title: Prevention of pressure ulcers among individuals cared for in the prone position: lessons for the COVID-19 emergency.

text: OBJECTIVE Pressure ulcers (PUs) involve the destruction of skin and underlying tissue due to prolonged pressure and shear forces. These ulcers are painful and significantly reduce a person's quality of life. PUs are also expensive to manage and impact negatively on the achievement of cost-effective, efficient care delivery. METHOD Prone positioning is a postural therapy that aims to enhance respiratory function through increasing oxygenation levels. In contemporary clinical practice, ventilation in the prone position is indicated for patients with severe acute respiratory distress syndrome. However, despite its advantages in terms of respiratory function, several studies have examined complications of prone position ventilation and have identified PUs (facial PUs as well as PUs on other weight-bearing areas of the body) as a frequent complication in patients who are already in a precarious medical situation. International data suggest that up to 57% of patients nursed in the prone position develop a PU. The aim of this clinical review is to identify and review evidence-based recommendations developed to facilitate the selection and application of preventive interventions aimed at reducing PU development in patients ventilated in the prone position. Given the current COVID-19 crisis, this review is timely as intensive care unit (ICU) patients with COVID-19 require ventilation in the prone position at a level that is disproportionate to the general intensive care population. Up to 28% of patients admitted to the ICU with confirmed infection due to severe COVID-19 are cared for in the prone position. The scope of this review is limited to adult individuals only. RESULTS The skin assessment should be undertaken before proning and following positioning the patient back into the supine position. Although it is essential to keep the skin clean and moisturised, using pH-balanced cleansers, there is inconsistency in terms of the evidence to support the type of moisturiser. Use of positioning devices in addition to repositioning is recommended to offload pressure points on the face and body. Further, using dressings such as hydrocolloids, transparent film and silicone may be of benefit in decreasing facial skin breakdown. CONCLUSION Given the importance of PU prevention in this cohort of patients, adopting a focused prevention strategy, including skin assessment and care, offloading and pressure redistribution, and dressings for prevention may contribute to a reduction in the incidence and prevalence of these largely preventable wounds.


title: Volume comparison of radiofrequency ablation at 3- and 5-cm target volumes for four different radiofrequency generators: MR volumetry in an open 1-T MRI system versus macroscopic measurement.

text: INTRODUCTION In a patient, it is usually not macroscopically possible to estimate the non-viable volume induced by radiofrequency ablation (RFA) after the procedure. The purpose of this study was to use an ex vivo bovine liver model to perform magnetic resonance (MR) volumetry of the visible tissue signal change induced by RFA and to correlate the MR measurement with the actual macroscopic volume measured in the dissected specimens. MATERIALS AND METHODS Sixty-four liver specimens cut from 16 bovine livers were ablated under constant simulated, close physiological conditions with target volumes set to 14.14 ml (3-cm lesion) and 65.45 ml (5-cm lesion). Four commercially available radiofrequency (RF) systems were tested (n=16 for each system; n=8 for 3 cm and n=8 for 5 cm). A T1-weighted turbo spin echo (TSE) sequence with inversion recovery and a proton-density (PD)-weighted TSE sequence were acquired in a 1.0-T open magnetic resonance imaging (MRI) system. After manual dissection, actual macroscopic ablation diameters were measured and volumes calculated. MR volumetry was performed using a semiautomatic software tool. To validate the correctness and feasibility of the volume formula in macroscopic measurements, MR multiplanar reformation diameter measurements with subsequent volume calculation and semiautomatic MR volumes were correlated. RESULTS Semiautomatic MR volumetry yielded smaller volumes than manual measurement after dissection, irrespective of RF system used, target lesion size, and MR sequence. For the 3-cm lesion, only 43.3% (T1) and 41.5% (PD) of the entire necrosis are detectable. For the 5-cm lesion, only 40.8% (T1) and 37.2% (PD) are visualized in MRI directly after intervention. The correlation between semiautomatic MR volumes and calculated MR volumes was 0.888 for the T1-weighted sequence and 0.875 for the PD sequence. CONCLUSION After correlation of semiautomatic MR volumes and calculated MR volumes, it seems reasonable to use the respective volume formula for macroscopic volume calculation. Hyperacute MRI after ex vivo intervention may result in the underestimation of the real expansion of the produced necrosis zone. This must be kept in mind when using MRI for validating ablation success directly after RFA. One reason for the discrepancy between macroscopic and MRI appearance immediately after RFA may be that the transitional zone shows no or only partially visible MR signal change.


title: Emerging Infectious Diseases in Pregnancy.

