title: Comparison of Enterprise with Neuroform stent-assisted coiling of intracranial aneurysms.

text: OBJECTIVE The Enterprise stent is the first closed-cell stent designed to treat wide-necked intracranial aneurysms. Advantages of the design can include improvement in keeping coils within an aneurysm and the ability of the stent to be recaptured. We compared the technical and clinical complications of the Enterprise stent with the open-cell Neuroform stent, its primary alternative. SUBJECTS AND METHODS Patients undergoing Enterprise and Neuroform stent-assisted aneurysm coiling were enrolled in prospective registries starting in March 2007 and February 2003, respectively. All consecutive patients through December 2011 were included. Deployment success and difficulty, stent movement and misplacement, and procedural complications were compared. RESULTS Enterprise deployment success was high (108 of 115 attempts, 93.9%) with 102 aneurysms receiving a stent compared with Neuroform (173 of 214 attempts, 80.8%, p = 0.001) with 163 aneurysms. Enterprise was easier to deploy (1.7% vs 15.9% difficult deployment, p < 0.0001). There were no significant differences in the rates of stent movement, misplacement, or symptomatic hemorrhage. Symptomatic thromboembolic events, however, were more frequent with the Enterprise stent (8.7% vs 1.4%, p = 0.0021). The Enterprise stent enabled treatment of 10 additional aneurysms that could not be treated with Neuroform and had a higher rate of immediate aneurysm occlusion (87.3% vs 73.0%, p = 0.0058). CONCLUSION Enterprise was easier to deploy and enabled treatment of additional aneurysms; however, there were more thromboembolic complications. On the basis of these findings, we prefer to use the Neuroform stent first and rely on the Enterprise stent as an easy-to-deliver backup for stent-assisted coiling.


title: Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with Suspected or Confirmed COVID-19 (HAHPS): Protocol for a Pragmatic, Open Label, Active Comparator Trial.

text: COVID-19 is a potentially fatal illness with no proven therapy beyond excellent supportive care. Treatments are urgently sought. Adaptations to traditional trial logistics and design to allow rapid implementation, evaluation of trials within a global trials context, flexible interim monitoring, and access outside traditional research hospitals (even in settings where formal placebos are unavailable) may be helpful. Thoughtful adaptations to traditional trial designs-especially within the global context of related studies-may also foster collaborative relationships among government, community, and the research enterprise. We describe here the protocol for a pragmatic, active comparator trial in as many as 300 patients comparing two current "off-label" treatments for COVID-19-hydroxychloroquine and azithromycin-in academic and non-academic hospitals in Utah. We developed the trial in response to local pressures for widespread, indiscriminate off-label use of these medications. We employ a hybrid Bayesian-frequentist design for interim monitoring to allow rapid, contextual assessment of the available evidence. We also developed an inference grid for the interpretation of the range of possible results from this trial within the context of parallel trials and prepared for network meta-analysis of the resulting data. This trial was prospectively registered (NCT04329832) before enrollment of the first patient.


title: Detection of active gastrointestinal hemorrhage with CT angiography: a 4(1/2)-year retrospective review.

text: PURPOSE To retrospectively evaluate the performance of computed tomography (CT) angiography in the detection and localization of clinically active gastrointestinal (GI) hemorrhage of an unknown source. MATERIALS AND METHODS Eighty-six CT angiograms were obtained in 74 patients with the clinical diagnosis of acute GI hemorrhage of an unknown source. Results of CT angiography were recorded, and the patients' electronic medical records were reviewed for documentation of subsequent interventional procedures performed within 24 hours of the reference CT angiogram to diagnose or control ongoing GI hemorrhage. Surgical, endoscopic, and final pathologic reports, if available, were reviewed. RESULTS Twenty-two of the 86 CT angiograms (26%) were positive for active hemorrhage, with findings confirmed in 19 of the 22 cases (86%). Thirteen cases were confirmed with angiography, five cases were confirmed with surgery, and one case was confirmed with autopsy. Sixty-four of the 86 CT angiograms were negative, and 59 (92%) of the CT angiograms required no further intervention. These patients were discharged without incident. There were no cases in which CT angiography was negative and subsequent angiography within 24 hours was positive. The overall sensitivity, specificity, accuracy, and positive and negative predictive value of CT angiography in the detection of active GI hemorrhage within this study population were 79%, 95%, 91%, 86%, and 92%, respectively. CONCLUSIONS CT angiography provides valuable information that can be used to determine the appropriateness of catheter angiography and guide mesenteric catheterization if a bleeding source is localized. The authors' experience with this study cohort supports its use before angiography in those patients with acute GI bleeding of an unknown source who are being considered for catheter-directed intervention.


title: Characterization of the Affective Component of Acute Postoperative Pain Associated with a Novel Rat Model of Inguinal Hernia Repair Pain.

text: AIMS Acute postoperative pain remains a significant healthcare issue. Historically, the assessment of postoperative pain in rodents has relied on evoked withdrawal or reflexive measures. Using a recently developed, anatomically relevant rat model of acute postoperative pain (J Pain, 16, 2015, 421), the present experiments sought to investigate the affective component of acute postoperative pain associated with inguinal hernia repair. METHODS Male Lister hooded rats underwent surgery to model Lichtenstein inguinal hernia repair (without hernia induction), or a sham procedure. Postsurgical characterization involved a modified place escape/avoidance paradigm (mPEAP), as well as home cage and open field locomotor activity monitoring. In pharmacological validation studies, rats received either morphine or carprofen prior to mPEAP testing. RESULTS Surgery was associated with a significantly increased proportion of the trial duration in the light compartment of the mPEAP arena, in avoidance of the noxious stimulus, compared with sham animals. When retested in the mPEAP at day 7 postsurgery, there was no difference between sham and surgery animals for time spent in either compartment, but surgery animals displayed a persistent increase in the percentage response to noxious stimulation. Morphine and carprofen treatment in surgery animals reduced escape/avoidance behavior at discrete time points over the trial. Surgery-induced reductions in home cage and open field locomotor activity were also observed. CONCLUSION The present studies report for the first time the characterization of the affective component of acute postoperative pain using the mPEAP in a rodent model, which may facilitate development of improved understanding and treatment of postoperative pain.


title: Transrectal specimen extraction after laparoscopic left colectomy: a case-matched study.

text: AIM Avoiding 'mini-laparotomy' to extract a colectomy specimen may decrease wound complications and further improve recovery after laparoscopic surgery. The aim of this study was to develop a new technique for transrectal specimen extraction (TRSE) and to compare it with conventional laparoscopy (CL) for left sided colectomy. METHOD Eleven patients with benign disease requiring either sigmoid or left colon resection underwent TRSE. The unfired circular stapler was inserted transanally and used as a guide to suture-close the recto-sigmoid junction laparoscopically and as a handle to pull the sutured sigmoid through the opened rectum inside a laparoscopic camera bag. The anvil was inserted into the lumen of the intussuscepted sigmoid and pushed to the level of the anastomosis. The anastomosis was fashioned end-to-end in the first patients and side-to-end in the following patients to improve safety. Intra-operative and postoperative outcomes of patients undergoing TRSE were compared with those of a group of 20 patients undergoing CL, who were matched for type of resection, body mass index and age. RESULTS The procedure was successful in all but the first patient who was converted to conventional laparoscopic colectomy without any additional morbidity. Two patients in the end-to-end anastomosis group, but none in the side-to-end group, developed peri-anastomotic sepsis. Compared with CL, patients undergoing TRSE did not show any significant differences in operative time, recovery or morbidity. CONCLUSION Transrectal specimen extraction after left colectomy using the circular stapler technique is feasible. A side-to-end anastomosis appears safer than an end-to-end anastomosis. Further studies are needed to explore the potential advantages of this procedure over CL.


Coronary artery disease in India: challenges and opportunities.


title: Analysis of human rotaviruses from a single location over an 18-year time span suggests that protein coadaption influences gene constellations.

text: UNLABELLED Rotaviruses (RVs) are 11-segmented, double-stranded RNA viruses that cause severe gastroenteritis in children. In addition to an error-prone genome replication mechanism, RVs can increase their genetic diversity by reassorting genes during host coinfection. Such exchanges allow RVs to acquire advantageous genes and adapt in the face of selective pressures. However, reassortment may also impose fitness costs if it unlinks genes/proteins that have accumulated compensatory, coadaptive mutations and that operate best when kept together. To better understand human RV evolutionary dynamics, we analyzed the genome sequences of 135 strains (genotype G1/G3/G4-P[8]-I1-C1-R1-A1-N1-T1-E1-H1) that were collected at a single location in Washington, DC, during the years 1974 to 1991. Intragenotypic phylogenetic trees were constructed for each viral gene using the nucleotide sequences, thereby defining novel allele level gene constellations (GCs) and illuminating putative reassortment events. The results showed that RVs with distinct GCs cocirculated during the vast majority of the collection years and that some of these GCs persisted in the community unchanged by reassortment. To investigate the influence of protein coadaptation on GC maintenance, we performed a mutual information-based analysis of the concatenated amino acid sequences and identified an extensive covariance network. Unexpectedly, amino acid covariation was highest between VP4 and VP2, which are structural components of the RV virion that are not thought to directly interact. These results suggest that GCs may be influenced by the selective constraints placed on functionally coadapted, albeit noninteracting, viral proteins. This work raises important questions about mutation-reassortment interplay and its impact on human RV evolution. IMPORTANCE Rotaviruses are devastating human pathogens that cause severe diarrhea and kill >450,000 children each year. The virus can evolve by accumulating mutations and by acquiring new genes from other strains via a process called reassortment. However, little is known about the relationship between mutation accumulation and gene reassortment for rotaviruses and how it impacts viral evolution. In this study, we analyzed the genome sequences of human strains found in clinical fecal specimens that were collected at a single hospital over an 18-year time span. We found that many rotaviruses did not reassort their genes but instead maintained them as specific sets (i.e., constellations). By analyzing the encoded proteins, we discovered concurrent amino acid changes among them, which suggests that they are functionally coadapted to operate best when kept together. This study increases our understanding of how rotaviruses evolve over time in the human population.


title: Novel Zero-Heat-Flux Deep Body Temperature Measurement in Lower Extremity Vascular and Cardiac Surgery.

