title: Sonic aerosol therapy to target maxillary sinuses.

text: AIM Intranasal aerosol administration of drugs is widely used by ENT specialists. Although clinical evidence is still lacking, intranasal nebulization appears to be an interesting therapeutic option for local drug delivery, targeting anatomic sites beyond the nasal valve. The sonic nebulizer NL11SN associates a 100Hertz (Hz) sound to the aerosolization to improve deposition in the nasal/paranasal sinuses. The aim of the present study was: to evaluate in vivo the influence of associating a 100Hz sound on sinus ventilation and nasal and pulmonary aerosol deposition in normal volunteers, and; to quantify in vitro aerosol deposition in the maxillary sinuses in a plastinated head model. MATERIAL AND METHODS Scintigraphic analysis of (81m)Kr gas ventilation and of sonic aerosol ((99m)Tc-DTPA) deposition using the NL11SN was performed in vivo in seven healthy volunteers. In parallel, NL11SN gentamicin nebulization was performed, with or without associated 100Hz sound, in a plastinated human head model; the gross amount of gentamicin delivered to the paranasal sinuses was determined by fluorescence polarization immunoassay. RESULTS Associating the 100Hz sound to (81m)Kr gas ensured paranasal sinus ventilation in healthy volunteers. (99m)Tc-DTPA particles nebulized with the NL11SN were deposited predominantly in the nasal cavities (2/3, vs 1/3 in the lungs). In vitro, the use of NL11SN in sonic mode increased gentamicin deposition threefold in the plastinated model sinuses (P<0.002); the resulting antibiotic deposit would be sufficient to induce a local therapeutic effect. CONCLUSION The NL11SN nebulizer ensured preferential nasal cavity aerosol deposition and successfully targeted the maxillary sinuses.


title: Nesiritide following maze and mitral valve surgery.

text: BACKGROUND Fluid retention following "maze" and mitral valve surgery has been associated with diminished levels of atrial natriuretic peptide (ANP). We hypothesized prophylactic administration of nesiritide (human recombinant brain natriuretic peptide, NES, Natrecor, Scios, Fremont, CA, USA), which has similar physiologic properties to ANP and would promote diuresis in maze and mitral patients postoperatively. METHODS Randomized, blinded, prospective pilot study comparing patients undergoing maze and mitral surgery including excision of the left atrial appendage. Three hours after cardiopulmonary bypass, patients received either a 72-hour infusion of NES at 0.01 mcg/kg/min (n = 9) or placebo (n = 10). Diuresis, diuretics, time to extubation, oxygenation, ANP, and serum Endothelin-1 levels were measured. Nonparametric analysis with Mann-Whitney test was performed with SPSS (SPSS Inc., Chicago, IL, USA). RESULTS In both groups, postoperative ANP levels fell from baseline (NES 330 to 280 ng/mL and control 220 to 150 ng/mL). There were no significant differences in patients receiving NES compared to controls in diuresis (1.33 mL/kg/hour urine output NES vs. 1.68 mL/kg/hour controls, p = 0.14); furosemide dosage (0.04 mg/kg/hour NES vs. 0.04 mg/kg/hour controls, p = 0.08); time to extubation (17.5 hours NES vs. 19.5 control, p = 0.42) or PaO2/FiO2 ratio at 48 hours (NES 200 vs. 273 control, p > 0.05). Endothelin-1 levels were higher at baseline with NES but not at 1 and 72 hours after cardiopulmonary bypass (NES 3.1, 3.8, 2.9 pg/mL vs. control 1.85, 4.05, 2.75 pg/mL; p = 0.01, 0.77, 0.47). CONCLUSIONS This pilot study did not demonstrate additional diuresis with nesiritide in postoperative mitral/maze patients already following a loop diuretic protocol.


title: Intraoperative use of transcranial motor/sensory evoked potential monitoring in the clipping of intracranial aneurysms: evaluation of false-positive and false-negative cases.

text: OBJECTIVESomatosensory and motor evoked potentials (SEPs and MEPs) are often used to prevent ischemic complications during aneurysm surgeries. However, surgeons often encounter cases with suspicious false-positive and false-negative results from intraoperative evoked potential (EP) monitoring, but the incidence and possible causes for these results are not well established. The aim of this study was to investigate the efficacy and reliability of EP monitoring in the microsurgical treatment of intracranial aneurysms by evaluating false-positive and false-negative cases.METHODSFrom January 2012 to April 2016, 1514 patients underwent surgery for unruptured intracranial aneurysms (UIAs) with EP monitoring at the authors' institution. An EP amplitude decrease of 50% or greater compared with the baseline amplitude was defined as a significant EP change. Correlations between immediate postoperative motor weakness and EP monitoring results were retrospectively reviewed. The authors calculated the sensitivity, specificity, and positive and negative predictive values of intraoperative MEP monitoring, as well as the incidence of false-positive and false-negative results.RESULTSEighteen (1.19%) of the 1514 patients had a symptomatic infarction, and 4 (0.26%) had a symptomatic hemorrhage. A total of 15 patients showed motor weakness, with the weakness detected on the immediate postoperative motor function test in 10 of these cases. Fifteen false-positive cases (0.99%) and 8 false-negative cases (0.53%) were reported. Therefore, MEP during UIA surgery resulted in a sensitivity of 0.10, specificity of 0.94, positive predictive value of 0.01, and negative predictive value of 0.99.CONCLUSIONSIntraoperative EP monitoring has high specificity and negative predictive value. Both false-positive and false-negative findings were present. However, it is likely that a more meticulously designed protocol will make EP monitoring a better surrogate indicator of possible ischemic neurological deficits.


title: Maturation mechanism of severe acute respiratory syndrome (SARS) coronavirus 3C-like proteinase.

text: The 3C-like proteinase (3CL(pro)) of the severe acute respiratory syndrome (SARS) coronavirus plays a vital role in virus maturation and is proposed to be a key target for drug design against SARS. Various in vitro studies revealed that only the dimer of the matured 3CL(pro) is active. However, as the internally encoded 3CL(pro) gets matured from the replicase polyprotein by autolytic cleavage at both the N-terminal and the C-terminal flanking sites, it is unclear whether the polyprotein also needs to dimerize first for its autocleavage reaction. We constructed a large protein containing the cyan fluorescent protein (C), the N-terminal flanking substrate peptide of SARS 3CL(pro) (XX), SARS 3CL(pro) (3CLP), and the yellow fluorescent protein (Y) to study the autoprocessing of 3CL(pro) using fluorescence resonance energy transfer. In contrast to the matured 3CL(pro), the polyprotein, as well as the one-step digested product, 3CLP-Y-His, were shown to be monomeric in gel filtration and analytic ultracentrifuge analysis. However, dimers can still be induced and detected when incubating these large proteins with a substrate analog compound in both chemical cross-linking experiments and analytic ultracentrifuge analysis. We also measured enzyme activity under different enzyme concentrations and found a clear tendency of substrate-induced dimer formation. Based on these discoveries, we conclude that substrate-induced dimerization is essential for the activity of SARS-3CL(pro) in the polyprotein, and a modified model for the 3CL(pro) maturation process was proposed. As many viral proteases undergo a similar maturation process, this model might be generally applicable.


title: Accelerated induction regimens of TNF-alpha inhibitors in patients with inflammatory bowel disease: a scoping review protocol.

text: INTRODUCTION Tumour necrosis factor (TNF)-alpha inhibitors are commonly used to treat inflammatory bowel disease (IBD). In patients with IBD who are unresponsive to their first induction dose, the implementation of an 'accelerated' induction dose schedule (doses more frequent than recommended in product monographs) is becoming increasingly common. It is unclear whether this practice results in favourable patient outcomes, such as avoidance of surgery and disease remission. As such, there is a need to identify and map the current evidence base on accelerated induction schedules of these medications in the treatment of IBD. METHODS AND ANALYSIS A scoping review will be employed to systematically identify and characterise the nature of scientific literature on accelerated induction regimens of TNF-alpha inhibitors. MEDLINE, Embase, International Pharmaceutical Abstracts and grey literature will be searched to identify relevant studies. The titles/abstracts of all records and full text of potentially relevant articles will be independently screened for inclusion by two reviewers. Data will be abstracted from included studies by one reviewer and verified for accuracy by another. The findings will be synthesised descriptively. ETHICS AND DISSEMINATION We intend to report the findings of this scoping review in a peer-reviewed journal and a scientific conference. TRIAL REGISTRATION This research was registered prospectively with the Open Science Framework (https://osf.io/z7n2d/).


title: Hand Awareness.

text: The concept of Hand Awareness affects a more comprehensive respiratory infection prevention plan than vaccine immunization alone, as most respiratory infections do not have a vaccine solution. Additionally, the resurgence of measles, mumps, and pertussis in those who have been vaccinated is a good reminder that we must improve our approach to respiratory infection prevention. Weak links exist in the vaccine production and administration chain. It is not the panacea we once hoped. Changing behavior, while very difficult, is critical in order to have a greater impact on reducing all respiratory infections. Hand Awareness is defined as an integrated approach of hand hygiene, respiratory etiquette, and cross-contamination awareness practices or, in lay terms, knowing where your hands are and what they are doing at all times. Teaching strategies and resources are explored to assist with student understanding and application of desired behaviors that will achieve the greatest impact of both student and staff productivity and wellness.


title: Mechanical Recanalization for Acute Embolic Occlusion at the Origin of the Superior Mesenteric Artery.

text: PURPOSE We report a combined technique consisting of thrombectomy and thromboaspiration for the treatment of acute embolic occlusion of the superior mesenteric artery (SMA) at the origin. CASE A 90-year-old female with chronic atrial fibrillation had a sudden onset of abdominal pain and hematochezia due to acute embolic occlusion at the origin of the SMA. Computed tomographic findings showed reversible bowel wall ischemia. We performed mechanical thrombectomy using the Solitaire FR revascularization device, a self-expanding and fully retrievable stent-based thrombectomy system for acute intracranial large artery occlusion, combined with manual aspiration through a 6F guiding sheath placed at the SMA origin via a right brachial approach. Prompt and complete recanalization of the SMA was obtained without distal embolism, and intestinal necrosis was avoided. CONCLUSION Combined endovascular procedures of mechanical thrombectomy using the Solitaire FR with thromboaspiration may allow prompt recanalization, clot removal, and prevention of distal embolism and therefore would be a new therapy for acute embolic occlusion at the origin of the SMA.


