title: South Korea's Reponses to Stop the COVID-19 Pandemic.

text: BACKGROUND South Korea's aggressive responses to the coronavirus disease 2019 (COVID-19) have greatly slowed the epidemic without regional lockdowns. METHODS The Korean Centers for Disease Control and Prevention's daily briefings were thoroughly reviewed. Information about hospital countermeasures and government coordination was collected via telephone interviews with 4 infection control team leaders, 1 emergency department nurse, and 1 infectious disease physician in Korea. RESULTS After the 2015 Middle East Respiratory Syndrome outbreak, the government and hospitals prepared for the inevitable outbreak of emerging infectious diseases by reforming the epidemic preparedness system. As a result, COVID-19 diagnostic test kits were quickly developed, enabling extensive early detection of potential cases. Other key steps were tracking cases, finding exposed individuals, coordinating case assignments with healthcare facilities, and selective clinic screenings for visitors' entering hospitals with mandatory mask wearing. Consequently, after overcoming the initial peak of the outbreak, which was related to a religious group, Korea has been able to maintain daily new cases at around 100 and to less than 50 daily cases in the second week of April. CONCLUSION To counter the COVID-19 pandemic, which may persist, long-term, sustained response strategies must be prepared along with coordination between government and health systems.


title: Morgagni hernia repair in children over two decades: Institutional experience, systematic review, and meta-analysis of 296 patients.

text: BACKGROUND/PURPOSE Morgagni diaphragmatic hernia (MH) is rare. We report our experience based on routine patch use in MH repair to curb recurrence. A systematic review and meta-analysis were performed to study the recurrence and complications associated with minimally invasive surgery and the use of patch. METHODS We retrospectively reviewed all cases of MH who underwent first-time repair in 2012-2017 in our institution to determine recurrence and complication rate. A MEDLINE search related to minimally invasive surgery (MIS) and patch repair of MH was conducted for systematic review. Eligible articles published from 1997-2017 with follow-up data available were included. Primary outcomes measured were recurrence and complication. Meta-analysis to compare open versus MIS and primary versus patch repair in the MIS group were performed in comparative cohorts. Continuous data were presented as median (range), and statistical significance was P<0.05. RESULTS In our institution, 12 consecutive patients aged 17-month-old (22 days-7 years), underwent laparoscopic patch repair of MH, with one conversion to laparotomy. No recurrence or significant complication occurred over a follow-up period of 8 months (1-48 months). Thirty-six articles were included from literature review and were combined with the current series. All were retrospective case reports or series, of which 6 were comparative cohorts with both MIS and open repairs. A total of 296 patients from 37 series were ultimately used for analysis: 80 had open repair (4 patch) and 216 had MIS repair (32 patch), with a patch rate of 12%. There were 13 recurrences (4%): no difference between open and MIS repairs (4/80 vs 9/216, p=0.75); recurrence rate following primary repair was 13/260 (5%), but no recurrence occurred with 36 patch repairs. Meta-analysis showed no difference in recurrence between open and MIS repair (p=0.83), whereas patch repair was associated with 14% less recurrence compared with primary repair, although it did not reach statistical significance (p=0.12). There were 13 complications (5%): no difference between open and MIS repairs (5/80 vs 8/216, p=0.35). One small bowel obstruction occurred in a patient who had laparoscopic patch repair. CONCLUSION In MH, recurrence and complication rates are comparable between MIS and open repairs. Use of patch appeared to confer additional benefit in reducing recurrence. TYPE OF STUDY Systematic review LEVEL OF EVIDENCE: 3A.


title: Role of endoscopy in early oesophageal cancer.

text: Incidence of oesophageal adenocarcinoma has increased exponentially in the West over the past few decades. Following detection of advanced cancers, 5-year survival rates remain bleak, making identification of early neoplasia, which has a better outcome, important. Detection of subtle oesophageal lesions during endoscopy can be challenging, and advanced imaging techniques might improve their detection. High-definition endoscopy has become a standard in most endoscopy centres, and this technology probably provides better delineation of mucosal features than standard-definition endoscopy. Various image enhancement techniques are now available with the development of new electronics and software systems. Image enhancement with chromoendoscopy using dyes has been a cost-effective option for many years, yet these techniques have been replaced in some contexts by electronic chromoendoscopy, which can be used with the press of a button. However, Lugol's chromoendoscopy remains the gold standard to identify squamous dysplasia. Identification and characterization of subtle neoplastic lesions could help to target biopsies and perform endoscopic resection for better local staging and definitive therapy. In vivo histology with techniques such as confocal endomicroscopy could make endotherapy feasible within a shorter timescale than when relying on histology on tissue samples. Once early neoplasia is identified, treatments include endoscopic resection, endoscopic submucosal dissection or various ablative techniques. Endotherapy has the advantage of being a less invasive technique than oesophagectomy, and is associated with lower mortality and morbidity. Endoscopic ablation therapies have evolved over the past few years, with radiofrequency ablation showing the best results in terms of success rates and complications in Barrett dysplasia.


title: Fibrinogen Level and Bleeding Risk During Catheter-Directed Thrombolysis Using Tissue Plasminogen Activator.

text: PURPOSE The purpose of this study was to determine whether low fibrinogen levels (fibrinogen level <1.5 g/L) during catheter-directed thrombolysis are associated with an increased bleeding risk. METHODS A retrospective review was performed on patients undergoing extremity arterial or venous thrombolysis between 2005 and 2013. RESULTS Patients in the low fibrinogen group were younger (P = .006) and had a higher number of venous occlusive events (P = .004). The low fibrinogen group received a larger dose of tissue plasminogen activator (tPA; P = .009) and had a longer duration of thrombolysis (P = .010). The rates of major bleeding were not significantly different (P = .139). Univariate analysis showed that larger total dose and longer duration of tPA infusion were associated with increased bleeding complications (P < .01 and P = .03). CONCLUSION A fibrinogen level <1.5 g/L during thrombolysis was not associated with an increased bleeding risk. However, larger dose and longer duration of thrombolysis were associated with increased bleeding risk.


title: Effect of coronavirus infection on the human heart: A scoping review.

text: BACKGROUND The global coronavirus disease 2019 pandemic has highlighted the importance of understanding the cardiovascular implications of coronavirus infections, with more severe disease in those with cardiovascular co-morbidities, and resulting cardiac manifestations such as myocardial injury, arrhythmias, and heart failure. DESIGN A systematic review of the current knowledge on the effects of coronavirus infection on the cardiovascular system in humans was performed and results were summarized. METHODS Databases such as MEDLINE, EMBASE, CENTRAL, Scopus, Web of Science, ClinicalTrials.gov, Chinese Knowledge Resource Integrated Database and Chinese Clinical Trial Registry were searched on 20 March 2020. RESULTS In total, 135 studies were included, involving severe acute respiratory syndrome, Middle East respiratory syndrome, coronavirus disease 2019 and other coronaviruses. Most were case reports, case series and cohort studies of poor to fair quality. In post-mortem examinations of subjects who died from infection, around half had virus identified in heart tissues in severe acute respiratory syndrome, but none in Middle East respiratory syndrome and coronavirus disease 2019. Cardiac manifestations reported include tachycardia, bradycardia, arrhythmias, and myocardial injury, secondary to both systemic infection and treatment. Cardiac injury and arrhythmias are more prevalent in coronavirus disease 2019, and elevated cardiac markers are associated with intensive care unit admission and death. In severe acute respiratory syndrome, Middle East respiratory syndrome, and coronavirus disease 2019, comorbidities such as hypertension, diabetes mellitus, and heart disease are associated with intensive care unit admission, mechanical ventilation, and mortality. There were cases of misdiagnosis due to overlapping presentations of cardiovascular diseases and coronavirus infections, leading to hospital spread and delayed management of life-threatening conditions. CONCLUSION This review highlighted the ways in which coronaviruses affect cardiovascular function and interacts with pre-existing cardiovascular diseases.


title: GOALS-incisional hernia: a valid assessment of simulated laparoscopic incisional hernia repair.

text: The Global Operative Assessment of Laparoscopic Skills (GOALS) is a valid and reliable measure of basic, non-procedure-specific laparoscopic skills. GOALS-incisional hernia (GOALS-IH) was developed to evaluate performance of laparoscopic incisional hernia repair (LIHR). The purpose of this study was to assess the validity and reliability of GOALS-IH during LIHR simulation. GOALS-IH assesses 7 domains with a maximum score of 35. A total of 12 experienced surgeons and 10 novices performed LIHR on the Surgical Abdominal Wall simulator. Performance was assessed by a trained observer and by self-assessment using GOALS-IH, basic GOALS and a visual analog scale (VAS) for overall competence. Both interrater reliability and internal consistency were high (.76 and .95 respectively). Experienced surgeons had higher mean GOALS-IH scores than novices (32.3 ± 2 versus 22.7 ± 5). There was excellent correlation between GOALS-IH and other measures of performance (GOALS r = .93 and VAS r = .93). GOALS-IH is easy to use, valid and reliable for assessment of simulated LIHR.


title: Neutralizing antibodies against previously encountered influenza virus strains increase over time: a longitudinal analysis.

text: Antigenic diversity shapes immunity in distinct and unexpected ways. This is particularly true of the humoral response generated against influenza A viruses. Although it is known that immunological memory developed against previously encountered influenza A virus strains affects the outcome of subsequent infections, exactly how sequential exposures to antigenically variant viruses shape the humoral immune response in humans remains poorly understood. To address this important question, we performed a longitudinal analysis of antibody titers against various pandemic and seasonal strains of influenza virus spanning a 20-year period (1987 to 2008) with samples from 40 individuals (birth dates, 1917 to 1952) obtained from the Framingham Heart Study. Longitudinal increases in neutralizing antibody titers were observed against previously encountered pandemic H2N2, H3N2, and H1N1 influenza A virus strains. Antibody titers against seasonal strains encountered later in life also increased longitudinally at a rate similar to that against their pandemic predecessors. Titers of cross-reactive antibodies specific to the hemagglutinin stalk domain were also investigated because they are influenced by exposure to antigenically diverse influenza A viruses. These titers rose modestly over time, even in the absence of major antigenic shifts. No sustained increase in neutralizing antibody titers against an antigenically more stable virus (human cytomegalovirus) was observed. The results herein describe a role for antigenic variation in shaping the humoral immune compartment and provide a rational basis for the hierarchical nature of antibody titers against influenza A viruses in humans.


title: Highly Pathogenic H5N1 and Novel H7N9 Influenza A Viruses Induce More Profound Proteomic Host Responses than Seasonal and Pandemic H1N1 Strains.

