title: CEACAM1 regulates TIM-3-mediated tolerance and exhaustion.

text: T-cell immunoglobulin domain and mucin domain-3 (TIM-3, also known as HAVCR2) is an activation-induced inhibitory molecule involved in tolerance and shown to induce T-cell exhaustion in chronic viral infection and cancers. Under some conditions, TIM-3 expression has also been shown to be stimulatory. Considering that TIM-3, like cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death 1 (PD-1), is being targeted for cancer immunotherapy, it is important to identify the circumstances under which TIM-3 can inhibit and activate T-cell responses. Here we show that TIM-3 is co-expressed and forms a heterodimer with carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), another well-known molecule expressed on activated T cells and involved in T-cell inhibition. Biochemical, biophysical and X-ray crystallography studies show that the membrane-distal immunoglobulin-variable (IgV)-like amino-terminal domain of each is crucial to these interactions. The presence of CEACAM1 endows TIM-3 with inhibitory function. CEACAM1 facilitates the maturation and cell surface expression of TIM-3 by forming a heterodimeric interaction in cis through the highly related membrane-distal N-terminal domains of each molecule. CEACAM1 and TIM-3 also bind in trans through their N-terminal domains. Both cis and trans interactions between CEACAM1 and TIM-3 determine the tolerance-inducing function of TIM-3. In a mouse adoptive transfer colitis model, CEACAM1-deficient T cells are hyper-inflammatory with reduced cell surface expression of TIM-3 and regulatory cytokines, and this is restored by T-cell-specific CEACAM1 expression. During chronic viral infection and in a tumour environment, CEACAM1 and TIM-3 mark exhausted T cells. Co-blockade of CEACAM1 and TIM-3 leads to enhancement of anti-tumour immune responses with improved elimination of tumours in mouse colorectal cancer models. Thus, CEACAM1 serves as a heterophilic ligand for TIM-3 that is required for its ability to mediate T-cell inhibition, and this interaction has a crucial role in regulating autoimmunity and anti-tumour immunity.


Anosmia: Five minutes with ENT consultant Claire Hopkins.


Management of patients with generalised myasthenia gravis and COVID-19: four case reports.


title: Characterization of the Inflammatory Response to Severe COVID-19 Illness.

text: RATIONALE Coronavirus disease 2019 (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood. OBJECTIVES To define the cytokine profile of COVID-19, and to identify evidence of immunometabolic alterations in those with severe illness. METHODS Levels of interleukin (IL)-1β, IL-6, IL-8, IL-10 and soluble TNF receptor 1 (sTNFR1) were assessed in plasma from healthy volunteers, hospitalized-but-stable COVID-19 patients (COVIDstable), COVID-19 patients requiring intensive care unit (ICU) admission (COVIDICU) and individuals with severe community-acquired pneumonia requiring ICU support (CAPICU). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of alpha-1 antitrypsin (AAT) to COVID-19 was also evaluated. MAIN RESULTS IL-1β, IL-6, IL-8 and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable, and demonstrated higher levels of IL-1β, IL-6 and sTNFR1 - but lower IL-10 - than CAPICU. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2, phosphorylated PKM2, HIF-1α and lactate. The production and sialylation of AAT increased in COVID-19, but this anti-inflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P<0.0001). In critically unwell COVID-19 patients, increases in IL-6:AAT predicted prolonged ICU stay and mortality, while improvement in IL-6:AAT was associated with clinical resolution (P<0.0001). CONCLUSIONS The COVID-19 cytokinemia is distinct from that of other types of pneumonia leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).


Editorial - COVID-19, more than a viral pneumonia.


If a coronavirus vaccine arrives, can the world make enough?


title: Thoracoscopic pericardial window for management of pericardial effusion in 15 dogs.

text: OBJECTIVES To report short-term complications and long-term outcomes of thoracoscopic pericardial window for management of pericardial effusion in dogs. METHODS Retrospective study of dogs in which thoracoscopic pericardial window was performed using a three-cannula technique. Surgery time, complications, postoperative management, area of resected pericardium, histopathology results and outcome were evaluated. RESULTS Diagnoses included dogs with idiopathic pericardial effusion (n = 10), cardiac mass (n = 4) and mesothelioma (n = 1). One case required conversion to sternotomy. Median thoracoscopic surgery time was 52 · 5 (range, 45-80) minutes. Complications occurred in four (26%) cases. Median time to discharge was one (range, 1-6) day. Of dogs with idiopathic pericardial effusion, one is alive at 150 days, one was lost to follow-up at 180 days while eight were euthanased of which five were for unrelated reasons. All dogs with neoplastic causes died or were euthanased because of their illness. Median survival time for dogs with idiopathic pericardial effusion (635 days; range, 70-1165) was significantly longer than that for dogs with neoplasia (30 days; range, 1-107). CLINICAL SIGNIFICANCE Thoracoscopic pericardial window is of low morbidity with short surgery and hospitalisation times. It provides good long-term control of idiopathic pericardial effusion but short-term palliation of clinical signs in dogs with neoplastic disease.


title: Systematic evaluation of dissolved lead sorption losses to particulate syringe filter materials.

text: Distinguishing between soluble and particulate lead in drinking water is useful in understanding the mechanism of lead release and identifying remedial action. Typically, particulate lead is defined as the amount of lead removed by a 0.45-μm filter. Unfortunately, there is little guidance regarding selection of filter membrane material and little consideration to the possibility of the sorption of dissolved lead to the filter. The objective of this work was to examine the tendency of 0.45-μm syringe filter materials to adsorb lead. Tests were performed with water containing 40 and 24 μg/L soluble lead at pH 7 buffered with 50 mg C/L dissolved inorganic concentration (DIC). The amounts of lead sorbed greatly varied by filter, and only two filter types, polypropylene and mixed cellulose esters, performed well and are recommended. Great care must be taken in choosing a filter when filtering soluble lead and interpreting filter results.


title: A critical review of the in vitro and in vivo models for the evaluation of anti-infective meshes.

text: BACKGROUND Infectious complications following mesh implantation for abdominal wall repair appear in 0.7 up to 26.6% of hernia repairs and can have a detrimental impact for the patient. To prevent or to treat mesh-related infection, the scientific community is currently developing a veritable arsenal of antibacterial meshes. The numerous and increasing reports published every year describing new technologies indicate a clear clinical need, and an academic interest in solving this problem. Nevertheless, to really appreciate, to challenge, to compare and to optimize the antibacterial properties of next generation meshes, it is important to know which models are available and to understand them. PURPOSE We proposed for the first time, a complete overview focusing only on the in vitro and in vivo models which have been employed specifically in the field of antibacterial meshes for hernia repair. RESULTS AND CONCLUSION From this investigation, it is clear that there has been vast progress and breadth in new technologies and models to test them. However, it also shows that standardization or adoption of a more restricted number of models would improve comparability and be a benefit to the field of study.


title: Effective method of gallbladder retraction for single-incision laparoscopic cholecystectomy.

text: INTRODUCTION Recently, single-incision laparoscopic cholecystectomy has been accepted as an alternative to conventional laparoscopic cholecystectomy. The aim of this study was to retrospectively evaluate the safety and feasibility of unique gallbladder retraction methods using an ENDOLOOP® (Ethicon, Tokyo, Japan) and Lapaherclosure™ (Hakko Medical, Tokyo, Japan). MATERIALS AND SURGICAL TECHNIQUE From May 2013 to April 2015, 77 patients underwent single-incision laparoscopic cholecystectomy with this retraction technique. During the same period, conventional laparoscopic cholecystectomy was performed in 85 patients; these patients were the control group. The patients' data, including the operative time, total blood loss, conversion rate to laparotomy, and perioperative complications, were compared. Alexis® Wound Retractor XS (Applied Medical, Tokyo, Japan) was inserted through a 25-30-mm vertical transumbilical incision to prevent bile contamination. Next, a SILS Port (Covidien, Tokyo, Japan) was inserted. A flexible 5-mm laparoscope was inserted through the port with a grasper (SILS Clinch, Covidien) and a normal 5-mm scalpel. The fundus of the gallbladder was tied by the ENDOLOOP. The Lapaherclosure was then directly inserted through a right lower intercostal space to capture and pull the Lapaherclosure out. After the cystic artery and duct were cut, the resected gallbladder was directly extracted from the umbilical incision. DISCUSSION Several methods and devices have been developed to perform single-incision laparoscopic cholecystectomy, including the suturing method, the Mini Loop Retractor II (Covidien), and the EndoGrab (Virtual Ports, Caesarea, Israel). However, considering medical costs and safety, our retraction method seems to be feasible and comparable to existing methods.


title: The impact of phenylephrine, ephedrine, and increased preload on third-generation Vigileo-FloTrac and esophageal doppler cardiac output measurements.

text: BACKGROUND Cardiac output (CO) monitoring based on pulse contour analysis (Vigileo-FloTrac) has the potential to be used for goal-directed fluid therapy in the perioperative setting. However, factors such as vasopressor usage may impact Vigileo-FloTrac's reliability in tracking CO changes. We tested third-generation Vigileo-FloTrac system's ability to accurately measure the changes in CO induced by vasopressor administration and increased preload in comparison with esophageal Doppler measurements. METHODS In 33 anesthetized patients, CO was monitored simultaneously by the third-generation Vigileo-FloTrac and esophageal Doppler. Hemodynamic challenges included phenylephrine (to increase vasomotor tone), ephedrine (to increase myocardial contractility and heart rate), and whole-body tilting (to increase preload). Measurements were performed before and after each intervention. RESULTS Overall, 176 pairs of CO measurements were obtained. The difference between paired pulse contour and Doppler measurements of CO was 0.14 ± 2.13 L/min (mean ± SD), and the percentage error (2 SD of the difference divided by the mean CO of the reference method) was 66%. The trending ability of pulse contour versus Doppler was 23% (concordance, the percentage of the total number of data points that are in 1 of the 2 quadrants of agreement) after phenylephrine treatment, 69% (concordance) after ephedrine treatment, and 96% (concordance) after whole-body tilting. CONCLUSIONS The pulse contour method of measuring CO, as implemented in the third-generation Vigileo-FloTrac device, accurately tracks changes in CO when preload changes. However, the pulse contour method does not accurately track changes in CO induced with phenylephrine and ephedrine.


title: Gender differences in the accuracy of dietary assessment methods to measure energy intake in adults: protocol for a systematic review and meta-analysis.

text: INTRODUCTION Diet is an important modifiable risk factor for many chronic diseases. Measurement of dietary intake usually relies on self-report, subject to multiple biases. There is a need to understand gender differences in the self-report of dietary intake and the implications of any differences in targeting nutrition interventions. Literature in this area is limited and it is currently unknown whether self-report dietary assessment methods are equally accurate for women and men. The aim of this systematic review is to determine whether there are differences by gender in reporting energy intake compared with a reference measure of total energy expenditure. METHODS AND ANALYSIS A comprehensive search of published original research studies will be performed in MEDLINE, Scopus, Web of Science, EMBASE, CINAHL and Cochrane library. Original research studies will be included if they were conducted in free-living/unhospitalised adults and included a measure for both women and men of (a) self-reported energy intake and (b) total energy expenditure by doubly labelled water. One author will conduct the electronic database searches, two authors will independently screen studies, conduct a quality appraisal of the included studies using standardised tools and extract data. If further information is needed, then study authors will be contacted. If appropriate, a random-effects meta-analysis will be conducted, with inverse probability weighting, to quantify differences in the mean difference in agreement between reported energy intake and measured energy expenditure between women and men, by self-report assessment method. Subgroup analyses will be conducted by participant factors, geographical factors and study quality. ETHICS AND DISSEMINATION All data used will be from published primary research studies or deidentified results provided at the discretion of any study authors that we contact. We will submit our findings to a peer-reviewed scientific journal and will disseminate results through presentations at international scientific conferences. PROSPERO REGISTRATION NUMBER CRD42019131715.