text: OBJECTIVE The aim of this study was to compare deep body temperature obtained using a novel noninvasive continuous zero-heat-flux temperature measurement system with core temperatures obtained using conventional methods. DESIGN A prospective, observational study. SETTING Operating room of a university hospital. PARTICIPANTS The study comprised 15 patients undergoing vascular surgery of the lower extremities and 15 patients undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS Zero-heat-flux thermometry on the forehead and standard core temperature measurements. MEASUREMENTS AND MAIN RESULTS Body temperature was measured using a new thermometry system (SpotOn; 3M, St. Paul, MN) on the forehead and with conventional methods in the esophagus during vascular surgery (n = 15), and in the nasopharynx and pulmonary artery during cardiac surgery (n = 15). The agreement between SpotOn and the conventional methods was assessed using the Bland-Altman random-effects approach for repeated measures. The mean difference between SpotOn and the esophageal temperature during vascular surgery was+0.08°C (95% limit of agreement -0.25 to+0.40°C). During cardiac surgery, during off CPB, the mean difference between SpotOn and the pulmonary arterial temperature was -0.05°C (95% limits of agreement -0.56 to+0.47°C). Throughout cardiac surgery (on and off CPB), the mean difference between SpotOn and the nasopharyngeal temperature was -0.12°C (95% limits of agreement -0.94 to+0.71°C). Poor agreement between the SpotOn and nasopharyngeal temperatures was detected in hypothermia below approximately 32°C. CONCLUSIONS According to this preliminary study, the deep body temperature measured using the zero-heat-flux system was in good agreement with standard core temperatures during lower extremity vascular and cardiac surgery. However, agreement was questionable during hypothermia below 32°C.


title: Technological Interventions for Medication Adherence in Adult Mental Health and Substance Use Disorders: A Systematic Review.

text: BACKGROUND Medication adherence is critical to the effectiveness of psychopharmacologic therapy. Psychiatric disorders present special adherence considerations, notably an altered capacity for decision making and the increased street value of controlled substances. A wide range of interventions designed to improve adherence in mental health and substance use disorders have been studied; recently, many have incorporated information technology (eg, mobile phone apps, electronic pill dispensers, and telehealth). Many intervention components have been studied across different disorders. Furthermore, many interventions incorporate multiple components, making it difficult to evaluate the effect of individual components in isolation. OBJECTIVE The aim of this study was to conduct a systematic scoping review to develop a literature-driven, transdiagnostic taxonomic framework of technology-based medication adherence intervention and measurement components used in mental health and substance use disorders. METHODS This review was conducted based on a published protocol (PROSPERO: CRD42018067902) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review guidelines. We searched 7 electronic databases: MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials, Web of Science, Engineering Village, and ClinicalTrials.gov from January 2000 to September 2018. Overall, 2 reviewers independently conducted title and abstract screens, full-text screens, and data extraction. We included all studies that evaluate populations or individuals with a mental health or substance use disorder and contain at least 1 technology-delivered component (eg, website, mobile phone app, biosensor, or algorithm) designed to improve medication adherence or the measurement thereof. Given the wide variety of studied interventions, populations, and outcomes, we did not conduct a risk of bias assessment or quantitative meta-analysis. We developed a taxonomic framework for intervention classification and applied it to multicomponent interventions across mental health disorders. RESULTS The initial search identified 21,749 results; after screening, 127 included studies remained (Cohen kappa: 0.8, 95% CI 0.72-0.87). Major intervention component categories include reminders, support messages, social support engagement, care team contact capabilities, data feedback, psychoeducation, adherence-based psychotherapy, remote care delivery, secure medication storage, and contingency management. Adherence measurement components include self-reports, remote direct visualization, fully automated computer vision algorithms, biosensors, smart pill bottles, ingestible sensors, pill counts, and utilization measures. Intervention modalities include short messaging service, mobile phone apps, websites, and interactive voice response. We provide graphical representations of intervention component categories and an element-wise breakdown of multicomponent interventions. CONCLUSIONS Many technology-based medication adherence and monitoring interventions have been studied across psychiatric disease contexts. Interventions that are useful in one psychiatric disorder may be useful in other disorders, and further research is necessary to elucidate the specific effects of individual intervention components. Our framework is directly developed from the substance use disorder and mental health treatment literature and allows for transdiagnostic comparisons and an organized conceptual mapping of interventions.


title: Objective sensory and functional outcomes at the donor site following endoscopic-assisted sural nerve harvest.

text: BACKGROUND The sural nerve is a common choice for a nerve graft. Understanding the potential morbidity associated with its harvest is important. In this study, we describe the objective sensory and functional outcomes associated with endoscopic sural nerve harvest from a combined paediatric and adult population. METHODS Data were collected prospectively from patients attending for follow-up between August 2015 and January 2016, who had previously undergone an endoscopic sural nerve graft harvest. Sensory loss was evaluated using a 5.07 Semmes-Weinstein monofilament. The lower extremity functional scale was used to evaluate the patients' lower limb function. Statistical comparison was made using the Student's t-test. RESULTS The outcomes from 46 sural nerve grafts were evaluated. The mean age of the patients was 18.1 years (range 4-45 years old). The mean time since surgery was 4.3 years. Those aged ≤18 years had a significantly smaller area of sensory loss (p = 0.003), which was not related to a difference in foot size. Those who had undergone surgery >6 months previously had a significantly smaller area of sensory loss than those who had undergone surgery <6 months ago (p = 0.0002). The mean lower extremity functional scale score was 78.7/80. CONCLUSION We demonstrated a significantly reduced post-harvest sensory deficit among a paediatric population compared to that seen in adults. Furthermore, sensory loss reduces with time. Despite the sensory loss resulting from sural nerve graft harvest, there is minimal loss of function. As such, the sural nerve continues to be an excellent donor for a nerve graft procedure.


Commercial Transport During a Pandemic: Network Analysis to Reconcile COVID-19 Diffusion and Vital Supply Chain Resilience.


title: Nosocomial transmission of avian influenza A (H7N9) virus in China: epidemiological investigation.

text: STUDY QUESTION Can avian influenza A (H7N9) virus be transmitted between unrelated individuals in a hospital setting? METHODS An epidemiological investigation looked at two patients who shared a hospital ward in February 2015, in Quzhou, Zhejiang Province, China. Samples from the patients, close contacts, and local environments were examined by real time reverse transcriptase (rRT) polymerase chain reaction (PCR) and viral culture. Haemagglutination inhibition and microneutralisation assays were used to detect specific antibodies to the viruses. Primary outcomes were clinical data, infection source tracing, phylogenetic tree analysis, and serological results. STUDY ANSWER AND LIMITATIONS A 49 year old man (index patient) became ill seven days after visiting a live poultry market. A 57 year old man (second patient), with a history of chronic obstructive pulmonary disease, developed influenza-like symptoms after sharing the same hospital ward as the index patient for five days. The second patient had not visited any poultry markets nor had any contact with poultry or birds within 15 days before the onset of illness. H7N9 virus was identified in the two patients, who both later died. Genome sequences of the virus isolated from both patients were nearly identical, and genetically similar to the virus isolated from the live poultry market. No specific antibodies were detected among 38 close contacts. Transmission between the patients remains unclear, owing to the lack of samples collected from their shared hospital ward. Although several environmental swabs were positive for H7N9 by rRT-PCR, no virus was cultured. Owing to delayed diagnosis and frequent hospital transfers, no serum samples were collected from the patients, and antibodies to H7N9 viruses could not be tested. WHAT THIS STUDY ADDS Nosocomial H7N9 transmission might be possible between two unrelated individuals. Surveillance on patients with influenza-like illness in hospitals as well as chickens in live poultry markets should be enhanced to monitor transmissibility and pathogenicity of the virus. FUNDING, COMPETING INTERESTS, DATA SHARING Funding support from the Program of International Science and Technology Cooperation of China (2013DFA30800), Basic Work on Special Program for Science and Technology Research (2013FY114600), National Natural Science Foundation of China (81402730), Special Program for Prevention and Control of Infectious Diseases in China (2013ZX10004218), US National Institutes of Health (1R01-AI108993), Zhejiang Province Major Science and Technology Program (2014C03039), and Quzhou Science and Technology Program (20111084). The authors declare no other interests and have no additional data.


title: High-throughput screening using pseudotyped lentiviral particles: a strategy for the identification of HIV-1 inhibitors in a cell-based assay.

text: Two decades after its discovery the human immunodeficiency virus (HIV) is still spreading worldwide and killing millions. There are 25 drugs formally approved for HIV currently on the market, but side effects as well as the emergence of HIV strains showing single or multiple resistances to current drug-therapy are causes for concern. Furthermore, these drugs target only 4 steps of the viral cycle, hence the urgent need for new drugs and also new targets. In order to tackle this problem, we have devised a cell-based assay using lentiviral particles to look for post-entry inhibitors of HIV-1. We report here the assay development, validation as well as confirmation of the hits using both wild-type and drug-resistant HIV-1 viruses. The screening was performed on an original library, rich in natural compounds and pure molecules from Traditional Chinese Medicine pharmacopoeia, which had never been screened for anti-HIV activity. The identified hits belong to four chemical sub-families that appear to be all non-nucleoside reverse transcriptase inhibitors (NNRTIs). Secondary tests with live viruses showed that there was good agreement with pseudotyped particles, confirming the validity of this approach for high-throughput drug screens. This assay will be a useful tool that can be easily adapted to screen for inhibitors of viral entry.


title: Evaluation of backbone-cyclized HER2-binding 2-helix affibody molecule for in vivo molecular imaging.

text: INTRODUCTION Affibody molecules, small scaffold proteins, have demonstrated an appreciable potential as imaging probes. Affibody molecules are composed of three alpha-helices. Helices 1 and 2 are involved in molecular recognition, while helix 3 provides stability. The size of Affibody molecules can be reduced by omitting the third alpha-helix and cross-linking the two remaining, providing a smaller molecule with better extravasation and quicker clearance of unbound tracer. The goal of this study was to develop a novel 2-helix Affibody molecule based on backbone cyclization by native chemical ligation (NCL). METHODS The HER2-targeting NCL-cyclized Affibody molecule ZHER2:342min has been designed, synthesized and site-specifically conjugated with a DOTA chelator. DOTA-ZHER2:342min was labeled with (111)In and (68)Ga. The binding affinity of DOTA-ZHER2:342min was evaluated in vitro. The targeting properties of (111)In- and (68)Ga-DOTA-ZHER2:342min were evaluated in mice bearing SKOV-3 xenografts and compared with the properties of (111)In- and (68)Ga-labeled PEP09239, a DOTA-conjugated 2-helix Affibody analogue cyclized by a homocysteine disulfide bridge. RESULTS The dissociation constant (KD) for DOTA-ZHER2:342min binding to HER2 was 18nM according to SPR measurements. DOTA-ZHER2:342min was labeled with (111)In and (68)Ga. Both conjugates demonstrated bi-phasic binding kinetics to HER2-expressing cells, with KD1 in low nanomolar range. Both variants demonstrated specific uptake in HER2-expressing xenografts. Tumor-to-blood ratios at 2h p.i. were 6.1±1.3 for (111)In- DOTA-ZHER2:342min and 4.6±0.7 for (68)Ga-DOTA-ZHER2:342min. However, the uptake of DOTA-ZHER2:342min in lung, liver and spleen was appreciably higher than the uptake of PEP09239-based counterparts. CONCLUSIONS Native chemical ligation enables production of a backbone-cyclized HER2-binding 2-helix Affibody molecule (ZHER2:342min) with low nanomolar target affinity and specific tumor uptake.