title: Using optogenetics to tackle systems-level questions of multicellular morphogenesis.

text: Morphogenesis of multicellular systems is governed by precise spatiotemporal regulation of biochemical reactions and mechanical forces which together with environmental conditions determine the development of complex organisms. Current efforts in the field aim at decoding the system-level principles underlying the regulation of developmental processes. Toward this goal, optogenetics, the science of regulation of protein function with light, is emerging as a powerful new tool to quantitatively perturb protein function in vivo with unprecedented precision in space and time. In this review, we provide an overview of how optogenetics is helping to address system-level questions of multicellular morphogenesis and discuss future directions.


title: Does COVID-2019 have an Impact on the Purchase Intention of Commercial Long-Term Care Insurance among the Elderly in China?

text: PURPOSE As an important measure to alleviate long-term care (LTC) costs for the disabled due to the aging of the population, long-term care insurance (LTCI) system has been paid more attention in China. In addition to the government-led public LTCI system that has been piloted in cities such as Qingdao, Chongqing and Shanghai, health insurers such as the China Life Insurance Company are also experimenting with various types of commercial LTCI in the private market. However, the commercial LTCI market is developing very slowly due to public awareness and other reasons. On the other hand, COVID-2019 has had an impact on the cognition of the importance of long-term care for the elderly due to the fact that the death cases of COVID-2019 have been mainly concentrated in the elderly population with chronic diseases such as hypertension. Therefore, the purpose of this study is to explore the differences in the purchase intention of commercial LTCI among the elderly in two different periods: before and after the outbreak of COVID-2019. METHODS By using the Andersen behavioral model and two investigations in two different periods before and after the outbreak of COVID-2019, this study explores the impacts of COVID-2019 on the purchase intention of commercial LTCI. RESULTS Some significant discoveries were found. For example, 25.8% of interviewees showed purchase intention in LTCI in the time before the COVID-2019 outbreak, while this proportion increased to 37.6% after the COVID-2019 outbreak. People who were younger (OR = 2.128, before COVID-2019; OR = 1.875, after COVID-2019) or who had more education (OR = 1.502, before COVID-2019; OR = 2.218, after COVID-2019) were more interested in commercial LTCI. CONCLUSION This study shows that COVID-2019 has had an obvious impact on the purchase intention of commercial LTCI, which provides some enlightenment for China to improve the LTCI system in the future, especially to accelerate the development of commercial LTCI. For example, it is essential to promote the importance of long-term care among the elderly in a focused and targeted way. In terms of the key target audience, it can be developed gradually from the groups with higher education levels and the middle elderly aged 45-64 years old.


COVID-19: Getting ahead of the epidemic curve by early implementation of social distancing.


title: Polyester vs polypropylene, do mesh materials matter? A meta-analysis and systematic review.

text: Purpose Controversy exists regarding the outcomes following ventral hernia repair with polypropylene (PP) or polyester (PET) mesh. Monofilament PP less frequently requires extraction in the setting of contamination compared to multifilament PET mesh. The purpose of this systematic review and meta-analysis was to analyze the clinical outcomes of ventral hernia repair with PP and PET mesh. Patients and methods A comprehensive literature search was performed using the Ovid search platform. Criteria included ventral hernia repair publications using either PP or PET mesh with a minimum follow-up duration of one year. Included studies were subject to data extraction including mesh position, weight, recurrence rates, infection, and complications. Random effect meta-analysis was run to provide pooled event rate and 95% CI. Results Ninety-seven studies including a total of 10,022 patients were included in the final analysis. Hernia recurrence rates are similar (4.8%, 95% CI [3.5-6.5] vs 4.7%, 95% CI [3.7-6.0]) as well as mesh infection rates (3.5%, 95% CI [2.5-4.9] vs 5.0%, 95% CI [3.9-6.3]) between PET and PP, respectively. Mesh infections occurred less frequently in laparoscopic repair compared to open (1.6%, 95% CI [0.9-2.6] vs 5.2%, 95% CI [4.3-6.3]). Conclusion This study suggests that mesh material does not affect recurrence or infection in ventral hernia repair and that surgery can be safely performed with both PP and PET mesh. A laparoscopic approach is associated with a decreased infection rate compared to open repair independent of mesh type.


title: Effects of collagen prosthesis cross-linking on long-term tissue regeneration following the repair of an abdominal wall defect.

text: Collagen prostheses used to repair abdominal wall defects, depending on their pretreatment (noncross-linked vs. cross-linked), besides repair may also achieve tissue regeneration. We assessed the host tissue incorporation of different bioprostheses using a new tool that combines immunofluorescence confocal microscopy with differential interference contrast images, making it possible to distinguish newly formed collagen. Partial hernial defects in the abdominal wall of rabbits were repaired using cross-linked/noncross-linked bioprostheses. Expanded polytetrafluoroethylene (ePTFE) was used as control. After 14/30/90/180 days of implant, specimens were taken for microscopy, immunohistochemistry, and quantitative-reverse transcription-polymerase chain reaction to determine host tissue ingrowth and collagen I/III protein and 1a1/3a1 gene expression. Shrinkage and stress resistance were also examined. At 14 days, cross-linked prostheses had suffered significantly less shrinkage than ePTFE or noncross-linked prostheses. Significantly higher shrinkage was recorded for ePTFE in the longer term. Microscopy revealed encapsulation of ePTFE by neoformed tissue, while the bioprostheses became gradually infiltrated by host tissue. Noncross-linked prosthesis showed better tissue ingrowth, more intense inflammatory reaction and more rapid degradation than the cross-linked prostheses. At 14 days, cross-linked prostheses induced up-regulated collagen 1a1 and 3a1 gene expression, while noncross-linked only showed increased collagen III protein expression at 90 days postimplant. At 6 months, the tensile strengths of cross-linked prostheses were significantly greater compared with ePTFE. Our findings demonstrate that despite the cross-linked collagen prostheses promoting less tissue ingrowth than the noncross-linked meshes, they became gradually replaced by good quality host tissue and were less rapidly degraded, leading to improved stress resistance in the long term.


title: Use of a HEHEHE purification tag instead of a hexahistidine tag improves biodistribution of affibody molecules site-specifically labeled with (99m)Tc, (111)In, and (125)I.

text: Affibody molecules are a class of small (∼7 kDa) robust scaffold proteins suitable for radionuclide molecular imaging in vivo. The attachment of a hexahistidine (His(6))-tag to the Affibody molecule allows facile purification by immobilized metal ion affinity chromatography (IMAC) but leads to high accumulation of radioactivity in the liver. Earlier, we have demonstrated that replacement of the His(6)-tag with the negatively charged histidine-glutamate-histidine-glutamate-histidine-glutamate (HEHEHE)-tag permits purification of Affibody molecules by IMAC, enables labeling with [(99m)Tc(CO)(3)](+), and provides low hepatic accumulation of radioactivity. In this study, we compared the biodistribution of cysteine-containing Affibody molecules site-specifically labeled with (111)In, (99m)Tc, and (125)I at the C-terminus, having a His(6)-tag at the N- or C-terminus or a HEHEHE-tag at the N-terminus. We show that the use of a HEHEHE-tag provides appreciable reduction of hepatic radioactivity, especially for radiometal labels. We hope that this information can also be useful for development of other scaffold protein-based imaging agents.


title: A novel approach to endobronchial closure of a bronchial pleural fistula.

text: Bronchopleural fistula presents an important and challenging management problem after lung parenchymal resection. The mainstay of treatment has been surgical revision of the bronchial stump, however increasingly endobronchial therapies are being employed. We report the novel use of a liquid embolic agent with an Amplatzer vascular plug to seal a chronic bronchopleural fistula. Using rigid bronchoscopy, fluoroscopy, radio opaque liquid embolic agent, and the Amplatzer vascular plug, we were able to demonstrate not only feasibility but also safety and a marked reduction in symptoms consistent with successful closure of the bronchopleural fistula.


title: [Nurses: A Voice to Lead, Nursing the World to Health-Viewing COVID-19 Epidemic Prevention Efforts in Light of Nightingale's Perspective on Infection Control].

text: Florence Nightingale (1820-1910), extolled as the founder of modern nursing, contributed greatly to the advancement of modern public health. Written 150 years ago, Nightingale's advice on infection control, addressing the importance of hand washing, environmental sanitation, ventilation, sunshine, statistical data, and health literacy, remains highly relevant in today's global fight against the coronavirus. In honor of Florence Nightingale's 200th birthday, World Health Organization declared 2020 the International Year of the Nurse and Midwife. The era of "Nurses: A Voice to Lead - Nursing the World to Health" is drawing near. This article addresses the profound impact of Nightingale's infection control and public health perspectives on measures currently being taken to contain coronavirus disease 2019 (COVID-19). Furthermore, we call on governments throughout the world to invest proactively in nursing to assure the safety of patients and promote public health in order to achieve the pledge of the United Nations' sustainable development goals to leave no one behind.