text: Influenza A viruses (IAV) are important human and animal pathogens with potential for causing pandemics. IAVs exhibit a wide spectrum of clinical illness in humans, from relatively mild infections by seasonal strains to acute respiratory distress syndrome during infections with some highly pathogenic avian influenza (HPAI) viruses. In the present study, we infected A549 human cells with seasonal H1N1 (sH1N1), 2009 pandemic H1N1 (pdmH1N1), or novel H7N9 and HPAI H5N1 strains. We used multiplexed isobaric tags for relative and absolute quantification to measure proteomic host responses to these different strains at 1, 3, and 6 h post-infection. Our analyses revealed that both H7N9 and H5N1 strains induced more profound changes to the A549 global proteome compared to those with low-pathogenicity H1N1 virus infection, which correlates with the higher pathogenicity these strains exhibit at the organismal level. Bioinformatics analysis revealed important modulation of the nuclear factor erythroid 2-related factor 2 (NRF2) oxidative stress response in infection. Cellular fractionation and Western blotting suggested that the phosphorylated form of NRF2 is not imported to the nucleus in H5N1 and H7N9 virus infections. Fibronectin was also strongly inhibited in infection with H5N1 and H7N9 strains. This is the first known comparative proteomic study of the host response to H7N9, H5N1, and H1N1 viruses and the first time NRF2 is shown to be implicated in infection with highly pathogenic strains of influenza.


title: Serial affinity chromatography as a selection tool in glycoproteomics.

text: Glycan-targeting affinity chromatography systems are becoming increasingly important as tools in the purification, enrichment, and identification of glycoproteins. The great advantage of this strategy is that immobilized lectin and antibody selectors allow specific glycan structures to be matched with a particular protein. It is also possible to show that a glycan seen at one site in a glycoprotein may not be present at another glycosylation site in the same glycoprotein. A problem with single-column affinity chromatography is how to obtain information on glycan diversity within the oligosaccharide portions of captured glycoproteins. Although all the glycoprotein species bearing a particular glycan feature will be captured by an affinity column, there is no way of knowing whether the ligand being targeted appears alone or coresides with a series of other glycan features in the same oligosaccharide conjugate. The work being described here examines the utility of serial affinity columns in determining whether individual glycan structures appear alone or together with other glycans in specific proteins. Four different types of affinity columns were examined in two series; the LEL → HPA → anti-Le(x)Ab → anti-sLe(x)Ab series and the anti-sLe(x)Ab → anti-Le(x)Ab → HPA → LEL series. Patterns in protein capture from these two series were very different. Thus, serial affinity chromatography (SAC) can be a valuable tool in recognizing diversity in protein glycosylation, especially when the order of columns in the SAC series is varied. Two clear types of diversity were recognized. One is the independent occurrence of different affinity-targetable glycan features in the same glycoprotein. The other is that multiple targetable glycan features were coresident in the same glycoprotein. The great advantage of this method is that it couples easily with current methods used in glycoproteomics.


title: In ovo delivery of Toll-like receptor 2 ligand, lipoteichoic acid induces pro-inflammatory mediators reducing post-hatch infectious laryngotracheitis virus infection.

text: Toll-like receptor (TLR) ligands are pathogen associated molecular patterns (PAMPs) recognized by the TLRs resulting in induction of host innate immune responses. One of the PAMPs that binds to TLR2 and cluster of differentiation (CD) 14 is lipotechoic acid (LTA), which activates downstream signals culminating in the release of pro-inflammatory cytokines. In this study, we investigated whether in ovo LTA delivery leads to the induction of antiviral responses against post-hatch infectious laryngotracheitis virus (ILTV) infection. We first delivered the LTA into embryo day (ED)18 eggs via in ovo route so that the compound is available at the respiratory mucosa. Then the LTA treated and control ED18 eggs were allowed to hatch and the hatched chicken was infected with ILTV intratracheally on the day of hatch. We found that in ovo delivered LTA reduces ILTV infection post-hatch. We also found that in ovo delivery of LTA significantly increases mRNA expression of pro-inflammatory mediators in pre-hatch embryo lungs as well as mononuclear cell infiltration, predominantly macrophages, in lung of post-hatch chickens. Altogether, the data suggest that in ovo delivered LTA could be used to reduce ILTV infection in newly hatched chickens.


title: The Interferon-Stimulated Gene Ifitm3 Restricts West Nile Virus Infection and Pathogenesis.

text: UNLABELLED The interferon-induced transmembrane protein (IFITM) family of proteins inhibit infection of several different enveloped viruses in cell culture by virtue of their ability to restrict entry and fusion from late endosomes. As few studies have evaluated the importance of Ifitm3 in vivo in restricting viral pathogenesis, we investigated its significance as an antiviral gene against West Nile virus (WNV), an encephalitic flavivirus, in cells and mice. Ifitm3(-/-) mice were more vulnerable to lethal WNV infection, and this was associated with greater virus accumulation in peripheral organs and central nervous system tissues. As no difference in viral burden in the brain or spinal cord was observed after direct intracranial inoculation, Ifitm3 likely functions as an antiviral protein in nonneuronal cells. Consistent with this, Ifitm3(-/-) fibroblasts but not dendritic cells resulted in higher yields of WNV in multistep growth analyses. Moreover, transcomplementation experiments showed that Ifitm3 inhibited WNV infection independently of Ifitm1, Ifitm2, Ifitm5, and Ifitm6. Beyond a direct effect on viral infection in cells, analysis of the immune response in WNV-infected Ifitm3(-/-) mice showed decreases in the total number of B cells, CD4(+) T cells, and antigen-specific CD8(+) T cells. Finally, bone marrow chimera experiments demonstrated that Ifitm3 functioned in both radioresistant and radiosensitive cells, as higher levels of WNV were observed in the brain only when Ifitm3 was absent from both compartments. Our analyses suggest that Ifitm3 restricts WNV pathogenesis likely through multiple mechanisms, including the direct control of infection in subsets of cells. IMPORTANCE As part of the mammalian host response to viral infections, hundreds of interferon-stimulated genes (ISGs) are induced. The inhibitory activity of individual ISGs varies depending on the specific cell type and viral pathogen. Among ISGs, the genes encoding interferon-induced transmembrane protein (IFITM) have been reported to inhibit multiple families of viruses in cell culture. However, few reports have evaluated the impact of IFITM genes on viral pathogenesis in vivo In this study, we characterized the antiviral activity of Ifitm3 against West Nile virus (WNV), an encephalitic flavivirus, using mice with a targeted gene deletion of Ifitm3 Based on extensive virological and immunological analyses, we determined that Ifitm3 protects mice from WNV-induced mortality by restricting virus accumulation in peripheral organs and, subsequently, in central nervous system tissues. Our data suggest that Ifitm3 restricts WNV pathogenesis by multiple mechanisms and functions in part by controlling infection in different cell types.


Implementing the international health regulations (2005) in the World Health Organization Western Pacific Region.


Challenges Estimating Total Lives Lost in COVID-19 Decisions: Consideration of Mortality Related to Unemployment, Social Isolation, and Depression.


title: A multi-criteria analysis of options for energy recovery from municipal solid waste in India and the UK.

text: Energy recovery from municipal solid waste plays a key role in sustainable waste management and energy security. However, there are numerous technologies that vary in suitability for different economic and social climates. This study sets out to develop and apply a multi-criteria decision making methodology that can be used to evaluate the trade-offs between the benefits, opportunities, costs and risks of alternative energy from waste technologies in both developed and developing countries. The technologies considered are mass burn incineration, refuse derived fuel incineration, gasification, anaerobic digestion and landfill gas recovery. By incorporating qualitative and quantitative assessments, a preference ranking of the alternative technologies is produced. The effect of variations in decision criteria weightings are analysed in a sensitivity analysis. The methodology is applied principally to compare and assess energy recovery from waste options in the UK and India. These two countries have been selected as they could both benefit from further development of their waste-to-energy strategies, but have different technical and socio-economic challenges to consider. It is concluded that gasification is the preferred technology for the UK, whereas anaerobic digestion is the preferred technology for India. We believe that the presented methodology will be of particular value for waste-to-energy decision-makers in both developed and developing countries.


title: ERK and AKT phosphorylation status in lung cancer and emphysema using nanocapillary isoelectric focusing.

text: BACKGROUND Emphysema is an independent risk factor for the development of lung cancer in smokers. Activation of oncogenic signalling proteins AKT and ERK by phosphorylation has an established role in the development of lung cancer and has also been implicated in the pathogenesis of emphysema. The aim of this study was to compare the protein level and phosphorylation status of AKT and ERK in paired lung cancer and emphysema tissue using a highly sensitive phosphoprotein analysis approach. METHODS An antibody-based, nanocapillary isoelectric focusing (cIEF) assay was used to determine the relative quantities and phosphorylation status of AKT and ERK in tumour and matched lung tissue from patients, with or without evidence of emphysema, undergoing curative resection for non-small cell lung cancer. RESULTS 20 patients with adenocarcinoma (n=9) or squamous cell carcinoma (n=11) of the lung were included (mean age 67.3 years (SD 7.5, range 47-80 years)), 12 were men and all were current (n=10) or former smokers (n=10). Paired macroscopically normal lung tissue was either histologically normal (n=7) or showed emphysema (n=13). Total and phosphorylated AKT levels were fourfold (p=0.0001) and fivefold (p=0.001) higher in tumour compared with matched lung, respectively. There was no correlation with tumour histology, stage or differentiation; however, total AKT signal in tumour was significantly correlated with fluorodeoxyglucose avidity on positron emission tomography-CT scan (r=0.53, p=0.035). Total ERK was not differentially expressed, but doubly phosphorylated (activated) ERK was threefold higher in emphysema (23.5%, SD 9.2) than either matched tumour (8.8%, SD 8.6) or normal lung tissue (8.3%, SD 9.0) and correlated with the histological severity of emphysema (p=0.005). CONCLUSIONS cIEF offers opportunities for quantifying subtle shifts in the phosphorylation status of oncoproteins in nanogram amounts of lung tissue. ERK activation is a feature of emphysema.


title: Is Energy Delivery Guided by Indirect Calorimetry Associated With Improved Clinical Outcomes in Critically Ill Patients? A Systematic Review and Meta-analysis.

