title: Double aortic arch in an adult.

text: We present the case of a 60-year old man who complained of severe dysphagia caused by a double aortic arch (DAA) with a right-sided descending thoracic aorta. The left-sided aortic arch had a compressive segment located between the left subclavian artery and the descending thoracic aorta. Using left third thoracotomy, the segment, which caused compression of the oesophagus, was ligated and divided. After the operation, the patient was completely relieved of his symptoms. We concluded that the removal of the compressive portion of the left aortic arch and the ligation of the ligamentum arteriosum are the only treatment measures needed in such cases.


title: Rupture Resemblance Score (RRS): toward risk stratification of unruptured intracranial aneurysms using hemodynamic-morphological discriminants.

text: OBJECTIVE We have previously developed three logistic regression models for discriminating intracranial aneurysm rupture status from 119 aneurysms based on hemodynamic-morphological parameters. In this study we exploit their use as a tool for predicting the risk of rupture of aneurysms with a defined Rupture Resemblance Score (RRS). METHODS We collected three-dimensional images of 85 consecutive aneurysms, applied the three regression models and compared model performance at predicting rupture status against anecdotal metrics (aneurysm size and aspect ratio). We then reinterpreted the model-predicted probability as RRS, where the higher the score the closer the resemblance to previously known rupture components, and applied the RRS prospectively to four unruptured aneurysms with borderline treatment decisions. RESULTS All three models yielded excellent sensitivity (0.78-0.83) and specificity (0.78-0.84) at a cutoff score of 50%, whereas aneurysm size and aspect ratio showed poor sensitivities (0.28 and 0.33, respectively). Lowering the cutoff score to 30% improved sensitivity to 0.90. The RRS identified most of the ruptured aneurysms and also some unruptured ones that closely resembled ruptured aneurysms hemodynamically and/or morphologically. The prospective application of the RRS to unruptured aneurysms shows that it could provide additional insights for treatment decisions. CONCLUSIONS Previous regression models based on hemodynamic-morphological parameters are able to discriminate rupture in a new cohort in the same population. A higher probability of rupture is associated with larger size ratio, lower normalized wall shear stress and higher oscillatory shear index. The RRS could potentially stratify rupture risk and assist in treatment decision-making for unruptured aneurysms.


title: A breath of fresh air: a quality-improvement study comparing an air-circulating technique versus conventional technique to prevent nasogastric tube dysfunction.

text: BACKGROUND Nasogastric tubes are an important component of care in patients with gastrointestinal obstructions. However, they are prone to malfunction despite conventional flushing techniques, with potentially severe consequences. There is no widely accepted, gold-standard way to ensure that a nasogastric tube succeeds in maintaining an empty stomach following flushing. METHODS We have developed a flushing technique to better ensure successful tube function. We compared this technique to conventional flushing both in vitro (using a plastic stomach model) and in vivo (in a pig model), and we provide a didactic video. RESULTS The mean gastric residual volume following our novel flushing technique is nearly 25-fold lower than following conventional flushing (13 mL vs. 330 mL). CONCLUSIONS Our simple technique is more effective than conventional techniques in maintaining nasogastric tube function and therefore should prevent dangerous vomiting and aspiration pneumonia better than conventional techniques.


title: Laparoscopic pancreaticoduodenectomy: single-surgeon experience.

text: BACKGROUND Innovations in surgical strategies and technologies have facilitated laparoscopic pancreaticoduodenectomy (LPD). However, data regarding the short-term and long-term results of LPD are sparse, and this procedure is the primary focus of the current study. METHODS Between October 2010 and October 2013, a total of 31 consecutive patients received LPD, including hand-assisted laparoscopic pancreaticoduodenectomy, total laparoscopic pancreaticoduodenectomy, and laparoscopic pylorus-preserving pancreaticoduodenectomy. Data regarding short-term surgical outcomes and long-term oncological results were collected prospectively. RESULTS The median operative time was 515.0 min (interquartile range 465.0-585.0 min). The median intraoperative estimated blood loss was 260.0 mL (interquartile range 150.0-430.0 mL). Conversion to open pancreaticoduodenectomy was required in three patients (9.7%) due to intraoperative pneumoperitoneum intolerance (n = 1, 3.2%) and tumor adherence to the superior mesenteric vein (n = 2, 6.5%). No significant differences between the surgical approaches were observed in regard to intraoperative and postoperative data. Postoperative severe complications (Clavien ≥ III) were detected in three (9.7%) patients, including one grade C pancreatic fistula, one grade B postoperative bleeding event, and one afferent loop obstruction. There were no deaths within 30 days following LPD. The final pathological results revealed duodenal adenocarcinoma in 14 (45.2%) patients, ampullary adenocarcinoma in four (12.9%) patients, distal common bile duct cancer in six (19.4%) patients, pancreatic ductal adenocarcinoma in five (16.1%) patients, gastrointestinal stroma tumor in one (3.2%) patient, and chronic pancreatitis in one (3.2%) patient. All patients suffering from tumors underwent R0 resection (n = 30, 100.0%), with the optimal number of collected lymph nodes (median: 13, interquartile range 11-19). At the most recent follow-up, 20 patients were still alive, and the 1-, and 3-year overall survival for patients with duodenal adenocarcinoma were 100.0 and 71.4%, respectively. CONCLUSIONS According to this study, LPD is feasible and technically safe for highly selected patients and can offer acceptable oncological outcomes and long-term survival.


title: Scandinavian SSAI clinical practice guideline on pre-hospital airway management.

text: BACKGROUND The Scandinavian society of anaesthesiology and intensive care medicine task force on pre-hospital airway management was asked to formulate recommendations following standards for trustworthy clinical practice guidelines. METHODS The literature was systematically reviewed and the grading of recommendations assessment, development and evaluation (GRADE) system was applied to move from evidence to recommendations. RESULTS We recommend that all emergency medical service (EMS) providers consider to: apply basic airway manoeuvres and airway adjuncts (good practice recommendation); turn unconscious non-trauma patients into the recovery position when advanced airway management is unavailable (good practice recommendation); turn unconscious trauma patients to the lateral trauma position while maintaining spinal alignment when advanced airway management is unavailable [strong recommendation, low quality of evidence (QoE)]. We suggest that intermediately trained providers use a supraglottic airway device (SAD) or basic airway manoeuvres on patients in cardiac arrest (weak recommendation, low QoE). We recommend that advanced trained providers consider using an SAD in selected indications or as a rescue device after failed endotracheal intubation (ETI) (good practice recommendation). We recommend that ETI should only be performed by advanced trained providers (strong recommendation, low QoE). We suggest that videolaryngoscopy is considered for ETI when direct laryngoscopy fails or is expected to be difficult (weak recommendation, low QoE). We suggest that advanced trained providers apply cricothyroidotomy in 'cannot intubate, cannot ventilate' situations (weak recommendation, low QoE). CONCLUSION This guideline for pre-hospital airway management includes a combination of techniques applied in a stepwise fashion appropriate to patient clinical status and provider training.


title: Effects of arterial load variations on dynamic arterial elastance: an experimental study.

text: Background. Dynamic arterial elastance (Ea dyn ), the relationship between pulse pressure variation (PPV) and stroke volume variation (SVV), has been suggested as a functional assessment of arterial load. The aim of this study was to evaluate the impact of arterial load changes during acute pharmacological changes, fluid administration, and haemorrhage on Ea dyn . Methods. Eighteen anaesthetized, mechanically ventilated New Zealand rabbits were studied. Arterial load changes were induced by phenylephrine ( n =9) or nitroprusside ( n =9). Thereafter, animals received a fluid bolus (10 ml kg -1 ), followed by stepwise bleeding (blood loss: 15 ml kg -1 ). The influence of arterial load and cardiac variables on PPV, SVV, and Ea dyn was analysed using a linear mixed-effects model analysis. Results. After phenylephrine infusion, mean ( sd ) Ea dyn decreased from 0.89 (0.14) to 0.49 (0.12), P <0.001; whereas after administration of nitroprusside, Ea dyn increased from 0.80 (0.23) to 1.28 (0.21), P <0.0001. Overall, the fluid bolus decreased Ea dyn [from 0.89 (0.44) to 0.73 (0.35); P <0.01], and haemorrhage increased it [from 0.78 (0.23) to 0.95 (0.26), P =0.03]. Both PPV and SVV were associated with similar arterial factors (effective arterial elastance, arterial compliance, and resistance) and heart rate. Furthermore, PPV was also related to the acceleration and peak velocity of aortic blood flow. Both arterial and cardiac factors contributed to the evolution of Ea dyn throughout the experiment. Conclusions. Acute modifications of arterial load induced significant changes on Ea dyn ; vasodilatation increased Ea dyn , whereas vasoconstriction decreased it. The Ea dyn was associated with both arterial load and cardiac factors, suggesting that Ea dyn should be more properly considered as a ventriculo-arterial coupling index.


title: Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease.

