with foam dressings found no statistically significant difference in ulcer healing (RR 0.67, 95% CI 0.41 to 1.08). There was no statistically significant difference in the number of diabetic foot ulcers healed when an anti-microbial (silver) hydrocolloid dressing was compared with a standard alginate dressing (RR 1.40, 95% CI 0.79 to 2.47). All studies had short follow-up times (six to 12 weeks), and small sample sizes. AUTHORS' CONCLUSIONS Currently there is no research evidence to suggest that alginate wound dressings are more effective in healing foot ulcers in people with diabetes than other types of dressing however many trials in this field are very small. Decision makers may wish to consider aspects such as dressing cost and the wound management properties offered by each dressing type e.g. exudate management.


title: Different contribution of splanchnic organs to hyperlactatemia in fecal peritonitis and cardiac tamponade.

text: BACKGROUND Changes in hepatosplanchnic lactate exchange are likely to contribute to hyperlactatemia in sepsis. We hypothesized that septic and cardiogenic shock have different effects on hepatosplanchnic lactate exchange and its contribution to hyperlactatemia. MATERIALS AND METHODS 24 anesthetized pigs were randomized to fecal peritonitis (P), cardiac tamponade (CT), and to controls (n = 8 per group). Oxygen transport and lactate exchange were calculated during 24 hours. RESULTS While hepatic lactate influx increased in P and in CT, hepatic lactate uptake remained unchanged in P and decreased in CT. Hepatic lactate efflux contributed 20% (P) and 33% (CT), respectively, to whole body venous efflux. Despite maintained hepatic arterial blood flow, hepatic oxygen extraction did not increase in CT. CONCLUSIONS Whole body venous lactate efflux is of similar magnitude in hyperdynamic sepsis and in cardiogenic shock. Although jejunal mucosal pCO2 gradients are increased, enhanced lactate production from other tissues is more relevant to the increased arterial lactate. Nevertheless, the liver fails to increase hepatic lactate extraction in response to rising hepatic lactate influx, despite maintained hepatic oxygen consumption. In cardiac tamponade, regional, extrasplanchnic lactate production is accompanied by hepatic failure to increase oxygen extraction and net hepatic lactate output, despite maintained hepatic arterial perfusion.


Response to: 'Hydroxychloroquine shortages during the COVID-19 pandemic' by Mendel et al.


title: Shape-based Machine Learning Models for the potential Novel COVID-19 protease inhibitors assisted by Molecular Dynamics Simulation.

text: BACKGROUND The vast geographical expansion of novel coronavirus and an increasing number of COVID-19 affected cases has overwhelmed health and public health services. AI and ML algorithms have extended its major role in tracking the disease patterns, and in identifying possible treatment of disease. OBJECTIVE To identify potential COVID-19 protease inhibitor through shape-based Machine Learning assisted by Molecular docking and Molecular Dynamics simulation. METHODS 31 repurposed compounds have been selected targeting coronavirus protease (6LU7) and a machine learning approach was employed to generate shape-based molecules starting from 3D shape to pharmacophoric features of its seed compound. Ligand-Receptor docking was performed with Optimized Potential for Liquid Simulations (OPLS3) algorithms to identify high-affinity compounds from the list of selected candidates for 6LU7. This compound was subjected to Molecular Dynamic Simulations followed by ADMET studies and other analysis. RESULTS Shape-based Machine learning reported Remdesivir, Valrubicin, Aprepitant, and Fulvestrant and a novel therapeutic compound as the best therapeutic agents with the highest affinity for its target protein. Among the best shape-based compounds, the novel theoretical compound was not indexed in any chemical databases (PubChem, Zinc, or ChEMBL). Hence, the novel compound was named 'nCorvEMBS'. Further, toxicity analysis showed nCorv-EMBS to be efficacious that can be qualified as a 6LU7 inhibitor in COVID-19. CONCLUSION An effective ACE-II, GAK, AAK1, and protease 3C blockers that can serve a novel therapeutic approach to block the binding and attachment of COVID-19 protein (PDB ID: 6LU7) to the host cell and thus inhibit the infection at AT2 Lung cells. The novel theoretical compound nCorv-EMBS herein proposed stands as a promising inhibitor that can be extended for entering phases of clinical trials for COVID-19 treatment.


title: Minimally Invasive Hysterectomy for Uteri Greater Than One Kilogram.

