title: Gadolinium contrast agents for CNS imaging: current concepts and clinical evidence.

text: SUMMARY The aim of this article was to review the properties of the various gadolinium-based contrast agents used for CNS imaging along with the clinical evidence and published data that highlight the impact these different properties can have on diagnostic performance. In addition, approaches to optimizing image acquisition that take into account the different properties of specific gadolinium-based contrast agents and an extensive review of the safety profiles of the various agents are presented.


Effectively Engaging Geriatric Patients via Teledermatology.


title: Comparative study of peritoneal adhesions after intraperitoneal implantation in rats of meshes of polypropylene versus polypropylene/polyglecaprone versus polyester/porcine collagen.

text: PURPOSE To Compare the extent and intensity of adhesions formed between the intra-abdominal organs and the intraperitoneal implants of polypropylene mesh versus polypropylene/polyglecaprone versus polyester/porcine collagen used for correction of abdominal wall defect in rats. METHODS After the defect in the abdominal wall, thirty Wistar rats were placed in three groups (ten animals each) for intraperitoneal mesh implant: polypropylene group, polypropylene/polyglecaprone group, and polyester/porcine collagen group. The macroscopic evaluation of the extent and intensity of adhesions was performed 21 days after the implant. RESULTS The polypropylene group had a higher statistically significant impairment due to visceral adhesions (p value = 0.002) and a higher degree of intense adherence in relation to polypropylene/polyglecaprone and polyester/porcine collagen groups (p value<0.001). The polyester/porcine collagen group showed more intense adhesions than the polypropylene/polyglecaprone group (p value=0.035). CONCLUSIONS The intraperitoneal implantation of polypropylene meshes to correct defects of the abdominal wall caused the appearance of extensive and firm adhesions to intra-abdominal structures. The use of polypropylene/polyglecaprone or polyester/porcine collagen tissue-separating meshes reduces the number and degree of adhesions formed.


title: A scoping review of the use of Twitter for public health research

text: Public health practitioners and researchers have used traditional medical databases to study and understand public health for a long time. Recently, social media data, particularly Twitter, has seen some use for public health purposes. Every large technological development in history has had an impact on the behaviour of society. The advent of the internet and social media is no different. Social media creates public streams of communication, and scientists are starting to understand that such data can provide some level of access into the people's opinions and situations. As such, this paper aims to review and synthesize the literature on Twitter applications for public health, highlighting current research and products in practice. A scoping review methodology was employed and four leading health, computer science and cross-disciplinary databases were searched. A total of 755 articles were retreived, 92 of which met the criteria for review. From the reviewed literature, six domains for the application of Twitter to public health were identified: (i) Surveillance; (ii) Event Detection; (iii) Pharmacovigilance; (iv) Forecasting; (v) Disease Tracking; and (vi) Geographic Identification. From our review, we were able to obtain a clear picture of the use of Twitter for public health. We gained insights into interesting observations such as how the popularity of different domains changed with time, the diseases and conditions studied and the different approaches to understanding each disease, which algorithms and techniques were popular with each domain, and more.


title: Structure-function analyses of a stereotypic rheumatoid factor unravel the structural basis for germline-encoded antibody autoreactivity.

text: Rheumatoid factors (RFs) are autoantibodies against the fragment-crystallizable (Fc) region of IgG. In individuals with hematological diseases such as cryoglobulinemia and certain B cell lymphoma forms, the RFs derived from specific heavy- and light-chain germline pairs, so-called "stereotypic RFs," are frequently produced in copious amounts and form immune complexes with IgG in serum. Of note, many structural details of the antigen recognition mechanisms in RFs are unclear. Here we report the crystal structure of the RF YES8c derived from the IGHV1-69/IGKV3-20 germline pair, the most common of the stereotypic RFs, in complex with human IgG1-Fc at 2.8 Å resolution. We observed that YES8c binds to the CH2-CH3 elbow in the canonical antigen-binding manner involving a large antigen-antibody interface. On the basis of this observation, combined with mutational analyses, we propose a recognition mechanism common to IGHV1-69/IGKV3-20 RFs: (1) the interaction of the Leu432-His435 region of Fc enables the highly variable complementarity-determining region (CDR)-H3 to participate in the binding, (2) the hydrophobic tip in the CDR-H2 typical of IGHV1-69 antibodies recognizes the hydrophobic patch on Fc, and (3) the interaction of the highly conserved RF light chain with Fc is important for RF activity. These features may determine the putative epitope common to the IGHV1-69/IGKV3-20 RFs. We also showed that some mutations in the binding site of RF increase the affinity to Fc, which may aggravate hematological diseases. Our findings unravel the structural basis for germline-encoded antibody autoreactivity.


title: No evidence of coronavirus infection by reverse transcriptase-PCR in bats in Belgium.

text: No coronavirus was detected by PCR in lung and intestine samples of 100 bats, mostly common pipistrelles (Pipistrellus pipistrellus), collected dead between 2008 and 2013 for rabies surveillance in Belgium. The negative results contrast with the high prevalence of coronaviruses detected in fecal pellets from live-captured bats in some European countries.


title: [Treatment strategies for colorectal cancer patients in tumor hospitals under the background of corona virus disease 2019].

text: In December 2019, a new outbreak of corona virus disease 2019 began to occur. Its pathogen is 2019-nCoV, which has the characteristics of strong infectivity and general susceptibility. The current situation of prevention and control of new coronavirus pneumonia is severe. In this context, as front-line medical workers bearing important responsibilities and pressure, while through strict management strategy, we can minimize the risk of infection exposure. By summarizing the research progress and guidelines in recent years in the fields of colorectal cancer disease screening, treatment strategies (including early colorectal cancer, locally advanced colorectal cancer, obstructive colorectal cancer, metastatic colorectal cancer and the treatment of patients after neoadjuvant therapy), the choice of medication and time limit for adjuvant therapy, the protective measures for patients undergoing emergency surgery, the re-examination of postoperative patients and the protection of medical staff, etc., authors improve treatment strategies in order to provide more choices for patients to obtain the best treatment under the severe epidemic situation of new coronavirus pneumonia. Meanwhile we hope that it can also provide more timely treatment modeling schemes for colleagues.


title: Ester-to-amide rearrangement of ethanolamine-derived prodrugs of sobetirome with increased blood-brain barrier penetration.

text: Current therapeutic options for treating demyelinating disorders such as multiple sclerosis (MS) do not stimulate myelin repair, thus creating a clinical need for therapeutic agents that address axonal remyelination. Thyroid hormone is known to play an important role in promoting developmental myelination and repair, and CNS permeable thyromimetic agents could offer an increased therapeutic index compared to endogenous thyroid hormone. Sobetirome is a clinical stage thyromimetic that has been shown to have promising activity in preclinical models related to MS and X-linked adrenoleukodystrophy (X-ALD), a genetic disease that involves demyelination. Here we report a new series of sobetirome prodrugs containing ethanolamine-based promoieties that were found to undergo an intramolecular O,N acyl migration to form the pharmacologically relevant amide species. Several of these systemically administered prodrugs deliver more sobetirome to the brain compared to unmodified sobetirome. Pharmacokinetic properties of the parent drug sobetirome and amidoalcohol prodrug 3 are described and prodrug 3 was found to be more potent than sobetirome in target engagement in the brain from systemic dosing.


title: Analysis of COVID-19 under-reporting in Brazil.

text: OBJECTIVE To estimate the reporting rates of coronavirus disease 2019 (COVID-19) cases for Brazil as a whole and states. METHODS We estimated the actual number of COVID-19 cases using the reported number of deaths in Brazil and each state, and the expected case-fatality ratio from the World Health Organization. Brazil's expected case-fatality ratio was also adjusted by the population's age pyramid. Therefore, the notification rate can be defined as the number of confirmed cases (notified by the Ministry of Health) divided by the number of expected cases (estimated from the number of deaths). RESULTS The reporting rate for COVID-19 in Brazil was estimated at 9.2% (95%CI 8.8% - 9.5%), with all the states presenting rates below 30%. São Paulo and Rio de Janeiro, the most populated states in Brazil, showed small reporting rates (8.9% and 7.2%, respectively). The highest reporting rate occurred in Roraima (31.7%) and the lowest in Paraiba (3.4%). CONCLUSION The results indicated that the reporting of confirmed cases in Brazil is much lower as compared to other countries we analyzed. Therefore, decision-makers, including the government, fail to know the actual dimension of the pandemic, which may interfere with the determination of control measures.


title: Technique of traction-free nerve-sparing robotic prostatectomy: delicate tissue handling by real-time penile oxygen monitoring.

text: It is postulated that intraoperative injury to the cavernosal nerves results in hemodynamic and histologic changes within the penis, which manifest clinically as ED. We hypothesize that non-neuronal cause, such as vascular insults due to intraoperative tissue handling, may also have a minor but definite role in penile ischemia and consequent postoperative sexual dysfunction. Between May 2008 and July 2008, 64 patients were enrolled in the study (group 1). Following sterilization, the Odissey Tissue Oximeter probe was placed on the shaft of the penis, 2 cm from its base. The patient underwent continuous penile tissue saturation monitoring. Surgical dissection was altered whenever the oxygen saturation alarm went off until it was restored to 85%. In addition, 192 patients, matched for age, preoperative prostate-specific antigen, clinical stage, baseline sexual function, Charlson comorbidity index and nerve-sparing status operated between October 2007 and July 2008, formed the control group (group 2). These patients did not have any intraoperative tissue oxygenation monitoring. Opening of the endopelvic fascia and steps of nerve sparing were associated with significant drops in oxygen levels, especially if done using torque. Drop in oxygen levels were also noted whenever excessive traction was applied on the Foley catheter, seminal vesicles or prostate during apical dissection. We deliberately modified our surgical steps to make surgery more traction free. A significantly higher percentage of group 1 patients with bilateral nerve sparing had no ED compared with group 2 patients at 6 weeks (24.5% vs 10.4%; P=0.014) and 52 weeks (83.7% vs 68%; P=0.029). Overall, 93.9% of patients in study group had Sexual Health Inventory for Men (SHIM) score of 17 (mild to no ED) at 1 year compared with 78.4% of patients in the control group. We demonstrated that avoidance of ischemic stress, aided by intraoperative penile oxygenation monitoring, may help surgeons improve their technique and thus functional outcomes in patients.


title: Variation in Normal Ear Temperature.