SARS-CoV-2 pandemic: clinical picture of COVID-19 and implications for research.


title: Recanalization with subsequent near-total occlusion of an internal carotid artery aneurysm after immediate thrombotic occlusion using a flow-diverting stent.

text: A flow-diverting stent is placed in the parent artery to reduce blood flow in the aneurysm sac to facilitate progressive thrombosis and neointimal remodeling while maintaining outflow in the side branches and perforators. All international multicenter registries have reported on the progressive occlusion of aneurysms with time and have implied that an occluded aneurysm would not recanalize given the protective effect of the altered hemodynamics. Recanalization of an occluded aneurysm after placement of a flow-diverting stent has not been reported in the literature. The authors here describe a case of aneurysm recanalization after immediate thrombotic occlusion of the aneurysm with a flow-diverting stent. A 46-year-old male chronic smoker with chronic hypertension and hypercholesterolemia had a recurrent internal carotid artery aneurysm 1 year after embolization. Immediate thrombotic occlusion of the aneurysm and cessation of blood flow to the posterior communicating artery (PCoA) occurred immediately after activating a flow-diverting stent, with corresponding ischemic complications. However, 3 months after insertion of the stent, follow-up MR angiography showed recanalization of the aneurysm as well as of the PCoA. Additional angiography studies at 6 months showed near-total occlusion of the aneurysm with the restoration of blood flow to the PCoA.


title: Usefulness in NOTES of an intra-abdominal antifogging wireless charge-coupled device (CCD) camera with pantograph-type needle unit for placement to the intra-abdominal wall.

text: BACKGROUND In natural orifice transluminal endoscopic surgery (NOTES), the endoscope has the disadvantages of an unstable visual field and wide blind space. We developed a compact charge-coupled device (CCD) camera unit that can be transgastrointestinally placed in the abdominal cavity. METHODS The requisites for a wireless CCD camera unit for use in NOTES have been cited as: monitoring performance, fixation to the abdominal wall, attitude control, and antifogging functionality. Models to meet these requisites were prepared to assess their performance. The monitor had a CCD with dimensions of 7 x 7 x 7 mm and resolution of 410,000 pixels. The unit had a structure that allowed its attachment to the endoscope apex when placed to the abdominal wall. The abdominal wall fixation unit was equipped with a pantograph-type needle structure that was easily activated and retained by changing the polarity of an electromagnetic force. The pantograph-type needle head was designed to rotate by 360 degrees as an attitude-control mechanism, and both the pantograph and attitude-control mechanisms enabled attitude control in horizontal and vertical directions by a magnetic force applied from outside the body. Fogging was prevented by a vibration mechanism that physically cleaned the CCD lens surface and by titanium dioxide coating of the lens surface. RESULTS The CCD camera unit was confirmed to have sufficient performance as an auxiliary monitor for endoscopy in terms of visual field and resolution. The pantograph-type needle structure successfully completed fixation of the CCD camera unit to the abdominal wall. Unit attitude was easily controlled, and fogging could be addressed by water supply before insertion of the CCD camera unit into the peritoneal cavity. CONCLUSIONS The wireless CCD camera unit was verified to function as an effective second eye in NOTES by using the described mechanisms and antifogging coating.


title: Anti-VEGFR agents ameliorate hepatic venous dysregulation/microcirculatory dysfunction, splanchnic venous pooling and ascites of NASH-cirrhotic rat.

text: BACKGROUND & AIMS Antivascular endothelial growth factor receptor (VEGFR) agents improve hepatic fibrosis and portal hypertension in cirrhosis. Detail interactions among recruited/activated leucocytes, hepatic angiogenesis and fibrogenesis, splanchnic blood pooling, decreased hepatic veins to fluctuated splanchnic blood volume (hepatic venous dysregulation), portal hypertensive syndrome and ascites have never explored in cirrhosis. Our study used two anti-VEGFR agents - brivanib and sorafenib - to elucidate the relationship between above abnormalities of nonalcoholic steatohepatitis (NASH)-cirrhotic rats. MATERIALS AND METHODS NASH-cirrhotic rats received 2-week brivanib, sorafenib or vehicle (NASH-cirrhotic+briv, NASH-cirrhotic+soraf and NASH-cirrhotic rats) were included for various measurements. RESULTS In comparison with NASH-cirrhotic rats, significant decreased plasma VEGF, fibroblast growth factor, platelet-derived growth factor, hepatic tumour necrosis factor (TNFα), IL-1β, IL-6, IL-17 were accompanied by decreased leucocyte mass/activity ((99 m) Tc-phytate and (18) F-FDG SPECT/PET/CT scans), hepatic leucocytes recruitment/microvascular density (fluorescence-enhanced intravital microscopy) and hydroxyproline content, and increased hepatic blood flow in NASH-cirrhotic+briv and NASH-cirrhotic+soraf rats. In addition, increased hepatic microvasculatures compliance-related improved buffering effect of portal vein to acute mannitol infusion was associated with decreased circulating nitric oxide and aldosterone, plasma volume expansion (dye dilution method), splanchnic blood pooling ((99 m) Tc-RBC SPECT/PET/CT scans), peripheral hypotension, portal hypertension and ascites in brivanib and sorafenib-treated NASH-cirrhotic rats. CONCLUSION Besides antifibrotic, antiangiogenic and portal hypertensive effects, chronic antagonism of anti-VEGFR with brivanib and sorafenib improves hepatic blood flow, hepatic venous dysregulation, inhibits leucocytes recruitment/activation, splanchnic blood pooling and ascites formation in NASH-cirrhotic rats. Thus, brivanib and sorafenib might be ideal therapeutic agents in cirrhotic patients suffering from severe haemodynamic disarrangement and ascites.


title: Evidence synthesis relevant to COVID-19: a protocol for multiple systematic reviews and overviews of systematic reviews.

text: Introduction The evidence on COVID-19 is being produced at high speed, so it is challenging for decision-makers to keep up. It seems appropriate, then, to put into practice a novel approach able to provide the scientific community and other interested parties with quality evidence that is actionable, and rapidly and efficiently produced. Methods and analysis We designed a protocol for multiple parallel systematic reviews and overviews of systematic reviews in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will search for primary studies and systematic reviews that answer different questions related to COVID-19 using both a centralized repository (Epistemonikos database) and a manual search in MEDLINE/PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. We will also search for literature in several other sources. At least two researchers will independently undertake the selection of studies, data extraction, and assessment of the quality of the included studies. We will synthesize data for each question using meta-analysis, when possible, and we will prepare Summary of Findings tables according to the GRADE approach. All the evidence will be organized in an open platform (L·OVE - Living OVerview of Evidence) that will be continuously updated using artificial intelligence and a broad network of experts. Ethics and dissemination No ethics approval is considered necessary. The results of these articles will be widely disseminated via peer-reviewed publications, social networks, and traditional media, and will be sent to relevant international organizations discussing this topic.


title: Pediatric mental and behavioral health in the period of quarantine and social distancing (COVID-19).

text: UNSTRUCTURED The COVID-19 pandemic has spread rapidly throughout the world and has generated a long-term impact. The pandemic has caused great harm to society and also caused serious psychological trauma to many people. Pediatrics are a vulnerable group in this global public health emergency, as their nervous systems, endocrine systems and hypothalamic-pituitary-adrenal axes are not well developed. Psychological crises often cause pediatrics to produce feelings of abandonment, despair, incapacity and exhaustion, and even raising the risk of suicide. Children with mental illnesses are especially vulnerable during the quarantine and social distancing period. The inclusion of psychosocial support for pediatrics and their families are part of the health responses to disaster and disaster recovery. Based on the bio-psycho-social model, some pediatrics may have catastrophic thoughts and are prone to experience despair, numbness, flashback and other serious emotional and behavioral reactions. In severe cases, there may be symptoms of psychosis or post-traumatic stress disorder. Timely and appropriate protections are needed to prevent the occurrence of psychological and behavioral problems. The emerging digital applications and health services such as telehealth, social media, mobile health and remote interactive online education are able to bridge the social distance and support mental and behavioral health for pediatric populations. Based on the psychological development characteristics of pediatrics, this study also illustrates interventions on the psychological impact from the COVID-19 pandemic. Even though the world has been struggling to curb the influences of the pandemic, the quarantine and social distancing policies will have long-term impacts on pediatrics. Innovative digital solutions and informatics tools are needed more than ever to mitigate the negative consequences on pediatrics. Healthcare delivery and services should envision and implement innovative paradigms to meet broad well-being needs and pediatric health as the quarantine and social distancing over a longer term become a new reality. Future research on pediatric mental and behavioral health should pay more attention to novel solutions that incorporate cutting edge interactive technologies and digital approaches, leveraging considerable advances in pervasive and ubiquitous computing, human-computer interaction, health informatics and among many others. Digital approaches, health technologies and informatics are supposed to be designed and implemented to support public health surveillance and critical responses to pediatrics' growth and development. For instance, human-computer interactions, augmented reality and virtual reality could be incorporated to remote psychological supporting service for pediatric health; mobile technologies could be used to monitor pediatrics' mental and behavioral health while protecting their individual privacy; big data and artificial intelligences could be utilized to support decision-making on whether pediatrics should go out for physical activities and whether schools should be reopened, etc. Implications to clinical practice, psychological therapeutic practices and future research directions to address current efforts gaps have been highlighted.