The effects of the COVID pandemic on the process of training in Occupational Medicine.


title: Fear, information and control during a pandemic.

text: When a threat is perceived as understandable and manageable, it is easier for people to adapt to the situation. That is why it is so important for the authorities to keep the public well-informed during the COVID-19 pandemic.


title: Vascular and interventional radiology radiofrequency ablation of benign thyroid nodules and recurrent thyroid cancers: literature review.

text: Thermal radiofrequency ablation is a relatively new, minimally invasive modality employed as an alternative to surgery in patients with benign thyroid nodules and recurrent thyroid cancers. Different recommendations are necessary for the optimal use of radiofrequency ablation for thyroid nodules. These recommendations are based on a comprehensive analysis of the current literature, the results of multicenter studies, and expert consensus.


title: Three intraoperative methods to determine limb-length discrepancy in THA.

text: Limb-length discrepancy (LLD) is a common concern for both surgeon and patient in the setting of elective total hip arthroplasty (THA). There is a paucity of evidence guiding surgeons to an optimal method for measuring intraoperative LLD and minimizing postoperative LLD. The primary objective of this prospective, randomized, double-blinded study was to determine which of 3 intraoperative methods used at the authors' institution was best correlated to postoperative radiographic LLD. From 2011 to 2012, 81 patients undergoing either primary (75) or revision (6) THA with an anterolateral (Watson-Jones) approach were prospectively randomized and received intraoperative measurement of LLD via 1 of 3 methods: abductor shuck (AS), tranosseous pins with calibrated caliper (TP), or patella electrocardiogram (EKG) leads (PL). Intraoperative measurements of LLD were compared to clinical and radiographic postoperative measurements of LLD, and absolute differences and correlation coefficients were calculated for each method. Overall, the mean LLD preoperatively was 8.09 mm, and mean radiographic LLD postoperatively was 4.20 mm. The AS method was associated with the highest correlation to postoperative radiographic LLD (R=0.360; P<.05), whereas the other methods had mildly positive but statistically insignificant correlations (TP R=0.275; P>.05; PL R=0.301; P>.05). The AS method best correlates to postoperative radiographic LLD among the 3 techniques, although all methods were positively correlated. Clinical measurements of LLD correlate poorly with radiographic measurements and may be of limited utility.


title: Residual symptoms in depressed outpatients who respond by 50% but do not remit to antidepressant medication.

text: Little is known about the quantity or quality of residual depressive symptoms in patients with major depressive disorder (MDD) who have responded but not remitted with antidepressant treatment. This report describes the residual symptom domains and individual depressive symptoms in a large representative sample of outpatients with nonpsychotic MDD who responded without remitting after up to 12 weeks of citalopram treatment in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Response was defined as 50% or greater reduction in baseline 16-item Quick Inventory of Depressive Symptomatology--Self-Report (QIDS-SR₁₆) by treatment exit, and remission as a final QIDS-SR₁₆ of less than 6. Residual symptom domains and individual symptoms were based on the QIDS-SR₁₆ and classified as either persisting from baseline or emerging during treatment. Most responders who did not remit endorsed approximately 5 residual symptom domains and 6 to 7 residual depressive symptoms. The most common domains were insomnia (94.6%), sad mood (70.8%), and decreased concentration (69.6%). The most common individual symptoms were midnocturnal insomnia (79.0%), sad mood (70.8%), and decreased concentration/decision making (69.6%). The most common treatment-emergent symptoms were midnocturnal insomnia (51.4%) and decreased general interest (40.0%). The most common persistent symptoms were midnocturnal insomnia (81.6%), sad mood (70.8%), and decreased concentration/decision making (70.6%). Suicidal ideation was the least common treatment-emergent symptom (0.7%) and the least common persistent residual symptom (17.1%). These findings suggest that depressed outpatients who respond by 50% without remitting to citalopram treatment have a broad range of residual symptoms. Individualized treatments are warranted to specifically address each patient's residual depressive symptoms.


title: Single-incision laparoscopic right colectomy for cancer: a single-centre preliminary experience.

text: The rationale for single-incision laparoscopic surgery (SILS) is minimizing morbidity, as well as improving cosmetic results of laparoscopic approach. This technique has been used for a variety of procedures and has recently been proposed for colonic resections as well. We report our preliminary experience of right colectomy, performed through a SILS approach. Five patients (3 males, 2 females, mean age 81.6 years) were selected to undergo SILS right colectomy for cancer. The procedure was carried out through a SILS multi-port device (SILS™ Port, Covidien Ltd, Norwalk, CT, USA), with either conventional or specially designed instruments. A medial-to-lateral approach and an extra-corporeal anastomosis were performed. In three cases, the procedure was completed through the SILS technique; in two of these cases a combined procedure was carried out (right colectomy plus cholecystectomy, right colectomy plus cholecystectomy plus i.o. colonoscopy and polypectomy). In one case, a switch to standard laparoscopy was necessary because of the large dimension of the tumour, while in the other case an intolerance of pneumoperitoneum was registered, thus requiring a conversion to open surgery. SILS procedures proved to be oncologically correct. No major complications occurred. In selected patients, SILS right colectomy for cancer appears to be feasible and oncologically safe. Beyond the cosmetic advantage, the procedure may reduce postoperative morbidity. Further studies are needed, with larger series and a longer follow-up, to determine the incidence of possible long-term complications and to evaluate possible cost-effectiveness of the procedure.


Nature Immunology turns 20.


title: Characterizing protein-protein interactions by sedimentation velocity analytical ultracentrifugation.

text: This unit introduces the basic principles and practice of sedimentation velocity analytical ultracentrifugation for the study of reversible protein interactions, such as the characterization of self-association, heterogeneous association, multi-protein complexes, binding stoichiometry, and the determination of association constants. The analytical tools described include sedimentation coefficient and molar mass distributions, multi-signal sedimentation coefficient distributions, Gilbert-Jenkins theory, different forms of isotherms, and global Lamm equation modeling. Concepts for the experimental design are discussed, and a detailed step-by-step protocol guiding the reader through the experiment and the data analysis is available as an Internet resource.


title: The COVID-19 pandemic: Clinical practice advice for gastroenterologists, hepatologists, and liver transplant specialists.

text: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel acute infectious disease that has rapidly reached staggering pandemic proportions. This review addresses gastroenterologists, hepatologists, liver transplant (LT) specialists, and health-care professionals working in the field of liver diseases and liver transplantation. It has been written based on a limited number of publications, recommendations of national and international liver and organ transplantation societies, and experiences of patients with COVID-19 around the world. The purpose of this review is to provide information addressing questions and concerns about COVID-19, to reveal the effects of the novel disease on patients with chronic liver disease and LT recipients, and to share information about ways in which this pandemic will affect clinical practices. We, the Turkish Association for the Study of the Liver (TASL), would like to remind you that this text is actually not a practical guide. It is imperative to act according to the standards set by health-care institutions and the Ministry of Health, Republic of Turkey.


Multiple myeloma and COVID-19.


title: Unilateral mechanical asymmetry: positional effects on lung volumes and transpulmonary pressure.

text: BACKGROUND Ventilated patients with asymmetry of lung or chest wall mechanics may be vulnerable to differing lung stresses or strains dependent on body position. Our purpose was to examine transpulmonary pressure (P TP) and end-expiratory lung volume (functional residual capacity (FRC)) during body positioning changes in an animal model under the influence of positive end-expiratory pressure (PEEP) or experimental pleural effusion (PLEF). METHODS Fourteen deeply anesthetized swine were studied including tracheostomy, thoracostomy, and esophageal catheter placement. Animals were ventilated at V T = 10 ml/kg, frequency of 15, I/E = 1:2, and FIO2 = 0.5. The animals were randomized to supine, prone, right lateral, left lateral, and semi-Fowler positions with a PEEP of 1 cm H2O (PEEP1) or a PEEP of 10 cm H2O (PEEP10) applied. Experimental PLEF was generated by 10 ml/kg saline instilled into either pleural space. P TP and FRC were determined in each condition. RESULTS No significant differences in FRC were found among the four horizontal positions. Compared to horizontal positioning, semi-Fowler's increased FRC (p < 0.001) by 56% at PEEP1 and 54% at PEEP10 without PLEF and by 131% at PEEP1 and 98% at PEEP10 with PLEF. Inspiratory or expiratory P TP showed insignificant differences across positions at both levels of PEEP. Consistently negative end-expiratory P TP at PEEP1 increased to positive values with PEEP10. CONCLUSIONS FRC did not differ among horizontal positions; however, semi-Fowler's positioning significantly raised FRC. P TP proved insensitive to mechanical asymmetry. While end-expiratory P TP was negative at PEEP1, applying PEEP10 caused a transition to positive P TP, suggestive of reopening of initially compressed lung units.


title: Prolonged sleep deprivation and continuous exercise: effects on melatonin, tympanic temperature, and cognitive function.

text: The purpose of this study was to examine tympanic temperature, melatonin, and cognitive function during a 36-hour endurance event. Nine male and three female participants took part in a 36-hour sustained endurance event without sleep (N = 12, mean age = 31.8 ± 5.0 yrs). Participants were stopped for data collection at checkpoints throughout the 36-hour event. Tympanic temperature was assessed, a psychomotor vigilance test (PVT) was administered, and saliva samples were collected. Salivary melatonin was determined via immunoassay. During the 36 hours of competition, melatonin levels were negatively correlated with the day of the race (rs = -0.277, P = 0.039) and positively associated with nighttime (rs = 0.316, P = 0.021). Significant main effects of tympanic temperature (P < 0.001), day of the competition (P = 0.018), and a tympanic temperature ∗ day of competition interaction (P < 0.001) were used to predict minor lapses in attention. No associations between melatonin levels and cognitive function were observed (P > 0.05). During the event tympanic temperature declined and was associated with an increase in lapses in attention. With sustained endurance events becoming more popular future research is warranted to evaluate the physiological impact of participation.