INTRODUCTION The leading cause of erectile dysfunction (ED) is arterial dysfunction, with cardiovascular disease as the most common comorbidity. Therefore, ED is typically linked to a web of closely interrelated cardiovascular risk factors such as physical inactivity, obesity, hypertension, and metabolic syndrome. Physical activity (PA) has proved to be a protective factor against erectile problems, and it has been shown to improve erectile function for men affected by vascular ED. This systematic review estimated the levels of PA needed to decrease ED for men with physical inactivity, obesity, hypertension, metabolic syndrome, and/or manifest cardiovascular diseases. AIM To provide recommendations of levels of PA needed to decrease ED for men with physical inactivity, obesity, hypertension, metabolic syndrome, and/or cardiovascular diseases. METHODS In accord with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was performed of research articles specifically investigating PA as a possible treatment of ED. The review included research on ED from physical inactivity, obesity, hypertension, metabolic syndrome, and/or cardiovascular diseases. All available studies from 2006 through 2016 were checked for the predetermined inclusion and exclusion criteria to analyze the levels of PA needed to decrease ED. RESULTS 10 articles met the inclusion criteria, all suggesting various levels of PA needed to decrease ED for men with relevant risk factors for ED. The results of the review provided sufficient research evidence for conclusions regarding the levels of PA necessary to decrease ED. CONCLUSION Recommendations of PA to decrease ED should include supervised training consisting of 40 minutes of aerobic exercise of moderate to vigorous intensity 4 times per week. Overall, weekly exercise of 160 minutes for 6 months contributes to decreasing erectile problems in men with ED caused by physical inactivity, obesity, hypertension, metabolic syndrome, and/or cardiovascular diseases. Gerbild H, Larsen CM, Graugaard C, Areskoug Josefsson K. Physical Activity to Improve Erectile Function: A Systematic Review of Intervention Studies. Sex Med 2018;6:75-89.


title: Staying Connected In The COVID-19 Pandemic: Telehealth At The Largest Safety-Net System In The United States.

text: NYC Health + Hospitals (NYC H+H) is the largest safety net health care delivery system in the United States. Prior to the novel coronavirus disease (COVID-19) pandemic, NYC H+H served over one million patients, including the most vulnerable New Yorkers, and billed fewer than 500 telehealth visits monthly. Once the pandemic struck, we established a strategy to allow us to continue to serve existing patients and treat the surge of new patients. Starting in March 2020 we were able to transform the system using virtual care platforms through which we conducted almost 83,000 billable televisits in one month and more than 30,000 behavioral health encounters via telephone and video. Telehealth also enabled us to support patient-family communication, post-discharge follow-up, and palliative care for COVID-19 patients. Expanded Medicaid coverage and insurance reimbursement for telehealth played a pivotal role in this transformation. As we move to a new blend of virtual and in-person care, it is vital that the major regulatory and insurance changes undergirding our COVID-19 telehealth response be sustained to protect access for our most vulnerable patients. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].


title: De Novo Computational Design for Development of a Peptide Ligand Oriented to VEGFR-3 with High Affinity and Long Circulation.

text: The overexpression of VEGFR-3 is correlated with a worse prognosis in lung cancer and has been regarded as a rational target for specific drug delivery. Here, VEGFR-3 homing peptide library was efficiently established by computational design. Strong fluorescent signals of selected peptides were observed in A549 cells, but much weaker in other cells. The positive immunostaining overlapped with VEGFR-3 confirmed high affinity and selectivity of one novel peptide (CP-7). In addition, cell uptake of FITC-CP-7 peptide was significantly blocked by coinjection of excess CP-7 peptide. After labeled with 131I, the profile of pharmacology and biodistribution could be traced in vivo. The 131I-radiolabeled CP-7 peptide conjugates were >85% stable in serum over 4 h and exhibited a specific uptake of 18.04 ± 2.04% ID/g at 0.5 h after injection to high VEGFR-3 expressing A549 tumor mice. More importantly, lower uptake concentration in heart (1.06 ± 0.15% ID/g) after 2 h demonstrated the safety of peptide in vivo. The high uptake in the kidneys revealed that renal clearance was the main route of 131I-CP-7 peptide elimination from the body. Lower accumulation of 131I-CP-7 peptide in VEGFR-3 negative HeLa tumor mice further indicated that CP-7 peptide exhibited a higher tumor-homing efficiency. These studies provided a straightforward analytical access to design and screen bioactive peptide based on protein structure and revealed that CP-7 peptide represented a promising homing peptide of VEGFR-3-positive cancer in vitro and in vivo which could be used as a novel target molecule to achieve efficient drug delivery.


title: Endovascular treatment of ruptured intracranial aneurysms.

text: Aneurysmal subarachnoid hemorrhage (SAH) is a catastrophic neurologic event. Early triage of patients with SAH should include cardiopulmonary stabilization, neurologic assessment, and imaging. Conventional angiography with 3-dimensional rendering is necessary to accurately assess aneurysm morphology and location, so that treatment can be planned appropriately. Current evidence suggests that coil embolization can be beneficial for aneurysms amenable to endovascular treatment. The use of remodeling techniques has expanded the range of aneurysms treatable by endovascular means. Balloon remodeling can be a powerful technique for treating ruptured aneurysms with unfavorable morphology. However, stent-assisted technique is associated with significantly higher complication rates in ruptured aneurysms and requires dual antiplatelet agents, and should therefore be considered with great caution for ruptured aneurysms. Complications of ruptured aneurysm embolization include aneurysm perforation, which should be addressed with immediate occlusion of the aneurysm, and thromboembolism, which can be managed most effectively with glycoprotein IIb/IIIa inhibitors.


title: Practical document on the management of hyponatremia in critically ill patients.

text: Hyponatremia is the most prevalent electrolyte disorder in Intensive Care Units. It is associated with an increase in morbidity, mortality and hospital stay. The majority of the published studies are observational, retrospective and do not include critical patients; hence it is difficult to draw definitive conclusions. Moreover, the lack of clinical evidence has led to important dissimilarities in the recommendations coming from different scientific societies. Finally, etiopathogenic mechanisms leading to hyponatremia in the critical care patient are complex and often combined, and an intensive analysis is clearly needed. A study was therefore made to review all clinical aspects about hyponatremia management in the critical care setting. The aim was to develop a Spanish nationwide algorithm to standardize hyponatremia diagnosis and treatment in the critical care patient.


title: Phase diagram of the frustrated FCC antiferromagnet from effective-field theory.

text: The phase diagram of a face-centred cubic (FCC) antiferromagnet is calculated from the effective field theory (EFT) of Honmura and Kaneyoshi taking into account not only the effect of interaction with nearest neighbours, $J_1$, but also the effect of second neighbours, $J_2$. The phase diagram for the nearest neighbour case away from the triple point, which in our calculations is predicted to be at $H=4$ and $T=0$, is close to cluster variation method (CVM) and Monte Carlo (MC) results. Similar to MC and CVM predictions, we observe that the increasing second neighbours interaction pushes the triple point towards zero field. Our calculations also show that for $\alpha=-J_2/J_1=0.3$, the triple point merges with the transition point of the L1$_{0}$ phase, one of the ground states, at $H=0$ and changes the nature of phase transition from first- to second-order, in full agreement with Monte Carlo predictions. The phase diagram with the effect of second neighbours calculated for several values of $\alpha$ are in good agreement with available MC and CVM predictions.


Will covid-19 change US healthcare for the better?


title: Breast contrast-enhanced MR imaging: semiautomatic detection of vascular map.

text: BACKGROUND The diagnostic value of breast vascular maps using contrast-enhanced MR imaging has recently been explored. We propose a semiautomatic method to obtain breast vascular maps and to measure the number of blood vessels in the breast. METHODS From January 2011 to December 2013, 188 patients underwent breast contrast-enhanced MRI; patients with unilateral and histopathologically confirmed breast lesions were included in this study; 123 patients had malignant lesions and 65 patients had benign tissue diagnoses. Breast semiautomatic vascular map detection was performed using Hessian matrix-based method and morphologic operators. Blood vessels detection was compared with radiologic interpretation findings to evaluate algorithm goodness. Increase in vascularity associated with ipsilateral cancer was also assessed. Chi square test was used to observe statistically significant difference. RESULTS A total of 1315 blood vessels were identified using semiautomatic procedure; 1034 were correctly classified (78.7 %), 261 (19.8 %) were incorrectly classified, and 20 (1.5 %) were missing. A significant association was found between one-sided increased breast vascularity and ipsilateral malignancy (p < 0.001). CONCLUSIONS In conclusion, detection of vascularity increase as risk factor for developing breast cancer could be performed with semiautomatic vascular mapping of contrast-enhanced MR imaging.


title: Self-gripping versus sutured mesh fixation methods for open inguinal hernia repair: A systematic review of clinical trials and observational studies.

text: BACKGROUND We performed this systematic review and meta-analysis to compare the outcomes of Lichenstein hernia repair using either self-gripping mesh or techniques of sutured mesh fixation. METHODS We searched PubMed, Cochrane CENTRAL, Scopus, Embase, and Web of Science for all clinical trials and observational studies that compared self-gripping mesh versus sutured mesh fixation in Lichtenstein hernia repair. Combined outcomes were pooled as odds ratios or mean differences in a fixed-effect model, using Comprehensive Meta-Analysis software for Windows. RESULTS Twelve randomized, controlled trials and 5 cohort studies (n = 3,722 patients) were included in the final analysis. The two groups, using self-gripping mesh or sutured mesh fixation, did not differ significantly in terms of recurrence rate (odds ratio = 0.66, 95% confidence interval 0.18-2.44; P = .54) or postoperative chronic groin pain (odds ratio = 0.75, 95% confidence interval 0.54-1.05; P = .09). The operative time was less in the self-gripping mesh group (mean difference = -7.85, 95% confidence interval -9.94 to -5.76; P < .0001). For safety analysis, there were comparable risks between self-gripping mesh and sutured mesh fixation groups in terms of postoperative infection (odds ratio = 0.81, 95% confidence interval 0.53-1.23; P = .32), postoperative hematoma (odds ratio = 0.97, 95% confidence interval 0.7-1.36; P = .9), and urinary retention (odds ratio = 0.66, 95% confidence interval 0.18-2.44; P = .54). CONCLUSION Data from our analysis did not favor either of the two fixation techniques over the other in terms of recurrence or postoperative chronic groin pain. Decreased operative time in the self-gripping mesh group cannot justify a recommendation for its routine use. Longer follow-up studies are needed to compare the risk of long-term recurrence for both meshes.


title: Endovascular management of distal ACA aneurysms: single-institution clinical experience in 22 consecutive patients and literature review.

text: BACKGROUND AND PURPOSE Distal ACA aneurysms remain difficult to treat with endovascular therapy, but improved technology and experience allows for the treatment of some of these aneurysms with excellent results. The purpose of this study was to assess the status of endovascular treatment of distal ACA aneurysms by comparing our results with recent endovascular and microsurgical series of distal ACA aneurysms. MATERIALS AND METHODS Between 2000 and 2008, a total of 22 consecutive patients (14 women; mean age, 58.4 years) with distal ACA aneurysms underwent coil placement at Barrow Neurological Institute. Clinical presentations, radiographic findings, endovascular management, and outcomes were reviewed retrospectively. RESULTS Of the 22 patients, 13 (59%) presented with subarachnoid hemorrhage. Six patients were HH grade I or II, 1 was grade III, 5 were grade IV, and 1 was grade V. Frontal lobe hematomas occurred in 5 patients with ruptured aneurysms. The mean aneurysm size was 7.5 mm (range, 2.8-25 mm); 55% were smaller than 7 mm. Twelve aneurysms (55%) arose from the origin of the callosomarginal artery (55%). Complete occlusion was achieved in 50% of the cases and near-complete occlusion in 45%. The few periprocedural complications included 1 retroperitoneal hematoma and 1 intraoperative rupture. Four patients had thromboembolic events adequately treated intraprocedurally with abciximab. No deaths occurred in the patients treated. CONCLUSIONS The characteristics of the patients and aneurysms treated in our series were comparable to previous reports of endovascular treatment of ACA aneurysms with respect to rupture status. Periprocedural morbidity and mortality rates in our series fared well compared with previous reports, as did our combined rate of complete or near-complete occlusions. Recent advances in endovascular devices and techniques have improved outcomes of distal ACA aneurysms.