text: It has been recognized for centuries that pregnant women have unique susceptibilities to many infectious diseases that predispose them to untoward outcomes compared with the general adult population. It is thought a combination of adaptive alterations in immunity to allow for the fetal allograft combined with changes in anatomy and physiology accompanying pregnancy underlie these susceptibilities. Emerging infectious diseases are defined as those whose incidence in humans has increased in the past two decades or threaten to increase in the near future. The past decade alone has witnessed many such outbreaks, each with its own unique implications for pregnant women and their unborn fetuses as well as lessons for the health care community regarding response and mitigation. Examples of such outbreaks include, but are not limited to, severe acute respiratory syndrome, the 2009 H1N1 pandemic influenza, Ebola virus, and, most recently, the Zika virus. Although each emerging pathogen has unique features requiring specific considerations, there are many underlying principles that are shared in the recognition, communication, and mitigation of such infectious outbreaks. Some of these key principles include disease-specific delineation of transmission dynamics, understanding of pathogen-specific effects on both mothers and fetuses, and advance planning and contemporaneous management that prioritize communication among public health experts, clinicians, and patients. The productive and effective working collaboration among the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine has been a key partnership in the successful communication and management of such outbreaks for women's health care providers and patients alike. Going forward, the knowledge gained over the past decade will undoubtedly continue to inform future responses and will serve to optimize the education and care given to pregnant women in the face of current and future emerging infectious disease outbreaks.


title: Does lopinavir measure up in the treatment of Covid-19?

text: INTRODUCTION Lopinavir in combination with ritonavir is approved for the treatment of HIV and has recently been subject to a clinical trial in severe Covid-19. AREAS COVERED This evaluation is of LOTUS China (the Lopinavir Trial for Suppression of SARS-Cov-2 in China), which was a randomised trial in hospitalised subjects with Covid-9 in a respiratory sample and pneumonia. As, in severe Covid-19, lopinavir/ritonavir had no beneficial effects but increased gastrointestinal adverse effects, this combination should not be used at this stage of Covid-19. EXPERT OPINION In my opinion, the rationale for undertaking a trial of lopinavir/ritonavir in Covid-19 was poor. The analysis of a modified intention to treat group analysis in LOTUS China may have introduced bias. After LOTUS China, there is probably no future for lopinavir in the treatment of severe Covid-19, but some clinical trials for prevention or in various stages of Covid-19 have recently started or are ongoing. The major limitation to these trials is that, as lopinavir does not inhibit Covid-19, it is unlikely to prevent infection, reduce viral load, or reduce severity. However, these trials may be worthwhile in finally determining whether lopinavir has any role in preventing or treating Covid-19.


title: Comparative evaluation of the cadaveric, radiographic and computed tomographic anatomy of the heads of green iguana (Iguana iguana), common tegu (Tupinambis merianae) and bearded dragon (Pogona vitticeps).

text: BACKGROUND Radiology and computed tomography are the most commonly available diagnostic tools for the diagnosis of pathologies affecting the head and skull in veterinary practice. Nevertheless, accurate interpretation of radiographic and CT studies requires a thorough knowledge of the gross and the cross-sectional anatomy. Despite the increasing success of reptiles as pets, only a few reports over their normal imaging features are currently available. The aim of this study is to describe the normal cadaveric, radiographic and computed tomographic features of the heads of the green iguana, tegu and bearded dragon. RESULTS 6 adult green iguanas, 4 tegus, 3 bearded dragons, and, the adult cadavers of: 4 green iguana, 4 tegu, 4 bearded dragon were included in the study. 2 cadavers were dissected following a stratigraphic approach and 2 cadavers were cross-sectioned for each species. These latter specimens were stored in a freezer (-20°C) until completely frozen. Transversal sections at 5 mm intervals were obtained by means of an electric band-saw. Each section was cleaned and photographed on both sides. Radiographs of the head of each subject were obtained. Pre- and post- contrast computed tomographic studies of the head were performed on all the live animals. CT images were displayed in both bone and soft tissue windows. Individual anatomic structures were first recognised and labelled on the anatomic images and then matched on radiographs and CT images. Radiographic and CT images of the skull provided good detail of the bony structures in all species. In CT contrast medium injection enabled good detail of the soft tissues to be obtained in the iguana whereas only the eye was clearly distinguishable from the remaining soft tissues in both the tegu and the bearded dragon. CONCLUSIONS The results provide an atlas of the normal anatomical and in vivo radiographic and computed tomographic features of the heads of lizards, and this may be useful in interpreting any imaging modality involving these species.


title: Intracranial dural arteriovenous fistulas: classification, imaging findings, and treatment.

text: Intracranial DAVFs are pathologic dural-based shunts and account for 10%-15% of all intracranial arteriovenous malformations. These malformations derive their arterial supply primarily from meningeal vessels, and the venous drainage is either via dural venous sinuses or through the cortical veins. DAVFs have a reported association with dural sinus thrombosis, venous hypertension, previous craniotomy, and trauma, though many lesions are idiopathic. The diagnosis is dependent on a high level of clinical suspicion and high-resolution imaging. Cross-sectional imaging techniques by using CT and MR imaging aid in the diagnosis, but conventional angiography remains the most accurate method for complete characterization and classification of DAVFs. The pattern of venous drainage observed on dynamic vascular imaging determines the type of DAVF and correlates with the severity of symptoms and the risk of hemorrhage.


title: Ablative therapy for esophageal dysplasia and early malignancy: focus on RFA.