text: Background Indirect calorimetry (IC) is recommended to guide energy delivery over predictive equations in critical illness due to its precision. However, the impact of using IC to measure energy expenditure on clinical outcomes is uncertain. Objective To evaluate whether using IC to measure energy expenditure to inform energy delivery reduced hospital mortality and improved other important outcomes compared to using predictive equations in critically ill adults. Methods A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Medline, Embase, CINAHL, and the Cochrane Library were searched for studies using IC to guide energy delivery compared to a predictive equation in adult critically ill patients with the primary outcome (hospital mortality) or any of the secondary outcomes reported (including but not limited to hospital and intensive care unit (ICU) length of stay (LOS) and duration mechanical ventilation (MV). Risk of bias within studies was assessed using the Cochrane "Risk of Bias" 1 tool. Random-effect meta-analyses were used when heterogeneity between studies existed (I2 > 50%). Data are reported as median (interquartile range [IQR]), binomial outcomes as odds ratio (OR), 95% confidence interval (CI), and continuous outcomes as mean difference (MD). Results Of 4060 articles, 4 randomized controlled trials were identified with 396 patients included in analysis. Three studies were considered low risk of bias and 1 as high risk. Two studies reported hospital mortality (n = 130 and 40 participants, respectively). When combined, no association between IC-guided energy delivery and hospital mortality was found (OR = 0.81, 95% CI = [0.25, 2.67], P = 0.73, I2 = 52). No differences were reported with ICU mortality and hospital LOS between groups, but ICU LOS and duration of MV varied across all studies. According to the meta-analysis, no differences were observed in ICU LOS (MD = 1.39, 95% CI = [-5.01, 7.79], P = 0.67, I2 = 81%), although the duration of MV was increased when energy delivery was guided by IC (MD = 2.01, 95% CI = [0.45, 3.57], P = 0.01, I2 = 26%). In all 4 studies, prescribed energy targets were more closely met when energy delivery was informed by IC compared to a predictive equation. Three studies reported the percentage delivered versus the prescribed energy target, with the median (IQR) delta between the IC and predictive equation arms 19% (10%-32%). Conclusion Limited data exist to assess the impact of using IC to inform energy delivery in comparison to predictive equations on hospital mortality. The association of IC use with other important outcomes, including duration of MV, needs to be further explored before definitive conclusions can be made.


title: Solitaire FR stent as an adjunctive tool for pipeline stent deployment in the treatment of giant intracranial aneurysms.

text: BACKGROUND AND IMPORTANCE The use of flow-diverting stents has gained acceptance during the past few years for the treatment of numerous intracranial aneurysms, especially large or giant ones. However, successful catheterization of the distal parent artery in giant intracranial aneurysms with a microcatheter can be extremely challenging. Forming a microcatheter loop in the aneurysm sac can aid distal catheterization. CLINICAL PRESENTATION We report the use of a Solitaire FR stent as an adjunctive tool in the successful treatment of 2 giant intracranial unruptured aneurysms with a Pipeline Embolization Device. After having formed a loop inside the aneurysm sac, the microcatheter was anchored distally by a Solitaire FR stent. With the Solitaire FR device opened, the loop in the giant aneurysm sac was completely reduced without loss of the microcatheter position in the distal parent artery. A Pipeline Embolization Device could be delivered in both cases without any difficulty. There were no complications. CONCLUSION The technique described results in ideal microcatheter alignment with a secure distal position before deployment of a flow-diverting stent.


title: Aberrant Expression of Syndecan-1 in Cervical Cancers.

text: Syndecan-1, is a transmembrane heparan/chondroitin sulfate proteoglycan necessary for cell-cell and cell-matrix interactions. Its decreased level on the cell surface correlates with poor prognosis in several tumor types. Aberrant stromal localization of syndecan-1 is also considered an unfavorable prognostic factor in various human malignancies. In the presented work the question was addressed if changes in syndecan-1 expression are related to the prognosis of cervical cancer. Immunohistochemistry for syndecan-1 extracellular domain was performed on surgical specimens of primary cervical cancer. To follow the communication between tumor cells and stromal fibroblasts, their mono-and co-cultures were studied, detecting the expression of syndecan-1, smooth muscle actin, vimentin, and desmin. Immunohistochemistry of tumorous specimens revealed that while cell surface syndecan-1 expression was reduced on cancer cells, it appeared on the surface of tumor-associated fibroblasts. Until year 7, the cohort with high cell surface syndecan-1 expression had significantly longer survival. No difference in the same time-period could be detected when stromal syndecan-1 expression was analyzed. In vitro analysis revealed, that tumor cells can induce syndecan-1 expression on fibroblast, and fibroblasts showed that fibroblast-like cells are built by two cell types: (a) syndecan-1 positive, cytokeratin negative real fibroblasts, and (b) syndecan-1 and cytokeratin positive epithelial-mesenchymal transformed tumor cells. Syndecan-1 on the surface of cancer cells appears to be a positive prognostic marker. Although syndecan-1 positive fibroblasts promote tumor cell proliferation in vitro, we failed to detect their cancer promoting effect in vivo.


title: Covid-19 in a patient with multiple sclerosis treated with natalizumab: May the blockade of integrins have a protective role?

text: The disease caused by the new coronavirus SARS-CoV-2 (COVID-19) is currently spread worldwide . Recent data supports SARS-CoV-2 may use integrins to enter human cells. Therefore, anti-integrins therapies might be an alternative against the infection . Natalizumab, approved for Multiple Sclerosis (MS) treatment, acts blocking α4-integrin. We report a MS patient treated with natalizumab who develops COVID-19, with excellent recovery and repeated negative results in 5 consecutive microbiological studies. We postulate this may be due to the blockade of integrins induced by natalizumab.


title: Efficacy and reliability of the use of a needle grasper to prevent trocar site hernia.

text: Introduction Port site herniation is one of the serious complications of laparoscopic surgery, which decreases its benefits. Closure of a fascia defect at the port site is an important problem of laparoscopic surgery, especially in obese patients. Aim To evaluate needle grasper fascia closure. Material and methods We closed the port site fascia using a percutaneous organ-holding device (needle grasper) in laparoscopic cholecystectomy patients. This study included 334 patients who underwent laparoscopic cholecystectomy between January 2015 and January 2017 in our hospital. Patients were divided into 2 fascia closure groups: group 1 with a standard simple suturing technique and group 2 with a needle grasper to close the port site. Patient demographics, operative details, and postoperative outcomes were collected and evaluated. Results There were 243 female and 91 male (total 334) patients with the mean age of 49.18 ±13.15 years. Only 1 patient in the BMI > 30 kg/m2 group of patients had port site hernia development with the needle grasper technique at the end of the 8-month follow-up period. The port site hernia incidence was higher in group 1 than group 2 (p < 0.001), but there was no significant difference in terms of operation duration between the two groups (p < 0.001, p = 0.709, respectively). In patients with a BMI > 30 kg/m2, both operation duration and port site hernia incidence were higher in simple suture closure than in the needle grasper technique (p < 0.001, p = 0.016, p = 0.005). Conclusions The needle grasper technique is easy, simple, safe, fast, and effective for fascia closure of port sites. This method can also be applied in obese patients easily, safely and in a short time.


title: Treatment failure definitions for non-purulent skin and soft tissue infections: a systematic review.

text: OBJECTIVE There is currently no uniform definition for antimicrobial treatment failure for adults with non-purulent skin and soft tissue infections (SSTIs). The objective of this systematic review was to identify treatment failure definitions and their common components in the literature. METHODS Five electronic databases were searched from inception to March 2019. Two independent reviewers identified studies involving adults (age ≥ 18 years) with non-purulent SSTIs in which antimicrobial treatment failure was a defined outcome. There were no language restrictions. Only randomized trials or observational studies were included. RESULTS After screening 4953 abstracts, 26 studies (N = 6629 patients) met full inclusion criteria. Reported treatment failure ranged from 0 to 29.5%. The most common definition components were hospital admission (78.9%), change in antibiotics (65.4%), and persistent or worsening signs and symptoms of infection (34.6%). Only one study listed specific criteria for persistent or worsening signs and symptoms of infection. CONCLUSIONS For studies involving non-purulent SSTIs, the outcome of treatment failure is inconsistently defined and reported failure rates are highly variable. This systematic review has highlighted the need for more robust treatment failure definitions for non-purulent SSTIs. Research should focus on the development of a uniform treatment failure definition that should be used in future studies.


title: Could radiofrequency ablation replace liver resection for small hepatocellular carcinoma in patients with compensated cirrhosis? A 5-year follow-up.

text: PURPOSE Treating hepatocellular carcinoma involves many different specialists and requires multidisciplinary management. In light of the current discussion on the role of ablative therapy, the aim of this study is to compare patients who undergo hepatic resection to those treated with radiofrequency ablation. METHODS The procedures have been conducted in two institutes following the same methodologies. Ninety-six patients with Child-Pugh class A cirrhosis, single or multinodular hepatocellular carcinoma (HCC) and a diameter less than or equal to 3 cm, have been included in this retrospective study: 52 patients have been treated by surgical resection and 44 by radiofrequency ablation. Patient characteristics, survival and disease-free survival have all been analysed. RESULTS Disease-free survival was longer in the resection group in comparison to the radiofrequency group with a median disease-free time of 48 versus 34 months, respectively (P = 0.04, hazard ratio = 1.5, 95 % confidence interval = 0.9-2.5). In the resection group, median survival was 54 months with a survival rate at 1, 3 and 5 years of 100, 98 and 46.2 %. In the radiofrequency group, median survival was 40 months with 1-, 3- and 5-year survival rate of 95.5, 68.2 and 36.4 %. CONCLUSION The current study shows that for small HCC in the presence of compensated cirrhosis, surgical resection gives better results than radiofrequency, both in terms of overall survival, as well as disease-free survival. Further evidence is required to clarify the role of ablative therapy as a curative treatment and whether it can replace surgery.


title: Fish as bioindicators: coal and mercury pollution in Colombia's ecosystems.

text: Mining in Colombia affects 488,672 ha (298,391 in coal mining and 190,281 in gold mining). However, Colombia has insufficient studies on mining and its repercussions, which limits estimates of mining impacts on ecosystems and the human population. Due to the rise of mining activities in Colombia, the negative impacts generated by coal and Hg will also continue to increase. This review analyzes national information levels on coal and Hg in island/coastal/marine as well as freshwater ecosystems and human groups using fishery resources as a framework. This is because fish are the main source of animal protein in marine coastal-island and mainland communities. Here, 15 of 32 Colombian departments have records on total mercury (THg) in water, sediments, fish, and human communities. Around 205 ton/year of mercury is discharged into the ecosystem. In human hair for example (15.3 to 50.15 μg/g), mercury exceeds the international maximum levels allowed (ILA) and the national standard (5.0 μg/g). Mercury levels in freshwater fish show 3.3 μg/g of THg and levels in marine and coastal-island fish are 1.2 μg/g THg exceeding the ILA (0.5 μg/g) standard for fish that will be consumed. Carnivorous species have a THg between 0.04 and 2.55 μg/g suggesting bioaccumulation and magnification of heavy metals. These findings were then compared with available international information.