text: BACKGROUND Some people with SARS-CoV-2 infection remain asymptomatic, whilst in others the infection can cause mild to moderate COVID-19 disease and COVID-19 pneumonia, leading some patients to require intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever or cough, and signs such as oxygen saturation or lung auscultation findings, are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19 disease, or select patients for further diagnostic testing. OBJECTIVES To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19 disease or COVID-19 pneumonia. SEARCH METHODS On 27 April 2020, we undertook electronic searches in the Cochrane COVID-19 Study Register and the University of Bern living search database, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. SELECTION CRITERIA Studies were eligible if they included patients with suspected COVID-19 disease, or if they recruited known cases with COVID-19 disease and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards including reverse transcription polymerase chain reaction (RT-PCR), clinical expertise, imaging, serology tests and World Health Organization (WHO) or other definitions of COVID-19. DATA COLLECTION AND ANALYSIS Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the QUADAS-2 checklist. Analyses were descriptive, presenting sensitivity and specificity in paired forest plots, in ROC (receiver operating characteristic) space and in dumbbell plots. We did not attempt meta-analysis due to the small number of studies, heterogeneity across studies and the high risk of bias. MAIN RESULTS We identified 16 studies including 7706 participants in total. Prevalence of COVID-19 disease varied from 5% to 38% with a median of 17%. There were no studies from primary care settings, although we did find seven studies in outpatient clinics (2172 participants), and four studies in the emergency department (1401 participants). We found data on 27 signs and symptoms, which fall into four different categories: systemic, respiratory, gastrointestinal and cardiovascular. No studies assessed combinations of different signs and symptoms and results were highly variable across studies. Most had very low sensitivity and high specificity; only six symptoms had a sensitivity of at least 50% in at least one study: cough, sore throat, fever, myalgia or arthralgia, fatigue, and headache. Of these, fever, myalgia or arthralgia, fatigue, and headache could be considered red flags (defined as having a positive likelihood ratio of at least 5) for COVID-19 as their specificity was above 90%, meaning that they substantially increase the likelihood of COVID-19 disease when present. Seven studies carried a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional four studies, we were unable to assess the risk for selection bias. These factors make it very difficult to determine the diagnostic properties of these signs and symptoms from the included studies. We also had concerns about the applicability of these results, since most studies included participants who were already admitted to hospital or presenting to hospital settings. This makes these findings less applicable to people presenting to primary care, who may have less severe illness and a lower prevalence of COVID-19 disease. None of the studies included any data on children, and only one focused specifically on older adults. We hope that future updates of this review will be able to provide more information about the diagnostic properties of signs and symptoms in different settings and age groups. AUTHORS' CONCLUSIONS The individual signs and symptoms included in this review appear to have very poor diagnostic properties, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out disease. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19 disease, are urgently needed. Results from such studies could inform subsequent management decisions such as self-isolation or selecting patients for further diagnostic testing. We also need data on potentially more specific symptoms such as loss of sense of smell. Studies in older adults are especially important.


title: E-Health in Norway Before and During the Initial Phase of the Covid-19 Pandemic.

text: The use of e-health services has for many years gradually increased in Norway as in most European countries. Searching for information about health and illness has previously by far been the most popular service. In this study, we review the literature with the aim of examining any changes in e-health use during the Covid-19 pandemic. We find that there has been a marked change in Norway, with an extreme increase in video consultations, especially in primary care and in the mental health field. The government has also released an app for tracking the illness, which so far has been downloaded by approximately 1/4 of the population. These changes are likely to impact the use of e-health also after the pandemic.


title: Immediate versus delayed surgery for hip fractures in the elderly patients: a protocol for a systematic review and meta-analysis.

text: BACKGROUND Hip fractures are a major public health problem in elderly populations and are accompanied by high-mortality rates. Whether timing of surgery has an impact on morbidity and mortality has been discussed controversially, numerous studies suggest that the delay of surgery can significantly increase the risk of morbidity and mortality; others report that achieving a stable medical condition is more important than early surgery. The goal of our systematic review is to assess the impact of timing of surgery on health outcomes in patients aged 60 years or older with acute hip fracture. In addition, we will investigate differences in beneficial or harmful effects of timing of surgery in subgroups of patients based on demographic characteristics, physical status, and the use of anticoagulant medications. METHODS We will systematically search MEDLINE via Ovid, the Cochrane Library, Embase, PubMed, and clinical trial registries (from 1997 to 2017). In addition, we will search reference lists of pertinent reviews, archives of annual meetings of orthopaedic societies, and contact experts. We will include randomized controlled trials and non-randomized studies assessing the impact of timing of surgery after hip fracture in patients 60 years or older, published in English or German. Our outcomes of interest include health outcomes such as mortality, perioperative complications, functional capacity, and quality of life. We plan to perform meta-analyses if we have at least three sufficiently similar studies. If data are sufficient, we will conduct subgroup-analyses testing for differences between age groups, sex, patients' physical status as assessed with ASA (American Society of Anesthesiologists) scores, and the use of anticoagulation. DISCUSSION Since this is the first systematic review on this topic since 2010, our findings will help to inform clinical practice guidelines concerning timing of surgery in hip fractures. Furthermore, our findings could contribute to define an optimal time period for surgery for different groups of patients with acute hip fracture. SYSTEMATIC REVIEW REGISTRATION PROSPERO 2017 CRD42017058216.


The morbidity and mortality of COVID-19 are associated with ABO and Rh blood groups.


title: Preliminary results of antiscarring therapy in the prevention of postendoscopic esophageal mucosectomy strictures.

text: BACKGROUND Esophageal endoscopic submucosal dissection (ESD) is an effective minimally invasive therapy for early esophageal cancer and high-grade Barrett dysplasia. However, esophageal stricture formation after circumferential or large ESD has limited its wide adoption. Mitomycin C (MMC), halofuginone (Hal), and transforming growth factor β3 (TGF-β3) exhibits antiscarring effects that may prevent post-ESD stricture formation. METHODS Using endoscopic mucosectomy (EEM) technique, an 8- to 10-cm-long circumferential esophageal mucosal segment was excised in a porcine model. The site was either untreated (control, n = 6) or received 40 evenly distributed injections of antiscarring agent immediately and at weeks 1 and 2. High and low doses were used: MMC 5 mg (n = 2), 0.5 mg (n = 2); Hal 5 mg (n = 2), 1.5 mg (n = 2), 0.5 mg (n = 2); TGF-β3 2 μg (n = 2), 0.5 μg (n = 2). The degree of stricture formation was determined by the percentage reduction of the esophageal lumen on weekly fluoroscopic examination. Animals were euthanized when strictures exceeded 80 % or the animals were unable to maintain weight. RESULTS The control group had a luminal diameter reduction of 78.2 ± 10.9 % by 2 weeks and were euthanized by week 3. Compared at 2 weeks, the Hal group showed a decrease in mean stricture formation (68.4 % low dose, 57.7 % high dose), while both TGF-β3 dosage groups showed no significant change (65.3 % low dose, 76.2 % high dose). MMC was most effective in stricture prevention (53.6 % low dose, 35 % high dose). Of concern, the esophageal wall treated with high-dose MMC appeared to be necrotic and eventually led to perforation. In contrast, low dose MMC, TGF-β3 and Hal treated areas appeared re-epithelialized and healthy. CONCLUSIONS Preliminary data on MMC and Hal demonstrated promise in reducing esophageal stricture formation after EEM. More animal data are needed to perform adequate statistical analysis in order to determine overall efficacy of antiscarring therapy.


Adapting to the impact of COVID-19 on mental health: an international perspective.


title: Association between cannabis use and treatment outcomes in patients receiving methadone maintenance treatment: a systematic review protocol.

text: BACKGROUND With the non-medical use of prescription opioids increasingly becoming a method of abuse in Canada, the number of patients requiring methadone maintenance treatment (MMT) for opioid use disorder has increased dramatically. The rate of cannabis use in this population is disproportionately high (~50 %). Because its use is generally perceived as harmless, cannabis use is often not monitored during MMT. Current literature regarding the effects of cannabis use on MMT is conflicting, and the presence and nature of an association has not been clearly established. The primary objective of this review will be to conduct a systematic review of the literature and, if appropriate, a meta-analysis to determine whether there is an association between cannabis use and MMT outcomes. A secondary objective will be to perform subgroup analyses (by age, sex, method of cannabis measurement, and country) to determine whether cannabis use differentially influences MMT outcomes within these subgroups. METHODS/DESIGN The search will be conducted on the following electronic databases using a predefined search strategy: MEDLINE, EMBASE, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Two authors (LZ and MB) will independently screen articles using predetermined inclusion/exclusion criteria and will extract data from included articles using a pilot-tested data extraction form. Disagreements at all stages of the screening process will be settled through discussion, and when consensus cannot be reached, a third author (ZS) will be consulted. An assessment of quality and risk of bias will be conducted on all included articles, and a sensitivity analysis will be used to compare results of studies with high and low risk of bias. We will perform random- and fixed-effects meta-analyses, if appropriate, with heterogeneity calculated using the I (2) statistic and formal evaluation of publication bias. DISCUSSION Results of this systematic review will elucidate the association between cannabis use and methadone maintenance treatment outcomes. We will provide evidence that will be useful to clinicians regarding whether monitoring cannabis use during MMT is advantageous for optimizing MMT outcomes. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42015029372.


title: Rational design of a flavivirus vaccine by abolishing viral RNA 2'-O methylation.

text: Viruses that replicate in the cytoplasm cannot access the host nuclear capping machinery. These viruses have evolved viral methyltransferase(s) to methylate N-7 and 2'-O cap of their RNA; alternatively, they "snatch" host mRNA cap to form the 5' end of viral RNA. The function of 2'-O methylation of viral RNA cap is to mimic cellular mRNA and to evade host innate immune restriction. A cytoplasmic virus defective in 2'-O methylation is replicative, but its viral RNA lacks 2'-O methylation and is recognized and eliminated by the host immune response. Such a mutant virus could be rationally designed as a live attenuated vaccine. Here, we use Japanese encephalitis virus (JEV), an important mosquito-borne flavivirus, to prove this novel vaccine concept. We show that JEV methyltransferase is responsible for both N-7 and 2'-O cap methylations as well as evasion of host innate immune response. Recombinant virus completely defective in 2'-O methylation was stable in cell culture after being passaged for >30 days. The mutant virus was attenuated in mice, elicited robust humoral and cellular immune responses, and retained the engineered mutation in vivo. A single dose of immunization induced full protection against lethal challenge with JEV strains in mice. Mechanistically, the attenuation phenotype was attributed to the enhanced sensitivity of the mutant virus to the antiviral effects of interferon and IFIT proteins. Collectively, the results demonstrate the feasibility of using 2'-O methylation-defective virus as a vaccine approach; this vaccine approach should be applicable to other flaviviruses and nonflaviviruses that encode their own viral 2'-O methyltransferases.


title: Increased Need for Gastrointestinal Surgery and Increased Risk of Surgery-Related Complications in Patients with Ehlers-Danlos Syndrome: A Systematic Review.