title: Revisión sobre las infecciones no bacterianas del aparato respiratorio: neumonías víricas

text: Resumen Aunque las bacterias son los principales patógenos involucrados en la neumonía adquirida en la comunidad, algunos virus son responsables directos o en coinfección de un importante número de neumonías adquiridas en la comunidad. La clínica de estas neumonías puede ser muy similar, en el caso de los virus afectan más frecuentemente a la población infantil y geriátrica, con frecuencia no elevan la cifra de leucocitos, la fiebre es inconstante y frecuentemente se acompañan de síntomas de vías respiratorias altas. Característicamente no elevan la procalcitonina. Durante años el diagnóstico ha recaído en cultivos celulares y en detección de antígenos; desde la incorporación en la clínica de la PCR, la identificación de estos patógenos ha aumentado, descubriéndose nuevos microorganismos como el bocavirus. En general, el virus influenza A y el virus respiratorio sincitial siguen siendo los principales virus implicados. Sin embargo, la irrupción en los últimos años de epidemias con alta letalidad de coronavirus y de zoonosis de virus influenza hace que sea necesario mostrarse alerta ante estos nuevos patógenos emergentes. Los inhibidores de la neuraminidasa para neumonías víricas han demostrado disminuir la transmisión en casos expuestos y mejorar la evolución clínica en pacientes en Cuidados Intensivos; su uso en infecciones banales no está recomendado. La ribavirina ha sido utilizada en niños con infecciones por virus respiratorio sincitial, así como en inmunodeprimidos. Fuera de estos fármacos, ningún otro antiviral ha probado su eficacia. Las medidas de prevención con vacunación para virus influenza y con anticuerpos monoclonales para virus respiratorio sincitial podrían disminuir la incidencia de neumonía. Abstract Although bacteria are the main pathogens involved in community-acquired pneumonia, a significant number of community-acquired pneumonia are caused by viruses, either directly or as part of a co-infection. The clinical picture of these different pneumonias can be very similar, but viral infection is more common in the pediatric and geriatric populations, leukocytes are not generally elevated, fever is variable, and upper respiratory tract symptoms often occur; procalcitonin levels are not generally affected. For years, the diagnosis of viral pneumonia was based on cell culture and antigen detection, but since the introduction of polymerase chain reaction techniques in the clinical setting, identification of these pathogens has increased and new microorganisms such as human bocavirus have been discovered. In general, influenza virus type A and syncytial respiratory virus are still the main pathogens involved in this entity. However, in recent years, outbreaks of deadly coronavirus and zoonotic influenza virus have demonstrated the need for constant alert in the face of new emerging pathogens. Neuraminidase inhibitors for viral pneumonia have been shown to reduce transmission in cases of exposure and to improve the clinical progress of patients in intensive care; their use in common infections is not recommended. Ribavirin has been used in children with syncytial respiratory virus, and in immunosuppressed subjects. Apart from these drugs, no antiviral has been shown to be effective. Prevention with anti-influenza virus vaccination and with monoclonal antibodies, in the case of syncytial respiratory virus, may reduce the incidence of pneumonia.


title: The effect of barbed suture tendon repair on work of flexion.

text: PURPOSE To compare the work of flexion, ultimate strength, and gap resistance of a conventional 4-strand tendon repair to a knotless barbed-suture 4-strand tendon repair. METHODS Tendon repairs were performed on 16 cadaver flexor digitorum profundus tendons using either a 4-strand double Kessler repair or a similar but knotless 4-strand repair with a unidirectional barbed suture. Work of flexion, gap resistance during cyclical loading, and ultimate strength of both techniques were determined and their means compared. RESULTS There was no difference in mean maximum load and gap formation between the 2 techniques. Work of flexion was higher for the barbed-suture repair group compared with the traditional repair group (39 N·mm vs 31 N·mm). CONCLUSIONS The higher work of flexion in the barbed-suture group suggests that barbed suture may negatively affect tendon gliding within the flexor tendon sheath. CLINICAL RELEVANCE Knotless barbed-suture tendon repair leads to increased work of flexion compared with traditional flexor tendon repairs, which may result in an increased rupture incidence.


title: German Heart Surgery Report 2019: The Annual Updated Registry of the German Society for Thoracic and Cardiovascular Surgery.

text: Based on a longtime voluntary registry, founded by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) in 1980, well-defined data of all cardiac, thoracic, and vascular surgery procedures performed in 78 German heart surgery departments during the year 2019 are analyzed. For this period, a total of 175,705 procedures were submitted to the registry, 100,446 summarized as heart surgery procedures in a classical sense. The unadjusted in-hospital survival rate for the 34,224 isolated coronary artery bypass grafting procedures (relationship on-/off-pump 3.8:1) was 97.3%. For the 36,650 isolated heart valve procedures (16,625 transcatheter interventions included), it was 96.4%. Concerning short- and long-term circulatory support, a total of 2,716 extracorporeal life support/extracorporeal membrane oxygenation implantations, resp. 953 assist device implantations (L-/ R-/ BVAD, TAH) were registered. In 2019, the number of isolated heart transplantations increased to 333, a rise of 6.7% compared to the previous year. The isolated lung transplantations amounted to 311, a decrease of 8.5%. This annually updated registry of the GSTCVS represents voluntary public reporting by accumulating actual information for nearly all heart surgical procedures in Germany, constitutes advancements in heart medicine, and represents a basis for quality management for all participating institutions. In addition, the registry demonstrates that the provision of cardiac surgery in Germany is up to date, appropriate, and nationwide patient treatment is guaranteed all the time.


title: Contrast-enhanced ultrasound-guided radiofrequency ablation in inconspicuous hepatocellular carcinoma on B-mode ultrasound.

text: BACKGROUND/AIMS B-mode ultrasound (US) has difficulty targeting small hepatocellular carcinomas (HCCs) with poor conspicuity during radiofrequency ablation (RFA). Contrast-enhanced ultrasound (CEUS) can improve visualization of small or inconspicuous HCCs. This study was conducted to evaluate the effectiveness of CEUS-guided RFA electrode insertion during the arterial phase in inconspicuous HCCs. MATERIALS AND METHODS Ninety-three treatment-naïve HCCs from 80 patients treated with RFA from August 2012 to December 2014 were retrospectively reviewed. Seventy-five HCCs from 65 patients underwent B-mode US-guided RFA, and 15 HCCs from 14 patients that were inconspicuous on B-mode US underwent CEUS-guided RFA during the arterial phase after injection of sulfur hexafluoride microbubbles (SonoVue®). Technical success was assessed by contrast-enhanced computed tomography within 1 week and 3 months after the procedure. RESULTS The mean size of HCCs treated with CEUS-guided RFA was smaller than that of HCCs treated with B-mode US-guided RFA (1.17±0.36 vs. 1.63±0.55 cm, p=0.003). Technical success rates of CEUS-guided RFA within 1 week and 3 months were 100% (15/15) and 93.3% (14/15), respectively. Technical success rates of B-mode US-guided RFA were 97.3% (73/75) and 94.5% (69/73), respectively. CONCLUSION CEUS-guided RFA is highly efficacious for ablation of very small and inconspicuous HCCs.


title: Photocatalytic degradation of Prozac® mediated by TiO2 nanoparticles obtained via three synthesis methods: sonochemical, microwave hydrothermal, and polymeric precursor.

text: Three different synthesis methods were applied to obtain TiO2 nanoparticles: microwave-assisted hydrothermal (TiO2-MW), sonochemical (TiO2-US), and polymeric precursor (TiO2-PP). The nanoparticles thus obtained presented 93% (TiO2-MW) and 92% (TiO2-US) anatase phase, and TiO2-PP 93% rutile phase. The TiO2-US sample performed best during the Prozac® photodegradation assays because of its lipophilic surface, attributable to the C-H groups therein. Additionally, adsorption rate and photodegradation were optimized by adjusting Prozac® solution to pH ~ 8. Following Prozac® photodegradation, quantitative monitoring of its by-products (PPMA, MAEB, and TFMP) was done using HPLC. This quantitative approach led us to conclude that semiconductor photoactivity cannot be discussed solely in terms of the main compound. Lastly, it was seen that these by-products compete with each other in the degradation mechanisms and are influenced by different materials. Graphical abstract.


title: Inhibition of Chikungunya virus infection in cultured human muscle cells by furin inhibitors: impairment of the maturation of the E2 surface glycoprotein.

text: Chikungunya virus (CHIKV) is a mosquito-transmitted Alphavirus that causes in humans an acute infection characterized by polyarthralgia, fever, myalgia, and headache. Since 2005 this virus has been responsible for an epidemic outbreak of unprecedented magnitude. By analogy with other alphaviruses, it is thought that cellular proteases are able to process the viral precursor protein E3E2 to produce the receptor-binding E2 protein that associates as a heterodimer with E1. Destabilization of the heterodimer by exposure to low pH allows viral fusion and infection. We show that among a large panel of proprotein convertases, membranous furin but also PC5B can process E3E2 from African CHIKV strains at the HRQRR(64) / ST site, whereas a CHIKV strain of Asian origin is cleaved at RRQRR(64) / SI by membranous and soluble furin, PC5A, PC5B, and PACE4 but not by PC7 or SKI-1. Using fluorogenic model peptides and recombinant convertases, we observed that the Asian strain E3E2 model peptide is cleaved most efficiently by furin and PC5A. This cleavage was also observed in CHIKV-infected cells and could be blocked by furin inhibitor decanoyl-RVKR-chloromethyl ketone. This inhibitor was compared with chloroquine for its ability to inhibit CHIKV spreading in myoblast cell cultures, a cell-type previously described as a natural target of this virus. Our results demonstrate the role of furin-like proteases in the processing of CHIKV particles and point out new approaches to inhibit this infection.


title: The Value of Secretin-Enhanced MRCP in Patients With Recurrent Acute Pancreatitis.