Increased importance of digital medicine and eHealth during the Covid-19 pandemic.


Complications of intrathoracic lines placed during cardiac surgery.


Pneumonia from human coronavirus in a macaque model.


title: Detection of small-bowel tumours with CT enteroclysis using carbon dioxide and virtual enteroscopy: A preliminary study.

text: PURPOSE The aim of this prospective study was to evaluate the feasibility, tolerance and performance of virtual enteroscopy (VE) using carbon dioxide for small-bowel distension in patients with suspected small-bowel tumours (SBTs). PATIENTS AND METHODS After IRB approval, 17 patients with suspected SBTs were prospectively included. Radiation dose was compared to 34 matched patients (2 for 1) for age, gender and body weight, who had undergone CT-enteroclysis with neutral contrast (CTE). Performance of VE was evaluated through comparison with the current standard of reference, including surgery and/or enteroscopy and/or follow-up. RESULTS Tolerance was excellent in 16/17 patients (94%). The radiation dose was lower for VE than for CTE (533 ± 282 vs. 974 ± 505 mGy.cm; p = 0.002). With VE, a total of 25 polyps >5 mm in size were depicted in 12/17 patients. On a per-lesion analysis, sensitivity and positive predictive value of VE were 92.0% and 92.0%, respectively. On a per-segment analysis VE had a sensitivity and specificity of 95.0% and 87.0%, respectively. CONCLUSION Our preliminary study suggests that VE is a feasible and well-tolerated technique with high sensitivity and specificity for the diagnosis of SBT. KEY POINTS • Virtual enteroscopy is feasible and well tolerated. • Virtual enteroscopy appears to be accurate for detection of small-bowel tumours. • Sensitivity and PPV of virtual enteroscopy is 92.0% and 92.0%. • Radiation dose is lower with virtual enteroscopy compared to MDCT-enteroclysis.


title: Thermal effusivity: a promising imaging biomarker to predict radiation-induced skin injuries.

text: An effective screening technology is needed to triage individuals at the time of radiation incidents involving a large population. Three-dimensional thermal tomography is a relatively new development in active thermal imaging technology that produces cross-sectional images based on the subject's ability to transfer heat-thermal effusivity-at the voxel level. This noninvasive imaging modality has been used successfully in nondestructive examination of complex materials; also it has been shown to predict the severity of radiation-induced skin injuries several days before the manifestation of severe moist desquamations or blister formation symptoms in mice at 40 Gy. If these results are confirmed at lower dose levels in human subjects, a thermal tomography imaging device may be an ideal screening tool in radiation emergencies. This imaging method is non-invasive, relatively simple, easily adaptable for field use, and when properly deployed, it will enhance public emergency preparedness for incidents involving unexpected radiation exposure.


Telephone based survey in adults with congenital heart disease during COVID-19 pandemic.


Is it wrong to prioritise younger patients with covid-19?


title: Comparison of the perioperative outcome of esophagectomy by thoracoscopy in the prone position with that of thoracotomy in the lateral decubitus position.

text: PURPOSE Traditional esophagectomy is a highly invasive procedure. Intrathoracic procedures in esophagectomy can be performed by thoracoscopy. This study compared the influence of prone positioning with that of lateral decubitus positioning on patient outcomes following esophagectomy. METHODS This study enrolled 24 patients that underwent esophagectomy with thoracoscopy in the prone position between July 2009 and November 2010 (group P) and 24 patients that underwent thoracotomy in the lateral decubitus position between July 2007 and June 2009 (group L). The ICU and hospital stay length, pulmonary complication frequency and time until walking ability was regained were recorded. RESULTS The patients' background was not significantly different. Total blood loss and pulmonary complication frequency were significantly lower in group P than in group L [209 (SD; 146) vs. 474 (279) ml, P = 0.002, and 4 vs. 38 %, P = 0.003]. The duration of ICU stay, time until walking ability was regained and hospital stay were significantly shorter in group P than in group L [865 (103) vs. 1349 (702) min, P = 0.002, 1.0 (0.2) vs. 3.1 (2.5) POD, P < 0.001 and 23 (16) vs. 35 (15) POD, P = 0.009]. CONCLUSION Thoracoscopic surgery in the prone position allows for earlier mobilization and also reduces respiratory complications.


title: Selective and Continuous Transarterial Heparin Infusion: Postmicrosurgical Therapy of Lower Leg Reconstruction for Cases with Recipient Artery Damage.

text: BACKGROUND Microsurgical lower extremity reconstruction is challenging because of high incidence of vascular thrombosis compared to microsurgical head and neck reconstruction. The risk of vascular pedicle thrombosis increases, if patients have arterial sclerosis or intimal dissection at the recipient artery. We performed selective and continuous transarterial heparin infusion for postoperative anticoagulant therapy. METHODS Fifteen patients (10 men and 5 women; mean age of 55.1 years; range of 16-86 years) received lower leg reconstruction using free flap. Postoperatively, a catheter was inserted into the femoral artery during surgery. Heparin infusion was performed through the catheter as a postoperative therapy for patients who had a risk factor of vascular pedicle thrombosis. Until two days post-operation, heparin was started between 5,000 and 10,000 IU per day. In postoperative days 3 and 4, half of the initial dose of heparin was administered. In postoperative days 5 and 6, 25% of the initial dose of heparin was administered. RESULTS Recipient arteries were the posterior tibial (n=11), anterior tibial (n=2), lateral circumflex femoral (n=1), and medial sural (n=1) arteries. Thirteen of the 15 cases showed arterial sclerosis or intimal dissection at the recipient artery. There was no case of vascular thrombosis. Hematoma formation at flap recipient was observed in four cases. Their initial heparin dose was than 8.5±1.7 U/kg/h. CONCLUSION Continuous transarterial heparin infusion was an effective anticoagulant therapy for the patients who had received free tissue transfer to a lower extremity. The initial dose of heparin should not exceed 6.5 U/kg/h.


As normalcy returns, can China keep COVID-19 at bay?


title: Comparative analysis of two venipuncture learning methods on nursing students.

text: INTRODUCTION Venus cannulation is one of the main nursing actions. For the safety of patients and nurses, this skill is important to be performed in a proper and responsible way. Thus, the need for adequate education on this skill is essential. STUDY OBJECTIVE Comparison between the 4-stage (demonstration, deconstruction, comprehension, performance) learning method and the simplified 2-stage method (deconstruction, performance) on venous cannulation. METHODS The study took place from November 2011 to March 2012. In total, 117 students of the Nursing Department of Technological Educational Institute of Athens were randomized into two education groups of the 2- (Group A) and 4- (Group B) stage method respectively. Students of both groups were assessed during training and 45days later for skill retention. For the assessment of all students, a check list with the steps required to venous cannulation was used. The time to complete the process was also assessed. RESULTS Group A included 54 students and Group B 50 students. During initial training, the average time to complete the process without any errors was lower for Group A compared to Group B (1.77±0.12min vs. 2.33±0.13min, p=0.006). Regarding the appropriate steps for venous cannulation, Group A made fewer errors compared to Group B (0.95±0.95 vs. 1.38±1.10, p=0.021). In addition, Group A omitted more steps than Group B (0.29±0.06 vs. 0.11±0.05, p=0.042). During skill retention assessment, no significant difference was observed in the number of incorrect steps or in the number of omitted steps between groups. CONCLUSION According to our findings, the 4-stage method, is associated with less omitted steps, while the 2-stage method, is associated with less time required to complete the procedure and less errors during performance, at initial stages. However, skill retention does not seem to be associated with the type of the educational methodology.


title: Factors Predicting Meniscal Allograft Transplantation Failure.

text: BACKGROUND Meniscal allograft transplantation (MAT) is performed to improve symptoms and function in patients with a meniscal-deficient compartment of the knee. Numerous studies have shown a consistent improvement in patient-reported outcomes, but high failure rates have been reported by some studies. The typical patients undergoing MAT often have multiple other pathologies that require treatment at the time of surgery. The factors that predict failure of a meniscal allograft within this complex patient group are not clearly defined. PURPOSE To determine predictors of MAT failure in a large series to refine the indications for surgery and better inform future patients. STUDY DESIGN Cohort study; Level of evidence, 3. METHODS All patients undergoing MAT at a single institution between May 2005 and May 2014 with a minimum of 1-year follow-up were prospectively evaluated and included in this study. Failure was defined as removal of the allograft, revision transplantation, or conversion to a joint replacement. Patients were grouped according to the articular cartilage status at the time of the index surgery: group 1, intact or partial-thickness chondral loss; group 2, full-thickness chondral loss 1 condyle; and group 3, full-thickness chondral loss both condyles. The Cox proportional hazards model was used to determine significant predictors of failure, independently of other factors. Kaplan-Meier survival curves were produced for overall survival and significant predictors of failure in the Cox proportional hazards model. RESULTS There were 125 consecutive MATs performed, with 1 patient lost to follow-up. The median follow-up was 3 years (range, 1-10 years). The 5-year graft survival for the entire cohort was 82% (group 1, 97%; group 2, 82%; group 3, 62%). The probability of failure in group 1 was 85% lower (95% CI, 13%-97%) than in group 3 at any time. The probability of failure with lateral allografts was 76% lower (95% CI, 16%-89%) than medial allografts at any time. CONCLUSION This study showed that the presence of severe cartilage damage at the time of MAT and medial allografts were significantly predictive of failure. Surgeons and patients should use this information when considering the risks and benefits of surgery.


title: Mesh-augmented versus direct abdominal closure in patients undergoing open abdomen treatment.