text: BACKGROUND AND OBJECTIVES To assess the feasibility and safety of minimally invasive hysterectomy for uteri >1 kg. METHODS Clinical and surgical characteristics were collected for patients in an academic tertiary care hospital. Included were patients who underwent minimally invasive hysterectomy by 1 of 3 fellowship-trained gynecologists from January 1, 2009, to July 1, 2015 and subsequently had confirmed uterine weights of 1 kg or greater on pathology report. Both robotic and conventional laparoscopic procedures were included. RESULTS During the study period, 95 patients underwent minimally invasive hysterectomy with confirmed uterine weight over 1 kg. Eighty-eight percent were performed with conventional laparoscopy and 12.6% with robot-assisted laparoscopy. The median weight (range) was 1326 g (range, 1000-4800). The median estimated blood loss was 200 mL (range, 50-2000), and median operating time was 191 minutes (range, 75-478). Five cases were converted to laparotomy (5.2%). Four cases were converted secondary to hemorrhage and one secondary to extensive adhesions. There were no conversions after 2011. Intraoperative transfusion was given in 6.3% of cases and postoperative transfusion in 6.3% of cases. However, after 2013, the rate of intraoperative transfusion decreased to 1.0% and postoperative transfusion to 2.1%. Of the 95 cases, there were no cases with malignancy. CONCLUSIONS This provides the largest case series of hysterectomy over 1 kg completed by a minimally invasive approach. Our complication rate improved with experience and was comparable to other studies of minimally invasive hysterectomy for large uteri. When performed by experienced surgeons, minimally invasive hysterectomy for uteri >1 kg can be considered feasible and safe.


title: Evaluation of an automated endotracheal tube cuff controller during simulated mechanical ventilation.

text: BACKGROUND Maintaining endotracheal tube cuff pressure within a narrow range is an important factor in patient care. The goal of this study was to evaluate the IntelliCuff against the manual technique for maintaining cuff pressure during simulated mechanical ventilation with and without movement. METHODS The IntelliCuff was compared to the manual technique of a manometer and syringe. Two independent studies were performed during mechanical ventilation: part 1, a 2-h trial incorporating continuous mannikin head movement; and part 2, an 8-h trial using a stationary trachea model. We set cuff pressure to 25 cm H2O, PEEP to 10 cm H2O, and peak inspiratory pressures to 20, 30, and 40 cm H2O. Clinical importance was defined as both statistically significant (P<.05) and clinically significant (pressure change [Δ]>10%). RESULTS In part 1, the change in cuff pressure from before to after ventilation was clinically important for the manual technique (P<.001, Δ=-39.6%) but not for the IntelliCuff (P=.02, Δ=3.5%). In part 2, the change in cuff pressure from before to after ventilation was clinically important for the manual technique (P=.004, Δ=-14.39%) but not for the IntelliCuff (P=.20, Δ=5.65%). CONCLUSIONS There was a clinically important drop in manually set cuff pressure during simulated mechanical ventilation in a stationary model and an even larger drop with movement, but this was significantly reduced by the IntelliCuff in both scenarios. Additionally, we observed that cuff pressure varied directly with inspiratory airway pressure for both techniques, leading to elevated average cuff pressures.


Oncology in 2050 - A Retrospective?


title: Energy-Based Ligation of Pulmonary Vessels: A Six-Year Experience With Ultrasonic Shears in Video-Assisted Thoracoscopic Lobectomy and Segmentectomy.

text: BACKGROUND Mechanical staplers are widely employed in minimally invasive anatomic lung resections, but have limitations when managing smaller pulmonary arterial and venous branches. Published data is lacking regarding the safety and efficacy of pulmonary vessel ligation using ultrasonic shears. We describe a single-surgeon experience employing ultrasonic shears for the ligation of pulmonary vasculature during lobectomy and segmentectomy, primarily in the setting of video-assisted thoracic surgery (VATS) resection. METHODS A retrospective chart review was conducted for all patients, who underwent anatomic resection, between 2008 and 2014. Charts were divided into 2 groups based on method of ligation (energy based or conventional). Dictated operative reports were reviewed and patient demographics, tumor characteristics, and complications were recorded. RESULTS Ultrasonic shears were used for pulmonary vessel ligation (5 to 6 mm) in 82 of 283 anatomic resections. A total of 118 vessels were ligated with ultrasonic shears. The majority of patients (83%) in the energy-based ligation group underwent VATS resection. There were fewer complications in the energy-based ligation group (26% vs 38%; p = 0.05); however, rates of intraoperative transfusion, prolonged air leak, empyema, and return to the operating room were similar across the 2 groups, and no statistically significant difference was found. There were no postoperative complications directly attributable to ultrasonic vessel ligation. CONCLUSIONS Energy-based ligation of small-diameter pulmonary vessels is a safe and useful adjunct in anatomic VATS resection and a viable alternative to mechanical stapling. Its narrow profile and thin blades make it ideal for ligation of pulmonary vasculature, particularly where the size and necessary clearance of mechanical staplers prohibit safe dissection.