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title: Knee effusion affects knee mechanics and muscle activity during gait in individuals with knee osteoarthritis.

text: OBJECTIVE To test the hypothesis that knee effusion presence in those with knee osteoarthritis (OA) alters knee joint muscle activation patterns and sagittal plane mechanics during gait. METHODS Thirty-five patients with medial compartment knee OA were assessed for the presence of effusion using a brush test. Based on the results, they were assigned to the knee effusion (n = 17) and no knee effusion (n = 18) groups. Electromyograms from seven lower extremity muscles (lateral and medial gastrocnemius, vastus lateralis and medialis, rectus femoris and the lateral and medial hamstrings), leg motion and ground reaction forces were recorded during self-selected walking. Isometric knee extensor, plantar flexor and knee flexor strength were measured. Discrete measures from angular knee motion and net external moment of force waveforms were identified. Principal component analysis extracted electromyographic waveform features. Analysis of variance models tested for main effects (group, muscle) and interactions (α = 0.05). Bonferroni post-hoc testing was employed. RESULTS No differences in age, body mass index, knee pain, Western Ontario McMaster Osteoarthritis Index scores, gait velocity and muscle strength were found between groups (P > 0.05). Individuals with effusion had a greater overall quadriceps activation and prolonged hamstring activation into mid-stance (P < 0.05). Knee joint flexion angles were higher (P < 0.05) and net external knee extension (KE) moments in mid to late stance lower in the effusion group. CONCLUSION Quadriceps and hamstrings activation during walking were altered when effusions were present. Increased knee flexion (KF) angles and decreased KE moment in mid-late stance provide a mechanical explanation for the effect of joint effusion on muscle activation in those with knee OA.


title: Robotic surgery in gynecologic oncology: impact on fellowship training.

text: OBJECTIVES To report the impact of a new robotic surgery program on the surgical training of gynecologic oncology fellows over a 12 month period of time. METHODS A robotic surgery program was introduced into the gynecologic oncology fellowship program at Northwestern University Feinberg School of Medicine in June 2007. A database of patients undergoing surgical management of endometrial and cervical cancer between July 2007 and July 2008 was collected and analyzed. Changes in fellow surgical training were measured and analyzed. RESULTS Fellow surgical training for endometrial and cervical cancer underwent a dramatic transition in 12 months. The proportion of patients undergoing minimally invasive surgery increased from 3.3% (4/110 patients) to 43.5% (47/108 patients). Fellow training transitioned from primarily an open approach (94.4%) to a minimally invasive approach (11% laparoscopic, 49% robotic, 40% open) for endometrial cancer stagings, and from an open approach (100%) to an open (50%) and robotic (50%) approach for radical hysterectomies. Fellow participation in robotic procedures increased from 45% in the first 3 months to 72% within 6 months, and 92% by 12 months. The role of the fellow in robotic cases transitioned from bedside assistant to console operator within 3 months. CONCLUSIONS Fellow surgical training underwent a dramatic change with the introduction of a robotic surgery program. The management of endometrial and cervical cancer was impacted the most by robotics. Robotic surgery broadened fellowship surgical training, but balanced surgical training and standardized fellow training modules remain challenges for fellowship programs.


title: Gross Morphometry, Histomorphometry, and Immunohistochemistry Confirm Early and Persistent Jejunal Crypt Hyperplasia in Poults with Enteritis and Depressed Growth.

text: Phosphorylated histone 3 (PH3) and cleaved caspase 3 (CCASP3) were used to detect proliferating and apoptotic cells, respectively, in the jejunums of female sibling poults, with and without enteritis and depressed growth, from hatch to day 35. Poults that developed enteritis and depressed growth (SIB flock) were raised on a commercial farm in eastern North Carolina, whereas poults with normal growth and no enteritis (TAU flock) were raised in the Teaching Animal Unit at North Carolina State University College of Veterinary Medicine. Beginning on day 5 through day 35 and at processing, TAU poults were significantly heavier than SIB poults. Jejunal weights, relative jejunal weights, and jejunal densities were greater in SIB poults from day 10 through 35. Jejunal efficiency (body weight /jejunal length) was higher in TAU poults at day 5 and days 10 through 35. Mucosal thickness was greater in SIB poults between days 7 and 21 but greater in TAU poults at days 28 and 35. From day 7 to 35, villus-to-crypt ratios were higher for TAU poults and lower for SIB poults because hyperplastic crypts formed a greater percentage of the mucosa in SIB poults. By day 7, PH3- and CCASP3-positive cells were increased in SIB poults, showing that mucosal changes resulted from combined crypt epithelial hyperplasia and increased apoptosis of villous enterocytes. Findings in this study confirm that enteritis, in the absence of clinical signs, and depressed growth in turkey poults begins by day 7, can be identified microscopically, persists for at least 35 days, is associated with lower processing weights, and has a profound negative effect on turkey growth.


title: Early Mobilization in Critically Ill Children: A Systematic Review.

text: OBJECTIVE To characterize how early mobilization is defined in the published literature and describe the evidence on safety and efficacy on early mobilization in critically ill children. STUDY DESIGN Systematic search of randomized and nonrandomized studies assessing early mobilization-based physical therapy in critically ill children under 18 years of age in MEDLINE, Embase, CINAHL, CENTRAL, the National Institutes of Health, Evidence in Pediatric Intensive Care Collaborative, Physiotherapy Evidence Database, and the Mobilization-Network. We extracted data to identify the types of mobility-based interventions and definitions for early, as well as barriers, feasibility, adverse events, and efficacy outcomes (mortality, morbidities, and length of stay). RESULTS Of 1199 titles found, we included 11 studies (2 pilot trials and 9 observational studies) and 1 clinical practice guideline in the analyses. Neurodevelopmentally appropriate increasing mobility levels have been described for critically ill children, and "early" mobilization was defined as either a range (within 48-72 hours) from admission to the pediatric intensive care unit or when clinical safety criteria are met. Current evidence suggests that early mobilization is safe and feasible and institutional practice guidelines significantly increase the frequency of rehabilitation consults, improve the proportion of patients who receive early mobilization, and reduce the time to mobilization. However, there were inconsistencies in populations and interventions across studies, and imprecision and risk of bias in included studies that precluded us from pooling data to evaluate the efficacy outcomes of early mobilization. CONCLUSIONS The definition of early mobilization varies, but seems to be feasible and safe in critically ill children. The efficacy for early mobilization in this population is yet undetermined because of the low certainty of the evidence available.


title: Haemorrhage control in the prehospital setting: a scoping review protocol.

text: INTRODUCTION Prehospital haemorrhage control has saved thousands of lives in the military over the last decade. While uncontrolled haemorrhage is a leading cause of preventable injury death in the USA for individuals under 45, military prehospital haemorrhage control techniques have not fully translated to the civilian sector in the USA. The effective implementation of haemorrhage control for civilian prehospital trauma is dependent on a more complex array of system and personnel-level factors than the military. OBJECTIVE This protocol describes the methodology of a scoping review on haemorrhage control strategies in the prehospital setting; specifically, education, logistics and implementation of these strategies. The aim of the review is to identify research gaps and create recommendations for future research surrounding prehospital layperson haemorrhage control. METHODS The protocol uses the framework published by The Joanna Briggs Institute and Arksey and O'Malley, while following the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols guidelines. The search strategy was refined with the help of a medical librarian. Three peer-reviewed databases (EMBASE, PubMed and Web of Science), databases dedicated to grey literature sources, and reference mining will be used. Two investigators will independently screen and extract data. Discrepancies will be resolved by a third investigator. The extracted data will undergo descriptive analysis of the contextual data and a quantitative analysis using the appropriate statistical methods. In addition, this search strategy will be supplemented by a grey literature search. ETHICS AND DISSEMINATION Research ethics approval is not required for this scoping review. This scoping review will serve to highlight existing gaps within the literature to guide further research and develop future strategies to improve prehospital haemorrhage management. The results of this review will be presented at relevant national and international conferences and published in a peer-reviewed journal.


title: Single-incision multiport laparoscopic cholecystectomy for a patient with situs inversus totalis: report of a case.

text: Laparoscopic cholecystectomy has become the standard treatment for symptomatic cholelithiasis in patients with situs inversus totalis (SIT). Nowadays, single-incision multiport laparoscopic surgery is safe and feasible for treating benign gallbladder disease. We report a case of successful single-incision multiport laparoscopic cholecystectomy for a patient with SIT, and describe its technical advantages.


title: Persistent infection and pancytopenia associated with ferret systemic coronaviral disease in a domestic ferret.

text: Ferret systemic coronaviral disease (FSCD) is a well-established cause of mortality in domestic ferrets. We describe herein novel findings in a case of FSCD that was diagnosed and medically managed following virus detection by immunohistochemical (IHC) staining of surgical biopsy samples. Hematologic changes in this ferret suggested spread of the virus to the bone marrow, which was confirmed by IHC staining of a postmortem sample. Genotyping of the virus indicated that the virus grouped with alphacoronaviruses and was most closely related to ferret enteric coronavirus (FRECV) MSU-2. Our clinical case demonstrates that a FRECV MSU-2-like ferret coronavirus associated previously with the enteric pathotype may cause systemic disease, including bone marrow involvement causing persistent pancytopenia.


title: Isolation, propagation, genome analysis and epidemiology of HKU1 betacoronaviruses.

text: From 1 January 2009 to 31 May 2013, 15 287 respiratory specimens submitted to the Clinical Virology Laboratory at the Children's Hospital Colorado were tested for human coronavirus RNA by reverse transcription-PCR. Human coronaviruses HKU1, OC43, 229E and NL63 co-circulated during each of the respiratory seasons but with significant year-to-year variability, and cumulatively accounted for 7.4-15.6 % of all samples tested during the months of peak activity. A total of 79 (0.5 % prevalence) specimens were positive for human betacoronavirus HKU1 RNA. Genotypes HKU1 A and B were both isolated from clinical specimens and propagated on primary human tracheal-bronchial epithelial cells cultured at the air-liquid interface and were neutralized in vitro by human intravenous immunoglobulin and by polyclonal rabbit antibodies to the spike glycoprotein of HKU1. Phylogenetic analysis of the deduced amino acid sequences of seven full-length genomes of Colorado HKU1 viruses and the spike glycoproteins from four additional HKU1 viruses from Colorado and three from Brazil demonstrated remarkable conservation of these sequences with genotypes circulating in Hong Kong and France. Within genotype A, all but one of the Colorado HKU1 sequences formed a unique subclade defined by three amino acid substitutions (W197F, F613Y and S752F) in the spike glycoprotein and exhibited a unique signature in the acidic tandem repeat in the N-terminal region of the nsp3 subdomain. Elucidating the function of and mechanisms responsible for the formation of these varying tandem repeats will increase our understanding of the replication process and pathogenicity of HKU1 and potentially of other coronaviruses.


