title: Antiviral treatment of severe non-influenza respiratory virus infection.

text: PURPOSE OF REVIEW Non-influenza respiratory virus infections are a frequent cause of severe acute respiratory infections, especially in infants, the elderly, and the immunocompromised. We review here the current treatment options for non-influenza respiratory viruses and promising candidate antiviral agents currently in development. RECENT FINDINGS Small molecule antiviral agents active against respiratory syncytial virus (RSV), such as ALS-8176 and GS-5806, show considerable promise in challenge studies and are undergoing late-phase clinical trials in hospitalised adults and children. Monoclonal antibodies (mAbs) active against non-influenza respiratory viruses are broadly at a preclinical stage. Broad-spectrum antivirals, such as favipiravir and nitrazoxanide, have potential utility in treating illness caused by non-influenza respiratory viruses but further definitive clinical trials are needed. SUMMARY Severe non-influenza respiratory virus infection is common and current treatment is largely supportive. Ribavirin is used in immunocompromised patients but its use is limited by toxicity and the evidence for its efficacy is weak. Effective antiviral treatment for RSV may shortly become available, pending the results of ongoing clinical trials. For other non-influenza viruses, effective treatments may become available in the medium term. Early detection of respiratory viruses with rapid molecular test platforms will be crucial in differentiating virus types and directing the prompt initiation of novel treatments when available.


title: One and done? The effect of number of Pipeline embolization devices on aneurysm treatment outcomes.

text: BACKGROUND Controversy exists regarding the optimum number of flow diverters for the treatment of intracranial aneurysms. We explored the effect of the number of Pipeline embolization devices (PEDs; Medtronic, Dublin, Ireland) deployed on rates of aneurysm occlusion and complications. METHODS Consecutive patients who underwent saccular intracranial aneurysm treatment solely with the PED were included in this retrospective study. Computed tomographic, magnetic resonance, or digital subtraction angiographic images at 6 and 12 months and last follow-up (>12 months) were reviewed for aneurysm occlusion. Complication and retreatment rates were recorded and analyzed statistically. RESULTS The study included 141 aneurysm treatments in 119 patients. A single PED was deployed in 105 cases, two PEDs in 31 cases, and three PEDs in 5 cases (total = 182 devices). Six-month angiographic data were available for 103 patients. Occlusion rates were 67.1% for single-PED cases and 90.0% for cases with > 1 PED (p = 0.028). The 12-month occlusion rate (follow-up available for 132) for single-PED cases was 74.7% compared to 91.7% for multiple-PED cases (p = 0.04). On multivariate analysis, number of PEDs was an independent predictor of aneurysm occlusion at 12 months (odds ratio 6.3, 95% confidence interval 1.8-22.8, p = 0.005). Thromboembolic complication rates were the same in the single- and multiple-PED treatment groups (2.8%). The retreatment rate was higher in patients treated with a single PED (16.2% vs. 0%, p = 0.01). CONCLUSIONS Deployment of > 1 Pipeline embolization device was associated with higher intracranial aneurysm occlusion and lower retreatment rates. No significant difference was found in complication rates.


title: Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb Wounds in Horses.

text: Distal extremity wounds are a significant clinical problem in horses and humans and may benefit from mesenchymal stem cell (MSC) therapy. This study evaluated the effects of direct wound treatment with allogeneic stem cells, in terms of gross, histologic, and transcriptional features of healing. Three full-thickness cutaneous wounds were created on each distal forelimb in six healthy horses, for a total of six wounds per horse. Umbilical cord-blood derived equine MSCs were applied to each wound 1 day after wound creation, in one of four forms: (a) normoxic- or (b) hypoxic-preconditioned cells injected into wound margins, or (c) normoxic- or (d) hypoxic-preconditioned cells embedded in an autologous fibrin gel and applied topically to the wound bed. Controls were one blank (saline) injected wound and one blank fibrin gel-treated wound per horse. Data were collected weekly for 6 weeks and included wound surface area, thermography, gene expression, and histologic scoring. Results indicated that MSC treatment by either delivery method was safe and improved histologic outcomes and wound area. Hypoxic-preconditioning did not offer an advantage. MSC treatment by injection resulted in statistically significant increases in transforming growth factor beta and cyclooxygenase-2 expression at week 1. Histologically, significantly more MSC-treated wounds were categorized as pro-healing than pro-inflammatory. Wound area was significantly affected by treatment: MSC-injected wounds were consistently smaller than gel-treated or control wounds. In conclusion, MSC therapy shows promise for distal extremity wounds in horses, particularly when applied by direct injection into the wound margin. Stem Cells Translational Medicine 2018;7:98-108.


The AORN Community Displays its Resiliency Amidst Pandemic Crisis.


title: Incidence of reexpansion pulmonary edema in minimally invasive cardiac surgery.

text: Minimally invasive cardiac surgery requires fewer blood transfusions and mediastinitis is less frequently observed compared to conventional median sternotomy surgical intervention, and it leads to earlier recovery and discharge. However, once reexpansion pulmonary edema occurs, the patient requires long-term management in the intensive care unit. This retrospective study was performed to investigate the incidence of reexpansion pulmonary edema in minimally invasive cardiac surgery. Patients who underwent minimally invasive cardiac valve surgery using cardiopulmonary bypass and port-access by a minimal right lateral thoracic incision between January 2010 and January 2018 were enrolled in this single-center retrospective study, which was approved by the institutional review board of Japanese Red Cross Nagoya Daiichi Hospital (Nagoya, Japan), and the requirement for written informed consent was waived. All data were collected from electronic charts. The primary outcome was the incidence rate of reexpansion pulmonary edema in patients undergoing minimally invasive cardiac surgery. A total of 662 patients underwent minimally invasive cardiac surgery, and we analyzed 651 of these cases. No case of reexpansion pulmonary edema was observed in this study. The statistically-calculated incidence rate of reexpansion pulmonary edema was less than 0.6% (95% confidence interval: 0.0-0.6). The incidence of cerebral infarction was 0.92% (n = 6). Intensive care unit stay days, hospital stay days after surgery, and the death rate after 30 days were 1.5 ± 2.0 days, 9.6 ± 3.9 days, and 0.15%, respectively. Although there was no incidence of clinical reexpansion pulmonary edema in this study, the predicted incidence of reexpansion pulmonary edema by statistical analysis was less than 0.6%.


title: Hydrogel dressings for healing diabetic foot ulcers.

text: BACKGROUND Foot ulcers in people with diabetes are a prevalent and serious global health issue. Dressings form a key part of ulcer treatment, with clinicians and patients having many different types to choose from including hydrogel dressings. A clear and current overview of current evidence is required to facilitate decision-making regarding dressing use. OBJECTIVES To assess the effects of hydrogel wound dressings compared with alternative dressings or none on the healing of foot ulcers in people with diabetes. SEARCH STRATEGY We searched the Cochrane Wounds Group Specialised Register (searched 10 June 2011); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2); Ovid MEDLINE (1950 to June Week 1 2011); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, June 8, 2011); Ovid EMBASE (1980 to 2011 Week 22) and EBSCO CINAHL (1982 to 3 June 2011). There were no restrictions based on language or date of publication. SELECTION CRITERIA Published or unpublished randomised controlled trials (RCTs) that have compared the effects on ulcer healing of hydrogel with alternative wound dressings or no dressing in the treatment of foot ulcers in people with diabetes. DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection, risk of bias assessment and data extraction. MAIN RESULTS We included five studies (446 participants) in this review. Meta analysis of three studies comparing hydrogel dressings with basic wound contract dressings found significantly greater healing with hydrogel: risk ratio (RR) 1.80, 95% confidence interval (CI) 1.27 to 2.56. The three pooled studies had different follow-up times (12 weeks, 16 weeks and 20 weeks) and also evaluated ulcers of different severities (grade 3 and 4; grade 2 and grade unspecified). One study compared a hydrogel dressing with larval therapy and found no statistically significant difference in the number of ulcers healed and another found no statistically significant difference in healing between hydrogel and platelet-derived growth factor. There was also no statistically significant difference in number of healed ulcers between two different brands of hydrogel dressing. All included studies were small and at unclear risk of bias and there was some clinical heterogeneity with studies including different ulcer grades. No included studies compared hydrogel with other advanced wound dressings. AUTHORS' CONCLUSIONS There is some evidence to suggest that hydrogel dressings are more effective in healing (lower grade) diabetic foot ulcers than basic wound contact dressings however this finding is uncertain due to risk of bias in the original studies. There is currently no research evidence to suggest that hydrogel is more effective than larval therapy or platelet-derived growth factors in healing diabetic foot ulcers, nor that one brand of hydrogel is more effective than another in ulcer healing. No RCTs comparing hydrogel dressings with other advanced dressing types were found.


title: Loop-mediated isothermal amplification (LAMP) for rapid detection of Renibacterium salmoninarum, the causative agent of bacterial kidney disease.

text: A loop-mediated isothermal amplification (LAMP) assay was developed for rapid, specific and sensitive detection of Renibacterium salmoninarum in 1 h without thermal cycling. A fragment of R. salmoninarum p57 gene was amplified at 63 degrees C in the presence of Bst polymerase and a specially designed primer mixture. The specificity of the BKD-LAMP assay was demonstrated by the absence of any cross reaction with other bacterial strains, followed by restriction digestion of the amplified products. Detections of BKD-LAMP amplicons by visual inspection, agrose gel electrophoresis, and real-time monitoring using a turbidimeter were equivalently sensitive. The BKD-LAMP assay has the sensitivity of the nested PCR method, and 10 times the sensitivity of one-round PCR assay. The lower detection limit of BKD-LAMP and nested PCR is 1 pg genomic R. salmoninarum DNA, compared to 10 pg genomic R. salmoninarum DNA for one-round PCR assay. In comparison to other available diagnostic methods, the BKD-LAMP assay is rapid, simple, sensitive, specific, and cost effective with a high potential for field application.


docid: scuawjhe

title: Prevention of ventilator-associated pneumonia.

text: Ventilator-associated pneumonia is the commonest, yet mostly preventable, infection in mechanically ventilated patients. Successful control of ventilator-associated pneumonia can save hospitalisation cost, and is possible by using a multidisciplinary clinical and administrative approach. The ventilator-associated pneumonia rate should be expressed as the number of ventilator-associated pneumonia days per 1000 ventilator days to take into account the device-utilisation duration for meaningful comparison. Various strategies address the issue, including general infection control measures, body positioning, intubation and mechanical ventilation, oral and gastro-intestinal tract, endotracheal tube, airway pressure, cuff pressure, selective digestive and/or oropharyngeal decontamination, and probiotic or early antibiotic treatment, as well as overall administration at a policy level. The rationale and controversy of these approaches are discussed in this article. The authors suggest that all units treating mechanically ventilated patients should have a ventilator-associated pneumonia prevention protocol in place, and ventilator-associated pneumonia should be seriously considered as a key performance indicator in local intensive care units.