text: OBJECTIVE The purpose of this study is to assess the additional value of secretin-enhanced MRCP over conventional (non-secretin-enhanced) MRCP in diagnosing disease in patients with recurrent acute pancreatitis. MATERIALS AND METHODS A retrospective review of a radiology database found 72 patients with recurrent acute pancreatitis who had secretin-enhanced MRCP and ERCP correlation within 3 months of each other between January 2007 and December 2011. Of these patients, 54 had no history of pancreatic tumor or surgery and underwent MRI more than 3 months after an episode of acute pancreatitis. In addition, 57 age- and sex-matched control subjects with secretin-enhanced MRCP and ERCP correlation and without a diagnosis of recurrent acute pancreatitis or chronic pancreatitis were enrolled as the control group. All studies were anonymized, and secretin-enhanced MRCP images (image set A) were separated from conventional 2D and 3D MRCP and T2-weighted images (image set B). Image sets A and B for each patient were assigned different and randomized case numbers. Two blinded reviewers independently assessed both image sets for ductal abnormalities and group A image sets for exocrine response to secretin. RESULTS There were statistically significantly more patients with recurrent acute pancreatitis with reduced exocrine function compared with patients in the control group (32% vs 9%; p < 0.01) on secretin-enhanced images. Patients with recurrent acute pancreatitis were more likely to have side branch dilation (p = 0.02; odds ratio, 3.6), but not divisum, compared with the control group. Secretin-enhanced images were superior to non-secretin-enhanced images for detecting ductal abnormalities in patients with recurrent acute pancreatitis, with higher sensitivity (76% vs 56%; p = 0.01) and AUC values (0.983 vs 0.760; p < 0.01). CONCLUSION Up to one-third of patients with recurrent acute pancreatitis showed exocrine functional abnormalities. Secretin-enhanced MRCP had a significantly higher yield for ductal abnormalities than did conventional MRI and should be part of the MRCP protocol for investigation of patients with recurrent acute pancreatitis.


title: Ventricular access devices are safe and effective in the treatment of posthemorrhagic ventricular dilatation prior to shunt placement.

text: Intraventricular hemorrhage of prematurity (IVH) is a diagnosis that has become more frequent in recent years. Advances in medical care have led to survival of increasingly premature infants, as well as infants with more complex medical conditions. Treatment with a ventricular access device (VAD) was reported almost 3 decades ago; however, it is unclear how effective this treatment is in the current population of premature infants. At our institution (from 2004 to present), we treat posthemorrhagic hydrocephalus (PHH) with a VAD. In order to look at safety and efficacy, we retrospectively combed the medical records of premature children, admitted to Lucile Packard Children's Hospital from January 2005 to December 2009, and identified 310 premature children with IVH. Of these, 28 children required treatment for PHH with a VAD. There were no infections associated with placement of these devices and a very low rate of other complications, such as need for repositioning (7.41%) or replacement (3.75%). Our data show that treatment with a VAD is very safe, with few complications and can be used to treat PHH in this very complex infant population.


title: Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate.

text: Dendritic cells (DCs) and monocytes develop from a series of bone-marrow-resident progenitors in which lineage potential is regulated by distinct transcription factors. Zeb2 is an E-box-binding protein associated with epithelial-mesenchymal transition and is widely expressed among hematopoietic lineages. Previously, we observed that Zeb2 expression is differentially regulated in progenitors committed to classical DC (cDC) subsets in vivo. Using systems for inducible gene deletion, we uncover a requirement for Zeb2 in the development of Ly-6Chi monocytes but not neutrophils, and we show a corresponding requirement for Zeb2 in expression of the M-CSF receptor in the bone marrow. In addition, we confirm a requirement for Zeb2 in development of plasmacytoid DCs but find that Zeb2 is not required for cDC2 development. Instead, Zeb2 may act to repress cDC1 progenitor specification in the context of inflammatory signals.


title: Is heat pain detection threshold associated with the area of secondary hyperalgesia following brief thermal sensitization? A study of healthy volunteers - design and detailed plan of analysis.

text: BACKGROUND Several factors are believed to influence the development and experience of pain. Human clinical pain models are central tools, in the investigation of basic physiologic pain responses, and can be applied in patients as well as in healthy volunteers. Each clinical pain model investigates different aspects of the human pain response. Brief thermal sensitization induces a mild burn injury, resulting in development of primary hyperalgesia at the site of stimulation, and secondary hyperalgesia surrounding the site of stimulation. Central sensitization is believed to play an important role in the development of secondary hyperalgesia; however, a possible association of secondary hyperalgesia following brief thermal sensitization and other heat pain models remains unknown. Our aim with this study is to investigate how close the heat pain detection threshold is associated with the size of the area of secondary hyperalgesia induced by the clinical heat pain model: Brief thermal sensitization. METHODS AND DESIGN We aim to include 120 healthy participants. The participants will be tested on two separate study days with the following procedures: i) Brief thermal sensitization, ii) heat pain detection threshold and iii) pain during thermal stimulation. Additionally, the participants will be tested with the Pain Catastrophizing Scale and Hospital Anxiety and Depression Scale questionnaires. We conducted statistical simulations based on data from our previous study, to estimate an empirical power of 99.9 % with α of 0.05. We define that an R(2) < 0.25 and predictive intervals larger than +/-150 cm(2) are indications of a weak association. DISCUSSION The area of secondary hyperalgesia may serve as a quantitative measure of the central sensitization induced by cutaneous heat stimulation, and thus may be a biomarker of an individual's pain sensitivity. The number of studies investigating secondary hyperalgesia is growing; however basic knowledge of the physiologic aspects of secondary hyperalgesia in humans is still incomplete. We therefore find it interesting to investigate if HPDT, a known quantitative sensory test, is associated with areas of secondary hyperalgesia following brief thermal sensitization TRIAL REGISTRATION Clinicaltrials.gov (Identifier: NCT02527395 ). Danish Research Ethics Committee (Identifier: H-8-2014-012). Danish Data Protection Agency (Identifier: 30-1436).


title: Humidification performance of humidifying devices for tracheostomized patients with spontaneous breathing: a bench study.

text: BACKGROUND Heat and moisture exchangers (HMEs) are commonly used for humidifying respiratory gases administered to mechanically ventilated patients. While they are also applied to tracheostomized patients with spontaneous breathing, their performance in this role has not yet been clarified. We carried out a bench study to investigate the effects of spontaneous breathing parameters and oxygen flow on the humidification performance of 11 HMEs. METHODS We evaluated the humidification provided by 11 HMEs for tracheostomized patients, and also by a system delivering high-flow CPAP, and an oxygen mask with nebulizer heater. Spontaneous breathing was simulated with a mechanical ventilator, lung model, and servo-controlled heated humidifier at tidal volumes of 300, 500, and 700 mL, and breathing frequencies of 10 and 20 breaths/min. Expired gas was warmed to 37°C. The high-flow CPAP system was set to deliver 15, 30, and 45 L/min. With the 8 HMEs that were equipped with ports to deliver oxygen, and with the high-flow CPAP system, measurements were taken when delivering 0 and 3 L/min of dry oxygen. After stabilization we measured the absolute humidity (AH) of inspired gas with a hygrometer. RESULTS AH differed among HMEs applied to tracheostomized patients with spontaneous breathing. For all the HMEs, as tidal volume increased, AH decreased. At 20 breaths/min, AH was higher than at 10 breaths/min. For all the HMEs, when oxygen was delivered, AH decreased to below 30 mg/L. With an oxygen mask and high-flow CPAP, at all settings, AH exceeded 30 mg/L. CONCLUSIONS None of the HMEs provided adequate humidification when supplemental oxygen was added. In the ICU, caution is required when applying HME to tracheostomized patients with spontaneous breathing, especially when supplemental oxygen is required.


title: Accounting for aetiology: can regional surveillance data alongside host biomarker-guided antibiotic therapy improve treatment of febrile illness in remote settings?

text: Background: Across Southeast Asia, declining malaria incidence poses a challenge for healthcare providers, in how best to manage the vast majority of patients with febrile illnesses who have a negative malaria test. In rural regions, where the majority of the population reside, empirical treatment guidelines derived from central urban hospitals are often of limited relevance. In these settings, relatively untrained health workers deliver care, often without any laboratory diagnostic support. In this paper, our aim was to model the impact on mortality from febrile illness of using point-of-care C-reactive protein testing to inform the decision to prescribe antibiotics and regional surveillance data to inform antibiotic selection, rooted in the real-world context of rural Savannakhet province, southern Laos. Methods: Our model simulates 100 scenarios with varying quarterly incidence of six key pathogens known to be prevalent in rural Laos. In the simulations, community health workers either prescribe antibiotics in-line with current practice as documented in health facilities in rural Laos, or with the aid of the two interventions. We provide cost-effectiveness estimates for each strategy alone and then for an integrated approach using both interventions. Results: We find that each strategy alone is predicted to be highly cost-effective, and that the combined approach is predicted to result in the biggest reduction in mortality (averting a predicted 510 deaths per year in rural Savannakhet, a 28% reduction compared to standard practice) and is highly cost-effective, with an incremental cost-effectiveness ratio of just $66 per disability-adjusted life year averted. Conclusions: Substantial seasonal variation in the predicted optimal empirical antibiotic treatment for febrile illness highlights the benefits of up-to-date information on regional causes of fever. In this modelling analysis, an integrated system incorporating point-of-care host biomarker testing and regional surveillance data appears highly cost-effective, and may warrant piloting in a real-life setting.


title: Complications of mechanical thrombectomy for acute ischemic stroke-a retrospective single-center study of 176 consecutive cases.

text: INTRODUCTION There is only very limited data about complications in mechanical thrombectomy for acute ischemic stroke. The purpose of this study was to evaluate the frequency and the clinical relevance of procedure-related complications in mechanical thrombectomy. METHODS We conducted a retrospective analysis of 176 consecutive acute ischemic stroke cases that were treated with mechanical thrombectomy. Primary outcome measures included the following: symptomatic intracranial hemorrhage (sICH), vessel dissection, emboli to new vascular territories, vasospasm, and stent dislocation/occlusion whenever appropriate. Secondary outcome measures included mTICI score, time from symptom onset to revascularization, and time from groin puncture to revascularization as well as the early clinical outcome at discharge. RESULTS Complications occurred in 20/176 patients (11 %) comprising 23 adverse events at the following rates: sICH 8/176 (5 %), emboli to new vascular territories 4/176 (2 %); vessel dissection 3/176 (2 %); vasospasm of the access vessel 5/176 (3 %); stent dislocation in 1/42 (2 %); and stent occlusion in 2/42 (5 %). Two out of 20 (10 %) suffered from two or more procedure-related complications. There was a statistically significant correlation of complications with time from groin puncture to revascularization, unfavorable revascularization results, and unfavorable clinical outcome. CONCLUSION Overall, the frequency of procedure-related complications lies within acceptable limits for an emergency procedure. The endovascular treatment does not seem to add significantly to the stroke patients' risk of sICH but implies an innate risk of stroke in an initially uninvolved territory. Furthermore, a prolonged endovascular procedure beyond an hour is correlated with higher complication rates, which underlines the importance of a swift and complete revascularization.


Train and deploy a community level public health workforce to combat covid-19.