Neurologic manifestations in an infant with COVID-19.


title: p64 Flow Modulation Device in the treatment of intracranial aneurysms: initial experience and technical aspects.

text: BACKGROUND Experience with the endovascular treatment of cerebral aneurysms by flow diverter devices (FDDs) is limited to four devices (Pipeline, Covidien; FRED, Microvention; Silk, Balt Extrusion; Surpass, Stryker), as reported in different studies. OBJECTIVE To describe the initial experience and the technical innovations of a new-generation FDD (p64 Flow Modulation Device, Phenox, Bochum, Germany). METHODS Between December 2014 and February 2015, six intracranial aneurysms in five patients (four women, one man; mean age 63 years) were treated with the p64 Flow Modulation Device. RESULTS Immediate post-treatment angiography showed reduced flow into all aneurysms. No long-term angiographic data are available. The device may be easily deployed and totally retrieved with a unique mechanical detachment. No periprocedural technical complications occurred. No early or delayed aneurysm rupture, no ischemic or hemorrhagic complications, and no neurological morbidity or death were seen. CONCLUSIONS Treatment of cerebral aneurysms with the p64 Flow Modulation Device is a safe procedure with no technical complications. The mechanical detachment and the 100% retrievability are significant advantages of this new device. However, large prospective studies with long-term clinical and angiographic follow-up are necessary to assess the role of the p64 in the endovascular treatment of intracranial aneurysms.


title: Assessment of the preparedness of obstetrics and gynecology healthcare systems during the COVID-19 pandemic in Libya.

text: Cases of COVID-19 have been reported in neonates, and although these were either asymptomatic or non-severe [1], it is apparent that obstetricians are at increased risk of infection. As a result, safety procedures must be reinforced by ensuring the availability of personal protective equipment (PPE) and the application of infection control measures [2].


Cerebral hyperperfusion syndrome after spontaneous recanalisation of carotid in-stent thrombosis.


title: Association Between Hyponatremia and Higher Bronchiolitis Severity Among Children in the ICU With Bronchiolitis.

text: BACKGROUND AND OBJECTIVES It remains unclear whether hyponatremia independently predicts a higher severity of bronchiolitis in children. The objective of this study was to investigate the association between hyponatremia and bronchiolitis severity in children hospitalized in the ICU for bronchiolitis. METHODS We conducted a 16-center, prospective cohort study of hospitalized children aged <2 years with bronchiolitis during the winters of 2007 through 2010. Patients were classified into 2 groups (normonatremic [135-145 mEq/L] and hyponatremic [<135 mEq/L]) based on the first-measured serum sodium concentration on the day of hospitalization. Outcomes were use of mechanical ventilation and ICU length of stay (LOS). To examine the association of sodium status with outcomes, we fit logistic and linear regression models with propensity score adjustment. RESULTS Of 231 children hospitalized in the ICU for bronchiolitis, 193 (84%) were categorized into the normonatremic group and 38 (16%) into the hyponatremic group. Compared with children with normonatremia, those with hyponatremia had higher risks of mechanical ventilation use (40% vs 58%; P = .04) and longer ICU LOS (median, 3 vs 6 days; P = .007). Likewise, in the adjusted analyses, children with hyponatremia had significantly higher risks of mechanical ventilation use (odds ratio, 2.14 [95% confidence interval, 1.03-4.48; P = .04) and longer ICU LOS (β-coefficient, 2.21 days [95% confidence interval, 0.68-3.73; P = .005]). CONCLUSIONS In this prospective, multicenter study of children hospitalized for bronchiolitis, hyponatremia on the day of hospitalization was associated with a higher severity of disease. Our data support hyponatremia as a prognostic factor that might improve the ability of clinicians to predict the disease course of children with severe bronchiolitis.


Covid-19: Low skilled men have highest death rate of working age adults.


title: Periprosthetic Capsule Formation and Contracture in a Rodent Model of Implant-Based Breast Reconstruction With Delayed Radiotherapy.

text: INTRODUCTION Capsular contracture (CC) is the most common complication of breast implantation, with an incidence of nearly 50% in patients undergoing breast reconstruction with subsequent radiotherapy. Although the move toward submuscular (SM) device placement led to a decreased incidence of CC, subcutaneous (SQ) implantation has seen a resurgence. The purpose of this study was to use a rodent model of breast reconstruction with smooth silicone implants and delayed radiotherapy to assess the occurrence of CC in SQ versus SM implantation. METHODS Custom 2 mL smooth round silicone implants were placed bilaterally into 12 female Sprague Dawley rats that were randomized into 4 groups of 3, with each group differing by implantation plane (SQ vs SM) and irradiation status (irradiated vs nonirradiated). Rats from the SQ group received implants bilaterally underlying the skin on the flank. Rats in the SM groups received implants bilaterally under the latissimus dorsi muscle. Irradiated rats received 20 Gy localized to each implant on postoperative day 10. One rat from each group was imaged with a micro-computed tomography scanner at baseline and at explant 3 months later, whereupon capsules from all rats were examined histologically. RESULTS Rats in the SQ group showed evidence of contracture on gross examination and greater evidence of morphologic disruption per micro-computed tomography scan. There was no evidence of contracture or morphologic disruption in either SM group. Mean ± SD capsule thickness was 39.0 ± 9.0 μm in the SQ versus 37.6 ± 9.8 μm in the SM nonirradiated groups and 43.9 ± 14.9 μm in the SQ versus 34.3 ± 8.3 μm in the SM irradiated groups (all P > 0.05). CONCLUSIONS In a rodent model of smooth silicone breast implantation and delayed radiotherapy, although there did not appear to be differences in capsule thickness regardless of device placement plane, SQ implants demonstrated gross evidence of CC. These data indicate that capsule thickness is only part of a larger pathogenetic picture, which should take into consideration the contribution from all peri-implant tissue.


title: Early angiographic signs of acute thrombus formation following cerebral aneurysm treatment with the Pipeline embolization device.

text: BACKGROUND AND OBJECTIVE Acute thrombus formation following aneurysm treatment with the Pipeline embolization device (PED) is a potentially devastating complication that may result in significant thromboembolic sequelae if not promptly treated. We therefore evaluated PED cases complicated by acute thrombus formation at our institution, with an emphasis on identifying early angiographic signs that may portend this event. MATERIALS AND METHODS We retrospectively identified cases of acute thrombosis following PED placement in 100 consecutive procedures performed at our institution from a prospectively maintained clinical database. Angiographic findings were analyzed for early signs of acute thrombus formation. We also evaluated the efficacy of treatment of this complication with a glycoprotein IIb/IIIa inhibitor (abciximab), as well as the results of pre-procedure platelet inhibition testing. RESULTS Acute thrombus formation was encountered in five patients following PED placement (5%). Early angiographic signs were present in all cases and included progressive stagnation of blood flow in covered side branches, occlusion of covered side branches, excessive stagnation of blood flow in the target aneurysm, as well as occlusion of the target aneurysm. These sequelae completely resolved following abciximab treatment in all five cases, with no permanent neurological morbidity or mortality. Four of the five patients had a pre-procedure P2Y12 value >200 (range 201-227). CONCLUSIONS Progressive stagnation or occlusion of covered side branches or target aneurysm are early angiographic signs of acute thrombus formation following PED placement and should prompt immediate treatment with a glycoprotein IIb/IIIa inhibitor. Platelet inhibition testing may help identify those patients who are at an increased risk for this complication.


title: Treatment of dysplasia in barrett esophagus.

text: Barrett esophagus is recognized as a risk factor for the development of dysplasia and adenocarcinoma of the esophagus. Cancer is usually diagnosed at an advanced stage with a 5-year survival rate of 15%. Most of these patients present de novo and are not part of a surveillance program. Endoscopic screening with improvement in recognition of early lesions may change this pattern. In the past, patients diagnosed with dysplasia and mucosal cancer were best managed by esophagectomy. Endoscopic techniques such as endoscopic mucosal resection and radiofrequency ablation have resulted in high curative rates and a shift away from esophagectomy. This pathway is supported by the literature review of esophagectomies performed for mucosal disease, as well as pathologists' interpretation of endoscopic mucosal specimens, which document the low risk of lymph node metastasis. The role of endoscopic therapy for superficial submucosal disease continues to be a challenge.