Food (in)security in Brazil in the context of the SARS-CoV-2 pandemic.


title: Surgical Intervention for Non-Small-Cell Lung Cancer Patients with Pleural Carcinomatosis: Results From the Japanese Lung Cancer Registry in 2004.

text: INTRODUCTION A subset of non-small-cell lung cancer (NSCLC) patients with malignant pleural effusion and/or malignant pleural nodules is now classified as stage IV and is generally considered a contraindication to surgery. However, several reports have demonstrated that the prognosis of patients with pleural carcinomatosis first detected at thoracotomy is relatively favorable. The aim of this study was to describe the results of surgical intervention in NSCLC patients with pleural carcinomatosis in Japan. METHODS In 2010, the Japanese Joint Committee of Lung Cancer Registry conducted a nationwide registration of lung cancer patients who underwent surgery in 2004. Using this database, we performed a retrospective study focused on pleural carcinomatosis. We examined the clinicopathological features, the current status of therapy, and surgical outcomes in patients with pleural carcinomatosis. RESULTS Among the 11,420 registered NSCLC patients, 329 (2.9%) patients had pleural carcinomatosis. The median survival time and 5-year survival rate of 313 patients without other metastatic disease were 34.0 months and 29.3%, respectively. Primary tumor resection was performed in 256 (81.8%) patients, and macroscopic complete resection was achieved in 152 (48.6%) patients, with 5-year survival rates of 33.1% and 37.1%, respectively. Multivariate analysis revealed that Eastern Cooperative Oncology Group performance status (p < 0.001), best stage nodal status (p = 0.002), and the presence or absence of gross residual tumor (p = 0.013) were independent predictors of survival. CONCLUSION In our surgical registry for NSCLC, patients with pleural carcinomatosis accounted for 2.9%, and macroscopic complete resection for them was associated with better survival.


title: Erratum: COVID-19, Australia: Epidemiology Report 15 (Reporting week to 23:59 AEST 3 May 2020).

text: An error in data processing resulted in the tabulation of incorrect crude case fatality rate values, for age groups of 50-59 and above, in Table 5 (Crude Case Fatality Rate of all cases and hospitalised cases, by age group) as originally published in the COVID-19 (Australia) epidemiology report 14. The table below provides the corrected values.


title: Optimizing working space in laparoscopy: CT-measurement of the effect of neuromuscular blockade and its reversal in a porcine model.

text: OBJECTIVE The objective of this paper was to determine the effect of neuromuscular blockade (NMB) on working space in a porcine laparoscopy model. BACKGROUND Conflicting results on the effect of NMB on laparoscopic working space are found in literature. Almost all studies are limited by absence of objective assessment of working space or use surrogate outcomes. METHODS In a standardized porcine laparoscopy model, laparoscopic working-space dimensions with and without NMB were investigated in 16 animals using computed tomography at intra-abdominal pressures of 0, 5, 10, and 15 mmHg during multiple runs of abdominal insufflation. RESULTS No statistically significant effect of NMB on abdominal dimensions and laparoscopic working-space volume was found during CO2 pneumoperitoneum. In contrast, the effect of pre-stretching of the abdominal wall by a previous abdominal insufflation was found to be significant. CONCLUSIONS This experimental study confirms the results from several clinical studies that NMB does not influence laparoscopic working space. Studies dealing with working space during laparoscopy should take note of pre-stretching bias.


title: Ceftriaxone-Resistant Neisseria gonorrhoeae, Canada, 2017.

text: We identified a ceftriaxone-resistant Neisseria gonorrhoeae isolate in a patient in Canada. This isolate carried the penA-60 allele, which differs substantially from its closest relative, mosaic penA XXVII (80% nucleotide identity). Epidemiologic and genomic data suggest spread from Asia. Antimicrobial susceptibility surveillance helps prevent spread of highly resistant N. gonorrhoeae strains.


title: Comparison of various methods of mesoappendix dissection in laparoscopic appendectomy.

text: PURPOSE Although laparoscopic appendectomy is one of the most commonly performed operations, operation procedures vary widely according to the surgeon. In particular, various methods using different instruments have been used for mesoappendix dissection, such as endostapler, endoclip (EC), Harmonic(®) (Ethicon Endo-Surgery, Cincinnati, OH) scalpel (HS), electrocautery, and LigaSure™ (Covidien, Mansfield, MA). Here we compared the results of mesoappendix dissection by EC, HS, and monopolar electrocautery (ME). SUBJECTS AND METHODS The study was performed on 1178 patients who received laparoscopic appendectomy at the Armed Forces Capital Hospital, Seongnam, Korea, from January 2003 to April 2013. Patients receiving mesoappendix dissection involving EC, HS, or ME were enrolled. Patient demographics, pathology of appendix, and perioperative data including operation time, hospital stay, and complications were analyzed. A theoretical model of disposable cost was constructed for each method to compare cost-effectiveness. RESULTS The average operation time for the 1178 patients was 58.0±24.9 minutes for the EC group, 51.4±25.5 minutes for the HS group, and 57.7±25.7 minutes for the ME group. The time for the HS group was significantly shorter. Hospital stay and complication rates did not differ. Disposable costs were 620,350 South Korean won (KRW) (571 U.S. dollars) for the EC group, 1,041,230 KRW (959 U.S. dollars) for the HS group, and 491,230 KRW (452 U.S. dollars) for the ME group. CONCLUSIONS The operation time of ME was similar to that of EC. Although HS had a significantly shorter operation time, the operation time of all three methods was under 60 minutes. All three methods had acceptable complication rates. ME was the most cost-effective method and, given the other similarities, can be recommended for mesoappendix dissection in laparoscopic appendectomy.


title: Anti-carbohydrate antibodies of normal sera: findings, surprises and challenges.

text: We have used microchip format glycan array to characterize the individual carbohydrate recognition patterns by antibodies (Ab) in sera of 106 healthy donors. The glycan library included blood group antigens and other most frequent terminal oligosaccharides and their cores of mammalian N- and O-linked glycoproteins and glycolipids, tumor-associated carbohydrate antigens, and common components of bacterial/pathogenic polysaccharides and lipopolysaccharides, totally 205 glycans. The serum Ab interacted with at least 50 normal human glyco-motifs. Apart from expected blood group-, xeno- (heterophil) and infection-related binding activities, we observed a number of new and unexpected features. The surprising, relatively high antibody binding was found to the blood group P(1) and P(k) trisaccharides and H(type 2) trisaccharide. Novel and very high binding activities have been observed towards Galbeta1-3GlcNAc (Le(C)) related glycans, especially 3'-O-Su-Le(C), and towards 4'-O-sulfated lactosamine. Relatively high and uniform Ab binding to GalNAcalpha1-3Gal disaccharide demonstrated absence of correlation with fucosylated blood group A GalNAcalpha1-3(Fucalpha1-2)Gal antigen-similarly to well known relationship between Galalpha1-3Gal and true, fucosylated blood group B Galalpha1-3(Fucalpha1-2)Gal antigen. The binding intensity to Galalpha1-3Galbeta1-4GlcNAc xenoantigen was shown to be rather modest. Absence or very low Ab binding was found against oligosialic acid, sialooligosaccharides except SiaT(n), type 2 backbone glycans such as Le(y), and biantennary N-chain as well as its truncated forms, i.e. without terminal Sia, SiaGal, and SiaGalGlcNAc motifs. We have also found that Ab are capable of recognizing the short inner core typical for glycolipids (-Galbeta1-4Glc) and glycoproteins (-GalNAcalpha) as a fragment of bigger glycans.


title: Laparoscopic adjustable gastric band revisional surgery: a single surgeon series.

text: BACKGROUND Laparoscopic adjustable gastric banding (LAGB) is a safe and proven surgical option for morbid obesity; however, the need for revisional surgery is being increasingly reported. This study reports outcomes and incidence for a large cohort of patients requiring revisional LAGB surgery for various indications. METHODS A retrospective review of prospectively collected data for 1524 primary LAGB placed between 2003 and 2013 by a single surgeon at a single institution was performed, analysing data for all patients in this cohort requiring revisional LAGB surgery. RESULTS A total of 434 revisions were performed on 349 patients. A total of 278 patients had a single revision, with 71 patients having two or more revisions. Revisions amounting to 213 were band repositions, 68 were band removal only and 153 were band removal with conversion to another bariatric procedure, mostly Roux-en-Y gastric bypass (n = 143). A total of 47 (35.1%) 'band-to-band' revision patients were lost to follow-up. Patients undergoing 'band-to-band' revision for a slipped band, patient intolerance and mechanical band failure had mean excess weight loss (EWL) at 4 years of 49.9% (n = 35), 38.6% (n = 10) and 67.4% (n = 6), respectively. Port or tubing revisions were not included. Mean follow-up for 'band-to-band' revision patients was 33.4 months (standard deviation 26.4 months). 22.9% of patients required one or more band revision procedures by 2013, increased from 13% in 2008. CONCLUSION Continued EWL is achieved with repositioning or replacement of a LAGB. However, a significant and increasing rate of re-operation over time exists.


title: CD10 in the developing human kidney: immunoreactivity and possible role in renal embryogenesis.

text: CD10 was first identified in tumor cells of acute lymphoblastic leukemia. Most studies on CD10 expression have dealt with tumor pathology. Since no data are available for specific role in the fetal kidney, this study aimed at investigating CD10 expression during the different phases of renal embryogenesis. To this end, the expression of CD10 was evaluated in the kidney of two human fetus and in three newborns. In both fetuses, immunostaining for CD10 was compartmentalized and mainly concentrated in the mid-deep cortex. Reactivity for CD10 was stronger in the glomerular epithelium, in proximal tubules and in metanephric mesenchymal cells. At 25 weeks of gestation, CD10 was also detected in the subcapsular regions, including some pretubular aggregates of cap mesenchymal cells and renal vesicles. At 34 weeks of gestation, we observed an increased immunoreactivity for CD10 in visceral and parietal glomerular epithelium. At 39 weeks of gestation, CD10 was also expressed in the collecting tubules and in the Henle loops. Our data show a strong expression of CD10 in all stage of human kidney development, characterized by dynamic changes and support the hypothesis that CD10 plays a relevant role in renal embryogenesis.