title: Correcting the typical Apert face: combining bipartition with monobloc distraction.

text: BACKGROUND Bipartition distraction is a novel procedure combining frontofacial bipartition and monobloc distraction. Apert syndrome and other syndromic craniofacial dysostoses are often characterized by hypertelorism, with a negative canthal axis and counterrotated orbits. Central midface hypoplasia can result in a biconcave face in both midsagittal and axial planes. Bipartition distraction can correct these facial abnormalities. METHODS Twenty patients (19 Apert syndrome patients and one Pfeiffer syndrome patient, aged 1.6 to 21 years) underwent bipartition distraction. Severity of appearance was graded preoperatively and postoperatively as mild, moderate, or severe. Functional problems were documented by a multidisciplinary team. Central and lateral midface skeletal advancement were measured. Follow-up ranged from 15 months to 7 years. RESULTS Bipartition distraction consistently produced more central than lateral facial advancement. Mean central advancement was 13.2 ± 5.9 mm at sella-nasion and 11.7 ± 5.4 mm at sella-A point. Lateral advancement was 4.7 ± 2.8 mm. Unbending the face improved aesthetic appearance. Airway function, eye exposure, and elevated intracranial pressure were improved. Complications included six temporary cerebrospinal fluid leaks (four needing a lumbar drain), five patients with postoperative seizures, five patients requiring Rigid External Distraction frame repositioning, one palatal fistula, one velopharyngeal incompetence, five pin-site infections, one abscess under frontal bone, three cases of sepsis, nine patients with worsened strabismus, two patients with enophthalmos, one patient with partial visual field loss, and three patients who required reintubation because of aspiration. CONCLUSIONS : Bipartition distraction is an effective procedure with which to differentially advance the central face in Apert syndrome. It improves both function and aesthetics. CLINICAL QUESTION/LEVEL OF EVIDENCE : Therapeutic, IV.


title: Antitumor potential of conjugable valinomycins bearing hydroxyl sites: in vitro studies.

text: Following our pioneering studies on the direct and efficient introduction of derivatizable hydroxyl handles into the valinomycin (VLM, 1) structure, a K(+)-ionophore with potent antitumor activity, the ensuing conjugable analogues (HyVLMs 2, 3, and 4) have herein been compared to the parent macrocycle for their potential antiproliferative effects on a panel of cancer cell lines, namely, human MCF-7, A2780, and HepG2, as well as rat C6 cells. On the basis of IC50 values, we find that hydroxyl analogues 3 and 4 are only moderately less active than 1, while analogue 2 experiences a heavily diminished activity. Cytofluorimetric analyses of MCF-7 cells treated with HyVLMs suggest that the latter depolarize mitochondria, thus retaining the typical VLM behavior. It is likely that C6 cells, for which the exceptionally potent cytotoxicity of VLM has never reported previously, follow the same fate, as evidenced by alteration of mitochondrial morphology upon incubation with each ionophore.


title: Appraising the Quality of Systematic Reviews for Age-Related Macular Degeneration Interventions: A Systematic Review.

text: Importance Age-related macular degeneration (AMD) is a leading cause of vision impairment. It is imperative that AMD care is timely, appropriate, and evidence-based. It is thus essential that AMD systematic reviews are robust; however, little is known about the quality of this literature. Objectives To investigate the methodological quality of systematic reviews of AMD intervention studies, and to evaluate their use for guiding evidence-based care. Evidence Review This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. All studies that self-identified as a systematic review in their title or abstract or were categorized as a systematic review from a medical subject heading and investigated the safety, efficacy and/or effectiveness of an AMD intervention were included. Comprehensive electronic searches were performed in Ovid MEDLINE, Embase, and the Cochrane Library from inception to March 2017. Two reviewers independently assessed titles and abstracts, then full-texts for eligibility. Quality was assessed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool. Study characteristics (publication year, type of intervention, journal, citation rate, and funding source) were extracted. Findings Of 983 citations retrieved, 71 studies (7.6%) were deemed eligible. The first systematic review relating to an AMD intervention was published in 2003. More than half were published since 2014. Methodological quality was highly variable. The mean (SD) AMSTAR score was 5.8 (3.2) of 11.0, with no significant improvement over time (r = -0.03; 95% CI, -0.26 to 0.21; P = .83). Cochrane systematic reviews were overall of higher quality than reviews in other journals (mean [SD] AMSTAR score, 9.9 [1.2], n = 15 vs 4.7 [2.2], n = 56; P < .001). Overall, there was poor adherence to referring to an a priori design (22 articles [31%]) and reporting conflicts of interest in both the review and included studies (16 articles [23%]). Reviews funded by government grants and/or institutions were generally of higher quality than industry-sponsored reviews or where the funding source was not reported. Conclusions and Relevance There are gaps in the conduct of systematic reviews in the field of AMD. Enhanced endorsement of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement by refereed journals may improve review quality and improve the dissemination of reliable evidence relating to AMD interventions to clinicians.


title: Predictors of Psychological Outcomes and the Effectiveness and Experience of Psychological Interventions for Adult Women with Chronic Pelvic Pain: A Scoping Review.

text: Objective CPP affects approximately 15% of women worldwide and has significant psychological, physical and financial impact on the lives of sufferers. Psychological interventions are often recommended as adjuncts to medical treatment for women with chronic pelvic pain (CPP). This is as women with CPP experience higher rates of mental health concerns and difficulties coping with their pain.. However, recent systematic reviews have highlighted that the efficacy of psychological interventions is not conclusive in this population. This review aimed to identify predictors of mental health outcomes and effective psychological techniques and interventions in women with CPP to inform the development of future psychological therapies. Methods Scoping review using the method outlined by Arskey & O'Malley (2005). Relevant databases, reference lists and grey literature were searched to identify effective mental health interventions and predictors of psychological outcomes for women with CPP. Results Methodological concerns made identifying predictors of mental health outcomes and effective psychological interventions difficult. However, cognitive behavioural therapy and Mensendieck therapy emerged as therapeutic interventions with the best evidence for women with CPP. A number of useful predictors of mental health outcomes and techniques included in effective interventions were identified. Conclusion The evidence provided in this review has the potential to inform future research directions and the development of targeted psychological interventions for women with CPP.


Acute Common Carotid Artery Bifurcation Thrombus: An Emerging Pattern of Acute Strokes in Patients with COVID-19?


title: Coronavirus respiratory illness in Saudi Arabia.

text: Although viruses that belong to the coronavirus family are known since the 1930s, they only gained public health attention when they were discovered to be the causative agent of the severe acute respiratory syndrome (SARS) outbreak in China in 2002-2003. On 22 September 2012, the Ministry of Health (MOH) in Saudi Arabia announced the detection of what was described as a "rare pattern" of coronavirus respiratory infection in three individuals, two Saudi citizens and one person from the Gulf Region. Neither Saudi citizen survived the infection. Molecular analysis of the isolates showed that the virus belongs to the genus beta-coronavirus. It is not known if the new isolates are circulating in the population or has recently diverged. The emergence of these novel isolates that resulted in fatal human infection ascertains that health authorities all over the world must be vigilant for the possibility of new global pandemics due to novel viral infection.


title: Placenta-Derived Decidua Stromal Cells for Hemorrhagic Cystitis after Stem Cell Transplantation.

text: BACKGROUND/AIMS Hemorrhagic cystitis (HC) is a serious complication after hematopoietic stem cell transplantation (HSCT). Stromal cells have been tested as therapy for HC. Decidua stromal cells (DSCs) protect the fetus from the mother's immune system. METHODS Eleven patients with HC of grades 3-4 were treated with DSCs after HSCT. The median age was 33 years (range 8-50), and the median dose of DSCs was 1.5 × 106/kg (range 0.7-2.5). The patients were given 1 dose (1-4). RESULTS In 5 patients, HC disappeared within 5 days after DSC infusion. Patients who received DSCs within 3 days after the start of HC had a duration of HC of 5 days and a shorter duration of pain than patients who were given DSCs later (p = 0.02). Three patients received DSCs prepared in albumin instead of AB-plasma and tended to have a shorter duration of pain (p = 0.07). There was no infusion toxicity. Adverse events were those often seen after HSCT. Nine of the 11 patients (82%) were alive 1 year after HSCT. CONCLUSIONS Based on this pilot study, we started a randomized, placebo-controlled double-blind study using 2 doses of 1 × 106 DSCs/kg suspended in albumin for treatment of early HC.


title: Unsupervised Machine Learning for the Discovery of Latent Clusters in COVID-19 Patients Using Electronic Health Records.

text: The goal of this paper was to apply unsupervised machine learning techniques towards the discovery of latent clusters in COVID-19 patients. Over 6,000 adult patients tested positive for the SARS-CoV-2 infection at the Mount Sinai Health System in New York, USA met the inclusion criteria for analysis. Patients' diagnoses were mapped onto chronicity and one of the 18 body systems, and the optimal number of clusters was determined using K-means algorithm and the elbow method. 4 clusters were identified; the most frequently associated comorbidities involved infectious, respiratory, cardiovascular, endocrine, and genitourinary disorders, as well as socioeconomic factors that influence health status and contact with health services. These results offer a strong direction for future research and more granular analysis.


title: Influence of age on clinical and revascularization outcomes in the North American Solitaire Stent-Retriever Acute Stroke Registry.