text: BACKGROUND Variation in baseline ear temperature, taken in the unadjusted mode, has yet to be established in different age groups. Because normal body temperatures show large variations, the same may be expected for increased temperatures in fever. The aims were to study variations in normothermic body temperatures measured with an ear thermometer and to determine differences between actual and perceived body temperature during a febrile episode (referred to as difftemp) in apparently healthy children and adults. METHODS Ear temperature was measured once in 2,006 individuals (61.7% females): 683 children aged 2 and 4 years, 492 adolescents aged 10-18 years, 685 adults aged 19-65 years and 146 elderly aged 66-89 years. Difftemp was estimated as the difference between the individual's ear body temperature, measured in the present study, and the respondent's reported temperature when feverish. RESULTS Mean ear temperature was 36.4 ± 0.6°C overall and in the child and adult groups. In adolescents, it was 36.5 ± 0.5°C, and in elderly, 36.1 ± 0.5°C. Temperature in men was 36.3 ± 0.6°C, and in women, 36.5 ± 0.5°C. Difftemp was 1.1 ± 0.7°C in adolescents, 1.5 ± 0.7°C in children and adults, and 1.6 ± 0.7°C in those >65 years. CONCLUSIONS Ear body temperature is lower than traditionally reported and differs with age and sex. An individual difftemp of 1.0-1.5°C along with malaise might indicate fever.


title: Assessment of the FDA Risk Evaluation and Mitigation Strategy for Transmucosal Immediate-Release Fentanyl Products.

text: Importance Transmucosal immediate-release fentanyls (TIRFs), indicated solely for breakthrough cancer pain in opioid-tolerant patients, are subject to a US Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy (REMS) to prevent them from being prescribed inappropriately. Objectives To evaluate knowledge assessments of pharmacists, prescribers, and patients regarding appropriate TIRF use; to describe sponsor assessments, based on claims data, of whether the REMS program was meeting its goals; and to characterize how the FDA responded to REMS assessments. Design, Setting, and Participants Qualitative analysis of 4877 pages of FDA documents obtained through a Freedom of Information Act request, including 6 annual REMS assessment reports (2012-2017), FDA evaluations of these reports, and FDA-sponsor correspondence about safety issues. Exposure A REMS program to reduce the risk of adverse outcomes, including misuse, abuse, addiction, and overdose, arising from use of TIRFs. Main Outcomes and Measures (1) Knowledge assessments of pharmacists, prescribers, and patients; (2) survey and claims-based prescribing assessments; (3) FDA and TIRF sponsor communications; (4) modifications to the REMS program; and (5) disenrollment of noncompliant prescribers. Results Twelve months after initiation of the program, 24 of 302 pharmacists (7.9%), 35 of 302 prescribers (11.6%), and 5 of 192 patients (2.6%) incorrectly reported that TIRFs can be prescribed to opioid-nontolerant patients, with similar levels of misunderstanding maintained in the subsequent reports. At 60 months, product-specific analyses of claims data indicated that between 34.6% and 55.4% of patients prescribed TIRFs were opioid-nontolerant. In the 48-month survey, 106 of 310 prescribers (34.2%) reported prescribing TIRFs for opioid-tolerant patients with chronic, noncancer pain; at 60 months, 54 of 302 prescribers (18.4%) and 148 of 310 patients (47.7%) erroneously reported that TIRFs were FDA-approved for such use. Over the 60-month period examined, there were few substantive changes made to the REMS to address evidence of high rates of off-label TIRF use, and, although the REMS program had a noncompliance plan, there was no report of prescribers being disenrolled for inappropriate prescribing. Conclusions and Relevance In this review of FDA documents pertaining to the TIRF REMS, surveys of pharmacists, prescribers, and patients reflected generally high levels of knowledge regarding proper TIRF prescribing, yet some survey items as well as claims-based analyses indicated substantial rates of inappropriate TIRF use. Despite these findings, the FDA did not require substantive changes to the program.


title: Molecular characterization of pig epidemic diarrhoea viruses isolated in Japan from 2013 to 2014.

text: Since October 2013, approximately 1000 outbreaks of porcine epidemic diarrhoea (PED) have occurred, spanning almost all prefectures of Japan, after a period of seven years without a reported case. In order to consider occurrence factor of PED outbreaks, we determined the whole-genome sequences of 38 PED virus (PEDV) strains from diarrheal samples collected at swine farms in 18 prefectures between 2013 and 2014 using next-generation sequencing technology. Using these data, we investigated genetic variation among the recent Japanese PEDV strains and the genetic relationships between these strains and global PEDV strains isolated recently from multiple swine-industrial countries. Eleven out of 38 PEDV strains were isolated successfully on Vero cells with trypsin treatment and subjected to genome sequence analysis. In a comparative genome analysis, we detected two novel PEDV variants, TTR-2/JPN/2014 and MYG-1/JPN/2014, with large deletions in the spike and ORF3 genes, respectively. A phylogenetic analysis based on the spike gene showed that the 38 Japanese PEDV strains were classified into two PEDV types: the North American type with high virulence (n=34) and the INDEL type (n=4). In addition, the recent Japanese PEDV isolates had a close relationship to global PEDV strains isolated in recent years than to the classical PEDV strains detected in Japan the past decades ago. Moreover, the phylogenetic dendrogram of the complete genomes also indicated that the 38 Japanese PEDV strains, including the two novel PEDV variants discovered in this study, are closely related to the PEDV strains that were widespread in the United States and Korea in 2013-2014. These findings suggest that the re-emergence of PED outbreaks since the last reported case in 2006 was caused by the introduction of recent PEDV strains to Japan from overseas.


title: Novel wearable and contactless monitoring devices to identify deteriorating patients in the clinical setting: a systematic review protocol.

text: BACKGROUND With technological advances, there has been increasing interest in developing contactless and/or non-invasive wearable technologies that continuously monitor vital signs in the clinical setting, and in particular in the deteriorating patient. These devices as of yet have not been well validated in the clinical setting in the clinical ranges observed in a critically unwell patient. We will perform a systematic review of all novel wearable and contactless devices in the clinical setting with focus on degree of novelty and the range of vital signs captured. METHODS Ovid MEDLINE including Epub Ahead of Print and In-Process & Other Non-Indexed Citations, Ovid Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL) Health Technology Assessment (HTA) database (Ovid), CINAHL with Full Text, searches of the grey literature, cited references of eligible studies through Web of Science, and reference lists of eligible studies will be searched. Outcomes of interest will include the quality of studies in relation to reporting guidelines, limitations of non-invasive technology, and application in different clinical populations. We will perform a qualitative assessment of the novelty of the device and discuss its validation in deteriorating patients. DISCUSSION While novel monitoring devices are often proposed as a solution to problems with infection, discomfort, and frequency of monitoring in the clinical setting it has not yet been established which devices have been validated in clinical settings in the pathological ranges of vital signs that reflect patient deterioration. It is equally unclear what additional value these devices might provide. This systematic review will synthesize published data regarding devices that have been tested and validated in patients AND in a clinical setting AND in reference ranges that reflect severe illness. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019130091.


Case records of the Massachusetts General Hospital. Case 31-2012. An 18-year-old man with blurred vision, dysarthria, and ataxia.


Canadian Public Health Laboratory Network Statement on Point-of-Care Serology Testing in COVID-19.


title: A Prospective One-Year Microbiologic Survey of Combined Pneumonia and Respiratory Failure.

text: BACKGROUND Pneumonia and respiratory failure are common problems in the intensive care unit (ICU) setting, often occurring together. The relative prevalence of pneumonia types (community acquired, hospital acquired, ventilator associated) and causative pathogens is not well described in patients with respiratory failure. METHODS This was a prospective observational cohort study conducted in the medical ICU (34 beds) of Barnes-Jewish Hospital, an academic referral center of 1,300 beds from January 2016-December 2016. All patients who were prospectively adjudicated to have respiratory failure and pneumonia (RFP) regardless of pneumonia type were classified into one of four microbiologic categories: pathogen negative, antibiotic-susceptible pathogen (according to ceftriaxone susceptibility), antibiotic-resistant pathogen, and viruses. The primary outcomes assessed were the hospital mortality rate and inappropriate initial antibiotic therapy (IIAT) for non-viral pathogens. RESULTS Among 364 consecutive patients with RFP, 63 (17.3%) had organisms that were antibiotic susceptible, 104 (28.6%) had antibiotic-resistant organisms, 118 (32.4%) were pathogen negative, and 79 (21.7%) had viral infections. For these categories, IIAT occurred in 3.2%, 21.2%, 0.8%, and 0, respectively (p < 0.001). Vasopressor-requiring shock was present in 61.9%, 72.1%, 68.6%, and 67.1%, respectively (p = 0.585), and the hospital mortality rates were 27.0%, 48.1%, 31.4%, and 36.7%, respectively (p = 0.020). Multivariable logistic regression analysis identified IIAT as an independent predictor of in-hospital death (adjusted odds ratio 5.28; 95% confidence interval 2.72-10.22; p = 0.012). Male gender, increasing Acute Physiology and Chronic Health Evaluation (APACHE) II scores, greater age, and the presence of shock also predicted death. CONCLUSIONS Microbiologic categorization of patients with RFP suggests that antibiotic-resistant pathogens and viruses are associated with the highest mortality rates. Vasopressor-requiring shock was common regardless of the microbiologic categorization of RFP. Future development and use of rapid diagnostics and novel therapeutics targeting specific RFP pathogens may allow more timely administration of appropriate antimicrobial therapy and enhance antibiotic stewardship practices.