Chest CT and Coronavirus Disease (COVID-19): A More Complete Review.


title: Rapid learning curve for Solitaire FR stent retriever therapy: evidence from roll-in and randomised patients in the SWIFT trial.

text: BACKGROUND In light of recent positive trial data for endovascular therapy in acute ischemic stroke (AIS), stent retriever use by practitioners without prior experience with these devices may become more common. OBJECTIVE To assess the safety and efficacy of thrombectomy for AIS using Solitaire for patients treated in the roll-in period of the Solitaire With the Intention For Thrombectomy (SWIFT) trial, which represented the first clinical use of the device for these interventionalists. METHODS Prospectively collected demographic, clinical, and angiographic data on patients treated in the initial roll-in and subsequent randomized phases of the SWIFT study were collected and analyzed. Key statistical analyses were validated by an independent external statistician. RESULTS Patients in the roll-in period achieved equivalently high rates of reperfusion (55%) compared with those treated with the device in the randomized phase (61%). Rates of adverse events were comparable (13% vs. 9%). Rates of good neurological outcome were equivalent between the roll-in and randomized patients treated with Solitaire (63% vs. 58%). Including the roll-in patients strengthened the conclusions of the study, that reperfusion rates without symptomatic hemorrhage with Solitaire were greater than with Merci (59% vs. 24%, p<0.001). CONCLUSIONS Thrombectomy in AIS using the Solitaire stent retriever device can be performed safely and effectively when used by experienced neurointerventionalists without previous experience with the device. TRIAL REGISTRATION NUMBER The SWIFT study is registered with ClinicalTrials.gov, number NCT 01054560.


title: Factor analysis of the COVID-19 Perceived Risk Scale: A preliminary study.

text: This study adapted an 8-item COVID-19 Perceived Risk Scale (CPRS) to assess COVID-19 related personal risk. The sample comprised 3,109 Turkish adults (49.98% males; Meanage = 38.64 ± 10.40). Exploratory and confirmatory factor analyses confirmed a two-factor structure (cognitive and emotional dimensions), with satisfactory reliability. The subscales were correlated with severity and self-efficacy related to COVID-19 and mental health. Women reported higher levels of emotional risk, overall risk, and severity than men. Findings indicate that the CPRS is a psychometrically-sound scale for assessing COVID-19 related perceived risk. The scale can be used to assess people who are vulnerable to the risk of COVID-19.


title: Psychotherapy in the Post-COVID-19 Era.

text: This column anticipates challenges likely to be faced by psychotherapists and their patients after the coronavirus disease 2019 (COVID-19) pandemic subsides. It looks beyond the current impact of loneliness, isolation, thwarted belongingness, and loss toward the longer term impact of moral injury and blocked opportunities for mourning.


title: Intraoperative surgical margin re-resection for colorectal liver metastasis: is it worth the effort?

text: OBJECTIVE This study was conducted to evaluate recurrence and survival among patients who underwent intraoperative margin re-resection for colorectal cancer liver metastases (CRLM). BACKGROUND Among patients who receive intraoperative margin re-resection, the relation between final margin status, pattern of recurrence, and survival is largely unknown. METHODS Three hundred thirty-two patients who underwent hepatic resection for CRLM between 2000 and 2013 were identified. Demographics, operative data, pathologic margin status, site of recurrence, and long-term survival data were collected and analyzed. Patients were stratified in three groups based on their margin status: R0, R1, and R1 → R0. RESULTS R0 resections were achieved in 247 (74.4%) patients, 61 (18.4%) patients had an R1 resection, whereas 24 (7.2%) had an R1 → R0. Median survival for patients undergoing R0 resections was 50.2 (95% confidence interval (CI) 49.2-66.2) months versus 63.0 (95% CI 50.3-70.5) months for patients undergoing R1 resections versus 49.2 (95% CI 29.9-NA) months for patients undergoing intraoperative margin re-resection (P > 0.05). Differences in recurrence rate and pattern were not significant between the three groups (P > 0.05). CONCLUSION In the era of modern systemic chemotherapy, it seems that the impact of margin status on outcomes may be minimal compared to that of patient and tumor factors. In this scenario, margin re-resection to achieve R0 status does not improve long-term outcomes.


title: Antihelminth compound niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations.

text: Wnt/β-catenin pathway activation caused by adenomatous polyposis coli (APC) mutations occurs in approximately 80% of sporadic colorectal cancers (CRC). The antihelminth compound niclosamide downregulates components of the Wnt pathway, specifically Dishevelled-2 (Dvl2) expression, resulting in diminished downstream β-catenin signaling. In this study, we determined whether niclosamide could inhibit the Wnt/β-catenin pathway in human CRCs and whether its inhibition might elicit antitumor effects in the presence of APC mutations. We found that niclosamide inhibited Wnt/β-catenin pathway activation, downregulated Dvl2, decreased downstream β-catenin signaling, and exerted antiproliferative effects in human colon cancer cell lines and CRC cells isolated by surgical resection of metastatic disease, regardless of mutations in APC. In contrast, inhibition of NF-κB or mTOR did not exert similar antiproliferative effects in these CRC model systems. In mice implanted with human CRC xenografts, orally administered niclosamide was well tolerated, achieved plasma and tumor levels associated with biologic activity, and led to tumor control. Our findings support clinical explorations to reposition niclosamide for the treatment of CRC.


title: Luciferase-tagged wild-type and tropism-deficient mouse cytomegaloviruses reveal early dynamics of host colonization following peripheral challenge.

text: Cytomegaloviruses (CMVs) establish persistent, systemic infections and cause disease by maternal-foetal transfer, suggesting that their dissemination is a key target for antiviral intervention. Late clinical presentation has meant that human CMV (HCMV) dissemination is not well understood. Murine CMV (MCMV) provides a tractable model. Whole mouse imaging of virus-expressed luciferase has proved a useful way to track systemic infections. MCMV, in which the abundant lytic gene M78 was luciferase-tagged via a self-cleaving peptide (M78-LUC), allowed serial, unbiased imaging of systemic and peripheral infection without significant virus attenuation. Ex vivo luciferase imaging showed greater sensitivity than plaque assay, and revealed both well-known infection sites (the lungs, lymph nodes, salivary glands, liver, spleen and pancreas) and less explored sites (the bone marrow and upper respiratory tract). We applied luciferase imaging to tracking MCMV lacking M33, a chemokine receptor conserved in HCMV and a proposed anti-viral drug target. M33-deficient M78-LUC colonized normally in peripheral sites and local draining lymph nodes but spread poorly to the salivary gland, suggesting a defect in vascular transport consistent with properties of a chemokine receptor.


title: Extracellular matrix collagen I promotes the tumor progression of residual hepatocellular carcinoma after heat treatment.

text: BACKGROUND Accelerated malignant behaviors induced by insufficient thermal ablation have been increasingly reported, however, the exact mechanisms are still unclear. Here, we investigated the importance of the extracellular matrix (ECM) in modulating the progression of residual hepatocellular carcinoma (HCC) after heat treatment. METHODS Heat-exposed residual HCC cells were cultured in different ECM gels. We used basement membrane gel (Matrigel) to simulate the normal microenvironment and collagen I to model the pathological stromal ECM. The alterations of morphology and parameters of proliferation, epithelial-mesenchymal transition (EMT) and stemness were analyzed in vitro and in vivo. RESULTS Increased collagen I deposition was observed at the periablational zone after incomplete RFA of HCC in a xenograft model. The markers of cell proliferation, EMT, motility and progenitor-like traits of heat-exposed residual HCC cells were significantly induced by collagen I as compared to Matrigel (p values all < 0.05). Importantly, collagen I induced the activation of ERK phosphorylation in heat-exposed residual HCC cells. ERK1/2 inhibitor reversed the collagen I-promoted ERK phosphorylation, cell proliferative, protrusive and spindle-like appearance of heat-treated residual HCC cells in vitro. Moreover, collagen I promoted the in vivo tumor progression of heat-exposed residual HCC cells, and sorafenib markedly reversed the collagen I-mediated protumor effects. CONCLUSIONS Our findings demonstrate that collagen I could enhance the aggressive progression of residual HCC cells after suboptimal heat treatment and sorafenib may be a treatment approach to thwart this process.


title: Amplitudes of SSEP and outcome in cardiac arrest survivors: A prospective cohort study.

text: OBJECTIVE To investigate the relationship between somatosensory evoked potential (SSEP) amplitudes and neurologic outcome after cardiac arrest. METHODS We prospectively studied SSEPs, recorded 24 hours to 4 days after cardiac arrest, in patients with targeted temperature management. SSEP amplitude was defined pragmatically as the highest short-latency amplitude of 4 cortical recordings (2 per side, CP3/CP4 vs Fz) at least 4.5 ms after the spinal SSEP. Cerebral performance category (CPC) was determined upon intensive care unit discharge. CPC 1-3 was defined as good, CPC 4-5 as poor outcome. RESULTS Of 318 patients, 25 had incomplete recordings, no reproducible spinal SSEP, or high noise level. Of the remaining 293 patients, 137 (47%) had poor and 156 (53%) good outcome. The lowest amplitude in a survivor with good outcome was 0.62 μV. All 78 patients with lower amplitudes had poor outcome. None of 27 patients with CPC 4 (unresponsive wakefulness) had amplitudes above 2.5 μV. In the majority of 24 patients who died despite amplitudes above 2.5 μV, clinical course and other prognostic parameters argued against severe hypoxic encephalopathy. CONCLUSIONS The prognostic value of SSEPs extends beyond an absent/present dichotomy. Absent and very low amplitude SSEPs appear to be highly predictive of poor outcome after cardiac arrest. Prospective external validation of the lower threshold found in our study is necessary. SSEP recordings should not be used for prognostication if noise could mask potentials with critically low amplitudes. High SSEP amplitudes argue against severe hypoxic encephalopathy.


title: Assessment of COVID-19 Knowledge Among University Students: Implications for Future Risk Communication Strategies.

text: The purpose of this study was to describe population knowledge and beliefs about COVID-19 and current social media coverage to address a gap in what is known about risk communication during health crises. A survey with 27 questions was developed. Twenty-three percent (N = 1,136) of respondents started the survey. Less than half of the students reported a high health literacy level (43%, n = 365/855). When asked where students have heard about COVID-19, the majority reported the Internet and social media. Students reported a basic level of COVID-19 knowledge, but few students (18%, n = 173/966) correctly identified all three signs and/or symptoms of COVID-19. Results highlight the need for an increased public health presence on social media and the urgent need to remain diligent in educating community members about COVID-19 myths.


title: Effect of Nonpharmaceutical Interventions on Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, South Korea, 2020.

text: We analyzed transmission of coronavirus disease outside of the Daegu-Gyeongsangbuk provincial region in South Korea. We estimated that nonpharmaceutical measures reduced transmissibility by a maximum of 34% without resorting to a strict lockdown strategy. To optimize epidemic control, continuous efforts to monitor the transmissibility are needed.