text: BACKGROUND/AIMS Ehlers-Danlos syndromes (EDSs) constitute a rare group of inherited connective tissue diseases, characterized by multisystemic manifestations and general tissue fragility. Most severe complications include vascular and gastrointestinal (GI) emergencies requiring acute surgery. The purpose of this systematic review was to assess the causes of GI-related surgery and related mortality and morbidity in patients with EDSs. METHODS A systematic search was conducted in PubMed, Embase, and Scopus to identify relevant studies. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines for systematic reviews were followed. According to eligibility criteria, data were extracted and systematically screened by 2 authors. RESULTS Screening process identified 11 studies with a total of 1,567 patients. Findings indicated that patients with EDSs had a higher occurrence of surgery demanding GI manifestations, including perforation, hemorrhage, rupture of intra-abdominal organs, and rectal prolapse. Most affected was the vascular subtype, of which up to 33% underwent GI surgery and suffered from a lowered average life expectancy of 48 years (range 6-78). Secondary complications of surgery were common in all patients with EDSs. CONCLUSION Studies suggested that patients with EDSs present an increased need for GI surgery, but also an increased risk of surgery-related complications, most predominantly seen in the vascular subtype.


title: siRNAs: their potential as therapeutic agents--Part II. Methods of delivery.

text: RNA interference (RNAi) is a sequence-specific mechanism to control the expression of target genes. This technique has proven potentials both in vivo and in vitro. The main hurdle for using RNAi-based therapy is the effective delivery of RNAi-based drugs to the target cells or tissues in vivo. The aspects of off-target effects, delivery methods, induction of immune response and dose determination for delivery should, however, be considered carefully. If these challenges associated with siRNA can be met, then the potentials of RNAi could be exploited to the full for the development of therapeutic tools and drugs.


title: Contraction of the type I IFN locus and unusual constitutive expression of IFN-α in bats.

text: Bats harbor many emerging and reemerging viruses, several of which are highly pathogenic in other mammals but cause no clinical signs of disease in bats. To determine the role of interferons (IFNs) in the ability of bats to coexist with viruses, we sequenced the type I IFN locus of the Australian black flying fox, Pteropus alecto, providing what is, to our knowledge, the first gene map of the IFN region of any bat species. Our results reveal a highly contracted type I IFN family consisting of only 10 IFNs, including three functional IFN-α loci. Furthermore, the three IFN-α genes are constitutively expressed in unstimulated bat tissues and cells and their expression is unaffected by viral infection. Constitutively expressed IFN-α results in the induction of a subset of IFN-stimulated genes associated with antiviral activity and resistance to DNA damage, providing evidence for a unique IFN system that may be linked to the ability of bats to coexist with viruses.


title: Clinical Manifestations Associated with Peripheral Joint Involvement in Patients with Acute Chikungunya Virus Infection.

text: AbstractChikungunya virus (CHIKV) causes an acute febrile illness usually accompanied by severe polyarthralgia and polyarthritis. Previous studies have shown that older age, female gender, and some comorbid conditions are associated with chronic CHIKV arthritis. However, the factors associated with acute arthralgia and arthritis are not well known. Thus, we studied the clinical manifestations associated with acute peripheral joint involvement in a group of CHIKV patients from Puerto Rico. Patients with a history of fever for < 7 days evaluated at the emergency department of a university-based hospital were tested for several pathogens including CHIKV. All patients with laboratory-positive CHIKV infection were studied. Demographic features, clinical manifestations, and comorbidities were determined. Patients with and without peripheral joint involvement were compared using bivariable and multivariable analyses. In total, 172 patients with CHIKV fever were evaluated; 52.9% were women. The mean (standard deviation) age was 21.1 years (19.3). Peripheral arthralgia and/or arthritis were seen in 156 (90.7%) patients. In the multivariable analysis adjusted for age and gender, peripheral joint involvement was associated with myalgia (odds ratio [OR] = 4.65, 95% confidence interval [CI] = 1.48-14.72), back pain (OR = 16.77, 95% CI = 3.07-313.82), ocular pain (OR = 8.88, 95% CI = 1.65-165.19), headache (OR = 3.63, 95% CI = 1.06-12.53), anorexia (OR = 5.68, 95% CI = 1.87-18.97), and nausea (OR = 6.88, 95% CI = 2.05-31.49). In conclusion, in this population of patients with acute CHIKV infection, peripheral joint involvement was associated with myalgia and back pain as well as nonmusculoskeletal manifestations such as headache, ocular pain, anorexia, and nausea.


Special Issue: Digital Health in Times of COVID-19.


title: Transmembrane Protein pUL50 of Human Cytomegalovirus Inhibits ISGylation by Downregulating UBE1L.

text: Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that can be conjugated to proteins via an enzymatic cascade involving the E1, E2, and E3 enzymes. ISG15 expression and protein ISGylation modulate viral infection; however, the viral mechanisms regulating the function of ISG15 and ISGylation are not well understood. We recently showed that ISGylation suppresses the growth of human cytomegalovirus (HCMV) at multiple steps of the virus life cycle and that the virus-encoded pUL26 protein inhibits protein ISGylation. In this study, we demonstrate that the HCMV UL50-encoded transmembrane protein, a component of the nuclear egress complex, also inhibits ISGylation. pUL50 interacted with UBE1L, an E1-activating enzyme for ISGylation, and (to a lesser extent) with ISG15, as did pUL26. However, unlike pUL26, pUL50 caused proteasomal degradation of UBE1L. The UBE1L level induced in human fibroblast cells by interferon beta treatment or virus infection was reduced by pUL50 expression. This activity of pUL50 involved the transmembrane (TM) domain within its C-terminal region, although pUL50 could interact with UBE1L in a manner independent of the TM domain. Consistently, colocalization of pUL50 with UBE1L was observed in cells treated with a proteasome inhibitor. Furthermore, we found that RNF170, an endoplasmic reticulum (ER)-associated ubiquitin E3 ligase, interacted with pUL50 and promoted pUL50-mediated UBE1L degradation via ubiquitination. Our results demonstrate a novel role for the pUL50 transmembrane protein of HCMV in the regulation of protein ISGylation.IMPORTANCE Proteins can be conjugated covalently by ubiquitin or ubiquitin-like proteins, such as SUMO and ISG15. ISG15 is highly induced in viral infection, and ISG15 conjugation, termed ISGylation, plays important regulatory roles in viral growth. Although ISGylation has been shown to negatively affect many viruses, including human cytomegalovirus (HCMV), viral countermeasures that might modulate ISGylation are not well understood. In the present study, we show that the transmembrane protein encoded by HCMV UL50 inhibits ISGylation by causing proteasomal degradation of UBE1L, an E1-activating enzyme for ISGylation. This pUL50 activity requires membrane targeting. In support of this finding, RNF170, an ER-associated ubiquitin E3 ligase, interacts with pUL50 and promotes UL50-mediated UBE1L ubiquitination and degradation. Our results provide the first evidence, to our knowledge, that viruses can regulate ISGylation by directly targeting the ISGylation E1 enzyme.


title: Simple, Rapid and Sensitive Portable Molecular Diagnosis of SFTS Virus Using Reverse Transcriptional Loop-Mediated Isothermal Amplification (RT-LAMP).

text: Recently, human infections caused by severe fever with thrombocytopenia syndrome virus (SFTSV), which can lead to fatality, have dramatically increased in East Asia. With the unavailability of vaccines or antiviral drugs to prevent and/or treat SFTSV infection, early rapid diagnosis is critical for prevention and control of the disease. Here, we report the development of a simple, rapid and sensitive portable detection method for SFTSV infection applying reverse transcription-loop mediated isothermal amplification (RT-LAMP) combined with one-pot colorimetric visualization and electro-free reaction platform. This method utilizes a pocket warmer to facilitate diagnosis in a resource-limited setting. Specific primers were designed to target the highly-conserved region of L gene of SFTSV. The detection limit of the RT-LAMP assay was approximately 100 viral genome copies from three different SFTSV strains. This assay exhibited comparable sensitivity to qRT-PCR and 10-fold more sensitivity than conventional RT-PCR, with a rapid detection time of 30 to 60 minutes. The RT-LAMP assay using SFTSV clinical specimens has demonstrated a similar detection rate to qRT-PCR and a higher detection rate compared to conventional RT-PCR. Moreover, there was no observed cross-reactive amplification of other human infectious viruses including Japanese Encephalitis Virus (JEV), Dengue, Enterovirus, Zika, Influenza and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This highly sensitive, electro- and equipment-free rapid colorimetric visualization method is feasible for resource-limited SFTSV field diagnosis.


Randomized controlled trials for everything?


title: The Effect of a Synthetic Heparan Sulfate on the Healing of Colonic Anastomoses.

text: BACKGROUND The mimetic compound OTR4120 may replace endogenous-degraded heparan sulfates that normally maintain the bioactivity of growth factors that are important for tissue repair. Herein, we investigated the effect of OTR4120 on the healing of normal colonic anastomoses. METHODS We evaluated the following two treatment groups of male Sprague Dawley rats (220-256 g): control-treated colonic anastomoses (n = 25) and OTR4120-treated colonic anastomoses (n = 25). We resected 10 mm of the left colon and then applied either saline alone (control) or OTR4120 (100 μg/mL) in saline to the colonic ends before an end-to-end single-layer anastomosis was constructed and again on the anastomosis before the abdomen and skin were closed. RESULTS On postoperative day 3, the anastomotic breaking strengths were 1.47 ± 0.32 N (mean ± SD) in the control group and 1.52 ± 0.27 N in the OTR4120-treated animals (P = 0.622). We also found that the hydroxyproline concentration (indicator of collagen) in the anastomotic wounds did not differ (P = 0.571) between the two groups. CONCLUSIONS Our data demonstrate that a single local application of OTR4120 intraoperatively did not increase the biomechanical strength of colonic anastomoses at the critical postoperative day 3 when the anastomoses are the weakest.


title: Flat detector angio-CT following intra-arterial therapy of acute ischemic stroke: identification of hemorrhage and distinction from contrast accumulation due to blood-brain barrier disruption.