Pediatric inflammatory syndrome temporally related to covid-19.


title: Adenoviruses of canine and human origins in stool samples from free-living pampas foxes (Lycalopex gymnocercus) and crab-eating foxes (Cerdocyon thous) in São Francisco de Paula, Rio dos Sinos basin.

text: The spread of enteric viruses of domestic animals and human beings to wild species can be facilitated by the resistance of these viruses on the environment and their ability to be transmitted by water and contaminated food. The health status of the populations of pampas foxes Lycalopex gymnocercus) and crab-eating foxes (Cerdocyon thous) is largely unknown and the landscapes occupied by these animals in southern Brazil have been threatened by human occupation and expansion of agriculture. In this work, the search of genomes of human and canine adenoviruses in feces from these wild carnivores was used to track the dissemination of domestic animals and human pathogens to the free-living populations in a wildlife reserve located in southern Brazil. This was performed by virus-specific differential real-time polymerase chain reactions (qPCR) on stool specimens, avoiding capture and additional stress to the animals. Genus-specific conventional reverse-transcriptase PCR (RT-PCR) was complementarily performed aiming the detection of enteroviruses (EV) and rotaviruses (RV) on these same samples. HAdV genomes were found on 14 out of the 17 (82.35%) stool samples analysed, whereas CAV was found co-infecting 5 of these samples. RV genomes were detected on 7 of the 17 samples (41.18%) and all samples were negative for EV. The results point to the dispersion of HAdV and RV at a high rate to these species of South American wild carnivores, which can be an effect of growing anthropisation of the habitat of these animals.


title: The effects of sensorimotor training on knee proprioception and function for patients with knee osteoarthritis: a preliminary report.

text: OBJECTIVE To investigate the effects of a sensorimotor training programme in osteoarthritic patients. DESIGN Randomized, single-blind, controlled trial. SETTING Kinesiology laboratory at School of Physical Therapy. PARTICIPANTS A total of 60 patients were randomly assigned to the training group and the control group. Only 29 patients (training group, 15; control group, 14) completed the study. INTERVENTION The training group underwent a sensorimotor training programme using a sling suspension system complemented by a routine physical therapy. The control group underwent a routine physical therapy. MAIN MEASURES Active joint repositioning, functional testings, and self-reported function with the Western Ontario & McMaster Universities Arthritis Index before and after the eight-week intervention. RESULTS There were significant differences between the two groups with respect to the improvement in proprioception as measured by active joint repositioning (the changes in the absolute error were 1.9+/- 1.7 degrees , training group versus 0.1 +/- 2.8 degrees , control group (P<0.05), and in self-reported functional difficulty (33.2 +/-35.1, training group versus 8.0+/- 10.2, control group; P<0.05)). There was no significant difference between the two groups in other outcomes. CONCLUSION A sensorimotor training using a sling suspension system improved the patients' proprioception in the knee joints and their self-reported function. Thus, these exercises may serve as an exercise programme for patients with knee osteoarthritis.


title: Management of the Open Abdomen after Liver Transplantation.

text: INTRODUCTION The optimal management of the open abdomen (OA) after liver transplantation (LT) is unclear. The negative pressure wound therapy (NPWT) has been shown to be safe and can increase the chance for early fascial closure in trauma or septic patients. However, little data are available on the specific setting of LT. We aimed to report our experience of OA after LT, marked by the recent use of NPWT. METHODS All patients with postponed wall closure after LT, from 2002 to 2014, in a single institution were included and retrospectively analyzed. Our management of OA after LT has shifted from skin-only closure (SOC) followed by abdominal wall reconstruction at a distance to the use of NPWT with early fascial closure. RESULTS Of the 1559 LTs performed during the study period, immediate abdominal wall closure at the end of transplantation could not be achieved in 46 (2.9%) patients. Of them, SOC was performed in 22 (47.8%) patients, whereas vacuum-assisted closure (VAC) therapy was used in 24 (52.1%) patients. The comprehensive complication indexes (CCI) were similar [CCI: 66 (0-100) in the SOC group vs. 56 (0-100) in the VAC group; p = 0.55]. No evisceration or fistula occurred in both groups. One (4.2%) postoperative bleeding case was reported in the VAC group. Early fascial closure was achieved within a median of 5.5 days (1-12) for the 24 patients (100%) of the VAC group. In four of them, a biological mesh was necessary. Only nine patients (52.9%) of the survivors in the SOC group underwent abdominal reconstruction. CONCLUSION The NPWT in patients with OA after LT enables early fascial closure with limited morbidity provided a specific attention is given to the risk of bleeding. These results support the use of NPWT as the first option in OA patients after LT.


title: COMPUTED TOMOGRAPHIC FEATURES OF PHARYNGEAL NEOPLASIA IN 25 DOGS.

text: Computed tomography (CT) is commonly used to investigate head tumors in dogs, however little information is available for lesions of the pharyngeal area. The purpose of this multicentric, retrospective, cross-sectional study was to describe the CT findings in a sample of dogs with pathologically confirmed pharyngeal neoplasia and determine whether any CT features allowed differentiation of tumor type. Location of lesions, size and shape, margins, relationship with surrounding structures and vessels, attenuation characteristics and enhancement pattern, regional lymph node changes, and presence of metastasis were recorded by three observers (1 DECVDI). The effect of final diagnosis on each CT feature was tested. A total of 25 dogs were included: 15 with carcinomas, five sarcomas, four melanomas, and one lymphoma. The oropharynx and laryngopharynx were more frequently involved. Among tumor groups, lesions were of similar size, irregularly shaped, had ill-defined margins, and had moderate-to-marked heterogeneous contrast enhancement. Lysis of hyoid bones was recorded in two carcinomas and infiltration of the lingual artery occurred in one case. Marked medial retropharyngeal lymphoadenomegaly was recorded in 11 of 14 carcinomas, in all sarcomas and in two of four melanomas. The single lymphoma case showed ill-defined thickening of the oropharyngeal and laryngeal wall with retropharyngeal and mandibular lymphadenomegaly. Lung metastases were found in two of five sarcomas and two of four melanomas. Findings from the current study did not support the hypothesis that CT features could be used to predict pharyngeal tumor type in dogs. However, CT was helpful for determining mass extension, lymph node involvement, and distant metastatic spread.


title: Spontaneous Effort During Mechanical Ventilation: Maximal Injury With Less Positive End-Expiratory Pressure.

text: OBJECTIVES We recently described how spontaneous effort during mechanical ventilation can cause "pendelluft," that is, displacement of gas from nondependent (more recruited) lung to dependent (less recruited) lung during early inspiration. Such transfer depends on the coexistence of more recruited (source) liquid-like lung regions together with less recruited (target) solid-like lung regions. Pendelluft may improve gas exchange, but because of tidal recruitment, it may also contribute to injury. We hypothesize that higher positive end-expiratory pressure levels decrease the propensity to pendelluft and that with lower positive end-expiratory pressure levels, pendelluft is associated with improved gas exchange but increased tidal recruitment. DESIGN Crossover design. SETTING University animal research laboratory. SUBJECTS Anesthetized landrace pigs. INTERVENTIONS Surfactant depletion was achieved by saline lavage in anesthetized pigs, and ventilator-induced lung injury was produced by ventilation with high tidal volume and low positive end-expiratory pressure. Ventilation was continued in each of four conditions: positive end-expiratory pressure (low or optimized positive end-expiratory pressure after recruitment) and spontaneous breathing (present or absent). Tidal recruitment was assessed using dynamic CT and regional ventilation/perfusion using electric impedance tomography. Esophageal pressure was measured using an esophageal balloon manometer. MEASUREMENTS AND RESULTS Among the four conditions, spontaneous breathing at low positive end-expiratory pressure not only caused the largest degree of pendelluft, which was associated with improved ventilation/perfusion matching and oxygenation, but also generated the greatest tidal recruitment. At low positive end-expiratory pressure, paralysis worsened oxygenation but reduced tidal recruitment. Optimized positive end-expiratory pressure decreased the magnitude of spontaneous efforts (measured by esophageal pressure) despite using less sedation, from -5.6 ± 1.3 to -2.0 ± 0.7 cm H2O, while concomitantly reducing pendelluft and tidal recruitment. No pendelluft was observed in the absence of spontaneous effort. CONCLUSIONS Spontaneous effort at low positive end-expiratory pressure improved oxygenation but promoted tidal recruitment associated with pendelluft. Optimized positive end-expiratory pressure (set after lung recruitment) may reverse the harmful effects of spontaneous breathing by reducing inspiratory effort, pendelluft, and tidal recruitment.


title: Characterization and antiinflammatory properties of fractionated pyroligneous acid from palm kernel shell.

text: Pyroligneous acid (PA) obtained from slow pyrolysis of palm kernel shell (PKS) has high total phenolic contents and exhibits various biological activities including antioxidant, antibacterial and antifungal. In this study, PA obtained using slow pyrolysis method and fractionated using column chromatography was characterized (chemical and antioxidative properties) and investigated for its cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibition activities using the in vitro and in silico approaches. The F9 PA fraction exhibited highest total phenolic content of 181.75 ± 17.0 μg/mL. Fraction F21-25 showed ferric reducing antioxidant power (FRAP) (331.80 ± 4.60 mg TE/g) and IC50 of 18.56 ± 0.01 μg/mL towards COX-2 and 5.25 ± 0.03 μg/mL towards the 5-LOX enzymes, respectively. Molecular docking analysis suggested favourable binding energy for all chemical compounds present in fraction F21-25, notably 1-(2,4,6-trihydroxyphenyl)-2-pentanone, towards both COX-2 (- 6.9 kcal/mol) and 5-LOX (- 6.4 kcal/mol) enzymes. As a conclusion, PA from PKS has the potential to be used as an alternative antioxidant and antiinflammatory agents which is biodegradable and a more sustainable supply of raw materials.


title: CD147/EMMPRIN acts as a functional entry receptor for measles virus on epithelial cells.

text: Measles is a highly contagious human disease caused by measles virus (MeV) and remains the leading cause of death in children, particularly in developing countries. Wild-type MeV preferentially infects lymphocytes by using signaling lymphocytic activation molecule (SLAM), whose expression is restricted to hematopoietic cells, as a receptor. MeV also infects other epithelial and neuronal cells that do not express SLAM and causes pneumonia and diarrhea and, sometimes, serious symptoms such as measles encephalitis and subacute sclerosing panencephalitis. The discrepancy between the tissue tropism of MeV and the distribution of SLAM-positive cells suggests that there are unknown receptors other than SLAM for MeV. Here we identified CD147/EMMPRIN (extracellular matrix metalloproteinase inducer), a transmembrane glycoprotein, which acts as a receptor for MeV on epithelial cells. Furthermore, we found the incorporation of cyclophilin B (CypB), a cellular ligand for CD147, in MeV virions, and showed that inhibition of CypB incorporation significantly attenuated SLAM-independent infection on epithelial cells, while it had no effect on SLAM-dependent infection. To date, MeV infection was considered to be triggered by binding of its hemagglutinin (H) protein and cellular receptors. Our present study, however, indicates that MeV infection also occurs via CD147 and virion-associated CypB, independently of MeV H. Since CD147 is expressed in a variety of cells, including epithelial and neuronal cells, this molecule possibly functions as an entry receptor for MeV in SLAM-negative cells. This is the first report among members of the Mononegavirales that CD147 is used as a virus entry receptor via incorporated CypB in the virions.


title: Semen clusterin is a novel DC-SIGN ligand.

text: The C-type lectin receptor dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is an important player in the recognition of pathogens by dendritic cells. A plethora of pathogens including viruses, bacteria, parasites, and fungi are recognized by DC-SIGN through both mannose and fucose-containing glycans expressed on the pathogen surface. In this study, we identified semen clusterin as a novel DC-SIGN ligand. Semen clusterin, but not serum clusterin, expresses an extreme abundance of fucose-containing blood-type Ags such as Le(x) and Le(y), which are both excellent DC-SIGN ligands. These motifs enable semen clusterin to bind DC-SIGN with very high affinity (K(d) 76 nM) and abrogate the binding of HIV-1 to DC-SIGN. Depletion of clusterin from semen samples, however, did not completely prevent the ability of semen to inhibit the capture of HIV-1 by DC-SIGN, supporting that besides clusterin, semen contains other DC-SIGN ligands. Further studies are needed to characterize these ligands and define their contribution to the DC-SIGN-blocking activity mediated by semen. Clusterin is an enigmatic protein involved in a variety of physiologic and pathologic processes including inflammation, atherosclerosis, and cancer. Our results uncover an unexpected heterogeneity in the glycosylation pattern of clusterin and suggest that the expression of high concentrations of fucose-containing glycans enables semen clusterin to display a unique set of biological functions that might affect the early course of sexually transmitted infectious diseases.