text: BACKGROUND Open abdomen (OA) may be required in patients with abdominal trauma, sepsis or compartment syndrome. Vacuum-assisted wound closure and mesh-mediated fascial traction (VAWCM) is a widely used approach for temporary abdominal closure to close the abdominal wall. However, this method is associated with a high incidence of re-operations in short term and late sequelae such as incisional hernia. The current study aims to compare the results of surgical strategies of OA with versus without permanent mesh augmentation. METHODS Patients with OA treatment undergoing vacuum-assisted wound closure and an intraperitoneal onlay mesh (VAC-IPOM) implantation were compared to VAWCM with direct fascial closure which represents the current standard of care. Outcomes of patients from two tertiary referral centers that performed the different strategies for abdominal closure after OA treatment were compared in univariate and multivariate regression analysis. RESULTS A total of 139 patients were included in the study. Of these, 50 (36.0%) patients underwent VAC-IPOM and 89 (64.0%) patients VAWCM. VAC-IPOM was associated with reduced re-operations (adjusted incidence risk ratio 0.48 per 10-person days; CI 95% = 0.39-0.58, p < 0.001), reduced duration of stay on intensive care unit (ICU) [adjusted hazard ratio (aHR) 0.53; CI 95% = 0.36-0.79, p = 0.002] and reduced hospital stay (aHR 0.61; CI 95% = 0.040-0.94; p = 0.024). In-hospital mortality [22.5 vs 18.0%, risk difference - 4.5; confidence interval (CI) 95% = - 18.2 to 9.3; p = 0.665] and the incidence of intestinal fistula (18.0 vs 22.0%, risk difference 4.0; CI 95% = -10.0 to 18.0; p = 0.656) did not differ between the two groups. In Kaplan-Meier analysis, hernia-free survival was significantly increased after VAC-IPOM (p = 0.041). CONCLUSIONS In patients undergoing OA treatment, intraperitoneal mesh augmentation is associated with a significantly decreased number of re-operations, duration of hospital and ICU stay and incidence of incisional hernias when compared to VAWCM.


title: Developing pandemic preparedness in Europe in the 21st century: experience, evolution and next steps.

text: PROBLEM Improving pandemic planning and preparedness is a challenge in Europe, a diverse region whose regional bodies (the Regional Office for Europe of the World Health Organization [WHO], the European Commission and the European Centre for Disease Prevention and Control) have overlapping roles and responsibilities. APPROACH European pandemic preparedness indicators were used to develop an assessment tool and procedure based on the 2005 global WHO checklist for pandemic preparedness. These were then applied to Member States of WHO's European Region, initially as part of structured national assessments conducted during short visits by external teams. LOCAL SETTING Countries in WHO's European Region. RELEVANT CHANGES From 2005 to 2008, 43 countries underwent a pandemic preparedness assessment that included a short external assessment visit by an expert team. These short visits developed into a longer self-assessment procedure involving an external team but "owned" by the countries, which identified gaps and developed plans for improving preparedness. The assessment tool and procedure became more sophisticated as national and local pandemic preparedness became more complex. The 2009 pandemic revealed new gaps in planning, surveillance communications and immunization. LESSONS LEARNT Structured national self-assessments with support from external teams allow individual countries to identify gaps in their pandemic preparedness plans and enable regional bodies to assess the regional and global resources that such plans require. The 2009 pandemic revealed additional problems with surveillance, pandemic severity estimates, the flexibility of the response, vaccination, involvement of health-care workers and communication. European national plans are being upgraded and global leadership is required to ensure that these plans are uniformly applied across the region.


Ebola Virus Disease Complicated by Late-Onset Encephalitis and Polyarthritis, Sierra Leone.


title: Working from home in medicine during coronavirus: What equipment do you need to get started and what can you do to help from home?

text: The COVID-19 pandemic looks set to significantly change how we practice medicine. It is vital that the vulnerable and immunocompromised members of our workforce are protected, which may mean that they do not go into clinical areas. While the medical field has been slower than many professional areas to catch on to working from home, many trusts are already moving towards telephone or video outpatient appointments during COVID-19. We describe the equipment needed to set up working from home for healthcare practitioners (HCPs) and discuss a variety of other opportunities for home-based HCPs, including teaching, learning, carrying out audit and quality improvement work and offering psychological support for colleagues working on the front line.


title: Using social network analysis to examine alcohol use among adults: A systematic review.

text: BACKGROUND Alcohol use and abuse constitute a major public health problem and identifying their determinants is a priority. Social network analysis can indicate how characteristics of social networks are related to individual health behaviors. A growing number of studies have used social network analysis to examine how social network characteristics influence adult alcohol consumption, but this literature has never been systematically reviewed and summarized. The current paper systematically reviews empirical studies that used social network analysis to assess the influence of social network characteristics on drinking behaviors in adults. METHODS A literature search of PubMed/MEDLINE, EMBASE, PsycINFO and Web of Science databases and a review of the reference lists of retrieved articles was conducted in March 2019. Two reviewers independently screened 5,510 non-duplicate records, and further screened the full text of 150 articles to determine their eligibility for inclusion. Seventeen articles were judged eligible and included. RESULTS Most studies were conducted among young adults (mean age<30), in university settings or follow up visits with adolescent networks moving into adulthood. The objectives and methods of the included studies were heterogeneous. All included studies reported a statistically significant association between a social network characteristic and an alcohol consumption-related outcome. Social network members drinking behaviors were associated with participants' drinking behaviors in multiple ways. DISCUSSION In young adults, among whom the majority of identified studies were conducted, with whom they socialize and how they socialize appears to be associated with alcohol consumption; this was observed across methodologies and settings. We still know very little about the relationship of social networks to drinking in older age groups, and in populations most impacted by alcohol. As social networks appear to play a role in the consumption of alcohol in young adulthood, interventions that utilize social networks to help reduce harmful alcohol consumption should be considered.


title: Investigation of Turkish dentists' clinical attitudes and behaviors towards the COVID-19 pandemic: a survey study.

text: Currently, the whole world is under the threat of the COVID-19 pandemic, and dentists are at high risk. The aim of this study was to investigate what kind of precautions Turkish dentists take in dental clinics during the COVID-19 pandemic. The study population consisted of dentists in Turkey. An online questionnaire (23 questions-57 items) was sent to a sample of Turkish dentists from March 16 to March 20, 2020. The questionnaire comprised a series of questions about dentists' demographic characteristics, their concerns, and the measures taken in dental clinics against COVID-19. This study included a total of 1,958 Turkish dentists. A total of 1,274 (65.1%) were general dentists, and 684 (34.9%) were specialists. Five hundred twenty-two (26.7%) dentists attended an informational meeting on COVID-19. Of these dentists, 69.8% were aware of COVID-19 according to their self-assessed knowledge scores. More than 90% of the dentists were concerned about themselves and their families. Only 12% of the dentists wore an N95 mask. Although Turkish dentists took some precautionary measures, they did not take enough precautions to protect themselves, the dental staff, and other patients from COVID-19. As the number of COVID-19 cases increased, the measures taken slightly increased in dental clinics as well. Dentists are strongly recommended to take maximum precautions in the clinical setting. The guidelines about the COVID-19 pandemic should be sent to all dentists by the regional and national dental associations.


title: One-Health: a Safe, Efficient, Dual-Use Vaccine for Humans and Animals against Middle East Respiratory Syndrome Coronavirus and Rabies Virus.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and is a highly pathogenic respiratory virus. There are no treatment options against MERS-CoV for humans or animals, and there are no large-scale clinical trials for therapies against MERS-CoV. To address this need, we developed an inactivated rabies virus (RABV) that contains the MERS-CoV spike (S) protein expressed on its surface. Our initial recombinant vaccine, BNSP333-S, expresses a full-length wild-type MERS-CoV S protein; however, it showed significantly reduced viral titers compared to those of the parental RABV strain and only low-level incorporation of full-length MERS-CoV S into RABV particles. Therefore, we developed a RABV-MERS vector that contained the MERS-CoV S1 domain of the MERS-CoV S protein fused to the RABV G protein C terminus (BNSP333-S1). BNSP333-S1 grew to titers similar to those of the parental vaccine vector BNSP333, and the RABV G-MERS-CoV S1 fusion protein was efficiently expressed and incorporated into RABV particles. When we vaccinated mice, chemically inactivated BNSP333-S1 induced high-titer neutralizing antibodies. Next, we challenged both vaccinated mice and control mice with MERS-CoV after adenovirus transduction of the human dipeptidyl peptidase 4 (hDPP4) receptor and then analyzed the ability of mice to control MERS-CoV infection. Our results demonstrated that vaccinated mice were fully protected from the MERS-CoV challenge, as indicated by the significantly lower MERS-CoV titers and MERS-CoV and mRNA levels in challenged mice than those in unvaccinated controls. These data establish that an inactivated RABV-MERS S-based vaccine may be effective for use in animals and humans in areas where MERS-CoV is endemic. IMPORTANCE Rabies virus-based vectors have been proven to be efficient dual vaccines against rabies and emergent infectious diseases such as Ebola virus. Here we show that inactivated rabies virus particles containing the MERS-CoV S1 protein induce potent immune responses against MERS-CoV and RABV. This novel vaccine is easy to produce and may be useful to protect target animals, such as camels, as well as humans from deadly MERS-CoV and RABV infections. Our results indicate that this vaccine approach can prevent disease, and the RABV-based vaccine platform may be a valuable tool for timely vaccine development against emerging infectious diseases.


title: Scientia Potentia Est: How the Italian World of Oncology Changes in the COVID-19 Pandemic.

text: PURPOSE After coronavirus disease 2019 (COVID-19) was declared a pandemic by the WHO, a response from the Italian Health System to react to an unprecedented condition became necessary and sudden. The COVID-19 pandemic has required oncologists to redefine clinical organization and patient management. The purpose of our study was to document the difficulties emerging during the SARS-CoV-2 pandemic in Italian oncology. METHODS We broadcasted an electronic survey to oncologic health care professionals. It consisted of 45 questions ranging from individual perception of pandemic management by hospital centers to physicians' and nurses' psychological distress and patient care. RESULTS A total of 383 oncology health workers participated in the survey. The majority were female (71.8%) and from central Italy (46.2%). Impressively, a total of 357 (93%) participants declared the oncologic department reorganized routine clinical activity, but only 40.5% were adequately trained about the required procedures; 20% of the survey respondents think they have not received adequate and timely protective devices. CONCLUSION Our survey demonstrated the flexibility of oncologic teams. However, the emergency response quality has been heterogeneous, and several drawbacks have emerged from the first analyses investigating how the world of oncology changes in the COVID-19 pandemic. Information, protection, testing, and training of health care professionals are key words that should be kept in mind to encourage recovery after this tragedy and to be ready to face a similar emergency in the future.