text: BACKGROUND AND PURPOSE The Solitaire With the Intention for Thrombectomy (SWIFT) and thrombectomy revascularization of large vessel occlusions in acute ischemic stroke (TREVO 2) trial results demonstrated improved recanalization rates with mechanical thrombectomy; however, outcomes in the elderly population remain poorly understood. Here, we report the effect of age on clinical and angiographic outcome within the North American Solitaire-FR Stent-Retriever Acute Stroke (NASA) Registry. METHODS The NASA Registry recruited sites to submit data on consecutive patients treated with Solitaire-FR. Influence of age on clinical and angiographic outcomes was assessed by dichotomizing the cohort into ≤80 and >80 years of age. RESULTS Three hundred fifty-four patients underwent treatment in 24 centers; 276 patients were ≤80 years and 78 were >80 years of age. Mean age in the ≤80 and >80 cohorts was 62.2±13.2 and 85.2±3.8 years, respectively. Of patients >80 years, 27.3% had a 90-day modified Rankin Score ≤2 versus 45.4% ≤80 years (P=0.02). Mortality was 43.9% and 27.3% in the >80 and ≤80 years cohorts, respectively (P=0.01). There was no significant difference in time to revascularization, revascularization success, or symptomatic intracranial hemorrhage between the groups. Multivariate analysis showed age >80 years as an independent predictor of poor clinical outcome and mortality. Within the >80 cohort, National Institutes of Health Stroke Scale (NIHSS), revascularization rate, rescue therapy use, and symptomatic intracranial hemorrhage were independent predictors of mortality. CONCLUSION Greater than 80 years of age is predictive of poor clinical outcome and increased mortality compared with younger patients in the NASA registry. However, intravenous tissue-type plasminogen activator use, lower NIHSS, and shorter revascularization time are associated with better outcomes. Further studies are needed to understand the endovascular therapy role in this cohort compared with medical therapy.


title: Ultrastructural Characterization of Turnip Mosaic Virus-Induced Cellular Rearrangements Reveals Membrane-Bound Viral Particles Accumulating in Vacuoles.

text: UNLABELLED Positive-strand RNA [(+) RNA] viruses remodel cellular membranes to facilitate virus replication and assembly. In the case of turnip mosaic virus (TuMV), the viral membrane protein 6K2 plays an essential role in endomembrane alterations. Although 6K2-induced membrane dynamics have been widely studied by confocal microscopy, the ultrastructure of this remodeling has not been extensively examined. In this study, we investigated the formation of TuMV-induced membrane changes by chemical fixation and high-pressure freezing/freeze substitution (HPF/FS) for transmission electron microscopy at different times of infection. We observed the formation of convoluted membranes connected to rough endoplasmic reticulum (rER) early in the infection process, followed by the production of single-membrane vesicle-like (SMVL) structures at the midstage of infection. Both SMVL and double-membrane vesicle-like structures with electron-dense cores, as well as electron-dense bodies, were found late in the infection process. Immunogold labeling results showed that the vesicle-like structures were 6K2 tagged and suggested that only the SMVL structures were viral RNA replication sites. Electron tomography (ET) was used to regenerate a three-dimensional model of these vesicle-like structures, which showed that they were, in fact, tubules. Late in infection, we observed filamentous particle bundles associated with electron-dense bodies, which suggests that these are sites for viral particle assembly. In addition, TuMV particles were observed to accumulate in the central vacuole as membrane-associated linear arrays. Our work thus unravels the sequential appearance of distinct TuMV-induced membrane structures for viral RNA replication, viral particle assembly, and accumulation. IMPORTANCE Positive-strand RNA viruses remodel cellular membranes for different stages of the infection process, such as protein translation and processing, viral RNA synthesis, particle assembly, and virus transmission. The ultrastructure of turnip mosaic virus (TuMV)-induced membrane remodeling was investigated over several days of infection. The first change that was observed involved endoplasmic reticulum-connected convoluted membrane accumulation. This was followed by the formation of single-membrane tubules, which were shown to be viral RNA replication sites. Later in the infection process, double-membrane tubular structures were observed and were associated with viral particle bundles. In addition, TuMV particles were observed to accumulate in the central vacuole as membrane-associated linear arrays. This work thus unravels the sequential appearance of distinct TuMV-induced membrane structures for viral RNA replication, viral particle assembly, and accumulation.


Vascular response after percutaneous sympathectomy: not all devices are equal.


title: Highly diversified coronaviruses in neotropical bats.

text: Bats host a broad diversity of coronaviruses (CoVs), including close relatives of human pathogens. There is only limited data on neotropical bat CoVs. We analysed faecal, blood and intestine specimens from 1562 bats sampled in Costa Rica, Panama, Ecuador and Brazil for CoVs by broad-range PCR. CoV RNA was detected in 50 bats representing nine different species, both frugivorous and insectivorous. These bat CoVs were unrelated to known human or animal pathogens, indicating an absence of recent zoonotic spill-over events. Based on RNA-dependent RNA polymerase (RdRp)-based grouping units (RGUs) as a surrogate for CoV species identification, the 50 viruses represented five different alphacoronavirus RGUs and two betacoronavirus RGUs. Closely related alphacoronaviruses were detected in Carollia perspicillata and C. brevicauda across a geographical distance exceeding 5600 km. Our study expands the knowledge on CoV diversity in neotropical bats and emphasizes the association of distinct CoVs and bat host genera.


docid: ronibrau

title: Facilitating Both Evidence and Access: Improving FDA's Accelerated Approval and Expanded Access Pathways.


title: Net -1 frameshifting on a noncanonical sequence in a herpes simplex virus drug-resistant mutant is stimulated by nonstop mRNA.

text: Ribosomal frameshifting entails slippage of the translational machinery during elongation. Frameshifting permits expression of more than one polypeptide from an otherwise monocistronic mRNA, and can restore expression of polypeptides in the face of frameshift mutations. A common mutation conferring acyclovir resistance in patients with herpes simplex virus disease deletes one cytosine from a run of six cytosines (C-chord) in the viral thymidine kinase (tk) gene. However, this mutation does not abolish TK activity, which is important for pathogenicity. To investigate how this mutant retains TK activity, we engineered and analyzed viruses expressing epitope-tagged TK. We found that the mutant's TK activity can be accounted for by low levels of full-length TK polypeptide produced by net -1 frameshifting during translation. The efficiency of frameshifting was relatively high, 3-5%, as the polypeptide from the reading frame generated by the deletion, which lacks stop codons (nonstop), was poorly expressed mainly because of inefficient protein synthesis. Stop codons introduced into this reading frame greatly increased its expression, but greatly decreased the level of full-length TK, indicating that frameshifting is strongly stimulated by a new mechanism, nonstop mRNA, which we hypothesize involves stalling of ribosomes on the polyA tail. Mutational studies indicated that frameshifting occurs on or near the C-chord, a region lacking a canonical slippery sequence. Nonstop stimulation of frameshifting also occurred when the C-chord was replaced with a canonical slippery sequence from HIV. This mechanism thus permits biologically and clinically relevant TK synthesis, and may occur more generally.


title: Management of multiple cerebral arteriovenous malformations in a non-pediatric population.

text: BACKGROUND The occurrence of concomitant multiple cerebral arteriovenous malformations (mAVMs) is often associated with hereditary hemorrhagic telangiectasia (HHT) or craniofacial arteriovenous metameric syndrome (CAMS) and frequently occurs in the pediatric population. METHODS Between 1995 and 2013, demographic, clinical, and angiographic data of cerebral AVMs have been prospectively collected. We retrospectively analyzed data of patients presenting multiple cerebral AVMs. RESULTS Six patients (mean age, 44 years, male-to-female ratio, 5) presented an angiographic diagnosis of cerebral mAVMs. Only one of them was known to have a HHT. Five patients presented two cerebral AVMs and one patient had three. Three AVMs (23.1 %) presented bleeding at admission. Three patients had supratentorial mAVMs only and the three others had supra and infratentorial AVMs. Only one patient suffered from bleeding of more than one of his mAVMs with an interval of 23 years. CONCLUSIONS For asymptomatic AVMs discovered incidentally without angiographic bleeding risk, we propose a therapeutic abstention. In case of AVM rupture and bleeding, the other "associated" AVMs (discovered through a complete angiographic assessment) should also be treated if they are not located in an eloquent area and if the treatment does not present technical difficulties. AVMs with a history of bleeding or associated to angiographic risks have to be treated more aggressively.


title: Surgical experience of laparoscopic retroperitoneal triple neurectomy for a patient with chronic neuropathic inguinodynia.

text: BACKGROUND Neuropathic inguinodynia following inguinal hernia repair sometimes becomes a disabling disease. We report a case of successful surgical treatment of chronic refractory neuropathic pain after inguinal hernia by laparoscopic retroperitoneal triple neurectomy. CASE PRESENTATION A seventy-year-old male who underwent right-side inguinal hernia repair using the Lichtenstein method revisited our hospital with inguinodynia 16 months after surgery. After a thorough assessment, the patient was diagnosed with neuropathic pain based on the following: 1) dermatomal mapping suggested ilioinguinal and iliohypogastric nerve problems, 2) pain was evoked by specific movement, 3) the site of maximum pain was slightly changed at every physical examination, and 4) no evidence of recurrence or meshoma was observed on MRI. Conservative therapies were ineffective. Surgical intervention using laparoscopic retroperitoneal triple neurectomy was performed 4 months after treatment initiation. In the lateral recumbent position, a three-port method was used. The ilioinguinal and iliohypogastric nerves and the genital branch of the genitofemoral nerves were identified and resected. Although a residual nerve emerged from L2/3 toward the inguinal region, the nerve remained in situ. Pain assessment 3h after surgery revealed that pain was decreased but remained. Reoperation involving resection of the residual nerve was performed on the same day. Although another type of mild pain appeared 3 months after surgery, the patient resumed normal life, without any restrictions. CONCLUSIONS Laparoscopic retroperitoneal triple neurectomy is useful for treating refractory neuropathic pain. The diagnosis of neuropathic pain via thorough preoperative assessment is vital for procedure success because the procedure would not be effective for other types of pain.


title: Laparoscopic surgery for solid pseudopapillary tumor of the pancreas.

text: BACKGROUND AND OBJECTIVES Solid pseudopapillary tumors of the pancreas are rare and occur most frequently in young women. They have an uncertain pathogenesis and unclear clinical behavior. Our aim was to evaluate the clinical presentation of solid pseudopapillary tumors and assess the efficacy of treatment with minimally invasive surgery. METHODS From March 1997 to February 2011, 13 of 273 patients who underwent laparoscopic procedures on the pancreas were found to have solid pseudopapillary tumors. There were 12 female patients and 1 male patient. The median age was 21 years (range, 15-77 years). Abdominal pain was the most common presenting symptom (n=9). Tumors were incidentally found in 3 patients on computed tomography scans obtained for other reasons. RESULTS Enucleation of the tumor was performed in 4 patients, including 3 in whom the tumor was located in the head of the pancreas. Eight patients underwent distal pancreatectomy with splenectomy, whereas spleen-preserving distal pancreatectomy was performed in one case. The median tumor size was 6 cm (range, 1.5-11 cm), the median operative time was 197 minutes (range, 68-320 minutes), and the median blood loss was 50 mL (range, <50-750 mL). Distal resections were performed with a linear stapler. Four patients had postoperative complications. The median length of hospital stay was 5 days (range, 2-12 days). During a median follow-up period of 11 months (range, 3-121 months), no local recurrences or distant metastases were found. CONCLUSION Laparoscopic resections and enucleations of solid pseudopapillary tumors of the pancreas can be performed safely and with adequate resection margins even if the tumors are located in the head of the organ.