title: Molecular Detection of Gamma Coronaviruses in Bird Parks of Iran.

text: Gamma Coronaviruses (GCoVs) are distributed worldwide, affecting a wide range of bird species, the beluga whale, and bottlenose dolphins. Because of the limited proofreading capability in the viral encoded polymerase, they emerge genetically diverse. There has been no molecular surveillance data to describe the epidemiology of GCOVs in avian species. The present study was conducted to detect GCOVs in Tehran birds’ parks, 2015. Cloacal swabs (267 samples) from eight different bird species ((Chickens (Gallus gallus), Pheasant (Phasianus colchicus), Turkey (Meleagris gallopavo), Partridge (Perdix perdix), Quail (Coturnix coturnix), Duck (Anas platyrhynchos), Goose (Anserini),and Guinea fowl (Numididae)) were collected, the viral RNA was extracted, the RT-PCR was performed using QIAGEN one step RT-PCR kit and the primers targeting “3'-UTR” and “Nucleocapsid” genes. The detection rate was approximately 8.99%. GCOVs were detected in the chicken, quail, pheasant, turkey, and the partridge with different prevalence rates. Phylogenetic tree based on partial nucleotide sequences of the N gene clustered the samples into two groups. It is the first report of GCOVs in non-commercial birds in Iran. According to our results, GCOVs are circulating in different avian species, and further studies are needed to isolate these viruses and evaluate their pathogenesis.


title: Sleep quality of mechanically ventilated patients sedated with dexmedetomidine.

text: PURPOSE Dexmedetomidine is thought to activate an endogenous pathway that naturally promotes non-rapid eye movement (NREM) sleep. Dexmedetomidine may induce restorative sleep, that is, NREM stage 3 and 4 (slow wave sleep; SWS) or sleep continuity in mechanically ventilated patients. Few data have been published, however, on the sleep characteristics of mechanically ventilated patients during dexmedetomidine infusion. METHODS We recorded polysomnography (PSG) for 24 h in mechanically ventilated patients sedated with dexmedetomidine. Dexmedetomidine (0.2-0.7 μg/kg/h) was administered intravenously to maintain the Richmond Agitation-Sedation Scale between -1 and -4 only during the nighttime (9:00 p.m. to 6:00 a.m.). During the daytime, we interrupted the sedatives and analgesics unless the patient complained of discomfort. When this occurred midazolam or opioids were administered intermittently. Sleep stages and the frequency of arousal/awakening during the nighttime were analyzed using Rechtschaffen and Kales criteria. RESULTS For the ten mechanically ventilated adult patients recruited into the study, the median total sleep time (TST) during the night was 4.7 h (IQR, 4.2-8.1 h), and 78 % of sleep occurred during the night (median 78 %, IQR: 69-88 %). Sleep architecture was exclusively NREM sleep stage 1 (median 28.9 % of TST) and stage 2 (median 71.2 % of TST). Neither SWS (median 0 % of TST) nor rapid eye movement (REM) sleep (median 0 % of TST) was observed. Median frequency of arousals/awakenings was 9.3/h (IQR, 3-19.5/h). CONCLUSIONS In mechanically ventilated patients, nighttime infusion of dexmedetomidine preserved the day-night cycle of sleep but induced severely disturbed sleep architecture without evidence of SWS or REM sleep.


title: Use of failure-to-rescue to identify international variation in postoperative care in low-, middle- and high-income countries: a 7-day cohort study of elective surgery.

text: Background The incidence and impact of postoperative complications are poorly described. Failure-to-rescue, the rate of death following complications, is an important quality measure for perioperative care but has not been investigated across multiple health care systems. Methods We analysed data collected during the International Surgical Outcomes Study, an international 7-day cohort study of adults undergoing elective inpatient surgery. Hospitals were ranked by quintiles according to surgical procedural volume (Q1 lowest to Q5 highest). For each quintile we assessed in-hospital complications rates, mortality, and failure-to-rescue. We repeated this analysis ranking hospitals by risk-adjusted complication rates (Q1 lowest to Q5 highest). Results A total of 44 814 patients from 474 hospitals in 27 low-, middle-, and high-income countries were available for analysis. Of these, 7508 (17%) developed one or more postoperative complication, with 207 deaths in hospital (0.5%), giving an overall failure-to-rescue rate of 2.8%. When hospitals were ranked in quintiles by procedural volume, we identified a three-fold variation in mortality (Q1: 0.6% vs Q5: 0.2%) and a two-fold variation in failure-to-rescue (Q1: 3.6% vs Q5: 1.7%). Ranking hospitals in quintiles by risk-adjusted complication rate further confirmed the presence of important variations in failure-to-rescue, indicating differences between hospitals in the risk of death among patients after they develop complications. Conclusions Comparison of failure-to-rescue rates across health care systems suggests the presence of preventable postoperative deaths. Using such metrics, developing nations could benefit from a data-driven approach to quality improvement, which has proved effective in high-income countries.


title: Long-Term Survival after Radiofrequency Ablation of Lung Oligometastases from Five Types of Primary Lesions: A Retrospective Evaluation.

text: PURPOSE To conduct a retrospective evaluation of long-term survival after radiofrequency (RF) ablation for lung oligometastases from 5 types of primary lesions. MATERIALS AND METHODS The study population consisted of 123 patients with lung oligometastases from colorectal cancer (CRC), non-small-cell lung cancer, hepatocellular carcinoma, esophageal cancer, and renal-cell carcinoma treated with RF ablation. Lung oligometastases were defined as 1-5 metastases confined to the lung while the primary cancer and other metastases were eradicated. Overall survival (OS) and recurrence-free survival (RFS) were estimated for the overall study population and for patients with each type of primary lesion. The OS and RFS rates were compared with those of the patients with any of the other four primary lesion types. Finally, various variables were analyzed to determine what factors influenced OS and RFS. RESULTS The median follow-up was 45.7 months, and the 5-year OS and RFS rates for all 123 patients were 62% and 25%, respectively. The OS time for patients with metastases from CRC was significantly longer (P = .042); it was significantly shorter (P = .022) in patients with metastases from esophageal cancer. Longer disease-free interval was significantly (P = .015) associated with better OS. There was no variable significantly associated with OS and RFS on multivariate analyses. CONCLUSIONS Data from this single-center study appear promising in terms of long-term survival after RF ablation of lung oligometastases from 5 primary lesions.


title: The role of ethylene-vinyl alcohol copolymer in association with other embolic agents for the percutaneous and endovascular treatment of type Ia endoleak.

text: AIM To evaluate safety, technical and clinical success of embolization of type Ia endoleak (T1a EL) using ethylene-vinyl alcohol copolymer as embolic agent alone or in combination with other materials. MATERIALS AND METHODS Five patients presented T1a EL after endovascular repair of aortic aneurysms (EVAR) with radiological evidence of expanding sac size; in particular, three had contained rupture. In one patient, proximal cuff insertion was previously performed, in three patients proximal cuff was urgently inserted but T1a EL persisted; one patient, previously treated with Ovation Abdominal Stent Graft System, was directly proposed for endovascular treatment. In all cases, endovascular embolization was successfully performed and the transfemoral approach was always chosen; in one case it failed and translumbar approach by direct puncture of the sac was required. Used embolization agents were glue, ethylene-vinyl alcohol copolymer (Onyx) and coils in three cases, n-butyl cyanoacrylate and Onyx in one case, Onyx and coils in the last case. RESULTS Technical success rate was 100% as well as clinical success. No major or minor complication, including non-target embolization, was registered. Clinical success was 100% until today and the sac diameter remained stable in four patients and decreased in one. CONCLUSIONS Onyx may be considered a suitable embolic agent in the treatment of patients with type Ia endoleaks after EVAR, after failure of conventional treatments such as prolonged balloon inflation of the aortic neck or deployment of large bare stent.


title: Evaluation of putative anti-cryptosporidial drugs in an in vitro culture system.

text: Cryptosporidium species are major pathogens severely affecting the health of neonate animals, in particular calves, but also cause life-threatening infection of immunocompromised humans. Currently, only halofuginone is approved for prophylactic and metaphylactic treatment of calves but this drug suffers from its limited safety margins. For treatment of immunodeficient human patients, only nitazoxanide and paramomycin are used but data regarding their efficacy are controversial. Aim of the present study was to test a substituted benzimidazole (BAY-AF76184) and a heterocyclic substituted 1,2,4-triazin (BAY-AB24992), both drugs with known anti-protozoal activity, for their potential ability to interfere with Cryptosporidium parvum development in vitro. Development of C. parvum in HCT-8 cells treated with these compounds was compared to negative controls and parasites treated with paromomycin or halofuginone using real-time PCR targeting the 18S rDNAs of parasites and host cells as template. Potential cytotoxic and anti-proliferative effects of drugs were analysed using a lactate dehydrogenase and a WST-1 assay, respectively. BAY-AF76184 and paromomycin dose-dependently inhibited development of C. parvum with EC50 values of 2.37 μM and 69.5 μM, respectively. Although high concentrations of halofuginone and BAY-AB24992 also significantly inhibited parasite development, effects of lower concentrations were very heterogeneous preventing calculation of EC50 values. Halofuginone and BAY-AF76184 dose-dependently interfered with host cell proliferation (EC50 values of 0.35 μM and 9.07 μM, respectively) and the latter also had direct cytotoxic effects (EC50=48.78 μM). However, drug concentrations required for cytopathic were higher than those for effects against C. parvum. Therefore, both BAY-AB24992 and BAY-AF76184 should be considered for further evaluation, e.g. using in vivo models.


title: Prenatal screening diagnosis and management in the era of coronavirus: the Sardinian experience.

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new coronavirus, was first identified in December 2019 in Wuhan, China and spread rapidly, affecting many other countries. The disease is now referred to as coronavirus disease 2019 (COVID-19).The Italian government declared a state of emergency on 31st January 2020 and on 11th March World Health Organization (WHO) officially declared the COVID-19 outbreak a global pandemic. Although the COVID-19 incidence remained considerably lower in Sardinia than in the North Italy regions, which were the most affected, the field of prenatal screening and diagnosis was modified because of the emerging pandemic. Data on COVID-19 during pregnancy are so far limited. Since the beginning of the emergency, our Ob/Gyn Department at Microcitemico Hospital, Cagliari offered to pregnant patients all procedures considered essential by the Italian Ministry of Health. To evaluate the influence of the COVID-19 pandemic on the activities of our center, we compared the number of procedures performed from 10th March to 18th May 2020 with those of 2019. Despite the continuous local birth rate decline, during the 10-week pandemic period, we registered a 20% increment of 1st trimester combined screening and a slight rise of the number of invasive prenatal procedures with a further increase in chorionic villi sampling compared to amniocentesis. Noninvasive prenatal testing remained unvariated. The request for multifetal pregnancy reduction as a part of the growing tendency of voluntary termination of pregnancy in Sardinia increased. The COVID-19 pandemic provides many scientific opportunities for clinical research and study of psychological and ethical issues in pregnant women.


title: EMA advice on renin-angiotensin system medicines during covid-19 pandemic.

text: Every month, DTB scans sources of information on treatments, disease management and other healthcare topics for key items to bring to our readers' attention and help them keep up to date. To do this, we produce succinct, contextualised summaries of the information concerned.