Discussing non-beneficial treatment.


title: Improved polarization and energy density in boron nitride nanosheets/poly(vinylidene fluoride-chlorotrifluoroethylene) nanocomposite with trilayered architecture regulation.

text: Polymer film capacitor with high energy density has attracted great attention in past decades to accomplish the requirements of miniaturization and lightweight for electronics and energy storage system. The multi-layered nanocomposite exhibits an effective route for developing polymer film with large energy capability due to the advantage of each layer. Here, two sandwich constructions of boron nitride nanosheets (BNNSs)/poly(vinylidene fluoride-chlorotrifluoroethylene) (P(VDF-CTFE)) nanocomposite film were designed to investigate the effects of architecture regulation on energy storage performance,i.e., the nanocomposite serving as inner layer with pristine films as outer layers, in which the nanocomposite film delivers a strongly polarized behavior and the pristine polymer provides a high breakdown strength. The BNNSs were liquid exfoliated from boron nitride bulk assisted with fluoro hyperbranched copolymer that was adsorbed on the surface of nanosheetsviaCH-π non-covalent interactions. The presence of fluoro segments improves the compatibility between nanosheets and P(VDF-CTFE) matrix. The maximum polarization of 7.9 μC cm-2at 300 MV m-1is achieved in the tailored sandwich film, and the discharged energy density of 9.1 J cm-3is obtained in current nanocomposite, which benefits from the barrier effect between adjacent layers induced by the redistribution of electric field and emerging charge traps at the interfaces. This sandwich BNNSs/P(VDF-CTFE) nanocomposite provides an insight prospect for structural design with respect to the advanced application of polymer film capacitor.


title: Bactericidal/Permeability-Increasing Fold-Containing Family B Member 4 May Be Associated with NSAID-Induced Enteropathy.

text: BACKGROUND There is considerable individual variability in nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. AIM To identify the SNP that is most significantly involved with NSAID-induced enteropathy. METHODS One hundred fifty human subjects who were known to have a certain degree of loxoprofen- or celecoxib-induced small-intestinal damage from a previous study were enrolled. The subjects were divided into groups based on treatments and also on the increased number of small intestinal mucosal breaks. The candidate SNP was selected by an initial analysis of GWAS among the groups in various combinations. After the initial analysis, the gene including the specified SNP was analyzed in detail using GWAS and genotype imputation. RESULTS After analysis, 70 subjects receiving the loxoprofen treatment and 69 subjects receiving celecoxib treatment were determined to be eligible for the analysis. The minimum p value in GWAS was detected in the analysis of 16 cases with an increase of five or more mucosal breaks and 123 controls with zero to four mucosal breaks. In the GWAS, five SNPs in the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) gene showed the lowest p value (p = 2.69 × 10-7 with an odds ratio of 40.9). Of the five SNPs, four were nonsynonymous SNPs (rs2070325: V268I, rs2889732: T320N, rs11699009: F527L, rs11696307: T533I, and rs11696310: intronic). Furthermore, 23 SNPs in BPIFB4 detected by genotype imputation based on the GWAS data also showed suggestive associations (p < 1 × 10-6). CONCLUSION The results indicate that SNPs in BPIFB4 were associated with NSAID-induced small intestinal mucosal injury (UMIN: 000007936).


title: Evidence against implant-derived cobalt toxicity: case report and retrospective study of serum cobalt concentrations in an orthopedic implant population.

text: OBJECTIVES Cobalt (Co) exposure has been documented to result in increased erythropoiesis. To evaluate the potential for implant-derived Co toxicity, we examined the relationship between serum Co (sCo) and erythrocyte counts (ERY) in a metal-containing total-hip arthroplasty implant population. METHODS Retrospective review of sCo concentrations identified 77 patients with concomitant ERY. Statistical analysis was performed to determine if there was a significant difference in ERY for patients divided into clinically relevant sCo ranges. A single detailed case review of a patient with a loose mal-positioned acetabular component and significantly elevated sCo was also performed for symptoms thought to arise from Co toxicity. RESULTS Statistical difference in ERY was not observed between patients with significantly elevated (>10 ng/mL), elevated (4-10 ng/mL), modestly elevated (1.0-3.9 ng/mL), or normal (<1.0 ng/mL) sCo. While the detailed case report was unremarkable for any of the clinical symptoms previously reported to be associated with Co toxicity and no increase in ERY was observed, this patient's sCo was 84 ng/mL. CONCLUSIONS Increased erythropoiesis was not observed in patients with implant-derived increased sCo. Even with a sCo 100 × the upper-limit of normal, the patient presented did not have increased ERY nor exhibit any symptoms ascribed with Co toxicity.


title: Predictors for postoperative esophageal stricture after balloon-based radiofrequency ablation for early esophageal squamous neoplasia: a multicenter validation study.

text: BACKGROUND Endoscopic radiofrequency ablation (RFA) is a rapidly evolving therapeutic modality for early flat esophageal squamous cell neoplasms (ESCNs), but the risk factors for postoperative stricture have not been elucidated. The objective of this study was to identify and validate a predictor for post-RFA stenosis. METHODS We consecutively enrolled patients with flat-type 'large' (length no less than 3 cm extending no less than half the circumference of the esophagus), early ESCNs, treated with balloon-based RFA (12 J/cm(2)-clean-12 J/cm(2) regimen). The tumor and technical factors for postoperative stricture were investigated and we validated the results externally with a society-based multicenter cohort using the same ablation regimen. RESULTS A total of 51 patients were enrolled (30 in the development set and 21 in the validation set). The complete remission rate at 12 months was 93%, and the rates of perforation and postoperative stenosis were 0% and 17%, respectively. Patients with post-RFA stenosis had a significantly larger longitudinal tumor size (mean 115 versus 61 mm, p = 0.003). There were no significant differences in age, body mass index, tumor circumferential extension, pretreatment histological grade, treatment efficacy or size of balloon catheter between the groups with or without stenosis. The optimal cut-off value was set as 9 cm to predict post-RFA stenosis by receiver operating characteristic curve [area under curve (AUC) = 0.881], which was then confirmed to be a reliable predictor by multivariate analysis (odds ratio, 12.7, 95% confidence interval, 1.18-136.28, p = 0.03) and have a good predictive performance in the validation set (AUC = 0.876). CONCLUSIONS The most frequent adverse event of RFA was esophageal stenosis, for which the longitudinal tumor size was a significant predictive factor. Early intervention or prevention for stricture should be applied for those with long segment (⩾9 cm) ESCNs.


Total pathway to method validation.


Physical activity/inactivity and COVID-19.


title: An update on topical haemostatic agents in liver surgery: systematic review and meta analysis.

text: Mortality and morbidity in hepatic surgery are affected by blood loss and transfusion. Topical haemostatic agents (THA) are composed by a matrix and/or fibrin sealants, and their association known as "carrier-bound fibrin sealant" (CBFS): despite widely used for secondary haemostasis, the level of evidence remains low. To realize a meta-analysis on the results of CBFS on haemostasis and postoperative complications. Searches in PubMed, PubMed Central, Cochrane and Google Scholar using keywords: "topical_haemostasis" OR "haemostatic_agents" OR "sealant_patch" OR "fibrin_sealant" OR "collagen_sealant" AND "liver_surgery" OR "hepatic_surgery" OR "liver_transplantation". Randomized clinical trials, large retrospective cohort studies, case control studies evaluating THA on open/laparoscopic liver surgery and transplantation. From 1993 to 2016 were found 22 studies for qualitative synthesis and 13 for quantitative meta-analysis. The time to haemostasis was lower in the CBFS group (mean difference -2.33 min; P = 0.00001). The risk of receiving blood transfusion, developing collections and bile leak was not influenced by the use of CBFS (OR 0.75; P = 0.25), (OR 0.72; P = 0.52), (OR 0.74; P = 0.30) respectively. The use of CBFS in liver surgery significantly reduce the time to haemostasis, but does not decrease transfusion, postoperative collection and bile leak.


title: Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial.

text: IMPORTANCE Muscle-related statin intolerance is reported by 5% to 20% of patients. OBJECTIVE To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab. DESIGN, SETTING, AND PARTICIPANTS Two-stage randomized clinical trial including 511 adult patients with uncontrolled low-density lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover procedure with atorvastatin or placebo to identify patients having symptoms only with atorvastatin but not placebo. In phase B, after a 2-week washout, patients were randomized to ezetimibe or evolocumab for 24 weeks. INTERVENTIONS Phase A: atorvastatin (20 mg) vs placebo. Phase B: randomization 2:1 to subcutaneous evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily). MAIN OUTCOME AND MEASURES Coprimary end points were the mean percent change in LDL-C level from baseline to the mean of weeks 22 and 24 levels and from baseline to week 24 levels. RESULTS Of the 491 patients who entered phase A (mean age, 60.7 [SD, 10.2] years; 246 women [50.1%]; 170 with coronary heart disease [34.6%]; entry mean LDL-C level, 212.3 [SD, 67.9] mg/dL), muscle symptoms occurred in 209 of 491 (42.6%) while taking atorvastatin but not while taking placebo. Of these, 199 entered phase B, along with 19 who proceeded directly to phase B for elevated creatine kinase (N = 218, with 73 randomized to ezetimibe and 145 to evolocumab; entry mean LDL-C level, 219.9 [SD, 72] mg/dL). For the mean of weeks 22 and 24, LDL-C level with ezetimibe was 183.0 mg/dL; mean percent LDL-C change, -16.7% (95% CI, -20.5% to -12.9%), absolute change, -31.0 mg/dL and with evolocumab was 103.6 mg/dL; mean percent change, -54.5% (95% CI, -57.2% to -51.8%); absolute change, -106.8 mg/dL (P < .001). LDL-C level at week 24 with ezetimibe was 181.5 mg/dL; mean percent change, -16.7% (95% CI, -20.8% to -12.5%); absolute change, -31.2 mg/dL and with evolocumab was 104.1 mg/dL; mean percent change, -52.8% (95% CI, -55.8% to -49.8%); absolute change, -102.9 mg/dL (P < .001). For the mean of weeks 22 and 24, between-group difference in LDL-C was -37.8%; absolute difference, -75.8 mg/dL. For week 24, between-group difference in LDL-C was -36.1%; absolute difference, -71.7 mg/dL. Muscle symptoms were reported in 28.8% of ezetimibe-treated patients and 20.7% of evolocumab-treated patients (log-rank P = .17). Active study drug was stopped for muscle symptoms in 5 of 73 ezetimibe-treated patients (6.8%) and 1 of 145 evolocumab-treated patients (0.7%). CONCLUSIONS AND RELEVANCE Among patients with statin intolerance related to muscle-related adverse effects, the use of evolocumab compared with ezetimibe resulted in a significantly greater reduction in LDL-C levels after 24 weeks. Further studies are needed to assess long-term efficacy and safety. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01984424.