text: BACKGROUND AND PURPOSE Flat panel detector CT in the angiography suite may be valuable for the detection of intracranial hematomas; however, abnormal contrast enhancement frequently mimics hemorrhage. We aimed to assess the accuracy of flat panel detector CT in detecting/excluding intracranial bleeding after endovascular stroke therapy and whether it was able to reliably differentiate hemorrhage from early blood-brain barrier disruption. MATERIALS AND METHODS Seventy-three patients were included for retrospective evaluation following endovascular stroke therapy: 32 after stent-assisted thrombectomy, 14 after intra-arterial thrombolysis, and 27 after a combination of both. Flat panel CT images were assessed for image quality and the presence and type of intracranial hemorrhage and BBB disruption by 2 readers separately and in consensus. Follow-up by multisection head CT, serving as the reference standard, was evaluated by a single reader. RESULTS Conventional head CT revealed intracranial hematomas in 12 patients (8 subarachnoid hemorrhages, 7 cases of intracerebral bleeding, 3 SAHs plus intracerebral bleeding). Image quality of flat panel detector CT was considered sufficient in all cases supratentorially and in 92% in the posterior fossa. Regarding detection or exclusion of intracranial hemorrhage, flat panel detector CT reached a sensitivity, specificity, positive and negative predictive values, and accuracy of 58%, 85%, 44%, 91%, and 81%, respectively. Maximum attenuation measurements were not valuable for the differentiation of hemorrhage and BBB disruption. CONCLUSIONS Flat panel CT after endovascular stroke treatment was able to exclude the rare event of an intracranial hemorrhage with a high negative predictive value. Future studies should evaluate the predictive value of BBB disruptions in flat panel detector CT for the development of relevant hematomas.


title: Diagnostic Ultrasound Services During the Coronavirus Disease (COVID-19) Pandemic.

text: OBJECTIVE. Nosocomial transmission of coronavirus disease (COVID-19) to frontline health care workers is well known, and health care workers may inadvertently become vectors for onward transmission. Ultrasound (US) service providers are at significant risk because scanning usually requires prolonged close patient contact. The bulky US equipment may also facilitate fomite transmission of disease. With increasing use of point-of-care and portable diagnostic US services, the risk is substantial. CONCLUSION. Our experience and protocols may help service providers with their own effective response against COVID-19.


title: Reduced Susceptibility to VIRIP-Based HIV-1 Entry Inhibitors Has a High Genetic Barrier and Severe Fitness Costs.

text: VIRIP has been identified as natural HIV-1 inhibitor targeting the gp41 fusion peptide. An optimized analogue (VIR-576) was effective in a phase I/II clinical trial and initial studies showed that HIV-1 resistance to VIRIP-based inhibitors has a high genetic barrier. Partially resistant CXCR4 (X4)-tropic HIV-1 NL4-3 variants could be obtained, however, after more than 15 months of passaging in MT-4 cells in the presence of another derivative (VIR-353). Sequence analyses identified the accumulation of seven mutations across the HIV-1 envelope glycoprotein but outside the gp41 fusion peptide. The authors suggested that the three initial alterations conferred resistance, while subsequent changes restored viral fitness. Here, we introduced these mutations individually and in combination into X4- and CCR5 (R5)-tropic HIV-1 constructs and determined their impact on VIR-353 and VIR-576 susceptibility, viral infectivity, replication fitness, and fusogenicity. We found that essentially all seven mutations contribute to reduced susceptibility to VIRIP-based inhibitors. HIV-1 constructs containing ≥4 changes were substantially more resistant to both VIRIP-based inhibitors and the VRC34.01 antibody targeting the fusion peptide. However, they were also much less infectious and fusogenic than those harboring only the three initial alterations. Furthermore, the additional changes attenuated rather than rescued HIV-1 replication in primary human cells. Thus, the genetic barrier to HIV-1 resistance against VIRIP-based inhibitors is higher than previously suggested, and mutations reducing viral susceptibility come at a severe fitness cost that was not rescued during long-term cell culture passage.IMPORTANCE Many viral pathogens are critically dependent on fusion peptides (FPs) that are inserted into the cellular membrane for infection. Initially, it was thought that FPs cannot be targeted for therapy because they are hardly accessible. However, an optimized derivative (VIR-576) of an endogenous fragment of α1-antitrypsin, named VIRIP, targeting the gp41 FP reduced viral loads in HIV-1-infected individuals. Characterization of HIV-1 variants selected during long-term cell-culture passage in the presence of a VIRIP derivative suggested that just three mutations in the HIV-1 Env protein might be sufficient for VIRIP resistance and that four subsequent changes restored viral fitness. Here, we show that all seven mutations contribute to reduced viral susceptibility to VIRIP-based inhibitors and demonstrate that the additional changes strongly impair rather than rescue HIV-1 infectivity, fusogenicity, and replication fitness. High genetic barrier to resistance and severe fitness cost support further clinical development of this class of antiviral agents.


title: Manual aspiration thrombectomy for basilar infarction in the setting of a persistent primitive hypoglossal artery: Case report and review of the literature.

text: BACKGROUND Persistent primitive hypoglossal artery (PPHA), a remnant of embryonal circulation, is a rare variant of the posterior cerebral circulation. Seven prior cases of posterior circulation stroke in the setting of PPHA have been described in the literature, with all but one case being attributable to atherosclerotic embolization from the internal carotid artery (ICA) through the PPHA. CASE DESCRIPTION We report a unique case of a young male with a PPHA presenting with a "top of the basilar" syndrome following the repair of his atrial septal defect who underwent emergent revascularization via endovascular mechanical aspiration thrombectomy. The patient underwent a successful aspiration thrombectomy with significant improvement in his clinical exam. CONCLUSIONS Considering the rarity of this persistent fetal anastamosis, it is important to be aware of the propensity for unusual presentations in the context of stroke, understand the management of the problem, and expeditiously treat the patient.


title: Robotic retroperitoneal partial nephrectomy: a step-by-step guide.

text: OBJECTIVE To describe a step-by-step guide for successful implementation of the retroperitoneal approach to robotic partial nephrectomy (RPN) PATIENTS AND METHODS: The patient is placed in the flank position and the table fully flexed to increase the space between the 12th rib and iliac crest. Access to the retroperitoneal space is obtained using a balloon-dilating device. Ports include a 12-mm camera port, two 8-mm robotic ports and a 12-mm assistant port placed in the anterior axillary line cephalad to the anterior superior iliac spine, and 7-8 cm caudal to the ipsilateral robotic port. RESULTS Positioning and port placement strategies for successful technique include: (i) Docking robot directly over the patient's head parallel to the spine; (ii) incision for camera port ≈1.9 cm (1 fingerbreadth) above the iliac crest, lateral to the triangle of Petit; (iii) Seldinger technique insertion of kidney-shaped balloon dilator into retroperitoneal space; (iv) Maximising distance between all ports; (v) Ensuring camera arm is placed in the outer part of the 'sweet spot'. CONCLUSION The retroperitoneal approach to RPN permits direct access to the renal hilum, no need for bowel mobilisation and excellent visualisation of posteriorly located tumours.


title: Porcine reproductive and respiratory syndrome virus (PRRSV) induces IL-12p40 production through JNK-AP-1 and NF-κB signaling pathways.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) mainly infects monocyte/macrophage cells and modulates cytokine production to regulate host immune response. IL-12p40 is the basic subunit of IL-12, a heterodimeric cytokine, which plays key roles in the cell-mediated immune response. In the present study, we demonstrated that PRRSV infection induced IL-12p40 production in vitro and in vivo. Subsequently, we showed that inhibitors of p38 MAPK, JNK, and NF-κB dramatically reduced PRRSV-induced IL-12p40 expression. To further characterize the molecular mechanism of IL-12p40 production induced by PRRSV infection, we cloned and analyzed the porcine IL-12p40 promoter, in which AP-1 and NF-κB motifs were found. In addition, both JNK-AP-1 and NF-κB signaling pathways were activated by PRRSV infection. Taken together, these data indicate that PRRSV induces IL-12p40 expression through the JNK-AP-1 and NF-κB signaling pathways. Our findings might facilitate our understanding of the molecular mechanisms of IL-12 production induced by PRRSV infection.


title: Management of bacterial infections in children with asthma.

text: Respiratory viruses are the single most common causes of asthma exacerbations in children. Rhinovirus-induced wheezing is a risk factor for chronic asthma, but its mechanism has remained unknown. Human bocavirus is a common finding in wheezing children, but its role as a respiratory pathogen is still unclear. Mycoplasma pneumoniae may, like viruses, induce wheezing and asthma exacerbation. Chlamydia pneumoniae and, in recent studies, Chlamydia trachomatis, may not only induce asthma exacerbations but may also be involved in the pathogenesis of chronic asthma. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are often involved in respiratory infections associated with wheezing, but there is no evidence for their active role in asthma pathogenesis or exacerbation. This review summarizes current knowledge on the association between respiratory infections and asthma in children, with a special focus on the role of antibiotics in incipient asthma, asthma exacerbation and chronic stable asthma.


title: COVID-19 safety in maternity care: lessons for the whole NHS.

text: John Tingle, Lecturer in Law, Birmingham Law School, University of Birmingham, discusses some recent reports in maternity care, which can be seen to also to have general application across all clinical specialities.


title: Short communication: immunogenicity of an inactivated influenza vaccine and postvaccination influenza surveillance in HIV-infected and noninfected children and adolescents.

text: Individuals infected with HIV are at higher risk for severe cases of seasonal influenza infection and should receive annual doses of vaccine. Our objectives were to evaluate the immunogenicity of an influenza vaccine in 37 HIV-infected patients (HIV group) compared to 29 uninfected individuals (control group) and to carry out a clinical and virological surveillance of influenza during a 6-month follow-up. Both groups received the vaccine recommended for the southern hemisphere in 2008. Antibody responses to antigens H1N1, H3N2, and B were measured in blood samples at vaccination (T0) and after 1 month (T1). Influenza surveillance was performed by weekly telephone calls for a follow-up period of 6 months. Nasal washes were taken from subjects with respiratory symptoms. The direct immunofluorescence assay in house polymerase chain reaction (PCR) and real-time PCR were used for the detection of different respiratory viruses. The median age of the participants was 13.3 years (sd = 2.2) and 12.1 years (sd = 1.3) for the HIV group and control group, respectively. One month after vaccination (T1), both groups showed significant increases in the antibody geometric mean titers (GMTs) for all antigens. However, healthy controls showed higher values for antigens A/H1N1 and A/H3N2 (p = 0.002 and 0.001, respectively). There was a higher increase in the percentage of HIV-uninfected subjects with protective A/H1N1 antibodies (96.6%) compared to HIV-infected vaccinees (67.6%) at T1 (p = 0.004). Rhinovirus (27.7%) and coronavirus (22.5%) were the most prevalent agents identified in HIV-infected individuals. In the control group, the viruses most frequently found were rhinovirus (24.2%) and adenovirus (21.2%). The seroprotection rate for the H1N1 antigen was higher in the control group, which also showed a greater increase in GMTs for H1N1 and H3N2 antigens after immunization. Viral agents were identified in 39/60 (65%) episodes of respiratory infections from the HIV-infected group and in 17/32 episodes (53.1%) from the control group (p = 0.273).