Clinical research protocol to evaluate the effectiveness and safety of individualized homeopathic medicine in the treatment and prevention of the COVID-19 epidemic.


title: Robot-like dexterity without computers and motors: a review of hand-held laparoscopic instruments with wrist-like tip articulation.

text: INTRODUCTION Conventional manual laparoscopic instruments for minimally invasive surgery have limited dexterity within the patient, making procedures challenging. Surgical robotic systems offer enhanced articulation, but at substantial financial costs. This has motivated the development of high-dexterity, low-cost laparoscopic instruments. AREAS COVERED This article reviews both commercial and academic results on creating fully mechanical (i.e. non-robotic) laparoscopic instruments that provide wrists or wrist-like dexterity within the patient. We review the state of the art in the development of these mechanical instruments, focusing on the surgeon interface, wrist mechanism, and the kinematic mapping between the two. Expert commentary: Current articulated mechanical laparoscopic instruments exhibit a wide range of designs, with no clear consensus on what makes such devices easy to use. As these technologies mature, user studies are needed to determine surgeon preferences. Articulated, low-cost instruments have the potential to impact the minimally invasive surgery market if they provide compelling benefits to surgeons.


title: Serum and Synovial Fluid Interleukin-6 for the Diagnosis of Periprosthetic Joint Infection.

text: A gold standard for diagnosis of periprosthetic joint infection (PJI) has not yet been established. The objective of this study was to evaluate the diagnostic value of serum and synovial fluid interleukin (IL)-6 levels for PJI. The MEDLINE and EMBASE databases were searched for studies describing PJI diagnosis using serum and synovial fluid IL-6 and published between January 1990 and October 2016. Seventeen studies were included in the analysis. The pooled sensitivities of serum and synovial fluid IL-6 were 0.72 (95% confidence interval [CI]: 0.63-0.80) and 0.91 (95% CI: 0.82-0.96), respectively. The pooled specificities of serum and synovial fluid IL-6 were 0.89 (95% CI: 0.77-0.95) and 0.90 (95% CI: 0.84-0.95), respectively. The pooled diagnostic odds ratios (DORs) of serum and synovial fluid IL-6 were 20 (95% CI: 7-58) and 101 (95% CI: 28-358), respectively, and the pooled areas under the curve (AUCs) were 0.83 (95% CI: 0.79-0.86) and 0.96 (95% CI: 0.94-0.98), respectively. Synovial fluid IL-6 had high diagnostic value for PJI. Although serum IL-6 test was less sensitive than synovial fluid IL-6 test, it may be regularly prescribed for patients with prosthetic failure owing to its high specificity.


title: Laparoscopic sleeve gastrectomy for mildly obese patients (Body Mass Index of 30 <35 kg/m²): operative outcome and short-term results.

text: BACKGROUND Data concerning laparoscopic sleeve gastrectomy (LSG) in mild obesity are under investigation. AIM/OBJECTIVE May 2010 to May 2012, 122 consecutive patients with preoperative body mass index (BMI) of 33 ± 2.5 kg/m² (range 30-34.9) undergoing LSG were studied. Mean age was 33 ± 10 years (range 15-60), and 105 (86%) were women. Mean preoperative weight was 91 ± 9.7 kg (range 66-121), and preoperative excess weight was 30 ± 6.7 kg (range 19-43). Comorbidities were detected in 44 (36%) patients. RESULTS Mean operative time was 58 ± 15 min (range 40-95), and postoperative stay was 1.8 ± 0.19 days (range 1.5-3). There were no admissions to intensive care unit and no deaths within 30 days of surgery. The rates of leaks and strictures were 0%, and of hemorrhage 1.6%. At 12 months, BMI decreased to 24.7 ± 2, and the percentage of excess weight loss (% EWL) reached 76.5%. None of the patients had a BMI below 20 kg/m². Comorbidities resolved in 70.5% or improved in 29.5%. Patient satisfaction scoring (1-5) at least 1 year after was 4.6 ± 0.8 for body image and 4.4 ± 0.6 for food tolerance. CONCLUSION LSG for mildly obese patients has proved to be technically relatively easy, safe, and benefic in the short term.


title: Ebola virus exploits a monocyte differentiation program to promote its entry.

text: Antigen-presenting cells (APCs) are critical targets of Ebola virus (EBOV) infection in vivo. However, the susceptibility of monocytes to infection is controversial. Studies indicate productive monocyte infection, and yet monocytes are also reported to be resistant to EBOV GP-mediated entry. In contrast, monocyte-derived macrophages and dendritic cells are permissive for both EBOV entry and replication. Here, freshly isolated monocytes are demonstrated to indeed be refractory to EBOV entry. However, EBOV binds monocytes, and delayed entry occurs during monocyte differentiation. Cultured monocytes spontaneously downregulate the expression of viral entry restriction factors such as interferon-inducible transmembrane proteins, while upregulating the expression of critical EBOV entry factors cathepsin B and NPC1. Moreover, these processes are accelerated by EBOV infection. Finally, ectopic expression of NPC1 is sufficient to rescue entry into an undifferentiated, normally nonpermissive monocytic cell line. These results define the molecular basis for infection of APCs and suggest means to limit APC infection.


Passing the acid test.


title: Laparoscopic management of an obstructed obturator hernia: should laparoscopic assessment be the default option?

text: An obturator hernia is a rare diagnosis that is frequently missed. Patients present with few clinical signs to identify the cause, apart from symptoms of intestinal obstruction. Therefore, obturator hernias are often diagnosed at exploratory laparotomy. The use of computed tomography (CT) has increased the chance of definitive preoperative diagnosis. However, despite these advances, patients who present acutely will frequently undergo an open procedure rather than laparoscopy. We present a case of an acute obstructed obturator hernia diagnosed in a 62-year-old female that was successfully managed laparoscopically.


title: Efficacy of Oral Mixed Tocotrienols in Diabetic Peripheral Neuropathy: A Randomized Clinical Trial.

text: Importance Management of painful diabetic peripheral neuropathy remains challenging. Most therapies provide symptomatic relief with varying degrees of efficacy. Tocotrienols have modulatory effects on the neuropathy pathway and may reduce neuropathic symptoms with their antioxidative and anti-inflammatory activities. Objective To evaluate the efficacy of oral mixed tocotrienols for patients with diabetic peripheral neuropathy. Design, Setting, and Participants The Vitamin E in Neuroprotection Study (VENUS) was a parallel, double-blind, placebo-controlled trial that recruited participants from January 30, 2011, to December 7, 2014, with 12 months of follow-up. This trial screened 14 289 patients with diabetes from 6 health clinics and ambulatory care units from 5 public hospitals in Malaysia. A total of 391 patients who reported neuropathic symptoms were further assessed with Total Symptom Score (TSS) and Neuropathy Impairment Score (NIS). Patients 20 years or older with a TSS of 3 or higher and an NIS of 2 or higher were recruited. Interventions Patients were randomized to receive 200 mg of mixed tocotrienols twice daily or matching placebo for 12 months. Patients with hyperhomocysteinemia (homocysteine level ≥2.03 mg/L) received oral folic acid, 5 mg once daily, and methylcobalamin, 500 μg thrice daily, in both groups. Main Outcomes and Measures The primary outcome was patient-reported neuropathy TSS (lancinating pain, burning pain, paresthesia, and asleep numbness) changes at 12 months. The secondary outcomes were NIS and sensory nerve conduction test result. Results Of 391 eligible patients, 300 were recruited (130 [43.3%] male; mean [SD] age, 57.6 [8.9] years; mean [SD] duration of diabetes, 11.4 [7.8] years) and 229 (76.3%) completed the trial. The TSS changes between the tocotrienols and placebo groups at 12 months (-0.30; 95% CI, -1.16 to 0.56; P = .49) were similar. No significant differences in NIS (0.60; 95% CI, -1.37 to 2.65; P = .53) and sensory nerve conduction test assessments were found between both groups. In post hoc subgroup analyses, tocotrienols reduced lancinating pain among patients with hemoglobin A1C levels greater than 8% (P = .03) and normohomocysteinemia (homocysteine level <2.03 mg/L; P = .008) at 1 year. Serious adverse events in both groups were similar, except more infections were observed in the tocotrienols group (6.7% vs 0.7%, P = .04). Results reported were of modified intention-to-treat analyses. Conclusions and Relevance Supplementation of oral mixed tocotrienols, 400 mg/d for 1 year, did not improve overall neuropathic symptoms. The preliminary observations on lancinating pain among subsets of patients require further exploration. Trial Registration National Medical Research Registry Identifier: NMRR-10-948-7327 and clinicaltrials.gov Identifier: NCT01973400.


title: A Conflict of Values: Nurses' Willingness to Work Under Threatening Conditions.

text: PURPOSE The purpose of this study was to determine the willingness of Israeli registered nurses to work under threatening conditions, their perceived level of threat, and perceptions of peer willingness to report to work. DESIGN This descriptive study was based on a convenience sample of registered nurses working in four hospitals throughout Israel from internal medicine, surgical, emergency, and intensive care units. METHODS A questionnaire designed by the investigators was administered to registered nurses while on duty. The questionnaire consisted of three sections: personal characteristics, perceived level of personal threat from five situations (caring for a patient with a dangerous infection, terror attack, war, radiation or chemical disaster, or natural disaster), and perceived personal and peer willingness to work under these threats. FINDINGS A convenience sample of 249 registered nurses from four hospitals responded. The highest level of perceived threat was a natural disaster (earthquake; M = 2.15, SD = 0.9). Terror (M = 0.83, SD = 0.6) and war (M = 1.01, SD = 0.6) received the lowest mean perceived threat scores. Most respondents were not willing to work during a natural disaster but were willing to care for patients with dangerous infections and during times of war. Weak positive statistically significant correlations were found between the level of perceived threat and willingness to work for all of the threats, except for terror (Spearman rank correlation = .16-.35). CONCLUSIONS Local culture, perceptions of the level of threat, and perceived peer responsiveness are associated with registered nurses' willingness to work under threat. CLINICAL RELEVANCE When faced with a threat to personal safety or security, many registered nurses might not be willing to work as usual. What is perceived as threatening is influenced by the local culture and environment. Therefore, managers should be aware of potential cultural and peer influences on this possible conflict of values.


title: CCL2: a potential prognostic marker and target of anti-inflammatory strategy in HIV/AIDS pathogenesis.

text: Chemokines are critical components of the immune system that participate in immune homeostasis and alterations in chemokine balance can result in severe inflammatory and autoimmune diseases. The role of chemokines and their receptors in viral infections including HIV-1 was predicted from the early studies of HIV-1 co-receptor CCR5 and its ligands and a divergent role of C-C chemokines in HIV-1 pathogenesis has been established. For example, CCL3 (MIP-1α), CCL4 (MIP-1β) and CCL5 (RANTES) have been shown to possess antiviral effects by binding to the HIV-1 co-receptor CCR5, whereas CCL2, a pro-inflammatory chemokine, supports HIV-1 replication despite being a member of same chemokine family. Furthermore, the well-established role of CCL2 in driving the Th2 immune response supports its potential role in HIV-1/AIDS. Recent reports suggest multiple pathways of CCL2 affect HIV-1 infection. In this review, we provide a comprehensive overview of the role and potential mechanisms of the HIV-1-CCL2 interplay in driving virus-induced immuno-pathology, suggesting that CCL2 could be an anti-inflammatory target in the treatment of HIV-1 infection.