title: Feasibility of Quantification of Intracranial Aneurysm Pulsation with 4D CTA with Manual and Computer-Aided Post-Processing.

text: BACKGROUND AND PURPOSE The analysis of the pulsation of unruptured intracranial aneurysms might improve the assessment of their stability and risk of rupture. Pulsations can easily be concealed due to the small movements of the aneurysm wall, making post-processing highly demanding. We hypothesized that the quantification of aneurysm pulsation is technically feasible and can be improved by computer-aided post-processing. MATERIALS AND METHODS Images of 14 cerebral aneurysms were acquired with an ECG-triggered 4D CTA. Aneurysms were post-processed manually and computer-aided on a 3D model. Volume curves and random noise-curves were compared with the arterial pulse wave and volume curves were compared between both post-processing modalities. RESULTS The aneurysm volume curves showed higher similarity with the pulse wave than the random curves (Hausdorff-distances 0.12 vs 0.25, p<0.01). Both post-processing methods did not differ in intra- (r = 0.45 vs r = 0.54, p>0.05) and inter-observer (r = 0.45 vs r = 0.54, p>0.05) reliability. Time needed for segmentation was significantly reduced in the computer-aided group (3.9 ± 1.8 min vs 20.8 ± 7.8 min, p<0.01). CONCLUSION Our results show pulsatile changes in a subset of the studied aneurysms with the final prove of underlying volume changes remaining unsettled. Semi-automatic post-processing significantly reduces post-processing time but cannot yet replace manual segmentation.


title: Endotracheal tubes for critically ill patients: an in vivo analysis of associated tracheal injury, mucociliary clearance, and sealing efficacy.

text: BACKGROUND Improvements in the design of the endotracheal tube (ETT) have been achieved in recent years. We evaluated tracheal injury associated with ETTs with novel high-volume low-pressure (HVLP) cuffs and subglottic secretions aspiration (SSA) and the effects on mucociliary clearance (MCC). METHODS Twenty-nine pigs were intubated with ETTs comprising cylindrical or tapered cuffs and made of polyvinylchloride (PVC) or polyurethane. In specific ETTs, SSA was performed every 2 h. Following 76 h of mechanical ventilation, pigs were weaned and extubated. Images of the tracheal wall were recorded before intubation, at extubation, and 24 and 96 h thereafter through a fluorescence bronchoscope. We calculated the red-to-green intensity ratio (R/G), an index of tracheal injury, and the green-plus-blue (G+B) intensity, an index of normalcy, of the most injured tracheal regions. MCC was assessed through fluoroscopic tracking of radiopaque markers. After 96 h from extubation, pigs were killed, and a pathologist scored injury. RESULTS Cylindrical cuffs presented a smaller increase in R/G vs tapered cuffs (P = .011). Additionally, cuffs made of polyurethane produced a minor increase in R/G (P = .012) and less G+B intensity decline (P = .022) vs PVC cuffs. Particularly, a cuff made of polyurethane and with a smaller outer diameter outperformed all cuffs. SSA-related histologic injury ranged from cilia loss to subepithelial inflammation. MCC was 0.9 ± 1.8 and 0.4 ± 0.9 mm/min for polyurethane and PVC cuffs, respectively (P < .001). CONCLUSIONS HVLP cuffs and SSA produce tracheal injury, and the recovery is incomplete up to 96 h following extubation. Small, cylindrical-shaped cuffs made of polyurethane cause less injury. MCC decline is reduced with polyurethane cuffs.


title: Dentistry and HIV/AIDS related stigma.

text: OBJECTIVE To analyze HIV/AIDS positive individual's perception and attitudes regarding dental services. METHODS One hundred and thirty-four subjects (30.0% of women and 70.0% of men) from Nuevo León, Mexico, took part in the study (2014). They filled out structured, analytical, self-administered, anonymous questionnaires. Besides the sociodemographic variables, the perception regarding public and private dental services and related professionals was evaluated, as well as the perceived stigma associated with HIV/AIDS, through a Likert-type scale. The statistical evaluation included a factorial and a non-hierarchical cluster analysis. RESULTS Social inequalities were found regarding the search for public and private dental professionals and services. Most subjects reported omitting their HIV serodiagnosis and agreed that dentists must be trained and qualified to treat patients with HIV/AIDS. The factorial analysis revealed two elements: experiences of stigma and discrimination in dental appointments and feelings of concern regarding the attitudes of professionals or their teams concerning patients' HIV serodiagnosis. The cluster analysis identified three groups: users who have not experienced stigma or discrimination (85.0%); the ones who have not had those experiences, but feel somewhat concerned (12.7%); and the ones who underwent stigma and discrimination and feel concerned (2.3%). CONCLUSIONS We observed a low percentage of stigma and discrimination in dental appointments; however, most HIV/AIDS patients do not reveal their serodiagnosis to dentists out of fear of being rejected. Such fact implies a workplace hazard to dental professionals, but especially to the very own health of HIV/AIDS patients, as dentists will not be able to provide them a proper clinical and pharmaceutical treatment.


title: Inhibited osteoclastic bone resorption through alendronate treatment in rats reduces severe osteoarthritis progression.

text: Osteoarthritis (OA) is a non-rheumatoid joint disease characterized by progressive degeneration of extra-cellular cartilage matrix (ECM), enhanced subchondral bone remodeling, osteophyte formation and synovial thickening. Alendronate (ALN) is a potent inhibitor of osteoclastic bone resorption and results in reduced bone remodeling. This study investigated the effects of pre-emptive use of ALN on OA related osteoclastic subchondral bone resorption in an in vivo rat model for severe OA. Using multi-modality imaging we measured effects of ALN treatment within cartilage and synovium. Severe osteoarthritis was induced in left rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with subcutaneous ALN injections and compared to twenty untreated controls. Animals were longitudinally monitored for 12weeks with in vivo μCT to measure subchondral bone changes and SPECT/CT to determine synovial macrophage activation using a folate-based radiotracer. Articular cartilage was analyzed at 6 and 12weeks with ex vivo contrast enhanced μCT and histology to measure sulfated-glycosaminoglycan (sGAG) content and cartilage thickness. ALN treatment successfully inhibited subchondral bone remodeling. As a result we found less subchondral plate porosity and reduced osteophytosis. ALN treatment did not reduce subchondral sclerosis. However, after the OA induction phase, ALN treatment protected cartilage ECM from degradation and reduced synovial macrophage activation. Surprisingly, ALN treatment also improved sGAG content of tibia cartilage in healthy joints. Our data was consistent with the hypothesis that osteoclastic bone resorption might play an important role in OA and may be a driving force for progression of the disease. However, our study suggest that this effect might not solely be effects on osteoclastic activity, since ALN treatment also influenced macrophage functioning. Additionally, ALN treatment and physical activity exercised a positive effect in healthy control joints, which increased cartilage sGAG content. More research on this topic might lead to novel insights as to improve cartilage quality.


title: IMPACT OF GLUCOCORTICOID TREATMENT IN SARS-COV-2 INFECTION MORTALITY: A RETROSPECTIVE CONTROLLED COHORT STUDY.

text: Background: Evidence to support the use of steroids in COVID-19 pneumonia is lacking. We aim to determine the impact of steroid use in COVID-19 pneumonia in-hospital mortality.Patients and Methods: We performed a single-center retrospective cohort study in a University hospital in Madrid, Spain, during March 2020. To determine the role of steroids in in-hospital mortality, patients admitted with SARS-CoV-2 pneumonia and treated with steroids were compared to patients not treated with steroids, adjusting by a propensity-score for steroid treatment. Survival times were compared using log-rank test. Different steroid regimens were compared, and adjusted with a second propensity score.Results: During the study period, 463 out of 848 hospitalized patients with COVID19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) patients were treated with steroids and 67 patients were not. Global mortality was 15.1%. Median time to steroid treatment from symptom onset was 10 days (IQR 8-13). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67], HR 0.51 [0.27-0.96], p= 0.044). Steroid treatment reduced mortality by 41.8% relative to no steroid treatment (RRR 0,42 [0.048- 0.65). Initial treatment with 1 mg/kg/day of methylprednisolone versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86], OR 0.880 [0.449-1.726], p=0.710).Conclusions: Our results show that survival of patients with SARS-CoV2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. In-hospital mortality was not different between initial regimens of 1 mg/kg/day of methylprednisolone and glucocorticoid pulses.


UK's alternative scientific advisers put public health first.


Audio Interview: Emerging Tools in the Fight against Covid-19.


title: Peripheral Nerve Single Cell Analysis Identifies Mesenchymal Ligands that Promote Axonal Growth.

text: Peripheral nerves provide a supportive growth environment for developing and regenerating axons and are essential for maintenance and repair of many non-neural tissues. This capacity has largely been ascribed to paracrine factors secreted by nerve-resident Schwann cells. Here, we used single cell transcriptional profiling to identify ligands made by different injured rodent nerve cell types and have combined this with cell surface mass spectrometry to computationally model potential paracrine interactions with peripheral neurons. These analyses show that peripheral nerves make many ligands predicted to act on peripheral and central nervous system neurons, including known and previously uncharacterized ligands. While Schwann cells are an important ligand source within injured nerves, more than half of the predicted ligands are made by nerve-resident mesenchymal cells, including the endoneurial cells most closely associated with peripheral axons. At least three of these mesenchymal ligands, ANGPT1, CCL11 and VEGFC, promote growth when locally applied on sympathetic axons. These data therefore identify an unexpected paracrine role for nerve mesenchymal cells and suggest that multiple cell types contribute to creating a highly pro-growth environment for peripheral axons.SIGNIFICANCE STATEMENT This work expands our understanding of the cellular sources of ligands in the injured peripheral nerve that are potentially important for promoting axon growth. Here, we used single cell RNA sequencing (scRNA-seq) to reveal that Schwann cells and, surprisingly, nerve mesenchymal cells are primary sources of ligands in the injured nerve. We then combined injured nerve scRNA-seq data with proteomic and transcriptomic data from sensory and sympathetic neurons and used a systems-biology/modeling approach to predict novel mesenchymal cell-derived factors that may promote peripheral axon growth. We tested some of these predictions and found three factors, ANGPT1, CCL11 and VEGFC, that promoted outgrowth of cultured sympathetic axons, supporting a potential role for mesenchymal-derived factors in axon growth.