Coronavirus shutdown forces research ship to break out of Arctic ice.


title: The Well-Being Index (WBI) for schools: A brief measure of adolescents' mental health.

text: Schools are increasingly concerned with the well-being of the whole child - likely, more so since the COVID-19 pandemic - and goals here were to document the psychometric properties of a brief new measure of adolescent mental health, the Well-Being Index (WBI). The measure assesses 4 symptom areas, 2 each of internalizing and externalizing symptoms-Depression, Anxiety, Rule-Breaking, and Substance Use-and an optional scale on Isolation at School. A total of 2,444 students from 2 high schools completed the WBI, the Youth Self-Report (YSR), and other related measures. Alpha coefficients showed acceptable internal consistency, with values for the 5 WBI subscales at .83, .84, .78, .79, and .74, respectively. Both exploratory and confirmatory factor analyses demonstrated consistent factorial validity. Correlations with corresponding YSR subscales indicated good convergent and discriminant validity. The WBI Substance Use and Isolation at School subscales, similarly, had high correlations with subscales from preexisting measures. Criterion-related validity was indicated in significant correlations between WBI subscales and conceptually related dimensions of close relationships. Also examined was the percentage of youth falling above clinical cutoffs on both the WBI and YSR, and findings demonstrated high concurrent validity. Collectively, results suggest the promise of the WBI as a brief, psychometrically sound measure to assess the adjustment of adolescents, along with perceptions of school climate that can be modified toward fostering their overall well-being. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Impact of pain in overweight to morbidly obese women: preliminary findings of a cross-sectional study.

text: OBJECTIVES To evaluate the effect of body mass index (BMI) on the prevalence, intensity and interference of pain in women, and how it affects quality of life and level of physical activity; and to determine independent predictors of pain intensity. DESIGN Cross-sectional observational study. SETTINGS Obesity treatment clinic, community and university laboratory. PARTICIPANTS Seventy-three of 133 women aged 25-75 years reported the presence of pain for at least 2 weeks and were categorised according to BMI (normal weight, overweight, obese or morbidly obese). MAIN OUTCOME MEASURES BMI and questionnaires [McGill Pain Questionnaire (MPQ), Brief Pain Inventory (BPI), Short-Form Health Survey-36 (SF-36) and Baecke Physical Activity Questionnaire]. RESULTS Pain intensity was 3 and 4.5 times higher in the MPQ and BPI, respectively, in morbidly obese women compared with women of normal weight. Morbidly obese women had 10.7 times higher pain interference and lower scores on the SF-36 domains of physical function and role function-physical compared with women of normal weight. Obese and morbidly obese women had less pain relief from treatment. Regression analysis showed that high BMI and low level of physical activity contributed to the intensity of pain, and these variables explained 16% of the variance of pain intensity. CONCLUSIONS This study found that the prevalence and intensity of pain are greater in morbidly obese women than women of normal weight, and pain is negatively associated with physical activity. The causal inter-relationships between pain, obesity and physical activity are complex and require further study.


title: Computed tomography and histopathological findings after embolization with inherently radiopaque 40μm-microspheres, standard 40μm-microspheres and iodized oil in a porcine liver model.

text: PURPOSE The present study compared standard computed tomography (CT) and histopathological findings after endovascular embolization using a prototype of inherently radiopaque 40μm-microspheres with both standard 40μm-microspheres and iodized oil in a porcine liver model. MATERIALS AND METHODS Twelve pigs were divided into six study groups, of two pigs each. Four pigs were embolized with iodized oil alone and four with radiopaque microspheres; two animals in each group were sacrificed at 2 hours and two at 7 days. Two pigs were embolized with radiopaque microspheres and heparin and sacrificed at 7 days. Two pigs were embolized with standard microspheres and sacrificed at 2 hours. CT was performed before and after segmental embolization and before sacrifice at 7 days. The distribution of embolic agent, inflammatory response and tissue necrosis were assessed histopathologically. RESULTS Radiopaque microspheres and iodized oil were visible on standard CT 2 hours and 7 days after embolization, showing qualitatively comparable arterial and parenchymal enhancement. Quantitatively, the enhancement was more intense for iodized oil. Standard microspheres, delivered without contrast, were not visible by imaging. Radiopaque and standard microspheres similarly occluded subsegmental and interlobular arteries and, to a lesser extent, sinusoids. Iodized oil resulted in the deepest penetration into sinusoids. Necrosis was always observed after embolization with microspheres, but never after embolization with iodized oil. The inflammatory response was mild to moderate for microspheres and moderate to severe for iodized oil. CONCLUSION Radiopaque 40μm-microspheres are visible on standard CT with qualitatively similar but quantitatively less intense enhancement compared to iodized oil, and with a tendency towards less of an inflammatory reaction than iodized oil. These microspheres also result in tissue necrosis, which was not observed after embolization with iodized oil. Both radiopaque and standard 40μm-microspheres are found within subsegmental and interlobar arteries, as well as in hepatic sinusoids.


title: HbA1c (Glycated Hemoglobin) Levels and Clinical Outcome Post-Mechanical Thrombectomy in Patients With Large Vessel Occlusion.

text: Background and Purpose- We analyzed the relationship between HbA1c (glycated hemoglobin) levels and clinical outcomes in patients with large vessel occlusion treated with mechanical thrombectomy (MT). Methods- A total of 534 patients with acute ischemic stroke (AIS) treated with MT were enrolled in this prospective cohort study. The primary outcome measured was the modified Rankin Scale score at 3 months, according to HbA1c level. High HbA1c levels were defined as a plasma level of HbA1c >6.5%. Favorable outcomes were defined as functional independence, with modified Rankin Scale scores of 0 to 2. Secondary functional outcomes included mortality, early clinical outcomes, and intracranial hemorrhage. Results- The number of patients with a favorable outcome was significantly lower in patients with HbA1c >6.5% than in those with HbA1c ≤6.5% (28.8% versus 42.1%; P=0.006). In multivariate analysis, high HbA1c levels (especially >7.0% HbA1c) were significantly associated with poor functional outcomes 3 months after AIS in patients with large vessel occlusion treated with MT. High HbA1c was also significantly associated with increased mortality and worse early clinical outcomes after AIS in patients treated with MT. Subgroup analyses showed that HbA1c >6.5% was associated with significantly lower odds of functional independence at 3 months after AIS, when comparing the recanalized group with nonrecanalized patients. Conclusions- These results suggest that high HbA1c level is an independent predictor of a poor outcome at 3 months after AIS in patients with large vessel occlusion treated with MT, particularly in those with recanalization, and may augment the risk of mortality and early clinical worsening after AIS.


title: SILK flow-diverting device for intracranial aneurysms.

text: BACKGROUND The SILK intracranial stent is a Conformité Européenne mark-approved endovascular device. This flow-diversion device is being used in Europe for intracranial aneurysm treatment by aneurysm occlusion. The device construct creates an intracranial bypass conduit that reconstructs the parent vessel while maintaining patency of the perforating arteries and branch arteries. The investigators report the first two patients in which the SILK stent was used for intracranial aneurysms in the United States. CASE DESCRIPTION Two patients, one with a symptomatic giant posterior communicating artery aneurysm and one with a symptomatic fusiform vertebrobasilar junction and basilar artery aneurysm, were treated at two separate institutions with the device. A total of three SILK stents were placed in these patients. In the first patient, a single device was sufficient to cause immediate angiographic stasis within the posterior communicating artery aneurysm. However, reversal of anticoagulation and antiplatelet therapy was required due to a spontaneous bleed from an intercostal artery, and this led to in-stent thrombosis and major stroke. In the second patient, the placement of two devices resulted in immediate stasis of the basilar artery aneurysm. The patient remained on antiplatelet therapy and was discharged without complication. His follow-up angiogram at approximately 2 months showed complete occlusion of the aneurysm with parent vessel reconstruction. In both patients, immediate stasis was identified, and no immediate neurological complications occurred. However, in one patient, a complication occurred that was related to reversal of/cessation of antiplatelet therapy. CONCLUSION In this initial U.S. experience with SILK flow-diversion devices, these devices were deployed easily and immediate flow stasis in the aneurysm was achieved. Further evaluation of this device is needed at multiple centers with adequately trained and experienced operators.


title: Randomized comparison of the effectiveness of nasal intubation using a GlideScope video laryngoscope with Magill forceps versus vascular forceps in patients with a normal airway.

text: PURPOSE The GlideScope® video laryngoscope (GVL) is widely used for nasotracheal intubation in dental and facial plastic surgery. The angle of the Magill forceps is different from that of the GVL blade, which suggests that the Magill forceps are not the ideal forceps for use with the GVL. The purpose of this study was to compare the effectiveness of the Magill forceps vs vascular forceps for nasotracheal intubation using the GVL. METHODS This study included 60 patients scheduled to undergo elective surgery requiring nasotracheal intubation. Patients were assigned to one of two groups-i.e., Magill forceps (group M) or vascular forceps along with a tube exchanger (group V), by computer randomization. The primary outcome was total intubation time, defined as the time from when the anesthesiologist picked up the device to the time when three successive end-tidal CO2 waves were obtained following intubation. Secondary outcomes were blood in the endotracheal tube and trauma to the oral tissues or teeth. A blind observer assessed the presence of sore throat one hour and 24 hr after surgery. RESULTS The total intubation time was significantly different between group M and group V (96.1 sec and 78.1 sec, respectively; mean difference, 18 sec; 95% confidence interval (CI), 13.7 to 49.7). The incidence of epistaxis in group M was significantly greater than that in group V (46.7% vs 16.7%, respectively; relative risk, 2.8; 95% CI, 1.2 to 6.8). CONCLUSION The total intubation time was significantly less with the vascular forceps (and tube exchanger) than with the Magill forceps. Using vascular forceps also reduced the incidence of epistaxis compared with that using the Magill forceps. Using a tube exchanger and vascular forceps offers advantages over use of Magill forceps when a GlideScope video laryngoscope is used for nasotracheal intubation. TRIAL REGISTRATION http://www.who.int/ictrp/network/cris2/en/ , CRIS, KCT0001310. Registered 29 July 2014.


title: Bariatric/Metabolic Surgery to Treat Type 2 Diabetes in Patients With a BMI <35 kg/m2.