text: Ablative therapies have been utilized with increasing frequency for the treatment of Barrett's esophagus with and without dysplasia. Multiple modalities are available for topical ablation of the esophagus, but radiofrequency ablation (RFA) remains the most commonly used. There have been significant advances in technique since the introduction of RFA. The aim of this paper is to review the indications, techniques, outcomes, and most common complications following esophageal ablation with RFA.


title: Laparoscopic total pelvic exenteration using transanal minimal invasive surgery technique with en bloc bilateral lymph node dissection for advanced rectal cancer.

text: A 59-year-old man presenting with fecal occult blood visited our hospital. He was diagnosed with advanced lower rectal cancer, which was contiguous with the prostate and the left seminal vesicle. There were no metastatic lesions with lymph nodes or other organs. We performed laparoscopic total pelvic exenteration (LTPE) using transanal minimal invasive surgery technique with bilateral en bloc lateral lymph node dissection for advanced primary rectal cancer after neoadjuvant chemoradiotherapy. The total operative time was 760 min, and the estimated blood loss was 200 ml. LTPE is not well established technically, but it has many advantages including good visibility of the surgical field, less blood loss, and smaller wounds. A laparoscopic approach may be an appropriate choice for treating locally advanced lower rectal cancer, which requires TPE.


title: Hybrid transvaginal incisional hernia repair.

text: AIM Natural orifice translumenal endoscopic surgery (NOTES(®); American Society for Gastrointestinal Endoscopy [Oak Brook, IL] and Society of American Gastrointestinal and Endoscopic Surgeons [Los Angeles, CA]) is a new approach that allows surgical manipulations and specimen extractions through the natural orifices such as the vagina. There have been limited numbers of cases about the adaptation of NOTES for ventral hernia repairs. Here, we aimed to present two more cases and highlight our technical differences compared with the previously reported instances. PATIENTS AND METHODS Two patients (43 and 46 years old; body mass index of 29 and 30 kg/m(2), respectively) were treated with hybrid transvaginal incisional hernia repairs. Two 5-mm abdominal trocars were used to monitor transvaginal access, adhesiolysis, dissection of the hernia, and tuckering of the mesh. A 15-mm transvaginal trocar was used for scope and mesh introduction into the abdomen. Defects were 3-5 cm in diameter. RESULTS A rigid 5-mm laparoscope was used. The composite synthetic meshes were, respectively, 11 and 13 cm in diameter. These were passed through the vagina without any protection such as a bag or sheath. No conversion or additional port was required. Respective operative times were 120 and 180 minutes, and the patients were discharged uneventfully on the second day. One patient had seroma, which was managed conservatively (aspiration of 20 mL on Day 7). There were no recurrences after 7 and 13 months, respectively. CONCLUSIONS Conventional laparoscopic equipment can be used for hybrid transvaginal incisional hernia repair. An anti-adhesive synthetic mesh can be inserted through the vaginal trocar without protective devices. The main advantage of this technique is to avoid 10-15-mm abdominal trocars, which increase the risk of trocar-site hernias themselves.


title: Assessing the Surrogate Susceptibility of Oxacillin and Cefoxitin for Commonly Utilized Parenteral Agents against Methicillin-Susceptible Staphylococcus aureus: Focus on Ceftriaxone Discordance between Predictive Susceptibility and in Vivo Exposures.

text: Susceptibility testing with the use of surrogate agents is common among clinical microbiology laboratories. One such example is oxacillin and cefoxitin for β-lactams against methicillin-susceptible Staphylococcus aureus (MSSA). This study aimed to assess the surrogate predictive value (SPV) of oxacillin and cefoxitin for the susceptibility of commonly utilized parenteral β-lactams against MSSA as well as to evaluate the concordance between predictive susceptibility testing and the in vivo exposures for ceftriaxone. Broth microdilution MICs were determined for cefazolin, cefoxitin, ceftaroline, ceftriaxone, nafcillin, and oxacillin against a national collection of 1238 MSSA from US hospitals. Pharmacodynamic profiling was utilized to establish a clinical breakpoint for commonly utilized doses of ceftriaxone. Oxacillin had good SPVs for all the β-lactams tested, whereas cefoxitin produced unacceptable major errors for all four agents and thus appears to be an unacceptable susceptibility surrogate. While oxacillin is an adequate surrogate based on the currently defined laboratory criteria, our data also suggest that caution should be exercised when incorporating this testing approach in the clinical setting in view of the fact that the MIC distribution of MSSA coupled with the commonly utilized low doses of ceftriaxone may result in inadequate in vivo exposures against this pathogen.


title: Dynamics and predisposition of respiratory viral co-infections in children and adults.