title: Performance measures for ERCP and endoscopic ultrasound: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative.

text: The European Society of Gastrointestinal Endoscopy and United European Gastroenterology present a short list of key performance measures for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). We recommend that endoscopy services across Europe adopt the following seven key and one minor performance measures for EUS and ERCP, for measurement and evaluation in daily practice at center and endoscopist level: 1: Adequate antibiotic prophylaxis before ERCP (key performance measure, at least 90 %); 2: Antibiotic prophylaxis before EUS-guided puncture of cystic lesions (key performance measure, at least 95 %); 3: Bile duct cannulation rate (key performance measure, at least 90 %); 4: Tissue sampling during EUS (key performance measure, at least 85 %); 5: Appropriate stent placement in patients with biliary obstruction below the hilum (key performance measure, at least 95 %); 6: Bile duct stone extraction (key performance measure, at least 90 %); 7: Post-ERCP pancreatitis (key performance measure, less than 10 %). 8: Adequate documentation of EUS landmarks (minor performance measure, at least 90 %).This present list of quality performance measures for ERCP and EUS recommended by ESGE should not be considered to be exhaustive: it might be extended in future to address further clinical and scientific issues.


title: Evaluation of single port access gastropexy and ovariectomy using articulating instruments and angled telescopes in dogs.

text: OBJECTIVE To describe in dogs, a technique for single port access gastropexy and ovariectomy (SPAGO) using a commercially available multitrocar port and to evaluate short-term outcome. DESIGN Retrospective case series. ANIMALS Dogs (n = 18). PROCEDURES A commercially available multitrocar port was inserted into the abdomen lateral to the rectus abdominis muscle and 2-5 cm caudal to the right rib. Dogs were tilted 45° in both left and right recumbency and bilateral ovariectomy performed using articulating graspers, a bipolar vessel sealing device and a 30° telescope. The laparoscopic assisted incisional gastropexy was performed after ovariectomy at the multitrocar port insertion site by grasping the antral portion of the stomach with a 10 mm DuVall forceps and suturing the seromuscular layer of the antral region of the stomach to the transversus abdominis muscle. RESULTS Eighteen dogs (median weight, 34.5 kg; range, 14.7-59.2 kg) met the inclusion criteria. Median surgical time for SPAGO was 65 minutes (range, 50-225 minutes). Intra-operative complications included, incorrect multitrocar port placement location (n = 3) and mild hemorrhage from a splenic laceration (1) All dogs recovered from surgery and were discharged from the hospital. CONCLUSIONS Single port access gastropexy and ovariectomy is a feasible procedure to provide prophylaxis against gastric dilation-volvulus and a simultaneous means of sterilization in female dogs. Careful and accurate initial multitrocar port insertion is necessary to have optimal operative viewing as well as to reduce the chances of inadvertent splenic laceration.


COVID-19 and Pediatric Orthopaedics: What's Different?


title: COVID-19: Pathogenesis, Genetic Polymorphism, Clinical Features and Laboratory Findings.

text: COVID-19 caused by a novel agent SARS-CoV-2 progressed to a pandemic condition and resulted in a major public health concern worldwide, leading to social and economic issues at the same time. The pathogenesis of COVID-19 starts with the bonding of the virus to ACE-2 receptors expressed in many tissues, and the triggered excessive immune response plays a critical role in the course of the disease. The cytokine storm that occurs upon excessive production of pro-inflammatory cytokines is considered responsible for the severe progression of the disease and the organ damage. However, the accurate pathophysiological mechanism of the disease, which progresses with various clinical presentations, is still substantially unknown. While various studies have been conducted on the effect of genetic polymorphism on the course and severity of the disease, the presence of a significant effect has not been proven yet. The clinical course of the disease is variable, with clinical representation ranging from 81% mild course to 14% severe course along with 5% critical course in patients. Asymptomatic course is considered to be higher than expected, although its frequency is not known exactly. Older adults and those with comorbidities are exposed to a more severe disease course. The disease progress with various symptoms, such as fever, cough, dyspnea, malaise, myalgia, taste and smell dysfunctions, diarrhea, and headache. A range of complications (Acute Respiratory Distress Syndrome, thromboembolic conditions, arrhythmia and cardiac events, secondary infections) could be seen during the course of the disease. Varied laboratory tests are vital to determine the severity and prognosis of the disease, along with the condition and exposure of the affected systems during the course of COVID-19.


Smartphone assisted slit lamp evaluation during the COVID-19 pandemic.


title: Dual-port laparoscopic abdominoperineal resection using the intended stoma site as the multichannel port.

text: We describe a novel minimally invasive procedure: dual-port laparoscopic abdominoperineal resection using a SILS port, and report our experience of using this to treat ten patients with lower rectal cancer. A SILS port was placed in the left lower quadrant at the intended colostomy site. A 5-mm trocar was inserted at the umbilicus at the subsequent drain site. Via a standard laparoscopic medial-to-lateral approach, the inferior mesenteric artery and vein were ligated and total mesorectal excision was performed. Via a perineal approach, the specimen was retrieved from the perineal wound, and a sigmoid colostomy was created at the site of the SILS port. Ten consecutive patients with lower rectal cancer at clinical stage T3 or lower underwent the procedure at our institution. The procedure was completed successfully in all patients, without any intraoperative problems and all postoperative outcomes were satisfactory. Thus, dual-port laparoscopic abdominoperineal resection can be performed safely and feasibly in selected patients.


title: Prolonged intermittent virus shedding during an outbreak of canine influenza A H3N2 virus infection in dogs in three Chicago area shelters: 16 cases (March to May 2015).

text: OBJECTIVE To estimate an appropriate isolation period for dogs infected with canine influenza A H3N2 virus on the basis of the duration of virus shedding. DESIGN Retrospective case series. ANIMALS 16 dogs, from 3 Chicago area shelters, naturally infected with canine influenza A H3N2 virus. PROCEDURES Medical records of 16 affected dogs were reviewed. Nasal swab specimens from each dog had been tested periodically for a minimum of 15 days following an initial positive real-time reverse transcriptase PCR (rRT-PCR) assay result for influenza A virus shedding. Amplicons were purified, quantified, and sequenced by the Sanger DNA sequencing technique. Virus isolation and sequence results of canine influenza A H3N2 virus from nasal swab specimens were obtained in conjunction with signalment, description of clinical signs, type of treatment, and outcome. RESULTS Viruses from each dog were identified as canine influenza A H3N2 virus on the basis of DNA sequencing. The interval between first and last positive rRT-PCR assay results ranged from 13 to 24 days, whereas the time interval from first reported clinical signs to last positive assay results ranged from 15 to 26 days. Isolation of canine influenza A H3N2 virus was successful in the late shedding period from nasal swab specimens of 4 dogs at 15 and 20 days after the first positive rRT-PCR assay result and 18 to 20 days after the first clinical signs. Clinical signs resolved for all dogs that remained in the shelters during the testing period. CONCLUSIONS AND CLINICAL RELEVANCE Dogs infected with H3N2 virus should be isolated for a period of ≥ 21 days following onset of illness. Even when resolution of clinical signs occurs sooner than 21 days, shedding of H3N2 virus may persist.


title: Comparative effectiveness and safety of gastric bypass, sleeve gastrectomy and adjustable gastric banding in a population-based bariatric program: prospective cohort study.

text: BACKGROUND Bariatric surgery in Canada is primarily delivered within publicly funded specialty clinics. Previous studies have demonstrated that bariatric surgery is superior to intensive medical management for reduction of weight and obesity-related comorbidities. Our objective was to compare the effectiveness and safety of laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (LSG) and adjustable gastric banding (LAGB) in a publicly funded, population-based bariatric treatment program. METHODS We followed consecutive bariatric surgery patients for 2 years. The primary outcome was weight change (in kilograms). Between-group changes were analyzed using multivariable regression. Last-observation-carried-forward imputation was used for missing data. RESULTS We included 150 consecutive patients (51 RYGB; 51 LSG; 48 LAGB) in our study. At baseline, mean age was 43.5 ± 9.5 years, 87.3% of patients were women, and preoperative body mass index (BMI) was 46.2 ± 7.4. Absolute and relative (% of baseline) weight loss at 2 years were 36.6 ± 19.5 kg (26.1 ± 12.2%) for RYGB, 21.4 ± 16.0 kg (16.4 ± 11.6%) for LSG and 7.0 ± 9.7 kg (5.8 ± 7.9%) for LAGB (p < 0.001). Change in BMI was greater for the RYGB (-13.0 ± 6.6) than both the LSG (-7.6 ± 5.7) and the LAGB (-2.6 ± 3.5) groups (p < 0.001). The reduction in diabetes, hypertension and dyslipidemia was greater after RYGB than after LAGB (all p < 0.05). There were no deaths. The anastomotic and staple leakage rate was 1.3%. CONCLUSION In a publicly funded, population-based bariatric surgery program, RYGB and LSG demonstrated greater weight loss than the LAGB procedure. Bypass resulted in the greatest reduction in obesity-related comorbidities. All procedures were safe.


title: Enhancing Engagement during Live Virtual Learning using Interactive Quizzes.

text: The COVID-19 pandemic has foisted unprecedented changes upon graduate medical education ranging from adjustments to patient care practices to adaptive modifications to educational activities. To comply with social distancing guidelines, in-person conferences and didactics have been suspended in most, if not all residency programs throughout the country. Many programs, however, have transitioned to live virtual platforms such as Zoom to continue educational activities. While live virtual learning has allowed for continued education, it presents its unique challenges. The impersonal nature of the virtual learning environment creates a propensity for detachment and disengagement. While the video function is turned off and the microphone is muted, a participant can completely disengage from virtual learning while still appearing to be present.


docid: kpocrqwg

title: Giant solitary fibrous tumor of the pleura: A case report.

text: A 62-year-old male farmer weighing 79 kg was taken to a hospital after experiencing exertional dyspnea and shortness of breath for a month. A chest roentgenogram and computed tomography showed a giant mass in his right thorax. A CT-guided biopsy demonstrated a solitary fibrous tumor of the pleura (SFTP). Because of the large size of the tumor and the substantial pleural effusion in the right hemithorax, the patient was referred to our institution for radiofrequency ablation. After one month, we performed an exploratory thoracotomy to dissect the giant mass with the right, middle, and lower lobes. The measurement of the tumor was 20 cm × 18 cm × 13 cm and it weighed 3250 g. The histopathology of the resected specimen confirmed SFTP. The patient had no postoperative complications; six months after surgery, no recurrence occurred.