title: High-resolution genotyping of Campylobacter species by use of PCR and high-throughput mass spectrometry.

text: In this work we report on a high-throughput mass spectrometry-based technique for the rapid high-resolution identification of Campylobacter jejuni strain types. This method readily distinguishes C. jejuni from C. coli, has a resolving power comparable to that of multilocus sequence typing (MLST), is applicable to mixtures, and is highly automated. The strain typing approach is based on high-performance mass spectrometry, which "weighs" PCR amplicons with enough mass accuracy to unambiguously determine the base composition of each amplicon (i.e., the numbers of A's, G's, C's, and T's). Amplicons are derived from PCR primers which amplify short (<140-bp) regions of the housekeeping genes used by conventional MLST strategies. The results obtained with a challenge panel that comprised 25 strain types of C. jejuni and 25 strain types of C. coli are presented. These samples were parsed and resolved with demonstrated sensitivity down to 10 genomes/PCR from pure isolates.


Will antibody tests for the coronavirus really change everything?


The psychological impact of quarantine on coronavirus disease 2019 (COVID-19).


title: Bariatric surgical anatomy and mechanisms of action.

text: Because bariatric surgery is becoming increasingly common, gastroenterologists need to be familiar with the surgical and endoscopic anatomy of the operations in use today. This review focuses on the 4 most commonly performed bariatric operations in the United States: Roux-en-Y gastric bypass, adjustable gastric band, sleeve gastrectomy, and biliopancreatic diversion with duodenal switch. The anatomy and mechanism of action of each procedure is discussed and illustrated. Emphasis is placed on the endoscopic anatomy, with review of the commonly encountered complications. Emerging techniques and devices are reviewed.


Covid-19 may be exacerbated by right-to-left interatrial shunt.


Covid-19: trials of four potential treatments to generate "robust data" of what works.


title: Infectious disease outbreaks and increased complexity of care.

text: AIM This study examined the effects of healthcare-associated infectious disease outbreaks on nurses' work in a large acute care hospital in Ontario, Canada. BACKGROUND The incidence of healthcare-associated infections has increased. Previous research focuses on epidemiology, healthcare systems, and the economic burden of outbreaks. Few published studies focus on the impact of outbreaks on nurses' work in acute care facilities. INTRODUCTION Since the severe acute respiratory syndrome epidemic in 2003, combating infectious diseases has become a key issue. Hospitals have implemented measures related to healthcare-associated infections. However, nurses experience challenges in preventing, controlling, and contending with outbreaks. METHODS A retrospective exploratory case study approach was used. Data were collected over a 4-month period in 2012. The incidence rates of site-specific HAIs were analysed, and individual interviews were held with 23 bedside nurses and five nurse managers. FINDINGS Five themes emerged from the interviews: comparison of healthcare-associated infections outbreaks; the nature of nurses' work; impact of outbreaks on patient care; innovation and quality control in clinical practice; and increased and expanded IPAC measures. The incidence rates of methicillin-resistant Staphylococcus aureus, Clostridium difficile and vancomycin-resistant enterococci at the study site decreased, but remained above provincial benchmarks. Nurses experienced workload challenges, time pressures and psychological effects stemming from outbreaks and developed various innovations in response. Patient care was also affected. CONCLUSION Nurses' work has been impacted by healthcare-associated infectious disease outbreaks. Nursing workloads should be quantified to facilitate the development of guidelines for optimum nurse-patient ratio during outbreaks. IMPLICATIONS FOR NURSING AND/OR HEALTH POLICY A strong evidence-based policy framework is required to address healthcare-associated infectious disease outbreaks. Infection prevention and control guidelines and procedures should be established provincially and nationally. An interdisciplinary approach is essential for the creation of comprehensive and innovative strategies. Nursing research has increased understanding of the implications of infectious diseases in hospitals. Building on the literature, findings from this study can be used to influence policies on the care of patients who have secondary infections. Nurse-driven protocols are important and can lead to the creation of best practice guidelines that can be implemented across settings.


title: International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family.

text: Formyl peptide receptors (FPRs) are a small group of seven-transmembrane domain, G protein-coupled receptors that are expressed mainly by mammalian phagocytic leukocytes and are known to be important in host defense and inflammation. The three human FPRs (FPR1, FPR2/ALX, and FPR3) share significant sequence homology and are encoded by clustered genes. Collectively, these receptors bind an extraordinarily numerous and structurally diverse group of agonistic ligands, including N-formyl and nonformyl peptides of different composition, that chemoattract and activate phagocytes. N-formyl peptides, which are encoded in nature only by bacterial and mitochondrial genes and result from obligatory initiation of bacterial and mitochondrial protein synthesis with N-formylmethionine, is the only ligand class common to all three human receptors. Surprisingly, the endogenous anti-inflammatory peptide annexin 1 and its N-terminal fragments also bind human FPR1 and FPR2/ALX, and the anti-inflammatory eicosanoid lipoxin A4 is an agonist at FPR2/ALX. In comparison, fewer agonists have been identified for FPR3, the third member in this receptor family. Structural and functional studies of the FPRs have produced important information for understanding the general pharmacological principles governing all leukocyte chemoattractant receptors. This article aims to provide an overview of the discovery and pharmacological characterization of FPRs, to introduce an International Union of Basic and Clinical Pharmacology (IUPHAR)-recommended nomenclature, and to discuss unmet challenges, including the mechanisms used by these receptors to bind diverse ligands and mediate different biological functions.


title: Epidemic dynamics at the human-animal interface.

text: Few infectious diseases are entirely human-specific: Most human pathogens also circulate in animals or else originated in nonhuman hosts. Influenza, plague, and trypanosomiasis are classic examples of zoonotic infections that transmit from animals to humans. The multihost ecology of zoonoses leads to complex dynamics, and analytical tools, such as mathematical modeling, are vital to the development of effective control policies and research agendas. Much attention has focused on modeling pathogens with simpler life cycles and immediate global urgency, such as influenza and severe acute respiratory syndrome. Meanwhile, vector-transmitted, chronic, and protozoan infections have been neglected, as have crucial processes such as cross-species transmission. Progress in understanding and combating zoonoses requires a new generation of models that addresses a broader set of pathogen life histories and integrates across host species and scientific disciplines.


title: PREVENTion of a parastomal hernia with a prosthetic mesh in patients undergoing permanent end-colostomy; the PREVENT-trial: study protocol for a multicenter randomized controlled trial.

text: BACKGROUND Parastomal hernia is a common complication of a colostomy. Ultimately, one-third of patients with a parastomal hernia will need surgical correction due to frequent leakage or life-threatening bowel obstruction or strangulation. However, treatment remains a challenge resulting in high recurrence rates. Two single center trials demonstrated that the frequency of parastomal hernias decreases by prophylactic placement of a mesh around the stoma at the time of formation. Unfortunately, both studies were small-sized, single-center studies and with these small numbers less common complications could be missed which were the reasons to initiate a prospective randomized multicenter trial to determine if a retromuscular, preperitoneal mesh at the stoma site prevents parastomal hernia and does not cause unacceptable complications. METHODS One hundred and fifty patients undergoing open procedure, elective formation of a permanent end-colostomy will be randomized into two groups. In the intervention group an end-colostomy is created with placement of a preperitioneal, retromuscular lightweight monofilament polypropylene mesh, and compared to a group with a traditional stoma without mesh. Patients will be recruited from 14 teaching hospitals in the Netherlands during a 2-year period. Primary endpoint is the incidence of parastomal hernia. Secondary endpoints are stoma complications, cost-effectiveness, and quality of life. Follow-up will be performed at 3 weeks, 3 months and at 1, 2, and 5 years. To find a difference of 20% with a power of 90%, a total number of 134 patients must be included. All results will be reported according to the CONSORT 2010 statement. DISCUSSION The PREVENT-trial is a multicenter randomized controlled trial powered to determine whether prophylactic placement of a polypropylene mesh decreases the incidence of a parastomal hernia versus the traditional stoma formation without a mesh. TRIAL REGISTRATION The PREVENT-trial is registered at: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2018.


title: A novel low-cost simulator for laparoscopic inguinal hernia repair.

text: Despite the advantages of laparoscopic inguinal hernia repair over the open approach in selected situations, laparoscopic inguinal hernia repair (LIHR) remains a challenge to teach and learn. The purpose of this study was to develop and validate a low-cost adaptable simulator for evaluation and training of LIHR. McGill Laparoscopic Inguinal Hernia Simulator (MLIHS) is a physical simulator that accurately represents inguinal anatomy. MLIHS permits to perform both transabdominal pre-peritoneal (TAPP) and totally extraperitoneal (TEP) repairs. Six experienced surgeons performed TAPP repairs using MLIHS. They were surveyed to establish face validity, and were scored using a previously validated global rating scale (maximum score = 25). Experienced surgeons considered MLIHS a useful tool for evaluating and training of LIHR. The mean (SD) global rating scores were 24.0 (± 0.6). The experienced surgeons considered MLIHS very useful for training and assessment. MLIHS is a valuable and affordable tool for training and evaluation of LIHR.


title: Proximal to distal approach in the treatment of tandem occlusions causing an acute stroke.

text: INTRODUCTION A tandem occlusion is a rare presentation of acute stroke that involves an occlusion of the internal carotid artery at the bifurcation with an intracranial middle cerebral artery occlusion. This study describes the experience at our institution in treating tandem occlusions with a proximal to distal approach in the acute stroke setting. METHODS A retrospective review of acute strokes caused by tandem occlusions requiring thrombectomy were performed. RESULTS 16 cases were identified with a mean National Institutes of Health Stroke Scale score at presentation of 13.1 ± 3.9. The proximal occlusion was crossed initially with a microwire in all cases. All carotid occlusions were treated with stenting, and intracranial vessel thrombectomy was performed with a variety of devices. Procedure related complications occurred in two (12.5%) patients. Eight patients (50%) achieved a good outcome (modified Rankin Scale score of 0-2). CONCLUSIONS A tandem occlusion of the carotid artery at the bifurcation with a concomitant intracranial occlusion is a relatively rare and complex presentation of acute stroke. We have found that addressing the proximal lesion first and covering it with a stent prior to performing distal thrombectomy appears to be a safe and effective option in the treatment algorithm.