text: OBJECTIVE Global usage of bariatric surgery has been dictated for the past quarter century by National Institutes of Health recommendations restricting these operations to individuals with a BMI ≥35 kg/m(2). Strong evidence now demonstrates that bariatric procedures markedly improve or cause remission of type 2 diabetes mellitus (T2DM), in part through weight-independent mechanisms, and that baseline BMI does not predict surgical benefits on glycemic or cardiovascular outcomes. This impels consideration of such operations as "metabolic surgery," which is used expressly to treat T2DM, including among patients with a BMI <35 kg/m(2) who constitute the majority of people with diabetes worldwide. Here, we review available evidence to inform that consideration. RESULTS A meta-analysis of the 11 published randomized clinical trials (RCTs) directly comparing bariatric/metabolic surgery versus a variety of medical/lifestyle interventions for T2DM provides level 1A evidence that surgery is superior for T2DM remission, glycemic control, and HbA1c lowering. Importantly, this is equally true for patients whose baseline BMI is below or above 35 kg/m(2). Similar conclusions derive from meta-analyses of high-quality nonrandomized prospective comparisons. Meta-analysis of all pertinent published studies indicates that T2DM remission rates following bariatric/metabolic surgery are comparable above and below the 35 kg/m(2) BMI threshold. The safety, antidiabetes durability, and benefits on other cardiovascular risk factors from bariatric/metabolic surgery appear roughly comparable among patients with a BMI below or above 35 kg/m(2). Further studies are needed to extend long-term findings and measure "hard" macrovascular/microvascular outcomes and mortality in RCTs. CONCLUSIONS Extant data, including level 1A evidence from numerous RCTs, support new guidelines from the 2nd Diabetes Surgery Summit that advocate for the consideration of bariatric/metabolic surgery as one option, along with lifestyle and medical therapy, to treat T2DM among patients with a BMI <35 kg/m(2).


title: Review of emerging surgical robotic technology.

text: BACKGROUND The use of laparoscopic and robotic procedures has increased in general surgery. Minimally invasive robotic surgery has made tremendous progress in a relatively short period of time, realizing improvements for both the patient and surgeon. This has led to an increase in the use and development of robotic devices and platforms for general surgery. The purpose of this review is to explore current and emerging surgical robotic technologies in a growing and dynamic environment of research and development. METHODS This review explores medical and surgical robotic endoscopic surgery and peripheral technologies currently available or in development. The devices discussed here are specific to general surgery, including laparoscopy, colonoscopy, esophagogastroduodenoscopy, and thoracoscopy. Benefits and limitations of each technology were identified and applicable future directions were described. RESULTS A number of FDA-approved devices and platforms for robotic surgery were reviewed, including the da Vinci Surgical System, Sensei X Robotic Catheter System, FreeHand 1.2, invendoscopy E200 system, Flex® Robotic System, Senhance, ARES, the Single-Port Instrument Delivery Extended Research (SPIDER), and the NeoGuide Colonoscope. Additionally, platforms were reviewed which have not yet obtained FDA approval including MiroSurge, ViaCath System, SPORT™ Surgical System, SurgiBot, Versius Robotic System, Master and Slave Transluminal Endoscopic Robot, Verb Surgical, Miniature In Vivo Robot, and the Einstein Surgical Robot. CONCLUSIONS The use and demand for robotic medical and surgical platforms is increasing and new technologies are continually being developed. New technologies are increasingly implemented to improve on the capabilities of previously established systems. Future studies are needed to further evaluate the strengths and weaknesses of each robotic surgical device and platform in the operating suite.


title: The wisdom of crowds in action: Forecasting epidemic diseases with a web-based prediction market system.

text: BACKGROUND The quest for an effective system capable of monitoring and predicting the trends of epidemic diseases is a critical issue for communities worldwide. With the prevalence of Internet access, more and more researchers today are using data from both search engines and social media to improve the prediction accuracy. In particular, a prediction market system (PMS) exploits the wisdom of crowds on the Internet to effectively accomplish relatively high accuracy. OBJECTIVE This study presents the architecture of a PMS and demonstrates the matching mechanism of logarithmic market scoring rules. The system was implemented to predict infectious diseases in Taiwan with the wisdom of crowds in order to improve the accuracy of epidemic forecasting. METHODS The PMS architecture contains three design components: database clusters, market engine, and Web applications. The system accumulated knowledge from 126 health professionals for 31 weeks to predict five disease indicators: the confirmed cases of dengue fever, the confirmed cases of severe and complicated influenza, the rate of enterovirus infections, the rate of influenza-like illnesses, and the confirmed cases of severe and complicated enterovirus infection. RESULTS Based on the winning ratio, the PMS predicts the trends of three out of five disease indicators more accurately than does the existing system that uses the five-year average values of historical data for the same weeks. In addition, the PMS with the matching mechanism of logarithmic market scoring rules is easy to understand for health professionals and applicable to predict all the five disease indicators. CONCLUSIONS The PMS architecture of this study affords organizations and individuals to implement it for various purposes in our society. The system can continuously update the data and improve prediction accuracy in monitoring and forecasting the trends of epidemic diseases. Future researchers could replicate and apply the PMS demonstrated in this study to more infectious diseases and wider geographical areas, especially the under-developed countries across Asia and Africa.


title: Composition vector method based on maximum entropy principle for sequence comparison.

text: The composition vector (CV) method is an alignment-free method for sequence comparison. Because of its simplicity when compared with multiple sequence alignment methods, the method has been widely discussed lately; and some formulas based on probabilistic models, like Hao’s and Yu’s formulas, have been proposed. In this paper, we improve these formulas by using the entropy principle which can quantify the nonrandomness occurrence of patterns in the sequences. More precisely, existing formulas are used to generate a set of possible formulas from which we choose the one that maximizes the entropy. We give the closed-form solution to the resulting optimization problem. Hence, from any given CV formula, we can find the corresponding one that maximizes the entropy. In particular, we show that Hao’s formula is itself maximizing the entropy and we derive a new entropy-maximizing formula from Yu’s formula. We illustrate the accuracy of our new formula by using both simulated and experimental data sets. For the simulated data sets, our new formula gives the best consensus and significant values for three different kinds of evolution models. For the data set of tetrapod 18S rRNA sequences, our new formula groups the clades of bird and reptile together correctly, where Hao’s and Yu’s formulas failed. Using real data sets with different sizes, we show that our formula is more accurate than Hao’s and Yu’s formulas even for small data sets.


title: Determinants of systemic hypertension in older adults in Africa: a systematic review.

text: BACKGROUND An estimated 55% of older adults in Africa have systemic hypertension, a major risk factor for stroke, heart failure and dementia in the region. The risk factors associated with hypertension in this population group in Africa have not been systematically evaluated. We, therefore, undertook a systematic review to identify these risk factors. METHODS We searched for population-based studies of adults aged ≥50 years living in Africa and reporting an estimate of hypertension and associated risk factors. We included articles published in any language between January 1980 and May 2018 using a comprehensive search strategy. We extracted data including the sample characteristics, prevalence of hypertension and risk factors with their effect sizes. RESULTS From an initial 10,719 records, we retained 63 eligible full text articles for review out of which we analyzed 23 studies made up of 19 primary and four multiple publications which had data on risk factors from bivariate or multivariable analysis. The primary studies, published from 2010 to 2018, involved a total of 30,500 participants in 12 different countries with mean ages ranging from 62.7 ± 9 years to 76.9 ± 8.4 years. Through narrative synthesis, we found consistent determinants of hypertension (overweight/obesity and history of stroke), less consistent but frequent determinants (including older age group, female sex and urban residence), inconsistent determinants (including education, wealth index, alcohol intake and physical activity) and nonsignificant covariates (marital status and having health insurance). Overall, the highest adjusted odds ratios were those associated with obesity and history of stroke. CONCLUSION The key determinants of systemic hypertension in older adults in Africa are older age group, overweight/obesity, history of stroke and female sex. Health programmes should promote weight reduction throughout the life course, including during the middle and older age of African adults.


title: Routine versus selective computed tomography in non-traumatic acute abdominal pain: meta-analysis of randomised trials.

text: PURPOSE To compare the routine vs. selective use of computed tomography (CT) in patients presenting with non-traumatic acute abdominal pain (AAP) to a surgical service. METHODS We conducted a systematic review of literature and meta-analysis of outcomes according to PRISMA statement standards to compare the routine vs. selective use of CT in adult patients presenting with non-traumatic AAP. RESULTS Analysis of 722 patients from 4 randomised controlled trials showed no difference between the routine CT and selective CT groups in terms of proportion of correct diagnoses (OR 1.36,95% CI 0.89, 2.07, P = 0.15), mortality (RD 0.03, 95% CI - 0.08, 0.02, P = 0.27] and length of hospital stay (LOS) [MD - 0.26, 95% CI - 2.07, 1.55, P = 0.78). CONCLUSIONS The routine use of CT does not improve the proportion of correct diagnoses and mortality compared to selective use of CT in adult patients with non-traumatic AAP. The available evidence regarding the influence of routine CT on LOS may be subject to type 2 error. These findings, however, may not apply to the elderly patient with AAP and further studies are required.


title: Transcatheter arterial embolisation in upper gastrointestinal bleeding in a sample of 29 patients in a gastrointestinal referral center in Germany.

text: OBJECTIVE This is a retrospective analysis of interventional embolisation performed with catheter angiography in 29 patients with upper gastrointestinal bleeding in the setting of a secondary care hospital. PATIENTS, MATERIALS, AND METHODS From April 2007 to February 2013, 29 patients with upper gastrointestinal bleeding underwent endovascular diagnostics and treatment. The diagnosis was established by endoscopy, computed tomography or clinically based on a significant decrease in hemoglobin. Transcatheter arterial embolisation was performed with coils, liquid embolic agents, and particles. The technical and clinical outcomes were assessed by postinterventional endoscopy, hemoglobin concentrations, number of necessary transfusions, or surgical interventions, as well as by post-interventional mortality within 28 days after the procedure. RESULTS Selective angiographic embolisation in upper gastrointestinal bleeding was primarily successful technically and clinically in 22 of 29 patients. In 4/29 cases an angiographic reintervention was performed, which was successful in 3 cases. In 3 cases of primarily technically unsuccessful procedures reintervention was not attempted. No catheterisation-related complications were recorded. Peri-interventional mortality was 31%, but only 2 of these patients died due to uncontrolled massive bleeding, whereas the lethal outcome in the other 7 patients was due to their underlying diseases. CONCLUSION Transcatheter arterial embolisation is an effective and rapid method in the management of upper gastrointestinal bleeding. Radiological endovascular interventions may considerably contribute to reduced mortality in GI bleeding by avoiding a potential surgical procedure following unsuccessful endoscopic treatment. The study underlines the importance of the combination of interventional endoscopy with interventional radiology in secondary care hospitals for patient outcome in complex and complicated upper gastrointestinal bleeding situations.