title: Fixed-dose combination of nifedipine gastrointestinal therapeutic system and candesartan cilexetil in patients with moderate-to-severe essential hypertension: an open-label, long-term safety and efficacy study.

text: WHAT IS KNOWN AND OBJECTIVE The nifedipine gastrointestinal therapeutic system (GITS)/candesartan cilexetil (N/C) combination was demonstrated to be an effective, well-tolerated antihypertensive therapy in a short-term study. The current study investigated the long-term safety and efficacy of a fixed-dose combination (FDC) of N/C therapy in moderate-to-severe essential hypertension. METHODS A multinational, 70-centre, open-label study of N/C treatment for 28 or 52 weeks at a target dose of N60 mg/C32 mg. The primary assessment included the incidence of treatment-emergent adverse events (TEAEs). Efficacy assessments included change from baseline in systolic and diastolic blood pressure (BP). RESULTS AND DISCUSSION A total of 508 patients were enrolled, with 417 (82·1%) completing week 28 of treatment. Of these, 200 patients continued treatment, as planned, to week 52, with 193 (96·5%) completing this period. At least one TEAE or drug-related TEAE were reported in 76·8% and 45·3% patients up to week 28, and in 80·7% and 46·9% up to week 52/end of study. Most TEAEs and drug-related TEAEs to week 52 (93·9% and 95·4%, respectively) were mild or moderate in intensity. Rates of drug-related serious AEs were low (0·6%). TEAE-related discontinuations occurred in 10% patients before week 28 and in no additional patients thereafter. N/C provided substantial, sustained reductions in mean systolic and diastolic BP from baseline: 30·1 ± 18·4 and 12·8 ± 10·7 mmHg, respectively, at week 52. WHAT IS NEW AND CONCLUSIONS Nifedipine GITS/candesartan cilexetil FDC at the target dose of 60 mg/32 mg was well tolerated for a study duration up to 52 weeks and provided sustained reductions in systolic and diastolic BP.


title: Photoplethysmography respiratory rate monitoring in patients receiving procedural sedation and analgesia for upper gastrointestinal endoscopy.

text: The value of capnography during procedural sedation and analgesia (PSA) for the detection of hypoxaemia during upper gastrointestinal (UGI) endoscopic procedures is limited. Photoplethysmography respiratory rate (RRp) monitoring may provide a useful alternative, but the level of agreement with capnography during PSA is unknown. We therefore investigated the level of agreement between the RRp and capnography-based RR (RRc) during PSA for UGI endoscopy. This study included patients undergoing PSA for UGI endoscopy procedures. Pulse oximetry (SpO2) and RRc were recorded in combination with Nellcor 2.0 (RRp) monitoring (Covidien, USA). Bland-Altman analysis was used to evaluate the level of agreement between RRc and RRp. Episodes of apnoea, defined as no detection of exhaled CO2 for minimal 36 s, and hypoxaemia, defined as an SpO2 < 92 %, were registered. A total of 1054 min of data from 26 patients were analysed. Bland-Altman analysis between the RRc and RRp revealed a bias of 2.25 ± 5.41 breath rate per minute (brpm), with limits of agreement from -8.35 to 12.84 brpm for an RR ≥ 4 brpm. A total of 67 apnoea events were detected. In 21 % of all apnoea events, the patient became hypoxaemic. Hypoxaemia occurred 42 times with a median length of 34 (19-141) s, and was preceded in 34 % of the cases by apnoea and in 64 % by an RRc ≥ 8 brpm. In 81 % of all apnoea events, photoplethysmography registered an RRp ≥ 4 brpm. We found a low level of agreement between capnography and the plethysmography respiratory rate during procedural sedation for UGI endoscopy. Moreover, respiratory rate derived from both the capnogram and photoplethysmogram showed a limited ability to provide warning signs for a hypoxaemic event during the sedation procedure.


title: Matched Comparison of Flow Diversion and Coiling in Small, Noncomplex Intracranial Aneurysms.

text: BACKGROUND Flow diversion is typically reserved for large, giant, or morphologically complex aneurysms. Coiling remains a first-line treatment for small, morphologically simple aneurysms. OBJECTIVE To compare coiling and flow diversion in small, uncomplicated intracranial aneurysms (typically amenable to coiling). METHODS Forty patients treated with the pipeline embolization device (PED) for small (<10 mm), morphologically simple aneurysms that would have also been amenable to coiling were identified. These patients were matched in a 1:1 fashion with 40 patients with comparable aneurysms treated with coiling. Matching was based on age, gender, aneurysm size, and aneurysm morphology. RESULTS The 2 groups were comparable with regard to baseline characteristics including age, gender, and aneurysm size. The complication rate did not differ between the 2 groups (2.5% with coiling vs 5% with PED; P = .6). Multivariate analysis did not identify any predictor of complications. Complete occlusion (100%) at follow-up was significantly higher in patients treated with PED (70%) than coiling (47.5%, P = .04). In multivariate analysis, treatment with PED predicted aneurysm obliteration ( P = .04). A significantly higher proportion of coiled patients (32.5%) required retreatment compared with flow diversion (5%, P = .003). In multivariate analysis, coiling predicted retreatment ( P = .006). All patients achieved a favorable outcome (modified Rankin Scale: 0-2) regardless of group. CONCLUSION This matched analysis suggests that flow diversion provides higher occlusion rates, lower retreatment rates, and no additional morbidity compared with coiling in small, simple aneurysms amenable to both techniques. These results suggest a potential benefit for flow diversion over coiling even in small, uncomplicated aneurysms.


title: Genetic diversity and evolutionary insights of respiratory syncytial virus A ON1 genotype: global and local transmission dynamics.

text: Human respiratory syncytial virus (RSV) A ON1 genotype, first detected in 2010 in Ontario, Canada, has been documented in 21 countries to date. This study investigated persistence and transmission dynamics of ON1 by grouping 406 randomly selected RSV-positive specimens submitted to Public Health Ontario from August 2011 to August 2012; RSV-A-positive specimens were genotyped. We identified 370 RSV-A (181 NA1, 135 NA2, 51 ON1 3 GA5) and 36 RSV-B positive specimens. We aligned time-stamped second hypervariable region (330 bp) of G-gene sequence data (global, n = 483; and Ontario, n = 60) to evaluate transmission dynamics. Global data suggests that the most recent common ancestor of ON1 emerged during the 2008-2009 season. Mean evolutionary rate of the global ON1 was 4.10 × 10(-3) substitutions/site/year (95% BCI 3.1-5.0 × 10(-3)), not significantly different to that of Ontario ON1. The estimated mean reproductive number (R0 = ∼ 1.01) from global and Ontario sequences showed no significant difference and implies stability among global RSV-A ON1. This study suggests that local epidemics exhibit similar underlying evolutionary and epidemiological dynamics to that of the persistent global RSV-A ON1 population. These findings underscore the importance of continual molecular surveillance of RSV in order to gain a better understanding of epidemics.


title: Surface contamination of counting tools after mock dispensing of cyclophosphamide in a simulated outpatient pharmacy.

text: PURPOSE The primary aim was to determine if dispensing of cyclophosphamide tablets resulted in accumulated residue on pharmacy counting tools during a simulated outpatient dispensing process. Secondary objectives included determining if cyclophosphamide contamination exceeded a defined threshold level of 1 ng/cm2 and if a larger number of prescriptions dispensed resulted in increased contamination. METHODS Mock prescriptions of 40 cyclophosphamide 50 mg tablets were counted on clean trays in three scenarios using a simulated outpatient pharmacy after assaying five cleaned trays as controls. The three scenarios consisted of five simulated dispensings of one, three, or six prescriptions dispensed per scenario. Wipe samples of trays and spatulas were collected and assayed for all trays, including the five clean trays used as controls. Contamination was defined as an assayed cyclophosphamide level at or above 0.001 ng/cm2 and levels above 1 ng/cm2 were considered sufficient to cause risk of human uptake. Mean contamination for each scenario was calculated and compared using one-way analysis of variance. P-values of < 0.05 implied significance. RESULTS Mean cyclophosphamide contamination on trays used to count one, three, and six cyclophosphamide prescriptions was 0.51 ± 0.10 (p=0.0003), 1.02 ± 0.10 (p < 0.0001), and 1.82 ± 0.10 ng/cm2 (p < 0.0001), respectively. Control trays did not show detectable cyclophosphamide contamination. Increasing the number of prescriptions dispensed from 1 to 3, 1 to 6, and 3 to 6 counts increased contamination by 0.51 ± 0.15 (p = 0.0140), 1.31 + 0.15 (p < 0.0001), and 0.80 ± 0.15 ng/cm2 (p = 0.0004), respectively. CONCLUSION Dispensing one or more prescriptions of 40 cyclophosphamide 50 mg tablets contaminates pharmacy counting tools, and an increased number of prescriptions dispensed correlates with increased level of contamination. Counting out three or more prescriptions leads to trays having contamination that surpasses the threshold at which worker exposure may be increased. Pharmacies should consider devoting a separate tray to cyclophosphamide tablets, as cross-contamination could occur with other drugs and the efficacy of decontamination methods is unclear. Employee exposure could be minimized with the use of personal protective equipment, environmental controls, and cleaning trays between uses. Future investigation should assess the extent of drug powder dispersion, the effects of various cleaning methods, and the potential extent of contamination with different oral cytotoxic drugs.


Reply to "Clinical Features and Chest CT Manifestations of Coronavirus Disease (COVID-19)".