Hopefulness of 'Hope'.


title: Felid herpesvirus 1 as a causative agent of severe nonsuppurative meningoencephalitis in a domestic cat.

text: Felid herpesvirus 1 is an important respiratory pathogen of domestic cats. This report presents the first case of severe nonsuppurative meningoencephalitis caused by this virus in a cat.


title: Bench evaluation of 7 home-care ventilators.

text: BACKGROUND Portable ventilators continue to decrease in size while increasing in performance. We bench-tested the triggering, battery duration, and tidal volume (V(T)) of 7 portable ventilators: LTV 1000, LTV 1200, Puritan Bennett 540, Trilogy, Vela, iVent 101, and HT50. METHODS We tested triggering with a modified dual-chamber test lung to simulate spontaneous breathing with weak, normal, and strong inspiratory effort. We measured battery duration by fully charging the battery and operating the ventilator with a V(T) of 500 mL, a respiratory rate of 20 breaths/min, and PEEP of 5 cm H(2)O until breath-delivery ceased. We tested V(T) accuracy with pediatric ventilation scenarios (V(T) 50 mL or 100 mL, respiratory rate 50 breaths/min, inspiratory time 0.3 s, and PEEP 5 cm H(2)O) and an adult ventilation scenario (V(T) 400 mL, respiratory rate 30 breaths/min, inspiratory time 0.5 s, and PEEP 5 cm H(2)O). We measured and analyzed airway pressure, volume, and flow signals. RESULTS At the adult settings the measured V(T) range was 362-426 mL. On the pediatric settings the measured V(T) range was 51-182 mL at the set V(T) of 50 mL, and 90-141 mL at the set V(T) of 100 mL. The V(T) delivered by the Vela at both the 50 mL and 100 mL, and by the HT50 at 100 mL, did not meet the American Society for Testing and Materials standard for V(T) accuracy. Triggering response and battery duration ranged widely among the tested ventilators. CONCLUSIONS There was wide variability in battery duration and triggering sensitivity. Five of the ventilators performed adequately in V(T) delivery across several settings. The combination of high respiratory rate and low V(T) presented problems for 2 of the ventilators.


Children diagnosed with coronavirus disease 2019 may have cardiac involvement.


title: Fast SARS-CoV-2 detection by RT-qPCR in preheated nasopharyngeal swab samples.

text: OBJECTIVES The gold-standard COVID-19 diagnosis relies on detecting SARS-CoV-2 using RNA purification and one-step retrotranscription and quantitative PCR (RT-qPCR). Based on the urgent need for high-throughput screening, we tested the performance of three alternative, simple and affordable protocols to rapidly detect SARS-CoV-2, bypassing the long and tedious RNA extraction step and reducing the time to viral detection. METHODS We evaluated three methods based on direct nasopharyngeal swab viral transmission medium (VTM) heating before the RT-qPCR: a) direct without additives; b) in a formamide-EDTA (FAE) buffer, c) in a RNAsnapTM buffer. RESULTS Although with a delay in cycle threshold compared to the gold-standard, we found consistent results in nasopharyngeal swab samples that were subject to a direct 70°C incubation for 10 min. CONCLUSIONS Our findings provide valuable options to overcome any supply chain issue and help to increase the throughput of diagnostic tests, thereby complementing standard diagnosis.


title: Repair of diaphragmatic hernia following spinal surgery by laparoscopic mesh application: a case report and review of the literature.

text: We describe the laparoscopic management of diaphragmatic hernia (DH) caused by vertebral pedicle screw displacement. A 58-year-old woman underwent surgery for scoliosis and underwent posterior pedicle screw fixation. In the first postoperative (PO)day, she developed mild dyspnea. An anteroposterior chest radiograph revealed bilateral pleural effusion, which was more pronounced on the left side. A thoracoabdominal computed tomography (CT) scan, performed in the second PO day, revealed a solid mass in the pleural cavity that was associated with screw displacement, which had also entered into the peritoneal cavity without apparent other lesion of hollow and solid viscous. In the third PO day, after the screw was removed, explorative laparoscopy was carried out. We observed herniation of the omentum through a small diaphragmatic tear. Once the absence of visceral injury was confirmed, we reduced the omentum into the abdomen. Then, we repaired the hernia by applying a dual layer polypropylene mesh over the defect with a 3-cm overlap. The remainder of the postoperative period was uneventful. Iatrogenic DH due to a pedicle screw displacement has never been described before. In cases of pleural effusion following spinal surgery, rapid assessment and treatment are crucial. We conclude that a laparoscopic approach to iatrogenic DH could be feasible and effective in a hemodynamically stable patient with negative CT findings because it enables the completion of the diagnostic cascade and the repair of the tear, providing excellent visualization of the abdominal viscera and diaphragmatic tears.


title: Supraglottic airway devices in the ambulatory setting.

text: Supraglottic airway devices (SGAs) offer certain advantages over endotracheal intubation, making them particularly well suited for the specific demands of outpatient anesthesia. Patients may tolerate the placement and maintenance of an SGA at a lower dose of anesthetic than that needed for an endotracheal tube; neuromuscular blocking agents are rarely necessary for airway management with an SGA; the incidence of airway morbidity is lower with SGAs than with endotracheal tubes; and SGAs may facilitate faster recovery and earlier discharge of patients. Two limitations of SGAs are incomplete protection against aspiration of gastric contents and inadequate delivery of positive pressure ventilation. Newer variants of the original laryngeal mask airway, the LMA Classic (LMA North America, Inc), as well as an array of other recently developed SGAs, aim to address these limitations. Their utility and safety in specific patient populations (eg, the morbidly obese) and during certain procedures (eg, laparoscopic surgery) remain to be determined.


title: Identification of the myelin oligodendrocyte glycoprotein as a cellular receptor for rubella virus.

text: Rubella virus (RV) is a highly transmissible pathogenic agent that causes the disease rubella. Maternal RV infection during early pregnancy causes the death of the fetus or congenital rubella syndrome in infants. However, the cellular receptor for RV has not yet been identified. In this study, we found that the myelin oligodendrocyte glycoprotein (MOG) specifically bound to the E1 envelope glycoprotein of RV, and an antibody against MOG could block RV infection. Most importantly, we also showed that ectopic expression of MOG on the cell surface of 293T cells rendered this nonpermissive cell line permissive for RV entry and replication. Thus, this study has identified a cellular receptor for RV and suggests that blocking the MOG attachment site of RV may be a strategy for molecular intervention of RV infection.


title: Sutures versus staples for wound closure in orthopaedic surgery: a pilot randomized controlled trial.

text: BACKGROUND In the spectrum of surgical decision-making, wound closure material is often an afterthought. However, the findings of a recent meta-analysis suggest that the rate of surgical site infections (SSIs) is increased by using staples to close surgical wounds. Less clear is the effect of closure material on the incidence of non-infectious wound complications.The aim of this study was to compare sutures and staples in terms of: incidence of wound complications to determine the sample size for a definitive trial comparing wound closure methods. METHODS Eligible adult orthopaedic patients were randomized to have wounds closed with sutures or staples. Time for skin closure was recorded. Wounds were assessed for complications for six weeks. The incidence of complications was compared using Fisher's exact test. Time to close and pain with removal of closure material were compared using a Student's t-test. RESULTS The total number of patients reporting a wound complication was 59 of 148 patients completing six-week followup (41%), with no differennce between sutures and staples (RR = 0.77, CI = 0.52-1.14). The time to close wounds was shorter in the staple group (mean=4.8 min, CI = 2.6-7.1) than the suture group (mean=12 min, CI = 7.9-16). Patients in the staple group (mean=3.7, CI =2.8-4.6) reported more pain with removal than suture group (mean=2.5, CI =1.6-3.4). CONCLUSIONS This study suggests that 42% of patients report a wound complication with no difference between sutures and staples. It was demonstrated that suturing skin requires more time and staples are more painful to remove. TRIAL REGISTRATION Clinicaltrials.gov identifier NCT01146236 (registered June 14, 2010).


title: The CD225 domain of IFITM3 is required for both IFITM protein association and inhibition of influenza A virus and dengue virus replication.

text: The interferon-induced transmembrane protein 3 (IFITM3) gene is an interferon-stimulated gene that inhibits the replication of multiple pathogenic viruses in vitro and in vivo. IFITM3 is a member of a large protein superfamily, whose members share a functionally undefined area of high amino acid conservation, the CD225 domain. We performed mutational analyses of IFITM3 and identified multiple residues within the CD225 domain, consisting of the first intramembrane domain (intramembrane domain 1 [IM1]) and a conserved intracellular loop (CIL), that are required for restriction of both influenza A virus (IAV) and dengue virus (DENV) infection in vitro. Two phenylalanines within IM1 (F75 and F78) also mediate a physical association between IFITM proteins, and the loss of this interaction decreases IFITM3-mediated restriction. By extension, similar IM1-mediated associations may contribute to the functions of additional members of the CD225 domain family. IFITM3's distal N-terminal domain is also needed for full antiviral activity, including a tyrosine (Y20), whose alteration results in mislocalization of a portion of IFITM3 to the cell periphery and surface. Comparative analyses demonstrate that similar molecular determinants are needed for IFITM3's restriction of both IAV and DENV. However, a portion of the CIL including Y99 and R87 is preferentially needed for inhibition of the orthomyxovirus. Several IFITM3 proteins engineered with rare single-nucleotide polymorphisms demonstrated reduced expression or mislocalization, and these events were associated with enhanced viral replication in vitro, suggesting that possessing such alleles may impact an individual's risk for viral infection. On the basis of this and other data, we propose a model for IFITM3-mediated restriction.


title: Perioperative Complications of Video-Assisted Thoracoscopic Pulmonary Procedures in Neonates and Infants.