title: Pregnancy and non-pregnancy related immune thrombotic thrombocytopenic purpura in women of reproductive age.

text: Pregnancy is a precipitating factor for immune thrombotic thrombocytopenic purpura (iTTP). We compared the clinical course and outcomes of iTTP in women of reproductive age, between those with pregnancy- and non-pregnancy-related iTTP. A review of all reproductive-aged women diagnosed with iTTP during 2010-2019 in seven university hospitals in Israel. Of 42 cases of iTTP, 12 (28.6%) were pregnancy-related. At presentation, the laboratory profiles did not differ significantly between those with pregnancy- and non-pregnancy-related iTTP, including hemoglobin (median 8.4 vs 8.0 g/dL), platelet count (12.5 vs. 11.5 X 109/L); and levels of bilirubin (1.23 vs. 1.82 mg/dL), lactate dehydrogenase (1615 vs. 1701 U/L), creatinine (0.61 vs. 0.79 mg/dL) and anti-ADAMTS13 antibodies titer (75 vs. 82 U/mL). The proportions of women with renal, neurologic, or hepatic involvement were similar between the groups. Cardiac involvement was more common among those with pregnancy-related disease (25.0% vs. 3.3%, P = 0.06). The median number of courses of plasma-exchange therapy was 11 for both groups. All the women were treated with parenteral corticosteroids and the rate of adjunctive treatments did not differ between the groups (P = 0.30). Four women (one-third) with pregnancy-related disease had preeclampsia. Two women (16.7%) with pregnancy-related iTTP died during the acute episode (P = 0.07); no deaths were observed in the non-pregnancy-related group. Among reproductive-aged women with iTTP, most clinical and laboratory profiles were similar between those with pregnancy- and non-pregnancy-related disease. However, the higher rates of cardiac involvement and mortality among women with pregnancy-related iTTP highlight its challenging management.


title: Development of a virtual reality robotic surgical curriculum using the da Vinci Si surgical system.

text: INTRODUCTION This study aimed to develop a training curriculum to evaluate the basic robotic skills necessary to reach an 80 % preset proficiency score and correlate the level of surgical experience with the overall performance obtained using the da Vinci Surgical Skills simulator. METHODS Twenty-two participants (4 faculty, 4 senior, and 14 junior residents) were enrolled in a 4-week robotic training curriculum developed at our institution. A set of seven robotic skills were selected based on the manufacturer's exercise primary endpoint. During their pretesting session, participants completed one trial of each of the seven simulated exercises. In two individual sessions over a 2 week period, trainees practiced a different set of exercises that evaluated the same basic robotic skills assessed during pretesting with the objective of reaching an overall score of 80 % on two consecutive attempts. If proficiency was not achieved, then a maximum of six trials per exercise was allowed before advancing to the next skill. During their fourth week of training, participants completed a post-testing session with the same set of exercises used during pretesting. Participants' overall performance and various metrics were recorded in an online database for further analysis. RESULTS A significant skills gain from pre- to post-test was observed for each of the seven basic robotic skills regardless of participant's level of training (p < .001). Interestingly, participants only achieved an overall score of 80 % or more in only five of the seven exercises. No statistical difference in gain of skills was found between groups suggesting robotic skills development is independent of level of prior surgical expertise. CONCLUSION A dedicated virtual reality robotic training curriculum significantly improves the seven basic robotic surgical skills necessary to operate the da Vinci Si surgical console. Six training trials appear to be insufficient to reach proficiency levels on more advanced skills.


title: Power Morcellation Using a Contained Bag System.

text: BACKGROUND AND OBJECTIVES The well-known advantages of minimally invasive surgery make the approach well suited for hysterectomy and other gynecological procedures. The removal of specimens excised during surgery has been a challenge that has been answered by the use of power morcellation. With this study we sought to assess the feasibility of power morcellation within a specimen bag. METHODS This was a retrospective cohort study including patients from a private practice in suburban Chicago, Illinois, who underwent contained electromechanical power morcellation during a laparoscopic or robot-assisted hysterectomy or myomectomy from May 2014 through December 2015. Contained power morcellation was performed with the Espiner EcoSac 230 (Espiner Medical Ltd., North Somerset, United Kingdom) specimen bag. Descriptive statistics were performed for both categorical and continuous data. RESULTS Of the 187 procedures performed, 73.8% were myomectomies, and 26.2% were hysterectomies. The patients' mean age was 40 (range, 25-54) years and mean body mass index was 28.7 (range, 17.3-57.6). The average specimen weight was 300 g, with the largest weighing 2134 g. Estimated blood loss averaged 98.4 mL. The postoperative admission rate was 12.3%, most of which were due to nausea and urinary retention. Seventeen patients (9.1%) had postoperative complications, most of which were minor, and 4 (2.1%) were readmitted. There were no bag failures or complications that were due to the use of the specimen bag or to power morcellation. CONCLUSIONS Performing electromechanical power morcellation within the Espiner EcoSac 230 specimen bag was successfully performed in 187 patients with no bag-related complications. This method of contained power morcellation is feasible, reliable, and reproducible, even for a large specimen.


Letter to the Editor: Use of Dental Radiography in the COVID-19 Pandemic.


title: Comparison of minilaparoscopy and single-incision intragastric surgery for gastric submucosal tumor resection in a porcine model.

text: BACKGROUND The aim of this study was to develop an easy-to-induce and reproducible model of gastric submucosal tumor in swine to compare minilaparoscopy (ML) with single-incision (SI) intragastric surgery. METHODS Twelve healthy female pigs (weight 30.94 ± 2.49 kg) underwent a transparietal injection of sterile alginate at the level of Z-line (n = 6) and at the pre-pyloric area (n = 6) creating a model of gastric submucosal pseudotumor. The operative procedures included intragastric resection with ML and SI approaches of cardiac and pre-pyloric lesions, with gastroscopic assistance. After resection, the gastric mucosal layer was closed using intracorporeal sutures. The operative time, complication rate and clinical evolution after 1 month were compared in the four groups that the pigs were arranged. RESULTS The pseudotumors ranged in size from 3 to 6 cm in diameter. The access of the gastric cavity and resection of the experimental SMP and suturing of the mucosa were performed successfully in 12 animals using both approaches. Mean time to perform the exeresis of gastric cardia tumors was significantly higher in single-incision approach. No significant differences were observed in the surgical time during pyloric surgery. Minilaparoscopic approach reduced significantly the mucosa closure time in esophagogastric and pyloric pseudotumors. One month after, no alterations were shown in the abdominal cavity using exploratory laparotomy. CONCLUSIONS The technical feasibility of performing safe and efficient intragastric approach of submucosal pseudotumors in swine model was verified in this study. Intragastric ML has advantages over SI, namely regarding the reduction in total surgical times and the fewer technical difficulties.


title: Biosensors as rapid diagnostic tests for tropical diseases.

text: Effective diagnosis of infectious pathogens is essential for disease identification and subsequent adequate treatment, to prevent drug resistance and to adopt suitable public health interventions for the prevention and control of epidemic outbreaks. Particular situations under which medical diagnostics operate in tropical environments make the use of new easy-to-use diagnostic tools the preferred (or even unique) option. These diagnostic tests and devices, usually based on biosensing methods, are being increasingly exploited as promising alternatives to classical, "heavy" lab instrumentation for clinical diagnosis, allowing simple, inexpensive and point-of-care testing. However, in many developing countries the lack of accessibility and affordability for many commercial diagnostic tests remains a major cause of high disease burden in such regions. We present a comprehensive overview about the problems of conventional medical diagnosis of infectious pathologies in tropical regions, while pointing out new methods and analytical tools for in-the-field and decentralized diagnosis of current major infectious tropical diseases. The review includes not only biosensor-based rapid diagnostic tests approved by regulatory entities and already commercialized, but also those at the early stages of research.


Laparoscopic repair of Morgagni hernia: an interesting case and complication.


title: Human leukocyte antigens A*3001 and A*3002 show distinct peptide-binding patterns of the Mycobacterium tuberculosis protein TB10.4: consequences for immune recognition.

text: High-tuberculosis (TB)-burden countries are located in sub-Saharan Africa. We examined the frequency of human leukocyte antigen (HLA) alleles, followed by recombinant expression of the most frequent HLA-A alleles, i.e., HLA-A*3001 and HLA-A*3002, to study differences in mycobacterial peptide presentation and CD8(+) T-cell recognition. We screened a peptide library (9-mer peptides with an 8-amino-acid overlap) for binding, affinity, and off-rate of the Mycobacterium tuberculosis-associated antigen TB10.4 and identified only three TB10.4 peptides with considerable binding to HLA-A*3001. In contrast, 22 peptides bound to HLA-A*3002. This reflects a marked difference in the binding preference between the two alleles, with A*3002 tolerating a more promiscuous peptide-binding pattern and A*3001 accommodating only a very selective peptide repertoire. Subsequent analysis of the affinity and off-rate of the binding peptides revealed a strong affinity (8 nM to 7 μM) and moderate off-rate (20 min to 3 h) for both alleles. Construction of HLA-A*3001 and HLA-A*3002 tetramers containing selected binding peptides from TB10.4, including a peptide which was shared among both alleles, QIMYNYPAM (TB10.4(3-11)), allowed us to enumerate epitope-specific T cells in HLA-A*3001- and HLA-A*3002-typed patients with active TB. HLA-A*3001 and HLA-A*3002 major histocompatibility complex-peptide complexes were recognized in individuals with active TB, irrespective of their homozygous HLA-A*3001 or HLA-A*3002 genetic background. The antigen-specific T cells exhibited the CD45RA(+) CCR7(+) precursor phenotype and the interleukin-7 receptor (CD127), which were different from the phenotype and receptor exhibited by the parental CD8(+) T-cell population.