title: Acquisition of sensorimotor fMRI under general anaesthesia: Assessment of feasibility, the BOLD response and clinical utility.

text: We evaluated whether task-related fMRI (functional magnetic resonance imaging) BOLD (blood oxygenation level dependent) activation could be acquired under conventional anaesthesia at a depth enabling neurosurgery in five patients with supratentorial gliomas. Within a 1.5 T MRI operating room immediately prior to neurosurgery, a passive finger flexion sensorimotor paradigm was performed on each hand with the patients awake, and then immediately after the induction and maintenance of combined sevoflurane and propofol general anaesthesia. The depth of surgical anaesthesia was measured and confirmed with an EEG-derived technique, the Bispectral Index (BIS). The magnitude of the task-related BOLD response and BOLD sensitivity under anaesthesia were determined. The fMRI data were assessed by three fMRI expert observers who rated each activation map for somatotopy and usefulness for radiological neurosurgical guidance. The mean magnitudes of the task-related BOLD response under a BIS measured depth of surgical general anaesthesia were 25% (tumour affected hemisphere) and 22% (tumour free hemisphere) of the respective awake values. BOLD sensitivity under anaesthesia ranged from 7% to 83% compared to the awake state. Despite these reductions, somatotopic BOLD activation was observed in the sensorimotor cortex in all ten data acquisitions surpassing statistical thresholds of at least p < 0.001uncorr. All ten fMRI activation datasets were scored to be useful for radiological neurosurgical guidance. Passive task-related sensorimotor fMRI acquired in neurosurgical patients under multi-pharmacological general anaesthesia is reproducible and yields clinically useful activation maps. These results demonstrate the feasibility of the technique and its potential value if applied intra-operatively. Additionally these methods may enable fMRI investigations in patients unable to perform or lie still for awake paradigms, such as young children, claustrophobic patients and those with movement disorders.


title: [2019 novel coronavirus, angiotensin converting enzyme 2 and cardiovascular drugs].

text: 2019年底，武汉出现了由2019新型冠状病毒（2019-nCoV）引发的新型冠状病毒肺炎（COVID-19）。该疫情在短时间内迅速蔓延，严重威胁着公共卫生安全，目前，COVID-19尚无有效的治疗手段。血管紧张素转化酶2（ACE2）作为受体介导2019-nCoV进入细胞，是目前最有可能防治COVID-19的靶点之一。中老年人是COVID-19的易感人群，多伴有基础疾病，且大部分为心血管疾病，因此这部分人更容易发展为重症和危重症，造成严重的临床后果。ACE2是肾素-血管紧张素系统重要的组成部分，以此系统为靶点的ACE抑制剂和血管紧张素受体阻断剂等药物，是目前临床治疗高血压、心肌重构和心力衰竭等心血管疾病的最主要的药物之一。本文系统的介绍了COVID-19以及肾素-血管紧张素系统相关药物及其临床应用，并且分析了肾素-血管紧张素系统相关药物在COVID-19防治中的价值，以及并发心血管疾病的COVID-19患者用药方面需要注意的问题。.


title: Uterine artery ligation at the beginning of total laparoscopic hysterectomy reduces total blood loss and operation duration.

text: The purpose of this study was to compare the feasibility, blood loss, duration of surgery and complications between patients in whom both uterine arteries were ligated by surgical clips and cut using a 5-mm ligature at the beginning of total laparoscopic hysterectomy (TLH) and patients in whom uterine arteries were not ligated at the beginning of TLH. In our prospective study, a total of 60 women underwent TLH. Uterine artery ligation (UAL) was done at the beginning of the procedure. Women were divided into TLH + UAL (n = 30) and TLH (n = 30) groups. In TLH group, TLH was done without ligating the uterine arteries at the beginning of the procedure. In TLH + UAL group, TLH was done with ligation of both uterine arteries at the beginning of the procedure. The mean operating time was longer for the TLH group (99.16 ± 7.01) than TLH + UAL group (63.27 ± 7.16). The median total blood loss was higher in TLH group (109.38 ± 33.03 mL) than TLH + UAL group (47.50 ± 8.12 mL). UAL at the beginning of TLH is a technically feasible procedure. It reduces the total blood loss and decreases the time taken for the procedure and length of hospital stay.


title: Respiratory viruses associated with community-acquired pneumonia in children: matched case-control study.

text: BACKGROUND Community-acquired pneumonia (CAP) is the leading cause of death in children worldwide and a substantial proportion of childhood CAP is caused by viruses. A better understanding of the role of virus infections in this condition is needed to improve clinical management and preventive measures. The aim of the study was therefore to assess the association between specific respiratory viruses and childhood CAP. METHODS A case-control study was conducted during 3 years in Stockholm, Sweden. Cases were children aged ≤5 years with radiological CAP. Healthy controls were consecutively enrolled at child health units during routine visits and matched to cases on age and calendar time. Nasopharyngeal aspirates were obtained and analysed by real-time PCR for 15 viruses. Multivariate conditional logistic regression was used to account for coinfections with other viruses and baseline characteristics. RESULTS A total of 121 cases, of which 93 cases met the WHO criteria for radiological pneumonia, and 240 controls were included in the study. Viruses were detected in 81% of the cases (n=98) and 56% of the controls (n=134). Influenza virus, metapneumovirus and respiratory syncytial virus were detected in 60% of cases and were significantly associated with CAP with ORs >10. There was no association with parainfluenza virus, human enterovirus or rhinovirus and coronavirus and bocavirus were negatively associated with CAP. CONCLUSIONS Our study indicates viral CAP is an underestimated disease and points out hMPV as a new important target for the prevention of childhood CAP.


title: Oxygenation time course and neuromuscular fatigue during repeated cycling sprints with bilateral blood flow restriction.

text: The aim was to evaluate changes in peripheral and cerebral oxygenation, cardiorespiratory, and performance differences, as well as neuromuscular fatigue across multiple levels of blood flow restriction (BFR) during a repeated cycling sprint test to exhaustion (RST). Participants performed three RST (10-sec maximal sprints with 20-sec recovery until exhaustion) with measurements of power output and V̇O2peak as well as oxygenation (near-infrared spectroscopy) of the vastus lateralis and prefrontal cortex. Neuromuscular fatigue was assessed by femoral nerve stimulation to evoke the vastus lateralis. Tests were conducted with proximal lower limb bilateral vascular occlusion at 0%, 45%, and 60% of resting pulse elimination pressure. Total work decreased with BFR (52.5 ± 22.9% at 45%, 68.6 ± 32.6% at 60%, P < 0.01 compared with 0%) as V̇O2peak (12.6 ± 9.3% at 45%, 18.2 ± 7.2% at 60%, compared with 0%, P < 0.01). Decreased changes in muscle deoxyhemoglobin (∆[HHb]) during sprints were demonstrated at 60% compared to 0% (P < 0.001). Changes in total hemoglobin concentrations (∆[tHb]) increased at both 45% and 60% compared with 0% (P < 0.001). Cerebral ∆[tHb] increased toward exhaustion (P < 0.05). Maximal voluntary contraction (MVC), voluntary activation level (VAL), and root mean square (RMS)/M-wave ratio decreased at 60% compared with 0% (P < 0.001, all). MVC and VAL decreased between 45% and 60% (P < 0.05, both). The application of BFR during RST induced greater changes in tissue perfusion (via blood volume, ∆[tHb]) suggesting a possible stimulus for vascular blood flow regulation. Additionally, high-intensity sprint exercise with partial ischemia may challenge cerebral blood flow regulation and influence local fatigue development due to protection of cerebral function.


title: Indocyanine green reinjection technique for use in fluorescent angiography concomitant with cholangiography during laparoscopic cholecystectomy.

text: BACKGROUND For safe laparoscopic cholecystectomy, surgeons must possess detailed knowledge of the anatomy of the bile duct and arterial system as seen through a laparoscope. STUDY DESIGN We developed an indocyanine green (ICG) reinjection technique for use in fluorescent angiography. Here, we evaluated the efficacy of the ICG reinjection technique in fluorescent angiography in discriminating the arterial system with the concomitant use of fluorescent cholangiography. RESULTS Twenty-eight patients were enrolled in the study. All patients underwent laparoscopic cholecystectomy without complication. After reinjection of ICG during surgery, fluorescence of the cystic artery was visualized in 25 patients (89%). CONCLUSIONS Fluorescent angiography using this ICG reinjection technique might enhance the safety of laparoscopic cholecystectomy.


title: Current status of pneumococcal vaccines: lessons to be learned and new insights.

text: One of the great success stories in pneumococcal vaccines is the 7-valent conjugated pneumococcal vaccine (PCV-7); and with wider coverage, the broad prevention it offers would be possible with new vaccines. The 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD-7) was held on the 14-18 March 2010 in Tel Aviv, Israel. During this symposium, clinical and epidemiological features in the post-PCV-7 era, current studies about two new approved PCVs (PHiD-CV and PCV-13) and new data about protein-based vaccines were extensively evaluated. Routine surveillance for pneumococcal infections is essential for all countries whether pneumococcal vaccines are available or not, and long-term results of surveillance help us to understand the PCVs potential benefits. Current epidemiological data about serotype 6C have also been presented from different countries and existing PCVs' efficacy against serotype 6C should be evaluated. In the post-PCV7 era, we have some new emerging serotypes and we also need new vaccines or interventions focused on protection for children against serotypes prevalent in the developing world or broad protection across all pneumococcal serotypes. Effectiveness of the new PCVs against nasopharyngeal carriage, acute otitis media and invasive infections need to be investigated in the real world; immunogenicity of investigational protein-based vaccines, are still evaluated in different settings. We will have a chance to hear and discuss all the new achievements in the many aspects related to pneumococcal diseases at the next ISPPD-8, which will be held in Iguaçu Falls in 2012.