title: A pilot cohort study of cerebral autoregulation and 2-year neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy who received therapeutic hypothermia.

text: BACKGROUND Neurodevelopmental disabilities persist in survivors of neonatal hypoxic-ischemic encephalopathy (HIE) despite treatment with therapeutic hypothermia. Cerebrovascular autoregulation, the mechanism that maintains cerebral perfusion during changes in blood pressure, may influence outcomes. Our objective was to describe the relationship between acute autoregulatory vasoreactivity during treatment and neurodevelopmental outcomes at 2 years of age. METHODS In a pilot study of 28 neonates with HIE, we measured cerebral autoregulatory vasoreactivity with the hemoglobin volume index (HVx) during therapeutic hypothermia, rewarming, and the first 6 h of normothermia. The HVx, which is derived from near-infrared spectroscopy, was used to identify the individual optimal mean arterial blood pressure (MAPOPT) at which autoregulatory vasoreactivity is greatest. Cognitive and motor neurodevelopmental evaluations were completed in 19 children at 21-32 months of age. MAPOPT, blood pressure in relation to MAPOPT, blood pressure below gestational age + 5 (ga + 5), and regional cerebral oximetry (rSO2) were compared to the neurodevelopmental outcomes. RESULTS Nineteen children who had HIE and were treated with therapeutic hypothermia performed in the average range on cognitive and motor evaluations at 21-32 months of age, although the mean performance was lower than that of published normative samples. Children with impairments at the 2-year evaluation had higher MAPOPT values, spent more time with blood pressure below MAPOPT, and had greater blood pressure deviation below MAPOPT during rewarming in the neonatal period than those without impairments. Greater blood pressure deviation above MAPOPT during rewarming was associated with less disability and higher cognitive scores. No association was observed between rSO2 or blood pressure below ga + 5 and neurodevelopmental outcomes. CONCLUSION In this pilot cohort, motor and cognitive impairments at 21-32 months of age were associated with greater blood pressure deviation below MAPOPT during rewarming following therapeutic hypothermia, but not with rSO2 or blood pressure below ga + 5. This suggests that identifying individual neonates' MAPOPT is superior to using hemodynamic goals based on gestational age or rSO2 in the acute management of neonatal HIE.


Laparoscopic gastrojejunostomy revision: a novel approach to intractable marginal ulcer management.


title: Hourly photosynthetically active radiation estimation in Midwestern United States from artificial neural networks and conventional regressions models.

text: The relationship between hourly photosynthetically active radiation (PAR) and the global solar radiation (R s ) was analyzed from data gathered over 3 years at Bondville, IL, and Sioux Falls, SD, Midwestern USA. These data were used to determine temporal variability of the PAR fraction and its dependence on different sky conditions, which were defined by the clearness index. Meanwhile, models based on artificial neural networks (ANNs) were established for predicting hourly PAR. The performance of the proposed models was compared with four existing conventional regression models in terms of the normalized root mean square error (NRMSE), the coefficient of determination (r (2)), the mean percentage error (MPE), and the relative standard error (RSE). From the overall analysis, it shows that the ANN model can predict PAR accurately, especially for overcast sky and clear sky conditions. Meanwhile, the parameters related to water vapor do not improve the prediction result significantly.


title: Molecular Epidemiology of the Human Rhinovirus Infection in Mongolia during 2008-2013.

text: Rhinovirus infections are common in all age groups world-wide, and they occur throughout the year. In this study, we examined 2,689 nasopharyngeal swabs collected in Mongolia during 2008-2013. Human rhinoviruses (HRVs) were detected in 295 (11.0%) samples, and 85 (28.8%) patients were co-infected with other respiratory viruses. HRV was co-detected with bocavirus, human coronavirus, and respiratory syncytial virus in 21 (24.7%), 17 (20.0%), and 14 (16.5%), respectively. We tested 170 (57.6%) of the 295 HRV-positive samples: 117 HRV strains were typed by using the VP4/VP2 method and 53 by using 5' UTR method. We found HVR-A, HVR-C, and HVR-B infections in 80 (47.1%), 76 (44.7%), and 14 (8.2%) samples, respectively.


Providing nutritional support for the patient with COVID-19.


docid: lfublowd

title: What was old is new again: using the host response to diagnose infectious disease.

text: A century of advances in infectious disease diagnosis and treatment changed the face of medicine. However, challenges continue to develop including multi-drug resistance, globalization that increases pandemic risks and high mortality from severe infections. These challenges can be mitigated through improved diagnostics, focusing on both pathogen discovery and the host response. Here, we review how 'omics' technologies improve sepsis diagnosis, early pathogen identification and personalize therapy. Such host response diagnostics are possible due to the confluence of advanced laboratory techniques (e.g., transcriptomics, metabolomics, proteomics) along with advanced mathematical modeling such as machine learning techniques. The road ahead is promising, but obstacles remain before the impact of such advanced diagnostic modalities is felt at the bedside.


title: Laparoscopic partial nephrectomy for the treatment of large cystic nephroma in children.

text: UNLABELLED Abstract Background: Cystic nephroma (CN) is a rare benign renal neoplasm. The differential diagnosis of cystic partially differentiated nephroblastoma is only possible with pathological findings. Therefore, surgical resection is necessary to diagnose suspected CN lesions. Because CN is usually well demarcated and has a good prognosis, partial nephrectomy is recommended for its treatment. However, to our knowledge, laparoscopic treatment of CN has not been reported. We describe 2 cases of large CNs successfully treated: Case 1 was a 9-month-old boy with a lower polar mass in the right kidney, which occupied two-thirds of the kidney, and Case 2 was a 9-month-old boy with an upper polar mass in the left kidney, which occupied three-fourths of the kidney. MATERIALS AND METHODS Using the transperitoneal approach, the lesion was detected by a laparoscopic ultrasound probe, and vessels in the affected region were dissected. After the renal artery was clamped with bulldog clips, the parenchyma of the affected region was divided with an ultrasonically activated scalpel. The partly cut pelvis was closed by suturing, and the resected stump was coated with hemostatic agents and covered with the pediculate peritoneum. RESULTS The lesion was not exposed during surgery, and the microscopic features were consistent with CN in both cases. Residual renal function was good, and no residual tumor was found in both cases for over a year. CONCLUSIONS Laparoscopic partial nephrectomy is a feasible approach to treat large CNs. When it is difficult to close the resection stump by parenchymal suturing, covering the stump with hemostatic agents and pediculate peritoneum is feasible.


Seroprevalence of SARS-CoV-2-Specific Antibodies Among Adults in Los Angeles County, California, on April 10-11, 2020.


title: A new type of absorbable barbed suture for use in laparoscopic myomectomy.

text: OBJECTIVE To compare effectiveness, feasibility, and suturing time required between an absorbable barbed wire (V-Loc) uterine suture and a classic continuous suture with intracorporeal knots among women undergoing laparoscopic myomectomy. METHODS From January 2010 to February 2011, women with single symptomatic intramural myoma were prospectively enrolled in a single-center study at a university hospital in Rome, Italy. A control group with characteristics meeting the criteria for study inclusion was retrospectively identified from the hospital databases. In the prospective group uterine wall defects were closed with V-Loc suture, whereas in the control group they were closed by classical continuous suture with intracorporeal knots. Data were analyzed via Student t test, Mann-Whitney U test, and Fisher exact test. RESULTS The mean operative time was shorter in the V-Loc (51±18.1 min) than in the control (58±17.8 min) group. Suturing time was significantly lower in the V-Loc than in the control (9.9±4.3 versus 15.8±4.7 min; P=0.0004) group. Both intraoperative bleeding and drop in hemoglobin were significantly lower in the V-Loc group (P=0.0076 and P=0.0176, respectively). CONCLUSION Use of a barbed suture may aid surgeons during laparoscopic suturing by reducing operative time, suturing time, and blood loss.


title: Experimental study of the potential hazards of surgical smoke from powered instruments.

text: BACKGROUND Many surgical instruments have been replaced with powered devices in open gastrointestinal and laparoscopic surgery. The production of smoke as a result of vaporization of surgical tissue is inevitable, and exposure to surgical smoke is a long-standing concern. These vapours are potentially hazardous to patients and surgical teams. The present research was designed to compare various surgical devices to determine whether viable cells exist in their surgical smoke. METHODS The search for viable cells in surgical smoke was conducted using both in vitro and in vivo experiments. Various cancers were cauterized with electrocautery, radiofrequency ablation and ultrasonic scalpels, and the resulting surgical smoke was aspirated with Transwell(®) membrane; viable cells were sought in the surgical smoke. In an in vivo experiment, samples of SCC7 were cauterized with an ultrasonic scalpel and the sediment from the rinsed Transwell(®) membrane liquid after centrifugation was injected subcutaneously into the lower back of mice. RESULTS Viable cells were found only in the smoke from ultrasonic scalpels (in all 25 samples taken 5 cm from the cautery; 2 of 25 samples at 10 cm). Viable cells in the surgical smoke from ultrasonic scalpels implanted in mice grew in 16 of 40 injection sites. Histological and biochemical analyses revealed that these cancer cells were identical to the cancer cells cauterized by the ultrasonic scalpel. CONCLUSION Viable tumour cells are produced in the surgical smoke from tumour dissection by ultrasonic scalpel. Surgical relevance Surgical smoke is a byproduct of dissection using a number of powered devices. Hazards to operating room personnel and patients are unclear. This study has shown that use of an ultrasonic dissection device can produce smoke that contains viable tumour cells. Although the model is somewhat artificial, a theoretical risk exists, and measures to evacuate surgical smoke efficiently are important.


title: A case of anaphylactoid reaction to acetate in acetate-containing bicarbonate dialysate.