text: Video-assisted thoracoscopic surgery (VATS) has gained broad acceptance among pediatric surgeons. Today, VATS can be regarded as a routine approach for various conditions in neonates and infants. However, there is a lack of information concerning the complications of thoracoscopic pulmonary surgery in neonates and infants. We aimed to review the available data. A systematic review of the literature was performed using PubMed. All publications reporting on VATS for pulmonary procedures in neonates and infants up to the age of 1 year were included. Articles were reviewed in detail for occurrence of perioperative complications and their treatment. Nine case series were eligible for analysis. Entities treated included lung sequestration, congenital pulmonary airway malformation, congenital lobar emphysema, and bronchogenic cyst. Case series reported on a total number of 135 patients. Complications occurred in 14 patients (10.4%). The major complication was an accidental transection of the middle lobar bronchus that concluded in a later resection of a prior unaffected lung lobe. Other relevant complications reported were bleeding in four patients (3.0%) and persistent air leak in four cases (3.0%). Infectious complications were reported in four patients (3.0%). Additionally, iatrogenic phrenic nerve paralysis occurred in one patient. There were no deaths related to the VATS technique. In 11 cases (8.1%), conversion to thoracotomy had been necessary. General recommendations on the treatment of complications could not be derived due to small patient numbers and lack of details of the complications reported. Reports on major complications of pulmonary VATS in neonates and infants below 1 year of age are scarce. As severe complications such as accidental bronchus transection have been described, feasibility of neonatal/infant VATS cannot be unequivocally confirmed. No literature-based recommendation can be given on the treatment of complications.


title: Impact of vedolizumab therapy on extra-intestinal manifestations in patients with inflammatory bowel disease: a multicentre cohort study nested in the OBSERV-IBD cohort.

text: BACKGROUND The effectiveness of vedolizumab as a treatment for extraintestinal manifestations (EIM) is questionable due to its gut-specificity. AIM To assess effectiveness of vedolizumab for EIM in patients with inflammatory bowel disease (IBD) in a large real-life experience cohort. METHODS Between June and December 2014, 173 patients with Crohn's disease and 121 with ulcerative colitis were treated with vedolizumab. Patients were followed until week 54. EIM activity was assessed at weeks 0, 6, 14, 22, 30 and 54 by using a 3-step scale: complete remission, partial response and no response. RESULTS At baseline, 49 (16.7%) patients had EIMs of which 47 had inflammatory arthralgia/arthritis, four had cutaneous lesions and two had both rheumatologic and skin EIM. At week 54, 21 (44.7%) patients had complete remission for inflammatory arthralgia/arthritis and three (75%) for cutaneous EIM. In multivariate analysis, complete remission of inflammatory arthralgia/arthritis was associated with clinical remission of IBD (OR = 1.89, IC95% [1.05-3.41], P = .03) and recent onset of inflammatory arthralgia/arthritis (OR = 1.99, IC95% [1.12-3.52], P = .02). During the follow-up period, 34 (13.8%) patients without any EIM at baseline, developed incident cases of inflammatory arthralgia/arthritis consisting mostly of peripheral arthralgia without evidence of arthritis and 14 (4.8%) incident cases of paradoxical skin manifestation. CONCLUSION Vedolizumab therapy is commonly associated with improvement in EIM. This was associated with quiescent IBD and recent EIM. However, paradoxical skin manifestation and inflammatory arthralgia/arthritis may occur upon vedolizumab therapy.


title: Use of plasma procalcitonin levels as an adjunct to clinical microbiology.

text: Procalcitonin (PCT) is synthesized by a large number of tissues and organs in response to invasion by pathogenic bacteria, fungi, and some parasites. Current PCT assays are rapid, specific, and of sufficient sensitivity to detect increases in PCT serum levels within 4 to 6 h of initiation of infection. Clinically, PCT levels may help in decisions regarding the need for empirical antibiotic therapy, "source control" of infection, and duration of antibiotic therapy. The addition of PCT levels to bacterial culture and viral detection results can assist with the separation of colonization and invasion by pathogenic bacteria.


title: Controlled viral glycoprotein expression as a safety feature in a bivalent rabies-ebola vaccine.

text: Using a recombinant rabies (RABV) vaccine platform, we have developed several safe and effective vaccines. Most recently, we have developed a RABV-based ebolavirus (EBOV) vaccine that is efficacious in nonhuman primates. One safety feature of this vaccine is the utilization of a live but replication-deficient RABV construct. In this construct, the RABV glycoprotein (G) has been deleted from the genome, requiring G trans complementation in order for new infectious viruses to be released from the initial infected cell. Here we analyze this safety feature of the bivalent RABV-based EBOV vaccine comprised of the G-deleted RABV backbone expressing EBOV glycoprotein (GP). We found that, while the level of RABV genome in infected cells is equivalent regardless of G supplementation, the production of infectious virus is indeed restricted by the lack of G, and most importantly, that the presence of EBOV GP does not substitute for G. These findings further support the safety profile of this replication-deficient RABV-EBOV bivalent vaccine.


title: Physical Distancing With Social Connectedness.

text: In light of concerns over the potential detrimental effects of declining care continuity, and the need for connection between patients and health care providers, our multidisciplinary group considered the possible ways that relationships might be developed in different kinds of health care encounters.We were surprised to discover many avenues to invest in relationships, even in non-continuity consultations, and how meaningful human connections might be developed even in telehealth visits. Opportunities range from the quality of attention or the structure of the time during the visit, to supporting relationship development in how care is organized at the local or system level and in the use of digital encounters. These ways of investing in relationships can exhibit different manifestations and emphases during different kinds of visits, but most are available during all kinds of encounters.Recognizing and supporting the many ways of investing in relationships has great potential to create a positive sea change in a health care system that currently feels fragmented and depersonalized to both patients and health care clinicians.The current COVID-19 pandemic is full of opportunity to use remote communication to develop healing human relationships. What we need in a pandemic is not social distancing, but physical distancing with social connectedness.


title: The Effect of Nebulizer Position on Aerosolized Epoprostenol Delivery in an Adult Lung Model.

text: BACKGROUND Aerosolized epoprostenol is an alternative for inhaled nitric oxide in the management of pulmonary arterial hypertension and possibly acute hypoxemia. Our objective was to determine differences in drug deposition based on different nebulizer positions in the ventilator circuit, using a vibrating mesh nebulizer. METHODS An 8.0-mm inner diameter endotracheal tube (ETT) was connected to a training test lung, compliance of 30 mL/cm H2O, with a collecting filter placed at the ETT-test lung junction. A mechanical ventilator, heated wire circuit, and pass-over humidifier were utilized. A syringe pump continuously instilled a 15,000-ng/mL epoprostenol solution at 30, 50, and 70 ng/kg/min into the vibrating mesh nebulizer at all 4 positions. Tidal volumes (VT) were set at 4, 6, and 8 mL/kg for a 70-kg patient with breathing frequencies of 25, 16, and 12 breaths/min, respectively. Epoprostenol was eluted from the filters (no. = 180) and analyzed with ultraviolet-visible spectrophotometry at 205 nm to estimate drug deposition. RESULTS Epoprostenol deposition increased significantly (P = .02) as the dosage increased from 30 ng/kg/min (median 4,520.0 ng, interquartile range [IQR] 2,285.0-6,712.2 ng) to 50 ng/kg/min (median 6,065.0 ng, IQR 3,220.0-13,002.5 ng) and 70 ng/kg/min (median 9,890.0 ng, IQR 6,270.0-16,140.0 ng). No significant difference was found between variations in ventilator settings. No difference in deposition was found between the humidifier inlet and outlet, but these positions resulted in greater deposition compared with the inspiratory limb and between the ETT and Y-piece. CONCLUSIONS The greatest amount of mean epoprostenol deposition resulted with the nebulizer placed at the humidifier inlet or outlet in a ventilator with bias flow.


title: Choosing Channels, Sources, and Content for Communicating Prostate Cancer Information to Black Men: A Systematic Review of the Literature.

text: The purpose of this study was to identify effective channels, sources, and content approaches for communicating prostate cancer prevention information to Black men. The Web of Science, PubMed and GoogleScholar databases, as well as reviews of reference lists for selected publications, were searched to select articles relevant to cancer communication channels, sources or content for Black men, focused on male-prevalent cancers and published in English. Articles were excluded if they examined only patient-provider communication, dealt exclusively with prostate cancer patients or did not separate findings by race. The selection procedures identified 41 relevant articles, which were systematically and independently reviewed by two team members to extract data on preferred channels, sources, and content for prostate cancer information. This review revealed that Black men prefer interpersonal communication for prostate cancer information; however, video can be effective. Trusted sources included personal physicians, clergy, and other community leaders, family (especially spouses) and prostate cancer survivors. Men want comprehensive information about screening, symptoms, treatment, and outcomes. Messages should be culturally tailored, encouraging empowerment and "ownership" of disease. Black men are open to prostate cancer prevention information through mediated channels when contextualized within spiritual/cultural beliefs and delivered by trusted sources.


title: The use of an acellular porcine dermal collagen implant in the repair of complex abdominal wall defects: a European multicentre retrospective study.

text: BACKGROUND The use of biological materials for the repair of complex abdominal wall defects has increased over the years; however, the role of these materials in routine practice remains unclear. The aim of the study was to evaluate clinical outcomes following the use of Permacol™ porcine collagen surgical implant in complex abdominal wall repair. METHODS This subset analysis of seven European sites from a multicentre retrospective study included patients undergoing open or laparoscopic surgery and treated with Permacol™ surgical implant. Inguinal, parastomal, diaphragmatic, perineal, and hiatal repairs were excluded. Only patients with at least 12 months of follow-up after surgery were included. RESULTS A total of 109 patients (56 males and 53 females) were included. Patients had a median of two comorbidities (range 0-6). Thirty-three per cent of patients were treated for recurrent hernia. All but one case used an open approach. Sixty-six per cent were Center for Disease Control wound class II-IV at the time of surgery. Fascial closure was achieved in 69%. Median follow-up length was 720 days (range 368-2857). Recurrence rates at 1 and 2 years were 9.2 and 18.3 %, respectively, and were higher in cases without fascial closure. One-year recurrence was higher following use of an onlay technique (P = 0.025). In a multivariate analysis, among 16 comorbidities examined only fascial closure significantly impacted 1-year recurrence (P = 0.049). CONCLUSIONS Data from this large retrospective multicentre European study strongly suggest the use of Permacol™ porcine collagen surgical implant to be safe and effective for complex abdominal wall repair. The recurrence rate was impacted by fascial closure.


Diagnosis and recovery from SARS-CoV-2 infection is challenging in kidney patients: tests are an issue.


Meningitis and Reversible Cerebral Vasoconstriction Syndrome During the Postpartum Period.