title: COVID-19 in Turkey: Lessons Learned.

text: Turkey reported its first COVID-19 case on March 10, 2020. We present here the mitigation efforts Turkey has undertaken so far, and also review the lessons learned for future proactive strategies. High number of intensive care unit beds and ventilators, national treatment algorithms, governmental support for free testing and medications, tedious contact-tracing with early detection and isolation of cases together with early shelter-in-place for the elderly and youngsters, and subsequent weekend curfews in selected cities have so far prevented the surge pressure on the health care system. At this phase, Turkey needs to adopt an evidence-based, proactive control system for an effective transition process to normalize the situation. Here, we underline the urgent need for detailed analysis of the national COVID-19 data and propose an epidemiologic investigation framework for better understanding, efficient control, and reliable forecasting of COVID-19 pandemic.


title: Robot-assisted laparoscopic myomectomy: current status.

text: Robotic-assisted surgery has seen a rapid development and integration in the field of gynecology. Since the approval of the use of robot for gynecological surgery and considering its several advantages over conventional laparoscopy, it has been widely incorporated especially in the field of reproductive surgery. Uterine fibroids are the most common benign tumors of the female reproductive tract. Many reproductive-aged women with this condition demand uterine-sparing surgery to preserve their fertility. Myomectomy, the surgical excision of uterine fibroids, remains the only surgical management option for fibroids that entails preservation of fertility. In this review, we focus on the role of robotic-assisted laparoscopic myomectomy and its current status, in comparison with other alternative approaches for myomectomy, including open, hysteroscopic, and traditional laparoscopic techniques. Several different surgical techniques have been demonstrated for robotic myomectomy. This review endeavors to share and describe our surgical experience of using the standard laparoscopic equipment for robotic-assisted myomectomy, together with the da Vinci Robot system. For the ideal surgical candidate, robotic-assisted myomectomy is a safe minimally invasive surgical procedure that can be offered as an alternative to open surgery. The advantages of using the robot system compared to open myomectomy include a shorter length of hospital stay, less postoperative pain and analgesic use, faster return to normal activities, more rapid return of the bowel function, and enhanced cosmetic results due to smaller skin incision sizes. Some of the disadvantages of this technique include high costs of the robotic surgical system and equipment, the steep learning curve of this novel system, and prolonged operative and anesthesia times. Robotic technology is a novel and innovative minimally invasive approach with demonstrated feasibility in gynecological and reproductive surgery. This technology is expected to take the lead in gynecological surgery in the upcoming decade.


title: Naloxone-precipitated withdrawal enhances ERK phosphorylation in prefrontal association cortex and accumbens nucleus of morphine-dependent mice.

text: Mitogen-activated protein kinases (MAPK) can be activated by opioids such as morphine via opioid receptor, and their activations have been observed in synaptic plasticity, learning, memory and addiction. Long-term exposure to morphine may induce physical dependence, manifested as somatic withdrawal symptoms such as diarrhea, body weight loss, jumping and headshaking, when drug is deprived. Though morphine dependence and withdrawal have been extensively studied, their molecular mechanisms have not been fully elucidated. In the present study, the physical dependence on morphine was developed in mice by an intermittent, escalating procedure of morphine injections, and was measured by the body weight loss and the behavioral signs (jumping and headshaking). We found that the mice with chronic morphine administration experienced dramatic body weight loss, compared with the saline-treated controls. Naloxone-precipitated withdrawal led to more body weight loss, compared with spontaneous withdrawal. Naloxone-precipitated withdrawal mice showed significantly aggravated morphine-withdrawal symptoms (including jumping and heading shaking), compared with spontaneous withdrawal mice. MAPK pathway activities in the frontal association cortex (FrA), accumbens nucleus (Acb) and caudate putamen (CPu) were examined to probe into molecular mechanism for morphine dependence and withdrawal. Compared with saline-treated mice, morphine-dependent mice and spontaneous withdrawal mice, naloxone-precipitated withdrawal mice showed a significantly increased ERK phosphorylation in FrA and Acb, but not in CPu. However, the activities of other protein kinases in the MAPK pathway, including p38 and JNK, showed no changes in FrA, Acb and CPu of the mice during the chronic morphine dependence and withdrawal phases. These results suggest that the ERK phosphorylation in FrA and Acb may be associated with naloxone-precipitated withdrawal syndrome.


title: Evaluation of the learning curve for a board-certified veterinary surgeon performing laparoendoscopic single-site ovariectomy in dogs.

text: OBJECTIVE To define the learning curve and evaluate the outcome for a board-certified veterinary surgeon performing laparoendoscopic single-site (LESS) ovariectomy in dogs. DESIGN Retrospective case review and learning curve evaluation with a skill acquisition model. Animals-27 client-owned dogs. Procedures-Between April 2011 and December 2012, 27 dogs underwent elective LESS ovariectomy performed by a single experienced board-certified laparoscopic surgeon by means of the same technique. Medical records for these patients were reviewed to determine whether a learning curve could be detected. A commercially available multitrocar port was inserted through a 15- to 20-mm incision at the umbilicus, and LESS ovariectomy was performed with articulating graspers, a bipolar vessel-sealing device, and a 30° telescope. Surgical performance of the surgeon was quantified with an exponential skill acquisition model, and how skill was gained with repetition of the same novel surgical procedure was examined. RESULTS Median patient body weight was 20 kg (44 lb; range, 3.5 to 41 kg [7.7 to 90.2 lb]). Median surgical time was 35 minutes (range, 20 to 80 minutes). Median patient age was 314 days (range, 176 to 2,913 days). The skill acquisition model revealed that a comparable surgeon could reach 90% of optimal surgery performance after approximately 8 procedures (8.6, 95% confidence interval, 0.5 to 16.6 procedures). According to the model, with each surgery, surgical time would be expected to decrease by 27% (95% confidence interval, 2% to 52%). Complications were limited to minor hemorrhage due to a splenic laceration and a postoperative incisional infection. Follow-up information was available for all 27 cases. All owners were satisfied and indicated that they would pursue LESS ovariectomy again. CONCLUSIONS AND CLINICAL RELEVANCE The learning curve for LESS ovariectomy was short and definable. Short-term outcome was excellent. Results of this study suggested that an experienced laparoscopic surgeon may anticipate achieving proficiency with this technique after performing approximately 8 procedures.


title: SPECT- and fluorescence image-guided surgery using a dual-labeled carcinoembryonic antigen-targeting antibody.

text: UNLABELLED Intraoperative visualization techniques promise to significantly improve the detection and resection of tumors. In this study, we used an anti-carcinoembryonic antigen (CEA) antibody (MN-14) tagged with both a radiolabel ((111)In) and a fluorophore (IRDye 800CW) for radionuclide detection and intraoperative fluorescence imaging, respectively. METHODS For this purpose, we prepared and characterized the dual-labeled antibody (111)In-diethylenetriaminepentaacetic acid (DTPA)-MN-14-IRDye 800CW and performed 4 studies on mice with subcutaneous and intraperitoneal CEA-expressing tumors: a dose escalation study to determine the optimal MN-14 protein dose, a biodistribution study comparing dual-labeled MN-14 and radiolabeled MN-14, a study to determine the optimal time for SPECT and fluorescence imaging after injection of dual-labeled MN-14, and finally a SPECT and fluorescence image-guided surgery study using this dual-labeled antibody. RESULTS The optimal protein dose of dual-labeled MN-14 was 10 μg per mouse, yielding a tumor-to-blood ratio of 3.5 within 72 h. The biodistribution of (111)In-DTPA-MN-14-IRDye 800CW in mice with subcutaneous LS174T tumors showed tumor uptake after 3 d (19.7% ± 17.0% injected dose/g) comparable to that of (111)In-DTPA-MN-14 but higher accumulation in the liver. The optimal time for imaging after administration of the dual-labeled antibody was 2-3 d after injection. Finally, in mice with intraperitoneally growing LS174T tumor nodules that received (111)In-DTPA-MN-14-IRDye 800CW, intraperitoneal tumor nodules could be localized with SPECT imaging after 3 d and subsequently resected using fluorescence image-guided surgery. CONCLUSION Thus, we showed the feasibility for assessment and image-guided resection of CEA antigen-expressing tumors using dual-labeled MN-14. Both radionuclide detection and fluorescence imaging may provide useful information to improve localization of tumors and radical excision of tumor tissue. Because humanized MN-14 (labetuzumab) is available for clinical use, translation to a clinical setting is the next step.