title: A contemporary comparative analysis of immediate postoperative prosthesis placement following below-knee amputation.

text: BACKGROUND Despite advances in the treatment of peripheral arterial disease, a significant number of patients ultimately require major amputations. Traditionally, postoperative management of a below-knee amputation involves soft compressive dressings to allow for complete stump healing before initial prosthesis fitting. This technique is associated with a prolonged period of limited mobility, placing patients at risk for deconditioning or fall with a risk of injury to the stump. In contrast, immediate postoperative prosthesis (IPOP) placement allows patients to begin ambulation and rehabilitation on postoperative day 1, which may be of significant physiologic and psychological benefit. The purpose of this study is to compare the outcomes of patients undergoing IPOP placement to those of a historical control group managed with traditional soft compressive dressing placement. METHODS Medical records of all consecutive below-knee amputation patients who underwent IPOP (IPOP group; 37 patients, 2007-2010) and all patients who underwent traditional soft compressive dressing placement and were IPOP candidates (non-IPOP group; 35 patients, 2006-2007) were retrospectively reviewed. Patient comorbidities and preoperative ambulation status were compared between the IPOP and the non-IPOP groups. Primary outcomes evaluated included perioperative systemic complications, wound complications, need for surgical revision, and the time until placement of a definitive prosthesis. Data were analyzed using the chi-squared and Student's t-test. RESULTS Preoperative comorbidities and patient characteristics of the 2 groups were similar, although the IPOP group was younger (61.5 vs. 69.0 years; P=0.01). Immediate perioperative systemic complication rates were not significantly different between the 2 groups (IPOP 29.7% vs. non-IPOP 31.4%; P=0.876). Postoperative wound complication rates were as follows: wound infection (IPOP 18.9% vs. non-IPOP 25.0%; P=0.555), wound dehiscence (IPOP 29.7% vs. non-IPOP 25.0%; P=0.673), and skin breakdown separate from the incision (IPOP 18.9% vs. non-IPOP 3.6%; P=0.062). Patients in the IPOP group trended towards fewer postoperative falls (IPOP 10.8% vs. non-IPOP 21.4%; P=0.240). The need for revision was significantly greater in the non-IPOP group (IPOP 5.4% vs. non-IPOP 27.6%; P=0.013). The time from surgery to placement of the preparatory prosthesis was 51 days in the IPOP group. CONCLUSIONS Patients undergoing IPOP have similar perioperative systemic and wound complication rates compared to those patients undergoing conventional below-knee amputation, but are less likely to require surgical revision. The use of IPOP allows for early ambulation and rehabilitation, which may be of psychological benefit and may decrease the sequelae of prolonged immobilization. IPOP application should be considered for all appropriate candidates requiring below-knee amputation.


title: Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes).

text: BACKGROUND Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). METHODS An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. RESULTS A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. CONCLUSIONS Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.


title: Systematic Review and Meta-analysis of Diagnostic Accuracy of Percutaneous Renal Tumour Biopsy.

text: CONTEXT The role of percutaneous renal tumour biopsy (RTB) remains controversial due to uncertainties regarding its diagnostic accuracy and safety. OBJECTIVE We performed a systematic review and meta-analysis to determine the safety and accuracy of percutaneous RTB for the diagnosis of malignancy, histologic tumour subtype, and grade. EVIDENCE ACQUISITION Medline, Embase, and Cochrane Library were searched for studies providing data on diagnostic accuracy and complications of percutaneous core biopsy (CB) or fine-needle aspiration (FNA) of renal tumours. A meta-analysis was performed to obtain pooled estimates of sensitivity and specificity for diagnosis of malignancy. The Cohen kappa coefficient (κ) was estimated for the analysis of histotype/grade concordance between diagnosis on RTB and surgical specimen. Risk of bias assessment was performed (QUADAS-2). EVIDENCE SYNTHESIS A total of 57 studies recruiting 5228 patients were included. The overall median diagnostic rate of RTB was 92%. The sensitivity and specificity of diagnostic CBs and FNAs were 99.1% and 99.7%, and 93.2% and 89.8%, respectively. A good (κ = 0.683) and a fair (κ = 0.34) agreement were observed between histologic subtype and Fuhrman grade on RTB and surgical specimen, respectively. A very low rate of Clavien ≥ 2 complications was reported. Study limitations included selection and differential-verification bias. CONCLUSIONS RTB is safe and has a high diagnostic yield in experienced centres. Both CB and FNA have good accuracy for the diagnosis of malignancy and histologic subtype, with better performance for CB. The accuracy for Fuhrman grade is fair. Overall, the quality of the evidence was moderate. Prospective cohort studies recruiting consecutive patients and using homogeneous reference standards are required. PATIENT SUMMARY We systematically reviewed the literature to assess the safety and diagnostic performance of renal tumour biopsy (RTB). The results suggest that RTB has good accuracy in diagnosing renal cancer and its subtypes, and it appears to be safe. However, the quality of evidence was moderate, and better quality studies are required to provide a more definitive answer.


title: Aging-Related Reduced Expression of CXCR4 on Bone Marrow Mesenchymal Stromal Cells Contributes to Hematopoietic Stem and Progenitor Cell Defects.

text: Aging impairs the regenerative potential of hematopoietic stem cells (HSC) and skews differentiation towards the myeloid lineage. The bone marrow (BM) microenvironment has recently been suggested to influence HSC aging, however the mechanisms whereby BM stromal cells mediate this effect is unknown. Here we show that aging-associated decreased expression of CXCR4 expression on BM mesenchymal stem cells (MSC) plays a crucial role in the development of the hematopoietic stem and progenitor cells (HSPC) aging phenotype. The BM MSC from old mice was sufficient to drive a premature aging phenotype of young HSPC when cultured together ex vivo. The impaired ability of old MSC to support HSPC function is associated with reduced expression of CXCR4 on BM MSC of old mice. Deletion of the CXCR4 gene in young MSC accelerates an aging phenotype in these cells characterized by increased production of reactive oxygen species (ROS), DNA damage, senescence, and reduced proliferation. Culture of HSPC from young mice with CXCR4 deficient MSC also from young mice led to a premature aging phenotype in the young HSPC, as evidenced by reduced hematopoietic regeneration and enhanced myeloid differentiation. Mechanistically, CXCR4 signaling prevents BM MSC dysfunction by suppressing oxidative stress, as treatment of old or CXCR4 deficient MSC with N-acetyl-L-cysteine (NAC), improved their niche supporting activity, and attenuated the HSPC aging phenotype. Our studies suggest that age-associated reduction in CXCR4 expression on BM MSC impairs hematopoietic niche activity with increased ROS production, driving an HSC aging phenotype. Thus, modulation of the SDF-1/CXCR4 axis in MSC may lead to novel interventions to alleviate the age-associated decline in immune/hematopoietic function.


title: Technical approaches to single port/incision laparoscopic appendicectomy: a literature review.

text: INTRODUCTION Single port/incision laparoscopic surgery (SPILS) is a modern advancement toward stealth surgery. Despite the paucity of high-quality scientific studies assessing its effectiveness, this procedure is being used increasingly. This review aims to describe commonly used techniques for SPILS appendicectomies (SPILA), to summarise complication rates in the literature and to provide discussion on indications and implementation. METHODS All available databases including the Cochrane Central Register of Controlled Trials, MEDLINE(®) and Embase™ were searched in February 2011 and cross-referenced for available English literature describing SPILA in patients of any age. RESULTS Three broad technical approaches are described: procedures using laparoscopic instruments through a single skin incision in the abdominal wall, regardless of the number of fascial incisions, with or without the additional use of percutaneous sutures or wires to 'assist' the operation, and hybrid procedures, in which the appendix is exteriorised using a single incision laparoscopically assisted operation but subsequently divided using a conventional 'open' appendicectomy technique. Complication rates seem to be highest in SPILA procedures unassisted by sutures or wires. CONCLUSIONS Future research assessing the efficacy of single incision laparoscopic procedures should consider variation in technique as a possible factor affecting outcome.


title: Use of technology by orientation and mobility professionals in Australia and Malaysia before COVID-19.

text: PURPOSE Orientation and Mobility (O&M) professionals teach people with low vision or blindness to use specialist assistive technologies to support confident travel, but many O&M clients now prefer a smartphone. This study aimed to investigate what technology O&M professionals in Australia and Malaysia have, use, like, and want to support their client work, to inform the development of O&M technologies and build capacity in the international O&M profession. MATERIALS AND METHODS A technology survey was completed by professionals (n = 36) attending O&M workshops in Malaysia. A revised survey was completed online by O&M specialists (n = 31) primarily in Australia. Qualitative data about technology use came from conferences, workshops and interviews with O&M professionals. Descriptive statistics were analysed together with free-text data. RESULTS Limited awareness of apps used by clients, unaffordability of devices, and inadequate technology training discouraged many O&M professionals from employing existing technologies in client programmes or for broader professional purposes. Professionals needed to learn smartphone accessibility features and travel-related apps, and ways to use technology during O&M client programmes, initial professional training, ongoing professional development and research. CONCLUSIONS Smartphones are now integral to travel with low vision or blindness and early-adopter O&M clients are the travel tech-experts. O&M professionals need better initial training and then regular upskilling in mainstream O&M technologies to expand clients' travel choices. COVID-19 has created an imperative for technology laggards to upskill for O&M tele-practice. O&M technology could support comprehensive O&M specialist training and practice in Malaysia, to better serve O&M clients with complex needs. Implications for rehabilitation Most orientation and mobility (O&M) clients are travelling with a smartphone, so O&M specialists need to be abreast of mainstream technologies, accessibility features and apps used by clients for orientation, mobility, visual efficiency and social engagement. O&M specialists who are technology laggards need human-guided support to develop confidence in using travel technologies, and O&M clients are the experts. COVID-19 has created an imperative to learn skills for O&M tele-practice. Affordability is a significant barrier to O&M professionals and clients accessing specialist travel technologies in Malaysia, and to O&M professionals upgrading technology in Australia. Comprehensive training for O&M specialists is needed in Malaysia to meet the travel needs of clients with low vision or blindness who also have physical, cognitive, sensory or mental health complications.