Covid care creates oxygen drought.


title: lncRNAPCAT29 inhibits pulmonary fibrosis via the TGF‑β1‑regulated RASAL1/ERK1/2 signal pathway.

text: Pulmonary fibrosis is a severe respiratory disease characterized by the aggregation of extracellular matrix components and inflammation‑associated injury. Studies have suggested that long non‑coding RNAs (lncRNA) may serve a role in the pathophysiological processes of pulmonary fibrosis. However, the potential molecular mechanisms involving the lncRNA, prostate cancer‑associated transcript 29 (lncRNAPCAT29) in the progression of pulmonary fibrosis are yet to be determined. In the present study, the role of lncRNAPCAT29 and the potential signaling mechanism in pulmonary fibrosis progression was investigated. Reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry revealed that the expression levels of lncRNAPCAT29 were downregulated within interstitial lung cells from mice with silica‑induced pulmonary fibrosis. Transfection with lncRNAPCAT29 was associated with upregulated expression of microRNA (miRNA)‑221 and downregulated expression of transforming growth factor‑β1 (TGF‑β1); reduced inflammation and fibrotic progression was also associated with lncRNAPCAT29 transfection. TGF‑β1 expression levels were inhibited within pulmonary fibroblasts due to lncRNAPCAT29 expression; NEDD4 binding protein 2 and Plexin‑A4 expression levels were also suppressed. Analysis of the potential mechanism underlying silica‑induced pulmonary fibrosis revealed that the expression levels of RAS protein activator like 1 (RASAL1) and extracellular signal‑regulated kinases 1/2 (ERK1/2) were suppressed due to lncRNAPCAT29 expression. The results of the present study demonstrated that lncRNAPCAT29 induced miRNA‑221 upregulation and TGF‑β1 downregulation. These observations were associated with reduced inflammation and progression of silica‑induced pulmonary fibrosis via the TGF‑β1‑regulated RASAL1/ERK1/2 signaling pathway, which may serve as a potential target for the treatment of pulmonary fibrosis.


title: Effectiveness and safety of direct oral anticoagulants in atrial fibrillation patients switched from vitamin K antagonists: a systematic review and meta-analysis.

text: A substantial proportion of atrial fibrillation patients initiating direct oral anticoagulants (DOAC) are vitamin K antagonists (VKA)-experienced, e.g., switchers from VKA to DOAC. With this study, we aimed to summarize available evidence on the effectiveness and safety of DOAC vs. VKA in real-life VKA-experienced atrial fibrillation patients. We searched EMBASE, MEDLINE and Cochrane Library systematically for English-language studies indexed any time before October 2018. We included studies of VKA-experienced atrial fibrillation patients initiating DOAC therapy, with continued VKA therapy as comparator. Outcomes included arterial thromboembolism and bleeding. When appropriate, meta-analysis was performed by calculating pooled, weighted, adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Eight cohort studies comparing VKA-experienced DOAC (dabigatran or rivaroxaban) users with continued VKA users were included. When comparing DOAC to VKA, an increased risk of ischaemic stroke and myocardial infarction was found for dabigatran (pooled aHR of 1.61 (95% CI 1.19-2.19, I2 =65%) and 1.29 (95% CI 1.10-1.52, I2 =0%)), respectively), but not for rivaroxaban. Use of dabigatran in VKA-experienced users was associated with an increased risk of gastrointestinal bleeding (pooled aHR 1.63 (95% CI 1.36-1.94, I2 =30%)), but a decreased risk of intracranial bleeding (pooled aHR 0.45 (95% CI 0.32-0.64, I2 =0%)). In conclusion, use of dabigatran in prior VKA users in clinical practice was associated with a slightly increased risk of arterial thromboembolism and gastrointestinal bleeding, but a decreased risk of intracranial bleeding. Importantly, observational studies of real-life VKA-experienced oral anticoagulant users may be confounded by the reason for switching. This article is protected by copyright. All rights reserved.


title: Best practice statements and recommendations for caring for critically ill patients with COVID-19.

text: SOURCE CITATION Alhazzani W, Møller MH, Arabi YM, et al. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. 2020;48:e440-69. 32224769.


title: Cilia-associated bacteria in fatal Bordetella bronchiseptica pneumonia of dogs and cats.