text: A 35-year-old man with end-stage kidney disease due to chronic glomerulonephritis was admitted to our hospital to start maintenance hemodialysis (HD). One hour after starting the first session of HD, he experienced general pruritus, urticaria, and dyspnea. Signs and symptoms were resolved by discontinuing HD and administrating an antihistamine drug; HD-associated anaphylactoid reactions were therefore suspected. Over the next few HD sessions, we changed the dialysis membrane, anticoagulant, HD circuit and needle, in that order, but general pruritus and urticaria again appeared within 3 h after starting each session of HD. Finally, when we changed the dialysate from acetate-containing bicarbonate dialysate to acetate-free bicarbonate dialysate, urticaria was clearly less than that seen in previous HD sessions, and subsided after discontinuation of HD. Subsequently, 20 mg of oral prednisolone (PSL) was administered 1 h before starting HD, and the patient did not experience general pruritus, urticaria, or dyspnea after starting the session. When administered acetate-containing bicarbonate dialysate after oral PSL pretreatment, the patient again experienced general pruritus, urticaria and dyspnea. Few reports have been published on the occurrence of anaphylactoid reactions during HD using acetate dialysate. We report a rare case of anaphylactoid reactions with acetate in acetate-containing bicarbonate dialysate that were reduced with the use of acetate-free bicarbonate dialysate and oral PSL pretreatment.


title: Understanding intestinal glucose transporter expression in obese compared to non-obese subjects.

text: INTRODUCTION The impact of Roux-en-Y gastric bypass (RYGB) on weight loss and co-morbid disease resolution is well established. However, the mechanisms underlying the procedure remain incompletely understood. Intestinal remodeling involving glucose transporters (GLUTs) may play a crucial role. Rat studies have demonstrated morphological adaptation of GLUTs within adipose and intestinal cells in association with the reprogramming of glucose metabolism. There is a limited understanding of the variations in expression amongst GLUT family receptors in the human intestine. The aim of this study was to evaluate and describe jejunal GLUT expression patterns in the obese versus non-obese. METHODS Tissue samples were collected from 19 adults (age ≥18) patients with morbid obesity undergoing elective RYGB. Specimens were obtained from excess jejunum removed during the stapled jejuno-jejunal anastomosis. All subjects met National Institutes of Health criteria for bariatric surgery (body mass index or BMI ≥40 or ≥35 with obesity-related comorbidities). Exclusion criteria included age less than 18, age greater than 65, patients undergoing a revision procedure, and the presence of a seizure disorder (possible association with GLUT-1 deficiency syndrome). Five samples were obtained from non-obese subjects (average BMI 26.7) without diabetes who were consenting organ donors after brain death. Samples of jejunum from non-obese individuals were obtained at the time of organ procurement. Institutional Review Board and Gift of Hope approval was obtained. Specimens underwent quantitative real-time PCR and Western blotting. Western blot densitometry was performed using Image J software. Student T test was performed using SPSS statistics software. RESULTS GLUT-1 and GLUT-7 expression were not detected in the jejunum of either group. No difference in expression pattern was observed for GLUT-2, GLUT-4, and GLUT-9 between the groups. Western blot band density of GLUT-5 to loading control (GADPH) mean ratio was 0.21 (SD = 0.20) in obese specimens compared to 0.56 (SD = 0.17) in non-obese. Densitometry revealed GLUT-5 levels in the jejunum of the obese were significantly lower than non-obese specimens (P < 0.05). CONCLUSION The absence of GLUT-1 expression in both the obese and non-obese groups is consistent with the established view of GLUT-1 being abundantly present in fetal intestine but diminished to negligible levels by adulthood. Decreased GLUT-5 expression in samples from subjects with obesity compared to non-obese samples may represent a down-regulation of gene expression amongst the obese. The differential expression of GLUT-5 suggests a possible role in obesity. Studies of GLUT family expression will aid in understanding the impact of intestinal remodeling on obesity.


title: The COVID-19 Pandemic and its Impact on Plastic Surgery in Europe - An ESPRAS Survey.

text: The present article provides an overview of the current and expected effects of plastic surgery in Europe. It presents the experience of departments for plastic and reconstructive surgery, as evaluated by interviews with members of the Executive Committee (ExCo) of the European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS). The objective of this overview is to summmarise current information in our area of work and to make this accessible to a broad group of readers. As our knowledge is rapidly increasing during the current pandemic, it is evident that we can only provide a snapshot and this will inevitably be incomplete.


A case of femoral arteriovenous fistula caused by central venous catheterization under inadequate ultrasound guidance.


title: A Population Pharmacokinetic Model of Intravenous Dexmedetomidine for Mechanically Ventilated Children after Neurosurgery.

text: Dexmedetomidine is a selective alpha-2 adrenergic agonist with concurrent sedative and analgesic effects, and it is being increasingly used in pediatric anesthesia and intensive care. This study aimed to investigate the pharmacokinetics of intravenous dexmedetomidine in mechanically ventilated children in the intensive care unit (ICU) after neurosurgery. Pediatric patients aged 2-12 years, who were mechanically ventilated in ICU after neurosurgery, were allocated into a low-dose (n = 15) or high-dose (n = 14) group. The low-dose group received dexmedetomidine at a loading dose of 0.25 µg/kg for 10 min, followed by a maintenance dose of 0.25 µg/kg/h for 50 min, whereas the high-dose group received dexmedetomidine at a loading dose of 0.5 µg/kg for 10 min, followed by a maintenance dose of 0.5 µg/kg/h for 50 min. Serial blood samples were collected for a pharmacokinetic analysis up to 480 min after the end of the infusion. The sedative effect of dexmedetomidine was assessed using the Bispectral Index and University of Michigan Sedation Scale. Adverse reactions, electrocardiography findings, and vital signs were monitored for a safety assessment. A population pharmacokinetic analysis was performed using non-linear mixed effects modeling. Dexmedetomidine induced a moderate-to-deep degree of sedation during infusion in both groups. The pharmacokinetics of dexmedetomidine were best described by a two-compartment disposition model with first-order elimination kinetics. The parameters were standardized for a body weight of 70 kg using an allometric power model. The population estimates (95% confidence interval) per 70 kg body weight were as follows: clearance of 81.0 (72.9-90.9) L/h, central volume of distribution of 64.2 (50.6-81.0) L, intercompartment clearance of 116.4 (90.6-156.0) L/h, and peripheral volume of distribution of 167 (132-217) L. No serious adverse reactions or hemodynamic changes requiring the discontinuation of dexmedetomidine were observed. Dexmedetomidine had increased clearance and volume of distribution in mechanically ventilated children in ICU after neurosurgery, thereby indicating the need to adjust the dosage to obtain a target plasma concentration.


title: Development of a nucleocapsid-based human coronavirus immunoassay and estimates of individuals exposed to coronavirus in a U.S. metropolitan population.

text: Coronaviruses cause respiratory infections ranging from common colds to severe acute respiratory syndrome (SARS) in humans. Estimates for exposure to non-SARS coronaviruses are high, particularly for 229E and OC43; however, less information regarding seroprevalence is available for HKU1 and NL63. To measure exposure rates to these four coronavirus strains (229E, HKU1, NL63, and OC43), we devised an immunoassay based on amino- and carboxy-terminally tagged recombinant coronavirus nucleocapsid antigens. Four human and one feline coronavirus antigen were cloned into baculoviruses expressed in insect cells and recovered proteins bound in the solid phase of an enzyme-linked immunosorbent assay-based system. We screened sera from 10 children and 196 adults and established primary cutoff points based on immunoglobulin G (IgG) antibody levels of the predominantly seronegative children. The proportion of seropositive adults for each coronavirus was as follows: 229E, 91.3%; HKU1, 59.2%; NL63, 91.8%; and OC43, 90.8%. No evidence of a significant serological response to the feline coronavirus was observed. Significant associations of coronavirus seropositivity and antibody levels with age, gender, race, socioeconomic status, smoking status, and season of the blood draw were tested with chi-square and regression analyses. The group II coronaviruses (OC43 and HKU1) were significantly associated with race (P<or=0.009 and P<or=0.03, respectively). Elevated OC43 IgG levels were further significantly associated with smoking status (P<or=0.03), as were high NL63 titers with socioeconomic status (P<or=0.04). The high-level immunoreactivity of each coronavirus was significantly associated with the summer season (P<or=0.01 to 0.0001). In summary, high rates of exposure to 229E, NL63, and OC43 and a moderate rate of exposure to HKU1 characterized the seroprevalence among individuals in this population. Demographic factors, such as race, smoking status, and socioeconomic status, may confer an increased risk of susceptibility to these viruses.


title: Clinical and pathological investigation of severe COVID-19 patients.

text: BACKGROUND Severe acute respiratory coronavirus 2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) has become a pandemic. This study addressed the clinical and immunopathological characteristics of severe COVID-19. METHODS Sixty-nine COVID-19 patients were classified into as severe and non-severe groups to analyze their clinical and laboratory characteristics. A panel of blood cytokines was quantified over time. Biopsy specimens from two deceased cases were obtained for immunopathological, ultrastructural, and in situ hybridization examinations. RESULTS Circulating cytokines, including IL8, IL6, TNFα, IP10, MCP1, and RANTES, were significantly elevated in severe COVID-19 patients. Dynamic IL6 and IL8 were associated with disease progression. SARS-CoV-2 was demonstrated to infect type II, type I pneumocytes and endothelial cells, leading to severe lung damage through cell pyroptosis and apoptosis. In severe cases, lymphopenia, neutrophilia, depletion of CD4+ and CD8+ T lymphocytes, and massive macrophage and neutrophil infiltrates were observed in both blood and lung tissues. CONCLUSIONS A panel of circulating cytokines could be used to predict disease deterioration and inform clinical interventions. Severe pulmonary damage was predominantly attributed to both SARS-CoV-2 caused cytopathy and immunopathologic damage. Strategies that encourage pulmonary recruitment and overactivation of inflammatory cells by suppressing cytokine storm might improve the outcomes of severe COVID-19 patients.


title: Methadone safety: a clinical practice guideline from the American Pain Society and College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society.

text: UNLABELLED Methadone is used for the treatment of opioid addiction and for treatment of chronic pain. The safety of methadone has been called into question by data indicating a large increase in the number of methadone-associated overdose deaths in recent years that has occurred in parallel with a dramatic rise in the use of methadone for chronic pain. The American Pain Society and the College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society, commissioned an interdisciplinary expert panel to develop a clinical practice guideline on safer prescribing of methadone for treatment of opioid addiction and chronic pain. As part of the guideline development process, the American Pain Society commissioned a systematic review of various aspects related to safety of methadone. After a review of the available evidence, the expert panel concluded that measures can be taken to promote safer use of methadone. Specific recommendations include the need to educate and counsel patients on methadone safety, use of electrocardiography to identify persons at greater risk for methadone-associated arrhythmia, use of alternative opioids in patients at high risk of complications related to corrected electrocardiographic QTc interval prolongation, careful dose initiation and titration of methadone, and diligent monitoring and follow-up. Although these guidelines are based on a systematic review, the panel identified numerous research gaps, most recommendations were based on low-quality evidence, and no recommendations were based on high-quality evidence. PERSPECTIVE This guideline, based on a systematic review of the evidence on methadone safety, provides recommendations developed by a multidisciplinary expert panel. Safe use of methadone requires clinical skills and knowledge in use of methadone to mitigate potential risks, including serious risks related to risk of overdose and cardiac arrhythmias.