Covid-19: Sweden should have done more, says architect of country's strategy.


title: Patient-Reported GI Outcomes in Patients With Anal Cancer Receiving Modern Chemoradiation.

text: PURPOSE Among patients with anal cancer, chemoradiotherapy is often associated with toxicities that diminish quality of life. We describe the GI-related patient-reported outcomes (PROs) of patients with anal cancer receiving chemoradiotherapy to improve patient-physician communication. METHODS We prospectively followed patients with nonmetastatic squamous cell carcinoma of the anal canal who received definitive chemoradiotherapy. Patients completed the bowel subdomain of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire before treatment and at 4 subsequent timepoints. We used the paired Wilcoxon test to compare EPIC scores at different times. RESULTS The study included 21 patients; median age was 57 years. Most patients (52%) had T2 and either N0 or N1 disease (81%). Most patients (91%) received chemotherapy with cisplatin-fluorouracil and either intensity-modulated radiotherapy or volumetric modulated arc therapy. Compared with the patients' median overall summary score at baseline (66), their median score at 1 week (82) was higher (P = .009), whereas their median score at 5 weeks (54) was lower (P = .025). The patients' median overall summary score at baseline and at 3 months did not differ (P = .919). Three months after radiotherapy, most patients reported minimal adverse effects compared with baseline. CONCLUSION The GI-related PROs of patients with anal cancer tend to fluctuate during radiotherapy but return to baseline by 3 months, at which time most patients report few or no residual adverse effects. We provide a clear timeline of GI acute toxicity using sequential PRO measurements that will improve patient-physician communication regarding expectations for cancer treatment.


title: Effect of ultrasound-guided central venous catheter insertion on the incidence of catheter-related bloodstream infections and mechanical complications.

text: BACKGROUND Central venous catheters (CVCs) are necessary for critically ill patients, including those with hematological malignancies. However, CVC insertion is associated with inevitable risks for various adverse events. Whether ultrasound guidance decreases the risk of catheter-related infection remains unclear. METHODS We observed 395 consecutive CVC insertions between April 2009 and January 2013 in our hematological oncology unit. Because the routine use of ultrasound guidance upon CVC insertion was adopted based on our hospital guidelines implemented after 2012, the research period was divided into before December 2011 (early term) and after January 2012 (late term). RESULTS Underlying diseases included hematological malignancies and immunological disorders. In total, 235 and 160 cases were included in the early- and late term groups, respectively. The median insertion duration was 26 days (range, 2-126 days) and 18 days (range, 2-104 days) in the early- and late term groups, respectively. The internal jugular, subclavian, and femoral veins were the sites of 22.6, 40.2, and 25.7% of the insertions in the early term group and 32.3, 16.9, and 25.4% of the insertions in the late term group, respectively. The frequency of catheter-related bloodstream infection (CRBSI) was 1.98/1000 catheter days and 2.17/1000 catheter days in the early- and late term groups, respectively. In the subgroup analysis, the detected causative pathogens of CRBSI did not differ between the two term groups; gram-positive cocci, gram-positive bacilli, and gram-negative bacilli were the causative pathogens in 68.9, 11.5, and 14.8% of the cases in the early term group and in 68.2, 11.4, and 18.2% of the cases in the late term group, respectively. In the multivariate analysis to determine the risk of CRBSI, only age was detected as an independent contributing factor; the indwelling catheter duration was detected as a marginal factor. A significant reduction in mechanical complications was associated with the use of ultrasound guidance. CONCLUSIONS Ultrasound-guided CVC insertion did not decrease the incidence of CRBSI. The only identified risk factor for CRBSI was age in our cohort. However, we found that the introduction of ultrasound-guided insertion triggered an overall change in safety management with or without the physicians' intent.


title: Hypomagnesaemia in suckler cows.

text: Hypomagnesaemia in housed and grazing suckler cows. Coronavirus infection in cows. Suspected nitrite toxicity in lambs associated with feeding broccoli. Maedi visna in ewes. Mycotic pneumonia in a wildcat. These are among matters discussed in the disease surveillance report for November 2015 from SAC Consulting: Veterinary Services (SAC C VS).


title: Cost-analysis of robotic-assisted laparoscopic hysterectomy versus total abdominal hysterectomy for women with endometrial cancer and atypical complex hyperplasia.

text: INTRODUCTION The aim of this study was to analyse the hospital cost of treatment with robotic-assisted laparoscopic hysterectomy and total abdominal hysterectomy for women with endometrial cancer or atypical complex hyperplasia and to identify differences in resource use and cost. MATERIAL AND METHODS This cost analysis was based on two cohorts: women treated with robotic-assisted laparoscopic hysterectomy (n = 202) or with total abdominal hysterectomy (n = 158) at Copenhagen University Hospital, Herlev, Denmark. We conducted an activity-based cost analysis including consumables and healthcare professionals' salaries. As cost-drivers we included severe complications, duration of surgery, anesthesia and stay at the post-anesthetic care unit, as well as number of hospital bed-days. Ordinary least-squares regression was used to explore the cost variation. The primary outcome was cost difference in Danish kroner between total abdominal hysterectomy and robotic-assisted laparoscopic hysterectomy. RESULTS The average cost of consumables was 12,642 Danish kroner more expensive per patient for robotic-assisted laparoscopic hysterectomy than for total abdominal hysterectomy (2014 price level: 1€ = 7.50 Danish kroner). When including all cost-drivers, the analysis showed that the robotic-assisted laparoscopic hysterectomy procedure was 9386 Danish kroner (17%) cheaper than the total abdominal hysterectomy (p = 0.003). When the robot investment was included, the cost difference reduced to 4053 Danish kroner (robotic-assisted laparoscopic hysterectomy was 7% cheaper than total abdominal hysterectomy) (p = 0.20). Increasing age and Type 2 diabetes appeared to influence the overall costs. CONCLUSION For women with endometrial cancer or atypical complex hyperplasia, robotic-assisted laparoscopic hysterectomy was cheaper than total abdominal hysterectomy, mostly due to fewer complications and shorter length of hospital stay.


title: Serotype and genotype diversity of infectious bronchitis viruses isolated during 1985-2008 in Guangxi, China.

text: The genetic diversity of the hypervariable region I of S1 gene (HVR I) of infectious bronchitis (IB) vaccine strains H120, Ma5 and 4/91 was compared to that of 26 infectious bronchitis virus (IBV) strains isolated from the field in Guangxi province of China during the years 1985-2008, and the field isolates were classified into five major genotypes. Monovalent antisera against three vaccine strains and seven field isolates of different genotypes were prepared by immunizing rabbits with mineral oil adjuvant preparations containing viruses propagated in chicken embryos. Virus neutralization (VN) tests were performed in tracheal organ cultures (TOCs) using these 10 strains with the antisera, and a one-way VN test was then used to compare the relationship of 10 monovalent antisera to the other 19 field isolates. As a result, seven different serotypes were classified based on the results of VN tests with the 26 isolates plus the three vaccine strains. We found that different serotypes were prevalent during different time periods, that more new serotypes have been prevalent in more recent years, and the prevalence of the original dominant serotype has been in constant decline since 2004. In addition, the concordance rate of the 26 field isolates between the S1 genotypes and serotypes was 57.7%.


title: Comparison of the Force Required for Dislodgement Between Secured and Unsecured Airways.

text: INTRODUCTION Airway device placement and maintenance are of utmost importance when managing critically ill patients. The best method to secure airway devices is currently unknown. STUDY OBJECTIVE We sought to determine the force required to dislodge 4 types of airways with and without airway securing devices. METHODS We performed a prospective study using 4 commonly used airway devices (endotracheal tube [ETT], laryngeal mask airway [LMA], King laryngeal tube [King], and iGel) performed on 5 different mannequin models. All devices were removed twice per mannequin in random order, once unsecured and once secured as per manufacturers' recommendations; Thomas Tube Holder (Laerdal, Stavanger, Norway) for ETT, LMA, and King; custom tube holder for iGel. A digital force measuring device was attached to the exposed end of the airway device and gradually pulled vertically and perpendicular to the mannequin until the tube had been dislodged, defined as at least 4 cm of movement. Dislodgement force was reported as the maximum force recorded during dislodgement. We compared the relative difference in the secured and unsecured force for each device and between devices using a random-effects regression model accounting for variability in the manikins. RESULTS The median dislodgment forces (interquartile range [IQR]) in pounds for each secured device were: ETT 13.3 (11.6, 14.1), LMA 16.6 (13.9, 18.3), King 21.7 (16.9, 25.1), and iGel 8 (6.8, 8.3). The median dislodgement forces for each unsecured device were: ETT 4.5 (4.3, 5), LMA 8.4 (6.8, 10.7), King 10.6 (8.2, 11.5), and iGel 3.9 (3.2, 4.2). The relative difference in dislodgement forces (95% confidence intervals) were higher for each device when secured: ETT 8.6 (6.2 to 11), LMA 8.8 (4.6 to 13), King 12.1 (7.2 to 16.6), iGel 4 (1.1 to 6.9). When compared to secured ETT, the King required greater dislodgement force (relative difference 8.6 [4.5-12.7]). The secured iGel required less force than the secured ETT (relative difference -4.8 [-8.9 to -0.8]). CONCLUSION Compared with a secured device, an unsecured airway device requires only half the force to cause airway dislodgement. The secured King had the highest dislodgement force relative to the other studied devices.


title: An experimental study exploring the relationship between the size of bacterial inoculum and bacterial adherence to prosthetic mesh.

text: BACKGROUND Infection is a major concern with medical implants. Surgical meshes used for the repair of abdominal wall hernias are associated with wound infection rates ranging from 7 to 18 %. Although mesh infection is relatively rare, once a patient shows clinical signs of mesh infection, the surgeon may be required to remove the mesh, resulting in additional surgery, morbidity, and cost. The usual causative organisms associated with cases of mesh infection are Staphylococcus species. The first stage of implant infection is bacterial adherence to the biomaterial. An accurate assessment of adherent bacteria to medical prosthetics is therefore important in order to determine the infection risk associated with surgical implants. METHODS This experimental study evaluated the relationship between the size of the bacterial inoculum and bacterial adherence to three commonly used hernia prosthetics (polypropylene, polyester, and ePTFE). Tenfold dilutions of S. epidermidis (Evans-ATCC 12228) and S. aureus (Rosenbach-ATCC 25923), created with phosphate-buffered saline, were used to inoculate each of the meshes in 3 ml of tryptone soya broth for 18 h at 37 °C, 95 % air/5 % CO(2). The number of viable bacteria in each dilution was calculated using a spot plate technique. The number of adherent bacteria to the meshes was counted using direct imaging analysis with scanning electron microscopy and expressed as a mean. RESULTS One hundred eight mesh samples were analysed. The size of the bacterial inoculum of S. epidermidis significantly influenced the number of adherent bacteria to the mesh, and lower rates of adhesion were observed with smaller inoculums for all three meshes (polypropylene, p = 0.02; ePTFE p = 0.03; polyester p = 0.02). A similar, albeit less profound, pattern of results was observed with S. aureus. Bacterial adherence was observed with inoculum sizes as small as <10 bacteria. CONCLUSIONS The results demonstrate that even a very low number of bacterial inoculums can result in adherence to hernia biomaterials and that the level of adherence is directly related to the size of the inoculum. These in vitro results provide evidence that the size of the inoculum is important in the colonization of hernia biomaterials and demonstrate the importance of minimising the bacterial inoculum in the clinical setting.