text: OBJECTIVES The epidemiology of respiratory co-infection pairings is poorly understood. Here we assess the dynamics of respiratory viral co-infections in children and adults and determine predisposition for or against specific viral pairings. METHODS Over 5 respiratory seasons from November 30, 2013 through June 6, 2018, mono- and co-infection prevalence of 13 viral pathogens were tabulated at The Cleveland Clinic. Employing a model to proportionally distribute viral pairs utilizing individual virus' co-infection rate with prevalence patterns of concurrent co-circulating viruses, we compared predicted-to-observed occurrences of 132 viral pairing permutations using binomial analysis. RESULTS Of 30,535 respiratory samples, 9,843 (32.2%) were positive for ≥1 virus of which 1,018 (10.8%) were co-infected. Co-infected samples predominantly originated from children. Co-infection rate in pediatric population was 35.0% (2068/5906), compared to only 5.8% (270/4591) in adults. Adenovirus C (ADVC) had the highest co-infection rate (426/623, 68.3%) while influenza B had the lowest (55/546, 10.0%). ADVC-rhinovirus (HRV), RSVA-HRV, and RSVB-HRV pairings occurred at significantly higher frequencies than predicted by the proportional distribution model (p<0.05). Additionally, several viral pairings had fewer co-infections than predicted by our model: notably metapneumovirus (hMPV)-PIV3, hMPV-RSVA, and RSVA-RSVB. CONCLUSIONS This is one of the largest studies on respiratory viral co-infections in children and adults. Co-infections are substantially more common in children, especially under 5 years of age and the most frequent pairings occurred at a higher frequency than would be expected by random. Specific pairings occur at altered rates than those predicted by proportional distribution suggesting either direct or indirect interactions result between specific viral pathogens.


title: Does Surgical Approach Affect Patient-reported Function After Primary THA?

text: BACKGROUND Total hip arthroplasty (THA) relieves pain and improves physical function in patients with hip osteoarthritis, but requires a year or more for full postoperative recovery. Proponents of intermuscular surgical approaches believe that the direct-anterior approach may restore physical function more quickly than transgluteal approaches, perhaps because of diminished muscle trauma. To evaluate this, we compared patient-reported physical function and other outcome metrics during the first year after surgery between groups of patients who underwent primary THA either through the direct-anterior approach or posterior approach. QUESTIONS/PURPOSES We asked: (1) Is a primary THA using a direct-anterior approach associated with better patient-reported physical function at early postoperative times (1 and 3 months) compared with a THA performed through the posterior approach? (2) Is the direct-anterior approach THA associated with shorter operative times and higher rates of noninstitutional discharge than a posterior approach THA? METHODS Between October 2008 and February 2010, an arthroplasty fellowship-trained surgeon performed 135 THAs. All 135 were performed using the posterior approach. During that period, we used this approach when patients had any moderate to severe degenerative joint disease of the hip attributable to any type of arthritis refractory to nonoperative treatment measures. Of the patients who were treated with this approach, 21 (17%; 23 hips) were lost to followup, whereas 109 (83%; 112 hips) were available for followup at 1 year. Between February and September 2011, the same surgeon performed 86 THAs. All 86 were performed using the direct-anterior approach. During that period, we used this approach when patients with all types of moderate to severe degenerative joint disease had nonoperative treatment measures fail. Of the patients who were treated with this approach, 35 (41%; 35 hips) were lost to followup, whereas 51 (59%; 51 hips) were available for followup at 1 year. THAs during the surgeon's direct-anterior approach learning period (February 2010 through January 2011) were excluded because both approaches were being used selectively depending on patient characteristics. Clinical outcomes included operative blood loss; allogeneic transfusion; adverse events; patient-reported Veterans RAND-12 Physical (PCS) and Mental Component Summary (MCS) scores, and University of California Los Angeles (UCLA) activity scores at 1 month, 3 months, and 1 year after surgery. Resource utilization outcomes included operative time, length of stay, and discharge disposition (home versus institution). Outcomes were compared using logistic and linear regression techniques. RESULTS After controlling for relevant confounding variables including age, sex, and BMI, the direct-anterior approach was associated with worse adjusted MCS changes 1 and 3 months after surgery (1-month score change, -9; 95% CI, -13 to -5; standard error, 2), compared with the posterior approach (3-month score change, -9; 95% CI, -14 to -3; standard error, 3) (both p < 0.001), while the direct-anterior approach was associated with greater PCS improvement at 3 months compared with the posterior approach (score change, 6; 95% CI, 2-10; standard error, 2; p = 0.008). There were no differences in adjusted PCS at either 1 month or 12 months, and no clinically important differences in UCLA scores. Although the PCS score differences are greater than the minimum clinically important difference of 5 points for this endpoint, the clinical importance of such a small effect is questionable. At 1 year after THA, there were no intergroup differences in self-reported physical function, although both groups had significant loss-to-followup at that time. Operative time (skin incision to skin closure) between the two groups did not differ (81 versus 79 minutes; p = 0.411). Mean surgical blood loss (403 versus 293 mL; p < 0.001; adjusted, 119 more mL; 95% CI, 79-160; p < 0.001) and in-hospital transfusion rates (direct-anterior approach, 20% [17/86] versus posterior approach, 10% [14/135], p = 0.050; adjusted odds ratio, 3.6; 95% CI, 1.3-10.1; p = 0.016) were higher in the direct-anterior approach group. With the numbers available, there was no difference in the frequency of adverse events between groups when comparing intraoperative complications, perioperative Technical Expert Panel complications, and other non-Technical Expert Panel complications within 1 year of surgery, although this study was not adequately powered to detect differences in rare adverse events. CONCLUSIONS With suitable experience, the direct-anterior approach can be performed with expected results similar to those of the posterior approach. There may be transient and small benefits to the direct-anterior approach, including improved physical function at 3 months after surgery. However, the greater operative blood loss and greater likelihood of blood transfusions, even when the surgeon is experienced, may be a disadvantage. Given some of the kinds of bias present that we found, including loss to followup, the conclusions we present should be considered preliminary, but it appears that any benefits that accrue to the patients who had the direct-anterior approach would be transient and modest. Prospective randomized studies on the topic are needed to address the differences between surgical approaches more definitively. LEVEL OF EVIDENCE Level III, therapeutic study.