title: Microwave ablation of pancreatic tumors.

text: OBJECTIVES To evaluate the clinical performance of percutaneous microwave ablation (MWA) for treatment of locally-advanced-pancreatic-cancer (LAPC). MATERIAL AND METHODS Twenty-two MWA sessions (August 2015-March 2017) in 20 patients with primary pancreatic cancer (13 men, 7 women, mean-age: 59.9 ± 8.6 years, range: 46-73 years), who had given informed consent, were retrospectively evaluated. All procedures were performed percutaneously under CT-guidance using the same high-frequency (2.45-GHz) MWA device. Tumor location and diameter, ablation diameter and volume, roundness, duration, technical success and efficacy, output energy, complications, and local tumor progression defined as a tumor focus connected to the edge of a previously technically efficient ablation zone were collected. RESULTS Seventeen pancreatic malignant tumors (77.3%) were located in the pancreatic head and five (22.7%) in the pancreatic tail. Initial Mean Tumor Diameter was 30 ± 6 mm. Technical success and efficacy were idem (100%). No major complications occurred. Two patients (9.1%) showed minor complications of severe local pain related to MWA. Post-ablation diameter was on average 34.4 ± 5.8 mm. Mean ablation volume was 7.8 ± 3.8 cm³. The mean transverse roundness index was 0.74 ± 0.14. Mean ablation time was 2.6 ± 0.96 min. The mean applied energy per treatment was 9627 ± 3953 J. Local tumor progression was documented in one case (10%) of the 10/22 available three-month follow-up imaging studies. CONCLUSION High-frequency (2.45 GHz) microwave ablation (MWA) for treatment of unresectable and non-metastatic locally-advanced-pancreatic-cancer (LAPC) shows promising results regarding feasibility and safety of percutaneous approach after short-term follow-up and should be further evaluated.


Treatment of catamenial pneumothorax with absorbable mesh, pleurectomy and pleural abrasion.


Pandemic pressure: policy, politics, profession, and rapid publication.


Let COVID-19 expand awareness of disability tech.


title: What will be the new normal for the dental industry?

text: The COVID-19 situation has seen the cessation of all non-urgent dental care in the UK. Regular practice activity has come to a virtual standstill and the dental industry has seen a very significant reduction in its provision of products and services. There are differing government financial mitigations in place across dental practices for NHS and, to an extent private, activity, as well as for the dental industry. Dentistry is generally classified in the very high-risk category of aerosol production through many aerosol generating procedures (AGPs). To facilitate any move towards the resumption of widespread dental treatment, possibly without mass vaccination or the widespread use of antibody testing, the aerosol issue will need to be addressed and solved. From a dental industry perspective, equipment and product manufacturers and suppliers are building upon, and further developing, the industry's extremely close relationship and partnership with the dental profession, in order to develop and implement new ways of thinking and new approaches, products and techniques to protect patients and clinicians, focusing on a return to the more widespread provision of dentistry.


title: Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3' to 5' exonuclease activity essential for immune suppression.

text: Lassa fever virus, a member of the family Arenaviridae, is a highly endemic category A pathogen that causes 300,000-500,000 infections per year in Western Africa. The arenaviral nucleoprotein NP has been implicated in suppression of the host innate immune system, but the mechanism by which this occurs has remained elusive. Here we present the crystal structure at 1.5 Å of the immunosuppressive C-terminal portion of Lassa virus NP and illustrate that, unexpectedly, its 3D fold closely mimics that of the DEDDh family of exonucleases. Accompanying biochemical experiments illustrate that NP indeed has a previously unknown, bona fide exonuclease activity, with strict specificity for double-stranded RNA substrates. We further demonstrate that this exonuclease activity is essential for the ability of NP to suppress translocation of IFN regulatory factor 3 and block activation of the innate immune system. Thus, the nucleoprotein is a viral exonuclease with anti-immune activity, and this work provides a unique opportunity to combat arenaviral infections.


Ebola, ethics, and public health: what next?


title: From Wearable Sensors to Smart Implants--Toward Pervasive and Personalized Healthcare.

text: OBJECTIVE This paper discusses the evolution of pervasive healthcare from its inception for activity recognition using wearable sensors to the future of sensing implant deployment and data processing. METHODS We provide an overview of some of the past milestones and recent developments, categorized into different generations of pervasive sensing applications for health monitoring. This is followed by a review on recent technological advances that have allowed unobtrusive continuous sensing combined with diverse technologies to reshape the clinical workflow for both acute and chronic disease management. We discuss the opportunities of pervasive health monitoring through data linkages with other health informatics systems including the mining of health records, clinical trial databases, multiomics data integration, and social media. CONCLUSION Technical advances have supported the evolution of the pervasive health paradigm toward preventative, predictive, personalized, and participatory medicine. SIGNIFICANCE The sensing technologies discussed in this paper and their future evolution will play a key role in realizing the goal of sustainable healthcare systems.


title: Functional evaluations comparing the double-tract method and the jejunal interposition method following laparoscopic proximal gastrectomy for gastric cancer: an investigation including laparoscopic total gastrectomy.

text: PURPOSE Functional outcomes were prospectively compared between two types of reconstruction [double tract (L-DT; n = 15) and jejunal interposition (L-JIP; n = 15)] following laparoscopic half-proximal gastrectomy (LPG), including laparoscopic total gastrectomy (L-TG; n = 30) as a control group, at 1 year after surgery. METHODS Clinical investigations were performed in each patient, and functional evaluations, involving the swallowing of an alimentary liquid containing acetaminophen (AAP), followed by measurements of the concentrations of AAP and hormones in the sitting (n = 5) and in the supine positions (n = 5), were carried out in each group. RESULTS The post-/preoperative body weight ratios were significantly higher in the L-DT and L-JIP groups than in the L-TG group. The AAP levels were significantly lower in the LPG group than in the LTG group. The AAP, insulin, and gastrin levels in the L-JIP group were markedly increased in the sitting position compared with the supine position, while those in the L-DT and L-TG groups were stable in both positions. CONCLUSIONS L-JIP and L-DT are procedures that maintain gradual intestinal absorption and help improve the quality of life. Intestinal absorption and hormonal secretion were relatively unaffected by the posture of the meal intake after L-DT, so L-DT might be the procedure providing the most stable results.


title: ADAURA: Phase III, Double-blind, Randomized Study of Osimertinib Versus Placebo in EGFR Mutation-positive Early-stage NSCLC After Complete Surgical Resection.

text: INTRODUCTION Currently, the role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as adjuvant therapy for early-stage non-small-cell lung cancer after complete surgical tumor resection remains under investigation. We present the rationale and study design for the ADAURA (ClinicalTrials.gov identifier, NCT02511106) trial, a multicenter, double-blind, randomized, placebo-controlled study. PATIENTS AND METHODS Study entry will be limited to adults aged ≥ 18 years (and in Japan and Taiwan, age ≥ 20 years) with primary nonsquamous stage IB-IIIA non-small-cell lung cancer with central confirmation of an EGFR exon 19 deletion or L858R mutation. Patients will be randomized 1:1 to receive osimertinib 80 mg once daily or placebo once daily until disease recurrence, a treatment discontinuation criterion is met, or patients achieve the maximum treatment duration of 3 years. The primary endpoint of this study is disease-free survival. Secondary endpoints include the disease-free survival rate at 2, 3, and 5 years, overall survival, overall survival rate at 5 years, and safety and tolerability. Health-related quality of life and pharmacokinetics will also be evaluated. The exploratory objectives include assessment of osimertinib efficacy in patients with a confirmed baseline T790M mutation status and postrecurrence outcomes, health resource use, and a comparison of plasma-derived circulating tumor DNA EGFR mutation status at baseline and at disease recurrence. RESULTS Study enrollment began in August 2015, and results are expected in the third quarter of 2021 (depending on the actual event rate).


title: Cutaneous Manifestations of a 21st Century Worldwide Fungal Epidemic Possibly Complicating the COVID-19 Pandemic to Jointly Menace Mankind.

text: In view of the new viral COVID-19 pandemic, the fungal Candida auris epidemic still in progress worldwide highlights non-Candida albicans candidal infections. We describe an immunocompetent woman with a cutaneous manifestation of Candida parasilopsis fungemia, a prominent eschar which proved to be the nidus for the candidemia. We stress the value of selectively removing eschars. C. parasilopsis and C. auris are increasingly important causes of sepsis and wound infections. We emphasize that commercially available biochemical-based tests may misidentify C. auris as C. parapsilosis, and stress the added danger of C. auris to critically ill hospitalized COVID-19 patients. Any health care facility with evidence of infection or colonization with C. auris requires very close monitoring, since this fungus is comparable to SARS-CoV-2 in its infectivity, mortality, and fomite adhesiveness! Both organisms must be closely observed as nosocomial infections in health care workers, who need to follow strict CDC guidelines. During this COVID-19 pandemic, every health care facility should closely monitor for the possible deadly combination of the SARS-CoV-2 and C. auris. The identification of C. auris necessitates use of sophisticated technology not readily available to make this essential diagnosis since C. auris is multi-drug resistant and isolation precautions would become paramount.


title: Prevalence of health services utilization in Brazil: a systematic review and meta-analysis.

text: OBJECTIVE to analyze the prevalence of use of health services in Brazil. METHODS systematic review and meta-analysis of population-based cross-sectional studies; MEDLINE, EMBASE, other sources, and microdata of surveys were searched; two researchers selected the studies, extracted the data and assessed methodological quality to include in the meta-analysis. RESULTS from 1,979 retrieved references, 27 studies were included; the prevalence of medical visits in the previous year was 71% (confidence interval of 95% [95%CI] = 69; 73%; I2=99%); the proportion of women in each study (p=0.001; R2=25%) and the recall period (p>0.001; R2= 72%) contributed to the heterogeneity; prevalence of dental consultation was 37% (95%CI = 32; 42%; I2=100%), and of hospitalization, 10% (95%CI = 9; 11%; I2=98%), in the last year. CONCLUSION more than half of the population had at least one medical visit, about one-third had a dental consultation and a tenth was hospitalized in the previous year.