text: Bordetella bronchiseptica frequently causes nonfatal tracheobronchitis, but its role in fatal pneumonia is less recognized. Our study evaluated histologic identification of cilia-associated bacteria as a method for diagnosis of B. bronchiseptica pneumonia. Cases of fatal bronchopneumonia were studied retrospectively, excluding neonates and cases of aspiration pneumonia, minor lung lesions, or autolysis. The study population comprised 36 canine and 31 feline cases of bronchopneumonia. B. bronchiseptica was identified in 8 of 36 canine and 14 of 31 feline cases based on immunohistochemistry (IHC) using serum from a rabbit hyperimmunized with pertactin, PCR testing (Fla2/Fla12), and/or bacterial culture data when available. Of these, IHC was positive in 4 canine and 7 feline cases, PCR was positive in 8 canine and 14 feline cases, and B. bronchiseptica was isolated in 2 of 5 canine and 3 of 9 feline cases tested. Examination of histologic sections stained with hematoxylin and eosin revealed bronchial cilia-associated bacteria in 4 of 36 canine and 5 of 31 feline cases; these were all positive by IHC and PCR. The presence of cilia-associated bacteria had been noted in the pathology report for only 2 of these 9 cases. Thus, the presence of cilia-associated bacteria seems frequently overlooked by pathologists, but is a diagnostically significant feature of B. bronchiseptica pneumonia. A specific diagnosis of B. bronchiseptica pneumonia is important because it suggests primary or opportunistic bacterial pneumonia rather than aspiration pneumonia, and because of the risk of animal-to-animal transmission of B. bronchiseptica, the availability of vaccines for disease prevention, and the potential zoonotic risk to immunocompromised pet owners.


docid: nafdfrzu

title: Paradoxes and wonders of intrinsic disorder: Prevalence of exceptionality.


Health care under attack in Syrian conflict.


title: Modified laparoscopic intraperitoneal onlay mesh in complicated inguinal hernia surgery.

text: PURPOSE To analyse the recurrence rate and postoperative complications in inguinal hernia patients where the laparoscopic intraperitoneal onlay mesh technique (IPOM) was used due to preperitoneal fibrosis. METHODS Patients who had undergone inguinal herniotomy with the IPOM technique at Horsens Regional Hospital during the calender years of 2004 through 2010 filled out a questionnaire specific for recurrence and postoperative complications and had a clinical examination. Furthermore the medical records and national databases were analysed for reoperations for recurrent hernias. RESULTS 37 patients (38 hernias) were operated. Two patients had a recurrent hernia (5 %), four patients (11 %) reported chronic pain and six patients (16 %) reported various bowel symptoms after the operation. CONCLUSIONS The optimal treatment of these relatively rare and complicated patients is still an issue of debate, but in the light of the present study it seems that the IPOM technique is equal to or has a better profile compared to Lichtenstein in terms of re-recurrence and chronic pain. We believe that the IPOM technique has a place in the treatment of these patients.


title: Resistance profile to antimicrobial agents in the main circulating bacteria isolated from acute periodontal and endodontic infections in Latin America (MICROBE- DENT): A systematic review protocol.

text: BACKGROUND Antimicrobial resistance is currently considered the main risk to global health. A variety of microbial species have been isolated from endodontic and periodontal infections. However, clinical endodontic and periodontics bacterial isolates have not been sufficiently characterized with regard to their capacity for antibiotic resistance. We aim to assess the existing evidence to estimate the prevalence of the main antimicrobial resistance and multidrug resistant organisms in endodontics and periodontics and to describe their geographic distribution in Latin America. METHODS All types of designs and will be restricted to Latin American studies will be included in this systematic review. MEDLINE, Embase, CINAHL, BVS (LILACS, BBO - bvsalud.org), IBECS (bases.bireme.br), Google Scholar, Cochrane Central Register of Controlled Trials, and Web of Science databases will be searched from 2013 to December 31, 2018 for all types of study designs that report microbial infection in endodontics and periodontics and their resistance and that define the microbiological methods used to identify microorganisms. The selection of articles for inclusion will be performed by 2 reviewers using predefined eligibility criteria. The Cochrane and ROBINS-I risk of bias assessment tools will be used to assess the methodological quality of randomized control trials. The Newcastle-Ottawa scale will be used to assess the quality of methodology in observational studies. The overall quality of evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) using the same principles and domains applied in the quality assessment of prognostic studies. The heterogeneity of the findings will be assessed using both the χ test and the I statistic. Sensitivity analysis will be performed by subgroup analyses and meta-regression to investigate the effect of study-level characteristics, such as age, gender, and methodological quality score, whenever possible. Publication bias across studies will be evaluated by visual inspection of the funnel plots and Begg's test for the results covered in 10 or more studies. RESULTS The evidence derived by this study will inform best practices for patients with endodontic and periodontal problems receiving antimicrobial agents. CONCLUSION Successful completion will significantly impact clinical practice and contribute to improved prescribing competency. PROTOCOL REGISTRATION PROSPERO-CRD42018077810.