title: Feline gastrointestinal eosinophilic sclerosing fibroplasia: 13 cases and review of an emerging clinical entity.

text: OBJECTIVE Feline gastrointestinal eosinophilic sclerosing fibroplasia (FGESF) is a recently described inflammatory disease of cats affecting stomach or intestines and draining regional lymph nodes. This study presents clinical and laboratory data on 13 newly described cases from Australia (11) and the UK (two). OBSERVATIONS The disease was most often observed in middle-aged cats (median 7 years of age; interquartile range 5-9 years). Ragdolls (7/13) and males (9/13) were overrepresented. Cats generally had a long history of vomiting and/or diarrhoea. Lesions were typically large, hard, non-painful, easily palpable and most commonly situated near the pylorus or ileocaecocolic junction. Lesions were heterogeneous ultrasonographically and on sectioning at celiotomy or necropsy. Masses were hard and 'gritty' on fine-needle aspiration due to internal trabeculae made up of mature collagen bundles. Bacteria were commonly detected within masses (9/13 cases) using either culture or conventional light microscopy and a panel of special stains, and/or fluorescence in situ hybridisation (FISH), although detection often required a diligent search of multiple tissue sections. A consistent bacterial morphology could not be appreciated among the different cases. OUTCOME Patients were treated with a variable combination of cytoreduction (debulking and biopsy, to complete surgical resection), immunosuppressive therapy and antimicrobial agents. Many cats had a poor outcome, which was attributable to late diagnosis combined with suboptimal management. It is hoped that suggestions outlined in the discussion may improve clinical outcomes and long-term survival in future cases.


title: How to perform the endoscopically assisted components separation technique (ECST) for large ventral hernia repair.

text: BACKGROUND The components separation technique (CST) is frequently used for reconstructing large ventral hernias. Unfortunately, it is associated with a high wound complication rate up to 50 %, caused by large wound surface and inherent trauma to abdominal skin vascularization. An endoscopically assisted modification of the original technique (ECST) spares skin vascularization and reduces wound surface, supposedly reducing wound complications. This study accurately describes ECST step by step with detailed illustrations and report the results of a 27 patient cohort. METHODS Since September 2012 patients with midline hernias without previous subcutaneous dissection and a maximum diameter of approximately 10-15 cm underwent ECST in an expert centre for abdominal wall reconstructions. Prospective data was gathered during inpatient care and 3-6 monthly follow-up. RESULTS Twenty-seven patients (17 male/10 female) with median age of 60 years (range 35-77), average BMI 27 (SD ±2) kg/m(2) and median ASA classification 2 (range 1-3) underwent ECST. Two patients were excluded due to bilateral conversion to conventional CST and finding of peritoneal metastases. Median defect size was 116 ± 48 cm(2). Median length of stay was 5 days (range 3-15). Wound complication rate was 11 %. Recurrence rate was 29 % after a median follow-up of 13 months. CONCLUSIONS Endoscopically assisted modification of the original technique can be used for reconstructing large and complex ventral hernias up to 15 cm in diameter. The results of this small sized cohort study showed that ECST is feasible in patients with a uro-, or enterostomy and suggest that ECST reduces wound complication rate when compared to CST.


title: Single incision laparoscopic right hemicolectomy for colon cancer: less is more?

text: Single incision laparoscopic colectomy has been reported to be safe and feasible using several techniques and devices. The authors' report their experience with a single incision laparoscopic colectomy performed in a lateral to medical fashion using a commercially developed access device with standard laparoscopic instruments.


title: The impact of patient navigation: a scoping review protocol.

text: REVIEW OBJECTIVE/QUESTION The objective of this review is to synthesize the evidence on the impact of patient navigation for all populations across all settings. The question of this review is: What is the existing evidence on the impact of patient navigation?


title: Reconstruction of a long defect of the median nerve with a free nerve conduit flap.