Don't forget about head and neck cancer.


title: Echinacea for preventing and treating the common cold.

text: CLINICAL QUESTION Are Echinacea products associated with a reduced incidence and a shorter duration of common colds compared with placebo? BOTTOM LINE Individual prophylaxis trials show no association with prevention of the common cold, but exploratory meta-analysis suggests that Echinacea products may be associated with a small reduction in cold incidence. In treatment trials, there was no association of Echinacea products with a shorter duration of colds.


title: Huge pseudomyxoma peritonei: Surgical strategies and procedures to employ to optimize the rate of complete cytoreductive surgery.

text: BACKGROUND Complete cytoreductive surgery (CCRS) plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is the best-known treatment for pseudomyxoma peritonei (PMP). In 30% of the cases, PMP realize a widespread involvement of the peritoneal cavity. In these extreme situations, we developed, devoted strategies to optimize the feasibility and safety of CCRS. This study describes the surgical resections required for CCRS and the consequent approaches that we propose to achieve CCRS. MATERIALS AND METHODS We defined "huge PMP" by a peritoneal cancer index (PCI) ≥ 28. Surgical procedures of patients operated on between 1994 and 2014 were retrospectively reviewed from a prospective database in a single institution. RESULTS During this period, 311 patients were operated on and 247 (79%) underwent CCRS + HIPEC. Among them, 100 patients presented "huge" PMP and 54 patients underwent CCRS + HIPEC. In patients with "huge" PMP, the rate of CCRS + HIPEC was 25% before 2002 and reached 71% between 2011 and 2014. We identified 3 conditions for CCRS 1) to guaranty a sufficient length of residual small bowel 2) to preserve the left gastric vessels in order to preserve the superior third of the stomach 3) to ensure that the hepatic pedicle can be entirely cleared from its tumor involvement. None of the other peritonectomy procedures were decisional for CCRS. CONCLUSION Our learning curve improved the selection and completion rate of CCRS + HIPEC for "huge PMP". Some anatomical and physiological prerequisites guarantee the feasibility and safety of such extensive surgeries.


Mortality rate and gender differences in COVID-19 patients dying in Italy: A comparison with other countries.


title: The vaccine journey for COVID-19: a comprehensive systematic review of current clinical trials in humans.

text: INTRODUCTION Since December 2019, there has been an outbreak of a novel beta-coronavirus (SARS-CoV-2) in Wuhan, China. On March the 11th the World Health Organization (WHO) declared COVID-19 as a pandemic, with over 118,000 cases in more than 110 countries around the world. In response to the global coronavirus disease 2019 (COVID-19) emergency, clinical trial research assessing the efficacy and safety of experimental vaccines to prevent COVID-19 are emerging at an unprecedented rate. The aim of this systematic review is to summarize the preliminary experiences and ongoing clinical trials of the major candidates and challenges of the vaccine strategies in humans. EVIDENCE ACQUISITION After a priori protocol registration with PROSPERO (181483), a systematic research of the published literature was conducted on 24 April 2020 using Medline (via PubMed), Embase (via Ovid), and WHO databases. Moreover, to explore the more recent literature we also searched the preprint server medRxiv. Finally, we scrutinized the Cochrane COVID-19 study register and the COVID-19 section of ClinicalTrials.gov database for identifying relevant ongoing clinical trials. Thereafter we selected the articles according to the PRISMA guidelines. Animal or in-vitro experimental studies were excluded. Moreover editorials, commentaries, abstracts, reviews, book chapters, and articles not in English were not included. EVIDENCE SYNTHESIS Our search identified 1359 published papers, 478 pre-print articles and 367 ongoing clinical trials. Finally, only ten ongoing clinical trials met the inclusion criteria. Specifically, seven developed vaccines for the S protein of SARS-CoV-2 and three clinical trials assessed the protective role of BCG vaccine against COVID-19. The first group included phase I/II trials with different types of molecules (DNA or mRNA vaccine, bacterial plasmid or viral vectors), the latter were phase III/IV trials designed on the basis of a heterologous lymphocyte activation by the BCG vaccine. CONCLUSIONS This new disease is pushing the scientific community to develop swiftly a safe and effective vaccine. Notwithstanding the limitations of our analysis, given by the absence of available results, we try to provide a comprehensive view of the ongoing clinical trials in humans. Our analysis reveals a worldwide effort of both scientists and enterprises to achieve one of the most challenging goals of our century.


The fight to end tuberculosis must not be forgotten in the COVID-19 outbreak.


title: The incidence of ventilator-associated pneumonia using the PneuX System with or without elective endotracheal tube exchange: A pilot study.

text: BACKGROUND The PneuX System is a novel endotracheal tube and tracheal seal monitor, which has been designed to minimise the aspiration of oropharyngeal secretions. We aimed to determine the incidence of ventilator-associated pneumonia (VAP) in patients who were intubated with the PneuX System and to establish whether intermittent subglottic secretion drainage could be performed reliably and safely using the PneuX System. FINDINGS In this retrospective observational study, data was collected from 53 sequential patients. Nine (17%) patients were initially intubated with the PneuX System and 44 (83%) patients underwent elective exchange to the PneuX System. There were no episodes of VAP while the PneuX System was in situ. On an intention to treat basis, the incidence VAP was 1.8%. There were no complications from, or failure of, subglottic secretion drainage during the study. CONCLUSIONS Our study demonstrates that a low incidence of VAP is possible using the PneuX System. Our study also demonstrates that elective exchange and intermittent subglottic secretion drainage can be performed reliably and safely using the PneuX System.


Life after COVID-19: preparing for changes in mental healthcare service demand.


title: Long-term use of noble metal alloy coated urinary catheters reduces recurrent CAUTI and decreases proinflammatory markers.

text: Background The objective of this study was to investigate a case of a permanently (suprapubic) catheterized woman with neurogenic bladder dysfunction. The patient had suffered from recurrent catheter-associated urinary tract infections (CAUTIs) since 2009, despite several prevention approaches and attempts. In 2013, the patient's catheter was substituted for the BIP Foley Catheter, coated with a noble metal alloy (NMA) of gold, silver, and palladium. Method This is a retrospective-prospective clinical case study covering 4 years history for the control catheters and up to 2.5 years for the anti-infective BIP Foley Catheter. CAUTI incidences, symptoms, antibiotics, catheter performance, and comfort were evaluated. Levels of proinflammatory cytokines were measured pre- and post-substitution to BIP Foley Catheter in urine of the case and of four other permanently catheterized patients. In addition, the levels of noble metals were assessed in urine of the case subject during use of the BIP Foley Catheter. Results While using control catheters, the patient experienced symptomatic CAUTIs requiring antibiotics almost every month for 4 years. After 1 month with the BIP Foley Catheter, the symptoms disappeared, and the patient remained free of symptomatic CAUTIs and antibiotic treatment for the following 2.5 years, despite bacteriuria. The patient was satisfied with the comfort during insertion, use, and removal of the BIP Foley Catheter. Urinary levels of the proinflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNFα) decreased towards normal levels post catheter type substitution. Traces of noble metals detected in a few urine samples were ⩽4% of the permitted daily exposure. The levels of the noble metals gold, silver, and palladium remaining on the BIP Foley Catheter after use were the same as for unused catheters. Conclusion Long-term use of a NMA-coated catheter was associated with cessation of frequent CAUTIs. The catheter was experienced as comfortable and inflammatory markers were reduced with time. The coating was stable, with no significant metal release into urine and is therefore safe for patient use.


title: Hospital Preparedness for Outbreak at Patan Hospital: Lesson Learnt from COVID-19.

text: Patan Academy of Health Sciences started preparedness for COVID-19 in response to increasing number of patient in neighboring country. Outbreak preparedness in resource limited setup is challenging. Despite this, preparedness was done in reference to WHO interim guidance utilizing best available resources. During this preparedness, one patient was isolated as suspected COVID-19. This paper presents level of preparedness achieved with the limited resources and the lesson learned while isolating the patient. Keywords: COVID-19; Disaster; hospital preparedness.


title: The usefulness of the McGrath MAC laryngoscope in comparison with Airwayscope and Macintosh laryngoscope during routine nasotracheal intubation: a randomaized controlled trial.

text: BACKGROUND McGrath MAC video laryngoscope offers excellent laryngosopic views and increases the success rate of orotracheal intubation in some cases. The aim of this study was to determine the usefulness of McGrath MAC for routine nasotracheal intubation by comparing McGrath MAC with Airway scope and Macintosh laryngoscope. METHODS A total of 60 adult patients with ASA physical status class 1 or 2, aged 20-70 years were enrolled in this study. Patients were scheduled for elective oral surgery under general anesthesia with nasotracheal intubation. Exclusion criteria included lack of consent and expected difficult airway. Patients were randomly allocated to three groups: McGrath MAC (n = 20), Airway scope (n = 20), and Macintosh laryngoscope (n = 20). After induction, nasotracheal intubation was performed by six expert anesthesiologists with more than 6 years of experience. RESULTS There were no significant differences in preoperative airway assessment among the three groups. Successful tracheal intubation time was 26.8 ± 5.7 (mean ± standard deviation) s for McGrath MAC, 36.4 ± 11.0 s for Airway scope, and 36.5 ± 8.9 s for Macintosh laryngoscope groups. The time for successful tracheal intubation for McGrath MAC group was significantly shorter than that for Airway scope and Macintosh laryngoscope (p < 0.01). McGrath MAC significantly improved the Cormack Lehane grade for nasotracheal intubation compared with Macintosh laryngoscope (p < 0.05). CONCLUSION McGrath MAC significantly facilitates routine nasotracheal intubation compared with Airwayscope and Macintosh laryngoscope by shortening the tracheal intubation time and improving the Cormack Lehane grade. TRIAL REGISTRATION UMINCTR Registration number UMIN000023506 . Registered 5 Aug 2016.


title: Competence and training in interventional pulmonology.

text: Interventional Pulmonology (IP) is experiencing a rapid evolution of new technologies. There is a need to develop structured training programs, organized in high volume expert centres in order to improve trainee education, and including the development of validated metrics for their competency assessment. Concerning teaching methods, a gradual progression from theory to practice, using new teaching techniques, including live sessions and low and high fidelity simulation, flipped classroom models and problem-based learning (PBL) exercises would provide a training setting more suitable for our current need to improve skills and update professionals. Training programs should be learner centered and competence-oriented, as well as being based on a spiral-shaped approach in which the same subject is addressed many times, from new and different perspectives of knowledge, ability, behaviour and attitude, until the trainee has demonstrated a high degree of skill and professionalism5. Furthermore there is a need to standardize the training programs as guide for physicians wishing to undertake a gradual and voluntary improvement of their own competencies, and assist those planning and organizing training programs in IP. The article includes a general part on Core Curriculum contents, innovative training methods and simulation, and introduces the following articles on the skills hat the Interventional Pulmonologist must master in order to perform the different procedures. This monography should be considered a starting point that will evolve over time and results in better training for practitioners and better care for our patients. The task of establishing a trainee's competence to practice independently as an Interventional Pulmonologist remains the responsibility of the IP fellowship program director and faculty, who validate logbooks and assess competence for each procedure. These standards need to be reviewed and approved by national and International Scientific Societies and Healthcare Institutions with the aim to improve, disseminate and incorporate them in healthcare programs.