Virology in the 21st century.


title: α-Defensins in human innate immunity.

text: Defensins are small, multifunctional cationic peptides. They typically contain six conserved cysteines whose three intramolecular disulfides stabilize a largely β-sheet structure. This review of human α-defensins begins by describing their evolution, including their likely relationship to the Big Defensins of invertebrates, and their kinship to the β-defensin peptides of many if not all vertebrates, and the θ-defensins found in certain non-human primates. We provide a short history of the search for leukocyte-derived microbicidal molecules, emphasizing the roles played by luck (good), preconceived notions (mostly bad), and proper timing (essential). The antimicrobial, antiviral, antitoxic, and binding properties of human α-defensins are summarized. The structural features of α-defensins are described extensively and their functional contributions are assessed. The properties of HD6, an enigmatic Paneth cell α-defensin, are contrasted with those of the four myeloid α-defensins (HNP1-4) and of HD5, the other α-defensin of human Paneth cells. The review ends with a decalogue that may assist researchers or students interested in α-defensins and related aspects of neutrophil function.


title: Experiences in managing arteriovenous malformations of the head and neck.

text: Arteriovenous malformations of the head and neck are difficult to treat and require a multidisciplinary approach. Interventional radiology can now be used to downgrade previously inoperable lesions to enable ablation, and the use of Onyx® (Covidien, Irvine, CA, USA), which has revolutionised their management by allowing precise obliteration of the nidus, has enabled the aggressive management of lesions in compromised anatomical areas. We report a series of 31 patients with lesions on the head and neck. They all presented with serious symptoms (Schobinger grade 2-3) and had embolisation with Onyx®. Some had additional operations. We describe the outcome including complications, and offer some lessons learned from our experience.


title: Capnographic Monitoring in Routine EGD and Colonoscopy With Moderate Sedation: A Prospective, Randomized, Controlled Trial.

text: OBJECTIVES Regulatory changes requiring the use of capnographic monitoring for endoscopic procedures using moderate sedation have placed financial challenges on ambulatory and hospital endoscopy centers across the United States due to the increased cost of training endoscopy personnel and purchasing both capnography-monitoring devices and specialized sampling ports. To date, there has been no published data supporting the use of capnographic monitoring in adult patients undergoing routine endoscopic procedures with moderate sedation. The aim of this randomized, parallel group assignment trial was to determine whether intervention based on capnographic monitoring improves detection of hypoxemia in patients undergoing routine esophagogastroduodenoscopy (EGD) or colonoscopy with moderate sedation. METHODS Healthy patients (ASA Physical Classification (ASAPS) I and II)) scheduled for routine outpatient EGD or colonoscopy under moderate sedation utilizing opioid and benzodiazepine combinations were randomly assigned to a blinded capnography alarm or open capnography alarm group. In both study arms, standard cardiopulmonary monitoring devices were utilized with additional capnographic monitoring. The primary end point was the incidence of hypoxemia defined as a fall in oxygen saturation (SaO2) to <90% for ≥10 s. Secondary outcomes included severe hypoxemia, apnea, disordered respirations, hypotension, bradycardia, and early procedure termination for any cause. RESULTS A total of 452 patients were randomized; 218 in the EGD and 234 in the colonoscopy groups; 75 subjects in the EGD group (35.9%) and 114 patients (49.4%) in the colonoscopy group were male, and average body mass index was 27.9 and 29.1 (kg/m(2)), respectively. The blinded and open alarm groups in each study arm were similar in regards to use of opioids and/or benzodiazepines and ASAPS classification. There was no significant difference in rates of hypoxemia between the blinded and open capnography arms for EGD (54.1% vs. 49.5; P=0.5) or colonoscopy (53.8 vs. 52.1%; P=0.79). CONCLUSIONS Capnographic monitoring in routine EGD or colonoscopy for ASAPS I and II patients does not reduce the incidence of hypoxemia (ClinicalTrials.gov number, NCT01994785).


title: Adverse effects of fibrin sealants in thoracic surgery: the safety of a new fibrin sealant: multicentre, randomized, controlled, clinical trial.

text: OBJECTIVES The safety of fibrin sealants (FS) has been questioned in the light of recent reports of adverse effects. We evaluated the safety of a new FS in a randomized controlled trial (RCT). METHODS Multicentre, open-label Phase II/III RCT to evaluate the safety of the new FS. The trial was approved by the Ethic Committee of each three participating Centre. FS includes two components (component 1: fibrinogen; component 2: thrombin), each of them subjected to two viral inactivation procedures. Out of 200 screened patients, 185 eligible patients (49 females, 136 males), aged between 18 and 75 years, undergoing major thoracic surgery were randomized to receive FS (#91 patients) as an adjuvant for air leak control or no treatment (#94 patients, control group). Safety variables were: percentage of subjects with adverse events associated with the therapy; formation of antibodies against bovine aprotinin; vital signs (blood pressure, body temperature, heart and respiratory rate); laboratory parameters. RESULTS Overall operative mortality was 3.2% (6/185), 1.1% in the FS group and 5.3% in the control group, respectively. Twenty patients (22%) had adverse events in the FS group and 22 (23.4%) in the control group. Atrial fibrillation (five patients in the FS group and four in the control group) and hyperpyrexia (five and seven patients, respectively, in the two groups) were the most common adverse events. No patient reported thromboembolic events (pulmonary embolism or deep vein thrombosis) during the in hospital stay or within 1 month from discharge. None of the adverse events was considered as treatment related. The formation of bovine aprotinin antibodies was reported in a total of 34 patients (37.4%) in the FS group and was not related to any adverse effect. CONCLUSIONS The present RCT did not show any increased risk of adverse events, and of surgical complications, related to the use of the new FS.


title: Variable ventilation enhances ventilation without exacerbating injury in preterm lambs with respiratory distress syndrome.

text: BACKGROUND As compared with constant respiratory rate (RR) and tidal volume (V(T)) during controlled conventional mechanical ventilation (CV), variable ventilation (VV) using the same breath-to-breath minute volume but variable V(T) and RRs enhances ventilation efficiency in preterm lambs. We hypothesized that if V(T) was adjusted to target permissive hypercarbia, VV would result in more efficient gas exchange without increasing inflammatory and injurious responses in the lung. METHODS Preterm lambs at 129 d gestation were anesthetized, tracheotomized, and randomized to either CV (n = 8) or VV (n = 8) using the same initial average V(T) and RR. Lung mechanics and gas exchange were measured intermittently, and average V(T) was adjusted to target partial pressure of arterial carbon dioxide (PaCO2) of 40-50 mm Hg for 3 h. Lung injury and inflammation were assessed from bronchoalveolar lavage fluid, lung tissue, and peripheral blood. RESULTS VV achieved permissive hypercarbia using a lower average V(T), peak inspiratory pressure, and elastance (increased compliance) as compared with CV. Oxygenation and markers of lung tissue inflammation or injury were not different apart from a lower wet:dry tissue ratio in the VV lungs. CONCLUSIONS VV improves ventilation efficiency and in vivo lung compliance in the ovine preterm lung without increasing lung inflammation or lung injury.


title: A randomized controlled trial of capnography during sedation in a pediatric emergency setting.

text: OBJECTIVE Data suggest that capnography is a more sensitive measure of ventilation than standard modalities and detects respiratory depression before hypoxemia occurs. We sought to determine if adding capnography to standard monitoring during sedation of children increased the frequency of interventions for hypoventilation, and whether these interventions would decrease the frequency of oxygen desaturations. METHODS We enrolled 154 children receiving procedural sedation in a pediatric emergency department. All subjects received standard monitoring and capnography, but were randomized to whether staff could view the capnography monitor (intervention) or were blinded to it (controls). Primary outcome were the rate of interventions provided by staff for hypoventilation and the rate of oxygen desaturation less than 95%. RESULTS Seventy-seven children were randomized to each group. Forty-five percent had at least 1 episode of hypoventilation. The rate of hypoventilation per minute was significantly higher among controls (7.1% vs 1.0%, P = .008). There were significantly fewer interventions in the intervention group than in the control group (odds ratio, 0.25; 95% confidence interval [CI], 0.13-0.50). Interventions were more likely to occur contemporaneously with hypoventilation in the intervention group (2.26; 95% CI, 1.34-3.81). Interventions not in time with hypoventilation were associated with higher odds of oxygen desaturation less than 95% (odds ratio, 5.31; 95% CI, 2.76-10.22). CONCLUSION Hypoventilation is common during sedation of pediatric emergency department patients. This can be difficult to detect by current monitoring methods other than capnography. Providers with access to capnography provided fewer but more timely interventions for hypoventilation. This led to fewer episodes of hypoventilation and of oxygen desaturation.


title: A systematic review of factors that enable psychological safety in healthcare teams.

text: PURPOSE The current systematic review will identify enablers of psychological safety within the literature in order to produce a comprehensive list of factors that enable psychological safety specific to healthcare teams. DATA SOURCES A keyword search strategy was developed and used to search the following electronic databases PsycINFO, ABI/INFORM, Academic search complete and PubMed and grey literature databases OpenGrey, OCLC WorldCAT and Espace. STUDY SELECTION Peer-reviewed studies relevant to enablers of psychological safety in healthcare setting that were published between 1999 and 2019 were eligible for inclusion. Covidence, an online specialized systematic review website, was used to screen records. Data extraction, quality appraisal and narrative synthesis were conducted on identified papers. DATA EXTRACTION Thirty-six relevant studies were identified for full review and data extraction. A data extraction template was developed and included sections for the study methodology and the specific enablers identified within each study. RESULTS OF DATA SYNTHESIS Identified studies were reviewed using a narrative synthesis. Within the 36 articles reviewed, 13 enablers from across organizational, team and individual levels were identified. These enablers were grouped according to five broader themes: priority for patient safety, improvement or learning orientation, support, familiarity with colleagues, status, hierarchy and inclusiveness and individual differences. CONCLUSION This systematic review of psychological safety literature identifies a list of enablers of psychological safety within healthcare teams. This list can be used as a first step in developing observational measures and interventions to improve psychological safety in healthcare teams.


title: Should chest compressions be considered an aerosol-generating procedure? A literature review in response to recent guidelines on personal protective equipment for patients with suspected COVID-19.

text: There is disagreement between international guidelines on the level of personal protective equipment (PPE) required for chest compressions for patients with suspected COVID-19. This discrepancy centres on whether they are considered to be an aerosol-generating procedure (AGP), thus requiring airborne protection to prevent transmission to healthcare workers (HCWs). The need to don higher-level PPE has to be weighed against the resulting delay to emergency treatment.We performed a literature search on this topic which found eight relevant studies. All were observational with low patient numbers and multiple confounding factors, but describe cases of acute respiratory infection transmission during chest compressions. One systematic review concluded that chest compressions were not an AGP. Two simulated studies (released as preprints) potentially demonstrate aerosol generation. Given that there is evidence for infection transmission during chest compressions, we conclude that a precautionary approach with appropriate PPE is necessary to protect HCW from contracting a potentially fatal infection.


title: Critical care in the austere environment: providing exceptional care in unusual places.