text: Upper limb nerve damage is a common condition, and evidence suggests that functional recovery may be limited following peripheral nerve repair in cases of delayed reconstruction or reconstruction of long nerve defects. A 26-year-old man presented with traumatic injury from a wide, blunt wound of the right forearm caused by broken glass, with soft tissue loss, complete transection of the radial and ulnar arteries, and a large median nerve gap. The patient underwent debridement and subsequent surgery with a microsurgical free radial fasciocutaneous flap to provide a direct blood supply to the hand; the cephalic vein within the flap was employed as a venous vascularized chamber to wrap the sural nerve graft and to repair the wide gap (14 cm) in the median nerve. During the postoperative period, the patient followed an intensive rehabilitation program and was monitored for functional performance over 5 years of follow-up. Our assessment demonstrated skin tropism and sufficient muscle power to act against strong resistance (M5) in the muscles previously affected by paralysis, as well as a good localization of stimuli in the median nerve region and an imperfect recovery of two-point discrimination (S3+). We propose a novel and efficient procedure to repair >10-cm peripheral nerve gap injuries related to upper limb trauma.


Scientists fear coronavirus spread in countries least able to contain it.


title: Oral administration of porcine epidemic diarrhea virus spike protein expressing in silkworm pupae failed to elicit immune responses in pigs.

text: The silkworm (Bombyx mori) and its pupae have been used for decades as nutritional additives and applied on the production of high-quality recombinant proteins via the baculovirus expression vector (BEV) system. The bio-capsule, the fat-rich body, and some body components of the silkworm pupae, which deliver antigens passing through the harsh environment of digestive tract and reaching the intestine, have been used as a vehicle for oral vaccines. In the present study, to develop a novel oral vaccine against porcine epidemic diarrhea virus (PEDV), the PEDV spike (S) protein was expressed in silkworm pupae and BmN cells using the BEV system. After three doses of oral administrations with 2-week intervals in pigs, neither PEDV S protein-specific humoral nor mucosal immune responses can be detected. The failure of eliciting the PEDV-specific immune response suggested that the BEV system using BmN cells or silkworm pupae as oral immunogen-expression vehicles was not able to overcome the immunological unresponsiveness, which was possibly due to gastrointestinal specific barriers and oral tolerance. Better strategies to enhance the delivery and immunogenicity of oral vaccines should be further investigated. Nevertheless, the PEDV S protein generated in the BmN cells and silkworm pupae herein provides an efficient tool to produce the recombinant antigen for future applications.


title: Patterns and Clinical Impact of Angiographically Visible Distal Emboli During Thrombectomy With Solitaire for Acute Ischemic Stroke.

text: BACKGROUND Revascularization rates with stent retrievers after acute ischemic stroke are 69% to 86%, but favorable clinical outcomes occur in just 43% to 58% of cases. New distal emboli may negatively impact clinical outcomes. OBJECTIVE To determine the prevalence and angiographic pattern of distal emboli associated with mechanical thrombectomy using the Solitaire Flow Restoration device and evaluate their correlation with clinical outcome. METHODS We retrospectively reviewed the cerebral angiography of all patients with acute ischemic stroke who underwent mechanical thrombectomy with the use of the Solitaire FR device from 2012 to 2013. Angiographic microcatheter runs prior to Solitaire deployment and after thrombectomy were compared to identify new distal filling defects. Clinical outcome was assessed at discharge and after 90 days. RESULTS Successful revascularization using the Solitaire device occurred in 36 of 39 patients (92%). Three distinct patterns were identified: new distal emboli in the same vascular territory (n = 3), new distal emboli in a new vascular territory (n = 3), and distal emboli that resolved after proximal revascularization (n = 7). Thirteen patients had distal emboli before and after Solitaire runs, and 13 showed no evidence of distal emboli. Favorable outcome (modified Rankin scores 0-2) was seen in 54% of all patients and 83% of patients with new distal emboli; thus, there was no correlation between new emboli and unfavorable clinical outcome (P = .67). CONCLUSION We report an incidence rate of at least 15% of new emboli associated with use of the Solitaire device during thrombectomy in our series. Filling defects after Solitaire use were not associated with poor outcomes at discharge or 90-day follow-up.


title: Effect of Continuous versus Intermittent Subglottic Suctioning on Tracheal Mucosa by the Mallinckrodt TaperGuard Evac Oral Tracheal Tube in Intensive Care Unit Ventilated Patients: A Prospective Randomized Study.