Covid-19: Two antibody tests are "highly specific" but vary in sensitivity, evaluations find.


Public Health Interventions for COVID-19: Emerging Evidence and Implications for an Evolving Public Health Crisis.


title: Bypasses and reconstruction for complex brain aneurysms.

text: Microsurgery for brain aneurysms is a current relevant technique, as advances in endovascular and stent-assisted coiling have not solved many of the difficulties inherent in the management of complex brain aneurysms. The following review highlights the importance of microsurgical bypass techniques for the management of complex cerebrovascular aneurysms and emphasizes, through two clinical cases, the technical difficulties and indications for bypass surgery. These cases demonstrate that in selected scenarios, bypass microsurgery still offers the only viable treatment for complex aneurysms.


The limits to our capacity: reflections on resiliency, community engagement, and recovery in 21st-century crises.


title: Both the middle and distal sections of the urethra may be regarded as optimal targets for 'outside-in' transobturator tape placement.

text: PURPOSE To investigate whether the position of the tape under the urethra may influence 'outside-in' transobturator sling (TOT) outcome. METHODS The study comprised 141 women who underwent TOT for clinically and urodynamically proved stress urinary incontinence. The postoperative ultrasound examination with an endovaginal biplane probe was performed before discharging the patients from hospital. The measurements obtained described the position of the tape relative to the urethra and pubic symphysis, as well as anatomical relationships in the anterior compartment. RESULTS Ninety-six (68.1 %) patients were cured, 27 (19.1 %) significantly improved, and in 18 cases (12.7 %), the surgery failed. The tape position under the midurethra (40-70th percentile of the urethral length) or distal urethra (>70th percentile) coincided with better results (cure rate 67.1 and 82.4 %, respectively) than the location in the proximity of the bladder neck (<40th percentile) (21.4 % cured, p = 0.0015 and p < 0.001, respectively). However, the risk of failure was the lowest when the tape was located under the distal urethra. Other ultrasonographic findings were not related to treatment results. CONCLUSIONS The highest failure rate for 'outside-in' TOT is associated with the location of the tape under the proximal third of the urethra. Both the middle and distal sections of the urethra may be regarded as targets for transobturator tape placement.


title: Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis.

text: AIMS To assess the efficacy and safety of semaglutide, a recently approved glucagon-like peptide 1 receptor agonist (GLP-1 RA) for type 2 diabetes. MATERIALS AND METHODS We searched major electronic databases and grey literature sources for randomized controlled trials comparing semaglutide with placebo or other antidiabetic agents. Primary outcome was change from baseline in HbA1c. Secondary endpoints included change from baseline in body weight, blood pressure, heart rate and incidence of hypoglycaemia, gastrointestinal adverse effects, pancreatitis and diabetic retinopathy. RESULTS A total of 6 placebo-controlled and 7 active-controlled studies with subcutaneous semaglutide were included. We identified only 1 trial with oral semaglutide. Compared with placebo, subcutaneous semaglutide 0.5 and 1 mg reduced HbA1c by 1.01% (95% CI, 0.56-1.47) and 1.38% (1.05-1.70), respectively. Both doses demonstrated superior glycaemic efficacy compared to other antidiabetic agents, including sitagliptin, exenatide, liraglutide, dulaglutide and insulin glargine. Semaglutide also had a beneficial effect on body weight (mean difference vs placebo -4.11 kg, 95% CI -4.85 to -3.37 for semaglutide 1 mg) and systolic blood pressure. We did not observe increased hypoglycaemia rates with semaglutide; nevertheless, we noted an increased incidence of nausea, vomiting and diarrhoea. Cases of pancreatitis were infrequent and the odds ratio for diabetic retinopathy compared with placebo was 1.32 (95% CI, 0.98-1.77). CONCLUSIONS Semaglutide is a potent once-weekly GLP-1 RA, significantly reducing HbA1c, body weight and systolic blood pressure. However, it is associated with increased incidence of gastrointestinal adverse events. Results for pancreatitis and retinopathy require further assessment in post-approval pharmacovigilance studies.


title: The thromboembolism in COVID-19: the unsolved problem.

text: INTRODUCTION The recent Sars-Cov-2 pandemic (COVID-19) has led to growing research to explain the poor clinical prognosis in some patients. EVIDENCE ACQUISITION While early observational studies highlighted the role of the virus in lung failure, in a second moment thrombosis emerged as a possible explanation of the worse clinical course in some patients. Despite initial difficulties in management of such patients, the constant increase of literature in the field is to date clarifying some questions from clinicians. However, several other questions need answer. EVIDENCE SYNTHESIS A novel disease (Covid-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was responsible for thousands of hospitalizations for severe acute respiratory syndrome, with several cases of thrombotic complications due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. Covid-19 and hospitalizations for Covid-19 may carry several potential risk factors for thrombosis. Severe coagulation abnormalities may occur in almost all of the severe and critical ill COVID-19 cases. CONCLUSIONS Despite a strong pathophysiological rationale, the evidences in literature are not enough to recommend an aggressive antithrombotic therapy in COVID- 19. However, it is our opinion that an early use, even at home at the beginning of the disease, could improve the clinical course.


title: COVID-19 and spontaneous singing to decrease loneliness, improve cohesion, and mental well-being: An Italian experience.

text: Since March 2020, Italy has been in lockdown due to COVID-19, and individuals have missed all kinds of networking opportunities. Already in the 1st weeks of March, Italian cities' silence was broken by singing. The use of singing as a coping strategy as well as to improve the sense of cohesion is evident. Greater attention should be paid to the development of social cohesion and to social support in terms of social networks and the development of social capital. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Key elements of interventions for heart failure patients with mild cognitive impairment or dementia: A systematic review.

text: BACKGROUND The purpose of this systematic review was to (a) examine the effects of interventions delivered by a heart failure professional for mild cognitive impairment and dementia on cognitive function, memory, working memory, instrumental activities of daily living, heart failure knowledge, self-care, quality of life and depression; and (b) identify the successful elements of these strategies for heart failure patients with mild cognitive impairment or dementia. METHODS AND RESULTS During March 2018, an electronic search of databases including CINAHL, MEDLINE, EMBASE and PsycINFO was conducted. All randomised controlled trials, which examined an intervention strategy to help heart failure patients with mild cognitive impairment or dementia cope with self-care, were included. An initial search yielded 1622 citations, six studies were included (N= 595 participants, mean age 68 years). There were no significant improvements in cognitive function and depression. However, significant improvements were seen in memory (p=0.015), working memory (p=0.029) and instrumental activities of daily living (p=0.006). Nurse led interventions improved the patient's heart failure knowledge (p=0.001), self-care (p<0.05) and quality of life (p=0.029). Key elements of these interventions include brain exercises, for example, syllable stacks, individualised assessment and customised education, personalised self-care schedule development, interactive problem-solving training on scenarios and association techniques to prompt self-care activities. CONCLUSIONS Modest evidence for nurse led interventions among heart failure patients with mild cognitive impairment or dementia was identified. These results must be interpreted with caution in light of the limited number of available included studies.


title: Venous thromboembolism in adult elective spinal surgery: a tertiary centre review of 2181 patients.

text: AIMS To evaluate the incidence of primary venous thromboembolism (VTE), epidural haematoma, surgical site infection (SSI), and 90-day mortality after elective spinal surgery, and the effect of two protocols for prophylaxis. PATIENTS AND METHODS A total of 2181 adults underwent 2366 elective spinal procedures between January 2007 and January 2012. All patients wore anti-embolic stockings, mobilised early and were kept adequately hydrated. In addition, 29% (689) of these were given low molecular weight heparin (LMWH) while in hospital. SSI surveillance was undertaken using the Centers for Disease Control and Prevention criteria. RESULTS In patients who only received mechanical prophylaxis, the incidence of VTE was 0.59% and that of SSI 2.1%. In patients who were additionally given LMWH, the incidence of VTE was 0% and that of SSI 0.7%. The unadjusted p-value was 0.04 for VTE and 0.01 for SSI. There were no cases of epidural haematoma or 90-day mortality in either group. When adjusted for case-mix, LMWH remained a significant factor (p = 0.006) for VTE, but not for SSI. CONCLUSION A peri-operative protocol involving mechanical anti-embolism stockings, adequate hydration, and early post-operative mobilisation is effective in significantly reducing the incidence of VTE. The addition of LMWH is safe in patients at higher risk of developing VTE. Cite this article: Bone Joint J 2017;99-B:1204-9.


title: (99m)Tc(CO)3(NTA): a (99m)Tc renal tracer with pharmacokinetic properties comparable to those of (131)I-OIH in healthy volunteers.

text: UNLABELLED Studies in rats showed that the pharmacokinetics of the tricarbonyl core radiopharmaceutical (99m)Tc(CO)(3)-nitrilotriacetic acid, (99m)Tc(CO)(3)(NTA), were essentially identical to those of (131)I ortho-iodohippuran ((131)I-OIH), the clinical gold standard for the measurement of effective renal plasma flow. Our objective was to compare the pharmacokinetics of these 2 tracers in healthy volunteers. METHODS (99m)Tc(CO)(3)(NTA) was prepared with commercially available NTA and a commercially available kit and isolated by reversed-phase high-performance liquid chromatography. Approximately 74 MBq (2 mCi) of (99m)Tc(CO)(3)(NTA) were coinjected with 9.25 MBq (250 microCi) of (131)I-OIH in 9 volunteers, and simultaneous imaging of each tracer was performed for 24 min. Plasma clearances were determined from 8 blood samples obtained 3-90 min after injection using the single-injection, 2-compartment model. Plasma protein binding, red cell uptake, and percentage injected dose in the urine at 30 and 180 min were determined. RESULTS There was no difference in the plasma clearances of (99m)Tc(CO)(3)(NTA) and (131)I-OIH, 475 +/- 105 mL/min versus 472 +/- 108 mL/min, respectively. The plasma protein binding and red cell uptake of (99m)Tc(CO)(3)(NTA) were 43% +/- 5% and 9% +/- 6%, respectively; both values were significantly lower (P < 0.001) than the plasma protein binding (75% +/- 3%) and red cell uptake (17% +/- 5%) of (131)I-OIH. There was no significant difference in the percentage injected dose recovered in the urine at 30 min and at 3 h; for comparison, the percentage dose in the urine at 3 h was 91% +/- 4% for (99m)Tc(CO)(3)(NTA) and 91% +/- 6% for (131)I-OIH (P = 0.96). Image quality with (99m)Tc(CO)(3)(NTA) was excellent, and the renogram parameters were similar to those of (131)I-OIH. CONCLUSION Preliminary results in healthy volunteers suggest that the pharmacokinetic behavior of (99m)Tc(CO)(3)(NTA) is comparable to that of (131)I-OIH.