text: BACKGROUND War and other disasters are inexorably linked to illness and injury. As a consequence of this, healthcare providers will be challenged to provide advanced physiological support to preserve human life. Given the mobility and modularity of modern medical systems, the ability to provide critical care outside of the confines of traditional hospitals under such circumstances has become not only a reality and periodic necessity, but an expectation. Austerity amplifies the complexity of providing high-level critical care, because resources are frequently limited, providers are asked to fill unexpected roles determined by necessity, security may be threatened, and the population at risk and their afflictions can be highly diverse. DISCUSSION Our current deployed military medical experience and a review of published literature pertaining to civilian medical disaster response efforts support these stated challenges. The fundamentals of successful critical care practice in unusual settings include proper planning with an emphasis on attention to detail, the careful management of all resources, using the proper equipment, leveraging aeromedical evacuation assets, and employing the right people with the right skills. SUMMARY Adherence to sound, evidence-based, routine practice, within bounds of the circumstances, must underscore everything.


title: Bovine plasmacytoid dendritic cells are the major source of type I interferon in response to foot-and-mouth disease virus in vitro and in vivo.

text: Type I interferons (alpha/beta interferons [IFN-α/β]) are the main innate cytokines that are able to induce a cellular antiviral state, thereby limiting viral replication and disease pathology. Plasmacytoid dendritic cells (pDCs) play a crucial role in the control of viral infections, especially in response to viruses that have evolved mechanisms to block the type I IFN signal transduction pathway. Using density gradient separation and cell sorting, we have highly enriched a population of bovine cells capable of producing high levels of biologically active type I IFN. These cells represented less than 0.1% of the total lymphocyte population in blood, pseudoafferent lymph, and lymph nodes. Phenotypic analysis identified these cells as bovine pDCs (CD3(-) CD14(-) CD21(-) CD11c(-) NK(-) TCRδ(-) CD4(+) MHC II(+) CD45RB(+) CD172a(+) CD32(+)). High levels of type I IFN were generated by these cells in vitro in response to Toll-like receptor 9 (TLR-9) agonist CpG and foot-and-mouth disease virus (FMDV) immune complexes. In contrast, immune complexes formed with UV-inactivated FMDV or FMDV empty capsids failed to elicit a type I IFN response. Depletion of CD4 cells in vivo resulted in levels of type I IFN in serum early during FMDV infection that were significantly lower than those for control animals. In conclusion, pDCs interacting with immune-complexed virus are the major source of type I interferon production during acute FMDV infection in cattle.


title: Testing the hypothesis of tissue selectivity: the intersection-union test and a Bayesian approach.

text: MOTIVATION Finding genes that are preferentially expressed in a particular tissue or condition is a problem that cannot be solved by standard statistical testing procedures. A relatively unknown procedure that can be used is the intersection-union test (IUT). However, two disadvantages of the IUT are that it is conservative and it conveys only the information of the least differing target tissue-other tissue pair. RESULTS We propose a Bayesian procedure that quantifies how much evidence there is in the overall expression profile for selective over-expression. In a small simulation study, it is shown that the proposed method outperforms the IUT when it comes to finding selectively expressed genes. An application to publicly available data consisting of 22 tissues shows that the Bayesian method indeed selects genes with functions that reflect the specific tissue functions. The proposed method can also be used to find genes that are underexpressed in a particular tissue. AVAILABILITY Both MATLAB and R code that implement the IUT and the Bayesian procedure in an efficient way, can be downloaded at http://ppw.kuleuven.be/okp/software/BayesianIUT/.


title: Minimally Invasive Ivor Lewis Esophagectomy Without Patient Repositioning.

text: INTRODUCTION The standard technique for Ivor Lewis minimally invasive esophagectomy involves a two-stage approach necessitating repositioning mid-procedure. TECHNIQUE We describe our technique for a one-stage hand-assisted minimally invasive esophagectomy that allows sequential access to the chest and abdomen within the same surgical field, eliminating the need for repositioning. The patient is positioned in a "corkscrew" configuration with the abdomen supine and the chest rotated to the left to allow access to the right chest. The abdomen and chest are prepped into a single operative field. This technique allows sequential access to the abdomen for gastric mobilization, chest for division of the esophagus, abdomen for construction of the gastric conduit, and chest for intrathoracic anastomosis. CONCLUSION This approach enables extracorporeal construction of the conduit, which helps ensure a clear distal margin on the specimen and facilitates conduit length by placing the stomach on stretch during stapling.


Cardiac Troponin I is an Independent Predictor for Mortality in Hospitalized Patients with Coronavirus Disease 2019.


title: The association between community mental health nursing and hospital admissions for people with serious mental illness: a systematic review.

text: BACKGROUND Relapse prevention is an important objective in the management of serious mental illness (SMI). While community mental health nurses (CMHN) might be well-placed to support people with SMI in averting relapse, no systematic reviews have examined this association. AIM To review the evidence from studies reporting an association between CMHN exposure and hospitalisation of persons living with SMI (a proxy for relapse). METHODS Searches were undertaken in ten bibliographic databases and two clinical trial registries. We included studies of patients with SMI, where CMHN was the exposure, and the outcome was relapse (i.e. readmission to a psychiatric inpatient facility). Quality assessment of included studies was completed using two risk-of-bias measures. RESULTS Two studies met the inclusion criteria. Studies were rated as being of low-moderate methodological quality. There was insufficient evidence to conclude that community mental health nursing reduced the risk of admission to psychiatric inpatient facilities. CONCLUSIONS The review found no evidence that CMHN was associated with higher or lower odds of admission to psychiatric inpatient facilities among patients with SMI. The findings of the review point to a need for further research to investigate the impact of CMHN exposure and relapse in people with SMI. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017058694.


Climate change brings the specter of new infectious diseases.


title: Does continuous infusion of local anaesthesia improve pain control and walking distance after coronary artery bypass graft surgery? A randomised controlled trial.

text: OBJECTIVES To evaluate the effects of continuous infusion of ropivacaine compared to sham infusion or usual care on pain scores before and after physiotherapy treatment, distance walked and time to discharge from physiotherapy, after coronary artery bypass graft (CABG) surgery. DESIGN Prospective, randomised, double blind controlled trial. SETTING AND PARTICIPANTS Seventy-five participants who underwent CABG surgery with left internal mammary artery grafts were allocated, to the ropivacaine group (n=26), the sham group (n=25), or usual care group (n=24). Participants in the ropivacaine group received 0.5% ropivacaine and participants in the sham group received normal saline, both as continuous infusions via two parasternally tunnelled catheters for 96hours continuously. The usual care group did not receive a device. All groups had patient-controlled analgesia and/or oral analgesia. RESULTS Seventy-two participants completed the study. There was no significant between-group differences in pain scores, distance walked on any post operative day (POD) or number of participants discharged from physiotherapy by POD 4. For the group as a whole there was a significant linear decrease in pain score from mean (SD) 42 (24) mm on POD1 to 15 (16) mm on POD4 (p<0.001), (MD 27mm, 95% CI 22 to 32) and walking distance increased from 1 (5) m on POD1 to 183 (239) m on POD4 (p<0.001) MD 181m, 95% CI 126 to 236). CONCLUSION Infusion of ropivacaine post CABG surgery was unable to reduce pain, increase distance walked or reduce time to physiotherapy discharge compared to sham or usual care. Trial registration number ACTRN12612001243808.


title: Depression, anxiety, stress, and dysmenorrhea: a protocol for a systematic review.

text: BACKGROUND Dysmenorrhea is one of the most common menstrual disorders and is influenced by various factors. Psychological disorders including anxiety, depression, and stress have been suggested as influencing dysmenorrhea, but previous findings are inconsistent. This study will investigate the relationship between depression/anxiety/stress and dysmenorrhea using a systematic review and meta-analysis. METHODS Online databases including PsycINFO, Scopus, PubMed, Science Direct, ProQuest, ISI Web of Knowledge, and Embase will be searched. Appropriate keywords and MeSH terms will be used to retrieve the journal papers published from 1990 until the end of December 2019. To improve search coverage, the reference lists of all included studies will be reviewed to find eligible papers. Inclusion criteria include the following: descriptive, cohort, case-control, and cross-sectional studies; the relationship between depression/anxiety/stress and dysmenorrhea being an objective of the study; and published in peer-reviewed journals. The paper selection, data extraction, and quality assessment of selected studies will be performed independently by two researchers, and disagreements will be resolved through discussions. The Newcastle-Ottawa Quality Assessment Scale will be used to assess the quality of selected studies. A quantitative synthesis will be performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) via the STATA software, if retrieving enough number of studies with no severe methodological heterogeneities. Otherwise, qualitative synthesis will be used to report the findings. DISCUSSION To the best of our knowledge, this will be the first systematic review on this topic. Performing an inclusive search in major databases over a wide timescale is one key strength of the proposed study and will maximize the coverage of the original research studies on this topic. Results of present study are expected to lead to deeper understanding the relationship between common mental health conditions and dysmenorrhea. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42018102199.


title: Muscular workload of veterinary students during simulated open and laparoscopic surgery: A pilot study.

text: OBJECTIVE To compare upper extremity muscle activity and workload between simulated open surgery, multiple port laparoscopic surgery (MLS), and single incision laparoscopic surgery (SLS) techniques in veterinary students. STUDY DESIGN Pilot study. POPULATION Veterinary students (n = 10) from years 1 to 4. METHODS Bipolar skin surface electrodes were fixed bilaterally to the forearm flexor, forearm extensor, biceps brachii, triceps brachii, and upper trapezius muscles. Electromyography data were recorded during one repetition of 2 simulated surgical exercises via open surgery, MLS, and SLS. Participants completed a validated workload survey after each simulated surgical technique. Muscle activity and perceived workload were compared between surgical techniques with 1-way ANOVAs and Fisher's LSD post hoc tests. RESULTS Muscle activity during peg transfer was higher with MLS and SLS compared to simulated open surgery in the right and left forearm extensors (both P < .0001), right (P < .0001) and left biceps (P = .0005), right triceps (P = .0004), and right upper trapezius muscles (P = .0211). Similar results were found for the right and left forearm extensors (both P < .0001), right (P = .0381) and left (P = .0147) forearm flexors, right biceps (P < .0001), and right triceps (P = .0004) during a simulated suture task. Participants found laparoscopic techniques more mentally demanding, physically demanding, complex, and stressful compared to a simulated open surgical technique. CONCLUSION In veterinary students, average muscle activity and perceived workload were highest using MLS and SLS compared to an open surgical technique when performing simulated surgical exercises in a laparoscopic box trainer.