USC referrals.


Covid-19: The inside story of the RECOVERY trial.


title: What to do when it is technically impossible to perform laparoscopic sleeve gastrectomy.

text: BACKGROUND Laparoscopic sleeve gastrectomy (LSG) is increasingly popular with surgeons because of its apparent technical ease. However, performing LSG safely is sometimes not possible during laparoscopy. The objectives of the present study were to (i) describe the context of LSG failure and (ii) suggest preoperative care options or strategies that enable secondary LSG to be performed safely. METHODS We studied patients having undergone primary and secondary LSG between January 2008 and July 2013. The primary efficacy criterion was the LSG success rate. The secondary efficacy criteria were preoperative care procedures, the complication rate, the failure rate, and the frequency of conversion to open surgery. RESULTS During the study period, 954 patients underwent first- or second-line LSG. Laparoscopic sleeve gastrectomy was technically impossible in 12 patients (1.2 %). The cause of failure was a large left liver lobe in seven cases (58.3 %) and a lack of space in five cases. Of these 12 patients, nine underwent secondary LSG. The median preoperative BMI before the first LSG was 51.5 kg/m(2). The median (range) time interval between the two LSG attempts was 6 months (3-37). Prior to secondary LSG, the preoperative weight reduction measure was a diet in seven cases (78 %), an intragastric balloon in one case, and no treatment in one case. The median preoperative excess weight loss (EWL) before the second LSG was 10 % (0-20). Five LSGs were successful, two required conversion to open surgery, and two failed again. There were two postoperative complications (22 %), both of which concerned the two patients with conversion to laparotomy. CONCLUSIONS In the event of LSG technical failure, preoperative weight loss may enable a second attempt at laparoscopic treatment. A preoperative EWL of at least 10 % appears to be required for the avoidance of conversion to laparotomy.


title: Correlation of abdominal rSO2 with superior mesenteric artery velocities in preterm infants.

text: OBJECTIVE Near-infrared spectroscopy (NIRS) is used to monitor brain and kidney perfusion in at-risk premature and term neonates. Although NIRS holds potential for bedside monitoring of intestinal perfusion, there is insufficient evidence showing correlation with mesenteric blood flow. To determine if an association exists between abdominal regional oxygen saturation (A-rSO2) and mesenteric blood flow, we compared changes in A-rSO2 to changes in blood flow velocity in the superior mesenteric artery (SMA) before and after feedings in very-low birthweight infants. STUDY DESIGN A-rSO2 was continuously monitored midline below the umbilicus for 3 days in 18 stable 25 to 31 week bolus-fed infants (median BW 1203 g, median age 5 days). We compared change in SMA velocity from immediately before to 10 min and 60 to 120 min after feeding with change in A-rSO2 over the same time. Spearman's rank correlation was used to ascertain if a significant association existed. RESULT Change in A-rSO2 was significantly associated with change in systolic, diastolic, and mean SMA velocity from fasting to 60 to 120 min after feeding (P=0.016, 0.021, 0.010) and from 10 min after a feed to 60 to 120 min after feeding (P=0.009, 0.035, 0.032). CONCLUSION In very preterm infants, A-rSO2 reflects blood flow in the SMA and can provide non-invasive continuous monitoring of intestinal perfusion. Further studies are indicated to determine the sensitivity of NIRS to detect early intestinal pathology in this population.


title: A comparison of functional and physical properties of self-expanding intracranial stents [Neuroform3, Wingspan, Solitaire, Leo+, Enterprise].

text: PURPOSE 5 self-expanding intracranial stents Neuroform (N), Wingspan (W), Solitaire (S), Leo(+) (L), and Enterprise (E) were subjected to an in vitro examination and comparison of their physical features and functional properties in order to better understand the clinical advantages and potential limitations of each device. MATERIAL AND METHODS The following features were examined for each stent: visual appearance, radial strength, wall apposition, bending stiffness, gator backing, kink resistance, ovalization, vessel wall coverage, cell size, ease of delivery. RESULTS Given are rankings for the 5 stents: radial force at 50% oversizing: L<N<E<S<W; radial force at 15% oversizing L<E<S<N<W; wall apposition: E<N=W<S; bending stiffness: N<L<W<S<E; gator backing: N and W only; kink resistance: N=W<E<S<L; ovalization: W<L<S<N<E; vessel wall coverage: S<E<N<W<L; cell size: L<W<E<N<S; ease of delivery: W<N<L<E<S. A comparative analysis of the in vitro test results with the clinical experience of the authors is presented in this paper. CONCLUSION The 5 stents have fundamentally different features and there is no stent that is superior in all tested aspects. The selection in an individual treatment should be based on clinical and technical requirements.


title: Flattening the emotional distress curve: A behavioral health pandemic response strategy for COVID-19.

text: This article proposes a framework for managing the behavioral health impacts of the COVID-19 global pandemic. This framework aligns and should be integrated with an existing public health pandemic intervals model. It includes six phases of a behavioral health pandemic response strategy: preplanning, response readiness, response mobilization, intervention, continuation, and amelioration. The ways behavioral health specialists can capitalize on their competence in the leadership, prevention, education, service, research, and advocacy domains within each behavioral health pandemic response phase are articulated. Behavioral health expertise can help ensure a more comprehensive, effective pandemic response that facilitates the flattening of the curve of disease spread, along with the corresponding emotional distress curve. A case illustration, the Caring Communities (CC) initiative, is offered as an exemplar of action steps in the leadership, prevention, education, service, research, and advocacy domains that behavioral health professionals can take within each of the behavioral health pandemic response phases. Key CC action steps include providing support groups, offering virtual wellness breaks, participating in educational outreach, creating and disseminating wellness guides, launching and leading a virtual behavioral health clinic for health care staff, participating in behavioral health research and program evaluation, and engaging in advocacy initiatives aimed at improving behavioral health care and addressing and reducing health disparities. Finally, recommendations for optimizing behavioral health contributions to future pandemic responses are proffered. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Endoscopic foregut surgery and interventions: The future is now. The state-of-the-art and my personal journey.

text: In this paper, I reviewed the emerging field of endoscopic surgery and present data supporting the contention that endoscopy can now be used to treat many foregut diseases that have been traditionally treated surgically. Within each topic, the content will progress as follows: "lessons learned", "technical considerations" and "future opportunities". Lessons learned will provide a brief background and update on the most current literature. Technical considerations will include my personal experience, including tips and tricks that I have learned over the years. Finally, future opportunities will address current unmet needs and potential new areas of development. The foregut is defined as "the upper part of the embryonic alimentary canal from which the pharynx, esophagus, lung, stomach, liver, pancreas, and part of the duodenum develop". Foregut surgery is well established in treating conditions such as gastroesophageal reflux disease (GERD), achalasia, esophageal diverticula, Barrett's esophagus (BE) and esophageal cancer, stomach cancer, gastric-outlet obstruction, and obesity. Over the past decade, remarkable progress in interventional endoscopy has culminated in the conceptualization and practice of endoscopic foregut surgery for various clinical conditions summarized in this paper. Regarding GERD, there are now several technologies available to effectively treat it and potentially eliminate symptoms, and the need for long-term treatment with proton pump inhibitors. For the first time, fundoplication can be performed without the need for open or laparoscopic surgery. Long-term data going out 5-10 years are now emerging showing extended durability. In respect to achalasia, per-oral endoscopic myotomy (POEM) which was developed in Japan, has become an alternative to the traditional Heller's myotomy. Recent meta-analysis show that POEM may have better results than Heller, but the issue of post-POEM GERD still needs to be addressed. There is now a resurgence of endoscopic treatment of Zenker's diverticula with improved technique (Z-POEM) and equipment; thus, patients are choosing flexible endoscopic treatment as opposed to open or rigid endoscopy options. In regard to BE, endoscopic submucosal dissection (ESD) which is well established in Asia, is now becoming more mainstream in the West for the treatment of BE with high grade dysplasia, as well as early esophageal cancer. In combination with all the ablation technologies (radiofrequency ablation, cryotherapy, hybrid argon plasma coagulation), the entire spectrum of Barrett's and related dysplasia and early cancer can be managed predominantly by endoscopy. Importantly, in regard to early gastric cancer and submucosal tumors (SMTs) of the stomach, ESD and full thickness resection (FTR) can excise these lesions en-bloc and endoscopic suturing is now used to close large defects and perforations. For treatment of patients with malignant gastric outlet obstruction (GOO), endoscopic gastro-jejunostomy is now showing better results than enteral stenting. G-POEM is also emerging as a treatment option for patients with gastroparesis. Obesity has become an epidemic in many western countries and is becoming also prevalent in Asia. Endoscopic sleeve gastroplasty (ESG) is now becoming an established treatment option, especially for obese patients with body mass index between 30 and 35. Data show an average weight loss of 16 kg after ESG with long-term data confirming sustainability. Finally, in respect to endo-hepatology, there are many new endoscopic interventions that have been developed for patients with liver disease. Endoscopic ultrasound (EUS)-guided liver biopsy and EUS-guided portal pressure measurement are exciting new frontiers for the endo-hepatologists.