text: Background and Aims A risk of tracheal mucosa injury induced by subglottic suctioning has been raised. Therefore, this prospective randomized study aims to compare the effect of continuous suctioning of subglottic secretions versus intermittent suctioning of subglottic secretions (CSSS vs. ISSS) secretions on tracheal mucosa in front of the suctioning port of the endotracheal tube. Patients and Methods Patients requiring intubation or reintubation in Intensive Care Unit with an expected ventilation duration > 24 h were eligible. Participants received CSSS at -20 mmHg or ISSS at -100 mmHg during 15 s and no suction during 8 s. The effect on tracheal mucosa in front of the suction port was assessed after intubation (T0) and before extubation (T1) using bronchoscopy. Tracheal mucosa damages were graded into five categories (no injury, erythema, edema, ulceration, or necrosis). The occurrence (no injury observed at T0 but present at T1) or the worsening (injury observed at T0 exacerbating at T1) was studied. Results Seventy-three patients were included and 53 patients (CSSS, n = 26 and ISSS, n = 27) were evaluable on the primary endpoint. The occurrence or worsening of tracheal mucosal damages did not differ between the two groups (CSSS, n = 7 [27%] vs. ISSS, n = 5 [17%], P = 0.465). Daily average volume of suctioned secretion was higher with ISSS (74 ± 100 ml vs. 20 ± 25 ml, P < 0.001). Impossibility to aspirate was higher with CSSS (0.14 ± 0.16 per day vs. 0.03 ± 0.07 per day, P < 0.001). Conclusions Our results suggest that tracheal mucosal damages did not differ between CSSS and ISSS. The aspirated volume was higher and impossibility to aspirate was lower with ISSS. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT01555229.


title: Improving palliative and end-of-life care with machine learning and routine data: a rapid review.

text: Introduction: Improving end-of-life (EOL) care is a priority worldwide as this population experiences poor outcomes and accounts disproportionately for costs. In clinical practice, physician judgement is the core method of identifying EOL care needs but has important limitations. Machine learning (ML) is a subset of artificial intelligence advancing capacity to identify patterns and make predictions using large datasets. ML approaches have the potential to improve clinical decision-making and policy design, but there has been no systematic assembly of current evidence. Methods: We conducted a rapid review, searching systematically seven databases from inception to December 31st, 2018: EMBASE, MEDLINE, Cochrane Library, PsycINFO, WOS, SCOPUS and ECONLIT. We included peer-reviewed studies that used ML approaches on routine data to improve palliative and EOL care for adults. Our specified outcomes were survival, quality of life (QoL), place of death, costs, and receipt of high-intensity treatment near end of life. We did not search grey literature and excluded material that was not a peer-reviewed article. Results: The database search identified 426 citations. We discarded 162 duplicates and screened 264 unique title/abstracts, of which 22 were forwarded for full text review. Three papers were included, 18 papers were excluded and one full text was sought but unobtainable. One paper predicted six-month mortality, one paper predicted 12-month mortality and one paper cross-referenced predicted 12-month mortality with healthcare spending. ML-informed models outperformed logistic regression in predicting mortality but poor prognosis is a weak driver of costs. Models using only routine administrative data had limited benefit from ML methods. Conclusion: While ML can in principle help to identify those at risk of adverse outcomes and inappropriate treatment near EOL, applications to policy and practice are formative. Future research must not only expand scope to other outcomes and longer timeframes, but also engage with individual preferences and ethical challenges.


title: Advances in laboratory assays for detecting human metapneumovirus.

text: Human metapneumovirus (HMPV) is one of the major causes of acute respiratory tract infection (ARI) and shows high morbidity and mortality, particularly in children and immunocompromised patients. Various methods for detecting HMPV have been developed and applied in clinical laboratories. When reviewing the literature, we found that polymerase chain reaction (PCR)-based assays have been most frequently and consistently used to detect HMPV. The most commonly used method was multiplex reverse transcriptase-PCR (RT-PCR; 57.4%), followed by real-time RT-PCR (38.3%). Multiplex RT-PCR became the more popular method in 2011-2019 (69.7%), in contrast to 2001-2009 (28.6%). The advent of multiplex PCR in detecting broader viral pathogens in one run and coinfected viruses influenced the change in user preference. Further, newly developed microarray technologies and ionization mass spectrometry were introduced in 2011-2019. Viral culture (including shell vial assays) and fluorescent immunoassays (with or without culture) were once the mainstays. However, the percentage of studies employing culture and fluorescent immunoassays decreased from 21.4% in 2001-2010 to 15.2% in 2011-2019. Meanwhile, the use of PCR-based methods of HMPV detection increased from 78.6% in 2001-2010 to 84.8% in 2011-2019. The increase in PCR-based methods might have occurred because PCR methods demonstrated better diagnostic performance, shorter hands-on and run times, less hazards to laboratory personnel, and more reliable results than traditional methods. When using these assays, it is important to acquire a comprehensive understanding of the principles, advantages, disadvantages, and precautions for data interpretation. In the future, the combination of nanotechnology and advanced genetic platforms such as next-generation sequencing will benefit patients with HMPV infection by facilitating efficient therapeutic intervention. Analytical and clinical validation are required before using new techniques in clinical laboratories.


title: Could a Feeding Jejunostomy be Integrated into a Standardized Preoperative Management of Oeso-gastric Junction Adenocarcinoma?