COVID-19 lockdown dropped the rate of paediatric asthma admissions.


title: [Pathogen reduction for platelets: available techniques and recent developments].

text: The will to reach for blood components a microbiological safety comparable to that of plasma-derived drugs led to the development of numerous pathogen reduction research programs for red blood cells and\or platelets in the 1990s. A consensus conference organized in 2007 allowed to define the main steps and precautions to be taken for the implementation of these processes. In the specific case of platelet concentrates, three processes stay this day in the run, even if they are not at the same development stage. A process using ultraviolet C only is at the stage of preclinical studies. The Mirasol® process, based on the activation of riboflavin by exposure to ultraviolet A and ultraviolet B is CE marked (class IIb), and a clinical study was published in 2010. The Intercept® process, involving the activation of a psoralen molecule by exposure to ultraviolet A, is CE marked (class III) since 2002, and has been licensed in France since 2005, in Germany since 2005 and in Switzerland since 2010. At least 12 clinical studies have been published. In regard to this last pathogen reduction process, the medical and scientific documentation, from in vitro investigations to post-marketing observational studies, is much more developed than the corresponding documentation of some innovative processes at the time of their generalization, such as the SAG-mannitol solution for red cell concentrates in 1979, leukoreduction filters for platelets and red cells concentrates in the 1990s, the solvent detergent therapeutic plasma in 1992 or the methylene blue therapeutic plasma in 2006.


title: Catheter tip malposition after percutaneous placement of tunneled hemodialysis catheters.

text: The percutaneous catheterization of central veins is increasingly used in nephrological practice as a temporary or permanent vascular access. The aim of our study was to present and to analyze episodes of catheter tip malposition during percutaneous tunneled hemodialysis catheter insertion in the large, unselected group of patients. All patients who underwent the procedure of catheter insertion in our department during year 2012 were analyzed retrospectively. One hundred four tunneled hemodialysis catheters were inserted in 101 patients. In 58 patients, the catheter was inserted at the initiation of hemodialysis therapy as the first access and in 46 the catheter was placed because of the failure of the existing one. In 68 patients, the catheter was inserted into the right internal jugular vein and in 20 patients into the left internal jugular vein (LIJV). Subclavian veins were used in five cases and femoral veins in 11 cases. Malposition of the catheter tips occurred in six patients. In all cases, the LIJV was cannulated. In two cases, the catheter tip malposition was in the right innominate vein and in four cases in the azygos vein. Our data demonstrate that with the blind insertion of tunneled hemodialysis catheters, the risk of catheter tip malposition is significantly higher with the left side insertion. As catheter insertion through the LIJV holds very high (30%) risk of the tip malposition, it should always be performed under the fluoroscopic control.


Reconsidering Risks of Gun Ownership and Suicide in Unprecedented Times.


title: Prognostic prediction models for pregnancy complications in women with gestational diabetes: a protocol for systematic review, critical appraisal and meta-analysis.

text: BACKGROUND Gestational diabetes (GDM) is increasingly common and has significant implications during pregnancy and for the long-term health of the mother and offspring. However, it is a heterogeneous condition with inter-related factors including ethnicity, body mass index and gestational weight gain significantly modifying the absolute risk of complications at an individual level. Predicting the risk of pregnancy complications for an individual woman with GDM presents a useful adjunct to therapeutic decision-making and patient education. Diagnostic prediction models for GDM are prevalent. In contrast, prediction models for risk of complications in those with GDM are relatively novel. This study will systematically review published prognostic prediction models for pregnancy complications in women with GDM, describe their characteristics, compare performance and assess methodological quality and applicability. METHODS Studies will be identified by searching MEDLINE and Embase electronic databases. Title and abstract screening, full-text review and data extraction will be completed independently by two reviewers. The included studies will be systematically assessed for risk of bias and applicability using appropriate tools designed for prediction modelling studies. Extracted data will be tabulated to facilitate qualitative comparison of published prediction models. Quantitative data on predictive performance of these models will be synthesised with meta-analyses if appropriate. DISCUSSION This review will identify and summarise all published prognostic prediction models for pregnancy complications in women with GDM. We will compare model performance across different settings and populations with meta-analysis if appropriate. This work will guide subsequent phases in the prognosis research framework: further model development, external validation and model updating, and impact assessment. The ultimate model will estimate the absolute risk of pregnancy complications for women with GDM and will be implemented into routine care as an evidence-based GDM complication risk prediction model. It is anticipated to offer value to women and their clinicians with individualised risk assessment and may assist decision-making. Ultimately, this systematic review is an important step towards a personalised risk-stratified model-of-care for GDM to allow preventative and therapeutic interventions for the maximal benefit to women and their offspring, whilst sparing expense and harm for those at low risk. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number CRD42019115223.


The Spread of COVID-19 in the Italian Population: Anxiety, Depression, and Post-traumatic Stress Symptoms.


Managing Ebola: Lessons Learned from the SARS Epidemic.


title: Robotic Sleeve Gastrectomy for Morbid Obesity.

text: OBJECTIVE To determine the weight loss, and complications as well as to exemplify the use of vessel sealer and the triple stapler establish the safety and efficacy of vessel sealer for robotic surgery and triple stapler in robotic sleeve gastrectomy. STUDY DESIGN Observational case series. PLACE AND DURATION OF STUDY Private Koru Hospital, Ankara, Turkey, from December 2015 till January 2016. METHODOLOGY Twenty robotic sleeve gastrectomy was performed. Demographics, body mass index, comorbidities, docking time, surgical time, leaks, bleeding, stapler number, strictures, mortality, conversion, weight loss, and hospital length of stay were included for data collection. RESULTS The mean age and body mass index were 40.73 ±11.2 years and 44.75 ±8.38 Kg/m2, respectively. Postoperative trocar site (assistance port) bleeding occurred in one patient. There were no conversions, stricture, leakage or mortality. The mean number of staplers used was 6.27 ±0.46 and excess body weight loss (EWL%) at three months was 24.91 ±2.84 kg. CONCLUSION Robotic surgery for obesity surgery was safe during our initial experience and use of vessel sealer and triple stapler was effective, safe and facilitates procedure in obese patients.


Coronavirus (COVID-19) Pandemic: What the Nuclear Medicine Departments Should Know.


Difficult intubation and anesthetic management in an adult patient with undiagnosed congenital tracheal stenosis: a case report.


title: Liver lobe torsion in pet rabbits: clinical consequences, diagnosis, and treatment.

text: This article reviews diagnosis and management of liver lobe torsion in rabbits. Practitioners should recommend initial diagnostics including radiographs and blood work on rabbits presenting with nonspecific signs of gastrointestinal (GI) stasis to better determine possible etiology and make the best treatment recommendations. If hepatic enzyme elevation is found in a rabbit with GI stasis, abdominal ultrasound is recommended to rule out liver lobe torsion. Prompt diagnosis and liver lobectomy are recommended for best outcome in rabbits with liver lobe torsion.


title: Feasibility and Safety of a New Chest Drain Wound Closure Method with Knotless Sutures.

text: Background A method of wound closure using knotless suture material in the chest tube site has been introduced at our center, and is now widely used as the primary method of closing chest tube wounds in video- assisted thoracic surgery (VATS) because it provides cosmetic benefits and causes less pain. Methods We included 109 patients who underwent VATS pulmonary resection at Samsung Medical Center from October 1 to October 31, 2016. Eighty-five patients underwent VATS pulmonary resection with chest drain wound closure utilizing knotless suture material, and 24 patients underwent VATS pulmonary resection with chest drain wound closure by the conventional method. Complications related to the chest drain wound were compared between the 2 groups. Results There were 2 cases of pneumothorax after chest tube removal in both groups (8.3% in the conventional group, 2.3% in the knotless suture group; p=0.172) and there was 1 case of wound discharge due to wound dehiscence in the knotless suture group (0% in the conventional group, 1.2% in the knotless suture group; p=0.453). There was no reported case of chest tube dislodgement in either group. The complication rates were non-significantly different between the 2 groups. Conclusion The results for the complication rates of this new chest drain wound closure method suggest that this method is not inferior to the conventional method. Chest drain wound closure using knotless suture material is feasible based on the short-term results of the complication rate.


title: Design and implementation of the Resuscitation Outcomes Consortium Pragmatic Airway Resuscitation Trial (PART).

text: Airway management is an important component of resuscitation from out-of-hospital cardiac arrest (OHCA). The optimal approach to advanced airway management is unknown. The Pragmatic Airway Resuscitation Trial (PART) will compare the effectiveness of endotracheal intubation (ETI) and Laryngeal Tube (LT) insertion upon 72-h survival in adult OHCA. Encompassing United States Emergency Medical Services agencies affiliated with the Resuscitation Outcomes Consortium (ROC), PART will use a cluster-crossover randomized design. Participating subjects will include adult, non-traumatic OHCA requiring bag-valve-mask ventilation. Trial interventions will include (1) initial airway management with ETI and (2) initial airway management with LT. The primary and secondary trial outcomes are 72-h survival and return of spontaneous circulation. Additional clinical outcomes will include airway management process and adverse events. The trial will enroll a total of 3000 subjects. Results of PART may guide the selection of advanced airway management strategies in OHCA.


title: Advances in laparoscopic colorectal surgery: a review on NOTES and transanal extraction of specimen.

text: Laparoscopic colorectal surgery has rapidly developed since the 1980s. Relative to open surgery, it offers the benefits of less invasiveness and earlier recovery. However, when a mini-laparotomy wound is needed to retrieve the specimen, the benefits of minimally invasive surgery may be compromised as a result of pain- and wound-related complications. The introduction of natural orifice transluminal endoscopic surgery (NOTES) makes "scarless" surgery a possibility; pain- and wound-related complications are totally abolished. However, a number of technical issues need to be overcome before this technique can be used widely. The development of natural orifice specimen extraction surgery abandons the need for a specimen-retrieval incision and helps overcome the technical hurdles of NOTES. As a bridge between true "scarless" surgery and conventional laparoscopic surgery, hybrid procedures combining laparoscopic resection and natural orifice specimen extraction surgery currently play an important role in minimally invasive colorectal surgery.


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Ethical guidelines for COVID-19 tracing apps.


Sick time.