An erythematous mass on the lip of a guinea pig (Cavia porcellus).


title: Laparoscopic repair of inguinal hernia with biomimetic matrix.

text: BACKGROUND AND OBJECTIVES Materials utilized for the repair of hernias fall into 2 broad categories, synthetics and biologics. Each has its merits and drawbacks. The synthetics have a permanent, inherent strength but are associated with some incidence of chronic pain. The biologics rely on variable tissue regeneration to give strength to the repair, limiting their use to specific situations. However, thanks to their transient presence and tissue ingrowth, the biologics do not result in a significant incidence of chronic pain. We studied the use of a biomimetic (REVIVE, Biomerix Corporation, Fremont, CA) in this setting in an attempt to obviate the disadvantages of each material. METHODS Fourteen patients underwent laparoscopic repair by totally extraperitoneal and transabdominal preperitoneal techniques of 16 inguinal hernias. Follow-up was as long as 19 mo, and 8 patients were followed for > 12 mo. There were no recurrences and a 5% incidence of functionally insignificant discomfort. RESULTS REVIVE is shown in histology and in vivo to demonstrate regeneration and tissue ingrowth into the polycarbonate/polyuria matrix similar to that in the biologics rather than scarring or encapsulation. There were no recurrences, indicating its strength and resilience as a permanent repair similar to that in the synthetics. CONCLUSION This is proof of the concept that a biomimetic may bridge the gap between the biologics and synthetics and may be able to be utilized on a regular basis with the benefits of both materials and without their drawbacks.


title: Internal retraction in single-port laparoscopic cholecystectomy: initial experience and learning curve.

text: INTRODUCTION We report our experience and learning curve in single-port laparoscopic cholecystectomy (SPLC) using an internal anchored retraction system. METHODS Usefulness of the retraction system was analysed in 18 SPLC. The first eight, the following ten SPLC and 20 consecutive four-port laparoscopic cholecystectomies (4PLC) were compared. Duration of operation, burns on nontarget tissue and gallbladder perforations were assessed by reviewing videotapes recorded during the procedures. RESULTS Use of the retraction system failed in three out of five patients (60%) with intraoperative signs of chronic inflammation and in one out of 13 (7.1%) without such signs (p = 0.0441). Median operation time was 90 (45-120) in the first eight and 55 (40-180) minutes in the following ten SPLC (p = 0.0361). Whereas the first eight SPLC lasted longer compared to 4PLC (70 (40-140) minutes, p = 0.0435) the difference disappeared after eight procedures (p = 0.2076). Median number of burns to nontarget tissue was seven (1-16) in the first eight and one (0-8) in the following ten SPLC (p = 0.0049). There was no difference in perforation of the gallbladder. DISCUSSION Internal retraction enables a safe exposure of the Calot triangle avoiding bile spillage in cholecystectomies without intraoperative signs of inflammation. Familiarisation with SPLC was rapidly achieved. Operation time and dexterity were equal to 4PLC after eight SPLC.


title: Extended protection against phlebovirus infection conferred by recombinant adenovirus expressing consensus interferon (DEF201).

text: Punta Toro virus (PTV; Bunyaviridae, Phlebovirus) is related to Rift Valley fever virus (RVFV), a pathogenic agent which causes severe disease in humans and livestock primarily in the sub-Saharan region of Africa. The recent range expansion of RVFV and the potential for its intentional release into naïve populations pose a significant threat to public health and agriculture. Studies modeling disease in rodents and nonhuman primates have shown that PTV and RVFV are highly sensitive to the antiviral effects of alpha interferon (IFN-α), an important component of the innate antiviral host response. While recombinant IFN-α has high therapeutic value, its utility for the treatment of neglected tropical diseases is hindered by its short in vivo half-life and costly production of longer-lasting pegylated IFNs. Here, we demonstrate extended preexposure protection against lethal PTV challenge following a single intranasal administration of DEF201, which is a replication-deficient human adenovirus type 5 vector engineered to constitutively express consensus IFN-α (cIFN-α) from transduced host cells. DEF201 was also efficacious when administered within 24 h as a postexposure countermeasure. Serum concentrations of cIFN-α could be detected as early as 8 h following treatment and persisted for more than 1 week. The prolonged antiphlebovirus prophylactic effect, low production costs, and ease of administration make DEF201 a promising agent for intervention during natural disease outbreaks and for countering possible bioterrorist acts.


title: Radiofrequency ablation of atypical cartilaginous tumors in long bones: a retrospective study.

text: Purpose: To determine the size of the ablation zone after radiofrequency ablation (RFA) of atypical cartilaginous bone tumors (ACT) using temperature-controlled 20 and 30 mm RFA straight non-cooled electrodes.Materials and methods: Sixteen patients with ACT in their long bones, who had undergone a single-session single-application CT-guided temperature-controlled RFA, were included retrospectively in the study. Tumors with a diameter of 10-25 mm were treated with 20 mm electrodes (n = 10), and tumors of 25-35 mm, with 30 mm electrodes (n = 6). The ablated zone was measured after three months on MRI images.Results: All the tumors were within the ablated zone on the 3-month follow-up MRI scan. The mean ablation time with the electrode, at a target temperature of 90 °C, was 7.6 minutes (range 6-10). The median of the largest ablation diameters, on applying the 20 and 30 mm electrodes, were 42 mm (IQR 8.5, range 30-51 mm) and 44.5 mm (IQR 4.5, range 42-63 mm), respectively.Conclusions: All the retrospectively viewed tumors in the long bones of ACT patients treated with RFA were completely ablated. The ablation zone diameters in the bones were larger than expected, when compared to other tissues, such as the liver.


title: Poliovirus unlinks TIA1 aggregation and mRNA stress granule formation.

text: In response to environmental stress and viral infection, mammalian cells form foci containing translationally silenced mRNPs termed stress granules (SGs). As aggregates of stalled initiation complexes, SGs are defined by the presence of translation initiation machinery in addition to mRNA binding proteins. Here, we report that cells infected with poliovirus (PV) can form SGs early that contain T-cell-restricted intracellular antigen 1 (TIA1), translation initiation factors, RNA binding proteins, and mRNA. However, this response is blocked as infection progresses, and a type of pseudo-stress granule remains at late times postinfection and contains TIA but lacks translation initiation factors, mRNA binding proteins, and most polyadenylated mRNA. This result was observed using multiple stressors, including viral infection, oxidative stress, heat shock, and endoplasmic reticulum stress. Multiple proteins required for efficient viral internal ribosome entry site-dependent translation are localized to SGs under stress conditions, providing a potential rationale for the evolution and maintenance of the SG inhibition phenotype. Further, the expression of a noncleavable form of the RasGAP-SH3 domain binding protein in PV-infected cells enables SGs whose constituents are consistent with the presence of stalled 48S translation preinitiation complexes to persist throughout infection. These results indicate that in poliovirus-infected cells, the functions of TIA self-aggregation and aggregation of stalled translation initiation complexes into stress granules are severed, leading to novel foci that contain TIA1 but lack other stress granule-defining components.


title: Surpass Flow Diverter for Treatment of Posterior Circulation Aneurysms.

text: BACKGROUND AND PURPOSE Flow diverters for the treatment of posterior circulation aneurysms remain controversial. We aimed to identify factors contributing to outcome measures in patients treated with the Surpass flow diverter for aneurysms in this location. MATERIALS AND METHODS We conducted an observational study of 53 patients who underwent flow-diverter treatment for posterior circulation aneurysms at 15 centers. Key outcome measures were mortality, complete aneurysm occlusion, and modified Rankin Scale score at follow-up. RESULTS At follow-up (median, 11.3 months; interquartile range, 5.9-12.7 months), 9 patients had died, resulting in an all-cause mortality rate of 17.3% (95% CI, 7%-27.6%); 7 deaths (14%) were directly related to the procedure and none occurred in patients with a baseline mRS score of zero. After adjusting for covariates, a baseline mRS of 3-5 was more significantly (P = .003) associated with a higher hazard ratio for death than a baseline mRS of 0-2 (hazard ratio, 17.11; 95% CI, 2.69-109.02). After adjusting for follow-up duration, a 1-point increase in the baseline mRS was significantly (P < .001) associated with higher values of mRS at follow-up (odds ratio, 2.93; 95% CI, 1.79-4.79). Follow-up angiography in 44 patients (median, 11.3 months; interquartile range, 5.9-12.7 months) showed complete aneurysm occlusion in 29 (66%; 95% CI, 50.1%-79.5%). CONCLUSIONS Clinical results of flow-diverter treatment of posterior circulation aneurysms depend very much on patient selection. In this study, poorer outcomes were related to the treatment of aneurysms in patients with higher baseline mRS scores. Angiographic results showed a high occlusion rate for this subset of complex aneurysms.


title: Imaging of human epidermal growth factor receptor type 2 expression with 18F-labeled affibody molecule ZHER2:2395 in a mouse model for ovarian cancer.

text: UNLABELLED Affibody molecules are small (7 kDa) proteins with subnanomolar targeting affinity. Previous SPECT studies in xenografts have shown that the Affibody molecule (111)In-DOTA-Z(HER2)(:2395) can discriminate between high and low human epidermal growth factor receptor type 2 (HER2)-expressing tumors, indicating that radiolabeled Affibody molecules have potential for patient selection for HER2-targeted therapy. Compared with SPECT, PET with positron-emitting radionuclides, such as (18)F, may improve imaging of HER2 expression because of higher sensitivity and improved quantification of PET. The aim of the present study was to determine whether the (18)F-labeled NOTA-conjugated Affibody molecule Z(HER2)(:2395) is a suitable agent for imaging of HER2 expression. The tumor-targeting properties of (18)F-labeled Z(HER2)(:2395) were compared with (111)In- and (68)Ga-labeled Z(HER2)(:2395) in mice with HER2-expressing SK-OV-3 xenografts. METHODS Z(HER2)(:2395) was conjugated with NOTA and radiolabeled with (18)F, (68)Ga, and (111)In. Radiolabeling with (18)F was based on the complexation of Al(18)F by NOTA. The 50% inhibitory concentration values for NOTA-Z(HER2)(:2395) labeled with (19)F, (69)Ga, and (115)In were determined in a competitive cell-binding assay using SK-OV-3 cells. Mice bearing subcutaneous SK-OV-3 xenografts were injected intravenously with radiolabeled NOTA-Z(HER2)(:2395). One and 4 h after injection, PET/CT or SPECT/CT images were acquired, and the biodistribution was determined by ex vivo measurement. RESULTS The 50% inhibitory concentration values for (19)F-, (69)Ga-, and (115)In-NOTA-Z(HER2)(:2395) were 5.0, 6.3, and 5.3 nM, respectively. One hour after injection, tumor uptake was 4.4 ± 0.8 percentage injected dose per gram (%ID/g), 5.6 ± 1.6 %ID/g, and 7.1 ± 1.4 %ID/g for (18)F-, (68)Ga-, and (111)In-NOTA-Z(HER2)(:2395), respectively, and the respective tumor-to-blood ratios were 7.4 ± 1.8, 8.0 ± 1.3, and 4.8 ± 1.3. Tumor uptake was specific, because uptake could be blocked efficiently by coinjection of an excess of unlabeled Z(HER2)(:2395). PET/CT and SPECT/CT images clearly visualized HER2-expressing SK-OV-3 xenografts. CONCLUSION This study showed that (18)F-NOTA-Z(HER2)(:2395) is a promising new imaging agent for HER2 expression in tumors. Affibody molecules were successfully labeled with (18)F within 30 min, based on the complexation of Al(18)F by NOTA. Further research is needed to determine whether this technique can be used for patient selection for HER2-targeted therapy.