From conference centre to hospital.


title: Electrofluidic control of bioactive molecule delivery into soft tissue models based on gelatin methacryloyl hydrogels using threads and surgical sutures.

text: The delivery of bioactive molecules (drugs) with control over spatial distribution remains a challenge. Herein, we demonstrate for the first time an electrofluidic approach to controlled delivery into soft tissue models based on gelatin methacryloyl (GelMA) hydrogels. This was achieved using a surgical suture, whereby transport of bioactive molecules, including drugs and proteins, was controlled by imposition of an electric field. Commonly employed surgical sutures or acrylic threads were integrated through the hydrogels to facilitate the directed introduction of bioactive species. The platform consisted of two reservoirs into which the ends of the thread were immersed. The anode and cathode were placed separately into each reservoir. The thread was taken from one reservoir to the other through the gel. When current was applied, biomolecules loaded onto the thread were directed into the gel. Under the same conditions, the rate of movement of the biomolecules along GelMA was dependent on the magnitude of the current. Using 5% GelMA and a current of 100 µA, 2 uL of fluorescein travelled through the hydrogel at a constant velocity of 7.17 ± 0.50 um/s and took less than 8 minutes to exit on the thread. Small molecules such as riboflavin migrated faster (5.99 ± 0.40 μm/s) than larger molecules such as dextran (2.26 ± 0.55 μm/s with 4 kDa) or BSA (0.33 ± 0.07 μm/s with 66.5 kDa). A number of commercial surgical sutures were tested and found to accommodate the controlled movement of biomolecules. Polyester, polyglactin 910, glycolide/lactide copolymer and polyglycolic acid braided sutures created adequate fluid connection between the electrodes and the hydrogel. With a view to application in skin inflammatory diseases and wound treatment, wound healing, slow and controlled delivery of dexamethasone 21-phosphate disodium salt (DSP), an anti-inflammatory prodrug, was achieved using medical surgicryl PGA absorbable suture. After 2 hours of electrical stimulation, still 81.1% of the drug loaded was encapsulated within the hydrogel.


title: Respiratory viral infections in infants: causes, clinical symptoms, virology, and immunology.

text: In global terms, respiratory viral infection is a major cause of morbidity and mortality. Infancy, in particular, is a time of increased disease susceptibility and severity. Early-life viral infection causes acute illness and can be associated with the development of wheezing and asthma in later life. The most commonly detected viruses are respiratory syncytial virus (RSV), rhinovirus (RV), and influenza virus. In this review we explore the complete picture from epidemiology and virology to clinical impact and immunology. Three striking aspects emerge. The first is the degree of similarity: although the infecting viruses are all different, the clinical outcome, viral evasion strategies, immune response, and long-term sequelae share many common features. The second is the interplay between the infant immune system and viral infection: the immaturity of the infant immune system alters the outcome of viral infection, but at the same time, viral infection shapes the development of the infant immune system and its future responses. Finally, both the virus and the immune response contribute to damage to the lungs and subsequent disease, and therefore, any prevention or treatment needs to address both of these factors.


title: Endoscopic treatment of obesity.

text: Obesity is a worldwide epidemic, complex metabolic disease associated with a variety of severe comorbidities. Bariatric surgery provides the patients with the benefits of sustained weight loss and improves obesity-related comorbidities, but can result in potentially life-threatening complications. Gastrointestinal endoscopy has recently been proposed as a scarless and noninvasive approach to obesity. Most of the current endoluminal devices and techniques are comparable to restrictive surgery. A variety of medical devices and procedures have been evaluated in recent years; however, with the exception of the intragastric balloon, evaluation of all the other endoluminal procedures is limited by the numbers of patients treated, the short follow-up and especially by the study design. Today, only a few devices have been evaluated in randomized controlled trials. The preliminary results of the first studies are extremely promising, but definitive statements cannot be drawn yet.


title: Lymphadenectomy along the left recurrent laryngeal nerve by a minimally invasive esophagectomy in the prone position for thoracic esophageal cancer.

text: BACKGROUND A thoracoabdominal esophagectomy for esophageal cancer is a severely invasive procedure. A thoracoscopic esophagectomy may minimize injury to the chest wall and reduce surgical invasiveness. Conventional thoracoscopic procedures are performed in the left lateral-decubitus position. Recently, procedures performed in the prone position have received more attention because of improvements in operative exposure or surgeon ergonomics. However, the efficacy of the prone position in an aggressive thoracoscopic esophagectomy with an extensive lymphadenectomy has not been fully documented. METHODS We successfully performed a thoracoscopic esophagectomy with a three-field extensive lymphadenectomy in 43 esophageal carcinoma patients in the prone position from December 2007 to December 2009. We describe our procedures with the patients in the prone position, focusing especially on a lymphadenectomy along the left recurrent laryngeal nerve where the nodes are frequently involved and precise dissection is technically challenging. To determine further the advantages of this position, we retrospectively compared surgical outcomes in 43 patients to those of 34 patients who underwent a thoracoscopic esophagectomy in the left lateral decubitus position as a historical control from January 2006 to November 2007. RESULTS It was easier to explore the operative field around the left recurrent laryngeal nerve during a thoracoscopic esophagectomy in the prone position. The mean duration of the aggressive thoracoscopic procedure in the prone position was 307 min, which was significantly longer than in the left lateral decubitus position, but the total estimated blood loss in the prone position was significantly lower. There was no difference in the incidence of postoperative complications between the two procedures. CONCLUSIONS A thoracoscopic esophagectomy in the prone position is technically safe and feasible and provides better surgeon ergonomics and better operative exposure around the left recurrent laryngeal nerve during an aggressive esophagectomy.


title: Efficacy of Perioperative Lumbar Drainage following Endonasal Endoscopic Cerebrospinal Fluid Leak Repair.

text: Objective Perioperative lumbar drain (LD) use in the setting of endoscopic cerebrospinal fluid (CSF) leak repair is a well-established practice. However, recent data suggest that LDs may not provide significant benefit and may thus confer unnecessary risk. To examine this, we conducted a meta-analysis to investigate the effect of LDs on postoperative CSF leak recurrence following endoscopic repair of CSF rhinorrhea. Data Sources A comprehensive search was performed with the following databases: Ovid MEDLINE (1947 to November 2015), EMBASE (1974 to November 2015), Cochrane Review, and PubMed (1990 to November 2015). Review Method A meta-analysis was performed according to PRISMA guidelines. Results A total of 1314 nonduplicate studies were identified in our search. Twelve articles comprising 508 cases met inclusion criteria. Overall, use of LDs was not associated with significantly lower postoperative CSF leak recurrence rates following endoscopic repair of CSF rhinorrhea (odds ratio: 0.89, 95% confidence interval: 0.40-1.95) as compared with cases performed without LDs. Subgroup analysis of only CSF leaks associated with anterior skull base resections (6 studies, 153 cases) also demonstrated that lumbar drainage did not significantly affect rates of successful repair (odds ratio: 2.67, 95% confidence interval: 0.64-11.10). Conclusions There is insufficient evidence to support that adjunctive lumbar drainage significantly reduces postoperative CSF leak recurrence in patients undergoing endoscopic CSF leak repair. Subgroup analysis examining only those patients whose CSF leaks were associated with anterior skull base resections demonstrated similar results. More level 1 and 2 studies are needed to further investigate the efficacy of LDs, particularly in the setting of patients at high risk for CSF leak recurrence.


title: [Prediction modeling with data fusion and prevention strategy analysis for the COVID-19 outbreak].

text: Since December 2019, the outbreak of COVID-19 in Wuhan has spread rapidly due to population movement during the Spring Festival holidays. Since January 23rd, 2020, the strategies of containment and contact tracing followed by quarantine and isolation has been implemented extensively in mainland China, and the rates of detection and confirmation have been continuously increased, which have effectively suppressed the rapid spread of the epidemic. In the early stage of the outbreak of COVID-19, it is of great practical significance to analyze the transmission risk of the epidemic and evaluate the effectiveness and timeliness of prevention and control strategies by using mathematical models and combining with a small amount of real-time updated multi-source data. On the basis of our previous research, we systematically introduce how to establish the transmission dynamic models in line with current Chinese prevention and control strategies step by step, according to the different epidemic stages and the improvement of the data. By summarized our modelling and assessing ideas, the model formulations vary from autonomous to non-autonomous dynamic systems, the risk assessment index changes from the basic regeneration number to the effective regeneration number, and the epidemic development and assessment evolve from the early SEIHR transmission model-based dynamics to the recent dynamics which are mainly associated with the variation of the isolated and suspected population sizes.


title: Environmental Factors as Key Determinants for Visceral Leishmaniasis in Solid Organ Transplant Recipients, Madrid, Spain.

text: During a visceral leishmaniasis outbreak in an area of Madrid, Spain, the incidence of disease among solid organ transplant recipients was 10.3% (7/68). Being a black person from sub-Saharan Africa, undergoing transplantation during the outbreak, and residing <1,000 m from the epidemic focus were risk factors for posttransplant visceral leishmaniasis.


Covid-19: Medical leaders call for rapid review to prepare for second wave.


title: [Experience of Practice-Based Psychiatrists and Neurologists During the COVID-19 Pandemic].

text: AIM To date, to our knowledge there are no studies regarding attitudes and experiences of outpatient medical personnel during a pandemic. This study's aim was to evaluate the impact of the COVID-19 pandemic in March 2020 on German psychiatrists and neurologists. METHODS An e-mail and fax-based short survey of 2,072 practice-based psychiatrists and neurologists was performed including Likert-type questions on personal burden and concerns, anticipated risk of infection, practice management as well as anxiety and sleep problems. RESULTS 396 physicians returned the questionnaire (19 %). More than 60 % of the participants felt restricted strongly or very strongly, more than 30 % were strongly and very strongly concerned. They anticipated a high own risk of infection. However, 91 % did not report any contact with patients positively screened for COVID-19, which they were aware of. One third felt financially threatened and loss of business volume was anticipated. 18 % reported, that the pandemic triggers substantial anxiety. Sleep problems, which occur at least almost every night, were rarely reported (9 %). CONCLUSION Practice-based psychiatrists and neurologists are negatively affected by the COVID-19 pandemic.


title: Estimating the relative probability of direct transmission between infectious disease patients.

text: BACKGROUND Estimating infectious disease parameters such as the serial interval (time between symptom onset in primary and secondary cases) and reproductive number (average number of secondary cases produced by a primary case) are important in understanding infectious disease dynamics. Many estimation methods require linking cases by direct transmission, a difficult task for most diseases. METHODS Using a subset of cases with detailed genetic and/or contact investigation data to develop a training set of probable transmission events, we build a model to estimate the relative transmission probability for all case-pairs from demographic, spatial and clinical data. Our method is based on naive Bayes, a machine learning classification algorithm which uses the observed frequencies in the training dataset to estimate the probability that a pair is linked given a set of covariates. RESULTS In simulations, we find that the probabilities estimated using genetic distance between cases to define training transmission events are able to distinguish between truly linked and unlinked pairs with high accuracy (area under the receiver operating curve value of 95%). Additionally, only a subset of the cases, 10-50% depending on sample size, need to have detailed genetic data for our method to perform well. We show how these probabilities can be used to estimate the average effective reproductive number and apply our method to a tuberculosis outbreak in Hamburg, Germany. CONCLUSIONS Our method is a novel way to infer transmission dynamics in any dataset when only a subset of cases has rich contact investigation and/or genetic data.