text: PURPOSE To evaluate the impact of a feeding jejunostomy (FJ) on the preoperative management of patients with an oesogastric adenocarcinoma (OGA). METHODS From January 2007 to December 2014, patients with potentially resectable OGA were enrolled in a perioperative chemotherapy protocol. FJ was performed before starting perioperative treatments in patients presenting with dysphagia or with a nutritional risk index (NRI) <97.5. The patients who did not require a FJ served as a control group. RESULTS Among the 114 patients with OGA consecutively admitted in our surgical department, 88 (77.2%) were enrolled for neoadjuvant treatment. A FJ was placed in 50 patients (56.8%) before the neoadjuvant treatment (FJ group), whereas 38 patients (43.2%) started neoadjuvant treatments without FJ (control group). Ninety-six percent of patients (n = 48) in the FJ group successfully completed the neoadjuvant treatment but only 81.6% of patients without FJ (n = 31; p = 0.004). The FJ group was divided between responders: 37 patients with a weight response (74%), and nonresponders: 13 patients without weight response (26%). In the FJ group, the nutritional response during preoperative chemotherapy was a significant predictive factor for the achievement of second stage oesogastric resection (p = 0.002). CONCLUSIONS FJ with enteral nutritional support during the preoperative management of OGA is a safe and effective support for the completion of the preoperative chemotherapy. The weight response to the enteral support is a predictor factor for a completion of the preoperative chemotherapy and could identify a group of patients who would have a better chance of reaching radical surgery.


title: Laparoscopic Appendectomy versus Mini-Incision Appendectomy in Patients with Lower Body Mass Index and Noncomplicated Appendicitis.

text: Laparoscopic appendectomy has become favored over open surgical methods for its association with decreased postoperative pain, more rapid return to daily activities, and improved cosmetic results. Mini-incision appendectomy was being performed in our clinic for a long time especially in patients with noncomplicated appendicitis and in patients with appropriate body mass index. Although laparoscopy presents obvious advantages especially for obese patients and young women, with respect to the results of our study, mini-incision appendectomy seems to be an alternative for selected patient groups.


docid: stmsrpqz

title: Meniscal repair with the newest fixators: which are best?


title: Issues in the diagnosis and management of the papilledema shunt.

text: BACKGROUND Dural arteriovenous fistulas (DAVFs) that shunt blood into the transverse or superior sagittal venous sinuses cause papilledema by raising intracranial pressure ("the papilledema shunt"). Such fistulas pose unique diagnostic and therapeutic challenges. METHODS Case report and literature review. RESULTS In a patient presenting with papilledema, non-invasive brain vascular imaging disclosed subtle signs of a DAVF. Digital angiography delineated the DAVF and revealed cortical venous reflux. After three transarterial embolizations with ethylene vinyl alcohol, the DAVF was closed and papilledema resolved. CONCLUSIONS The imaging features of a DAVF that cause papilledema may be subtle on non-invasive vascular imaging. If overlooked, and lumbar puncture is performed, there is a substantial risk of brain herniation. Cortical venous reflux, which may be relatively common in these DAVFs, impels the need for endovascular closure. The transvenous route, often employed for closing cavernous sinus DAVFs, should be avoided because of the dangers of dural venous sinus thrombosis.


title: Role of C-arm VasoCT in the use of endovascular WEB flow disruption in intracranial aneurysm treatment.

text: BACKGROUND AND PURPOSE The WEB aneurysm embolization system is still under evaluation but seems to be a promising technique to treat wide-neck bifurcation aneurysms. However, this device is barely visible using conventional DSA; thus, high-resolution contrast-enhanced flat panel detector CT (VasoCT) may be useful before detachment to assess the sizing and positioning of the WEB. The purpose of this study was to evaluate the interest of VasoCT during WEB procedures. MATERIALS AND METHODS From March 2012 to July 2013, twelve patients (10 women and 2 men; age range, 44-55 years) were treated for 13 intracranial aneurysms with the WEB device. DSA and VasoCT were used and compared to depict any protrusion of the device in parent arteries before detachment. Two neuroradiologists reviewed each VasoCT scan, and the quality was graded on a subjective quality scale. RESULTS The mesh of the WEB was very well-depicted in all cases, allowing a very good assessment of its deployment. Device protrusion was clearly detected with VasoCT in 5 cases, leading to WEB repositioning or size substitution. During follow-up, VasoCT also allows good assessment of eventual residual blood flow inside the aneurysm or the WEB device. CONCLUSIONS Unlike DSA, VasoCT is an excellent tool to assess WEB deployment and positioning. In our experience, it allowed a precise evaluation of the WEB sizing and its relation to the parent vessel. Such information very likely enhances the ability to safely use this device, avoiding potential thromboembolic events in cases of protrusion in the parent arteries.


Making Decisions in a COVID-19 World.


Expansion of the Priority Review Voucher Program Under the 21st Century Cures Act: Implications for Innovation and Public Health.


title: Comparison of surgical plume among laparoscopic ultrasonic dissectors using a real-time digital quantitative technology.

text: BACKGROUND This study aimed to analyze the effect of surgical plume generation from various ultrasonic dissectors on laparoscopic visibility, including the first cordless ultrasonic dissector, using a novel real-time digital quantification technique. METHODS The Covidien Cordless Sonicision, the Harmonic ACE, and the Olympus SonoSurg were applied to bovine liver with industry-specified settings. Consecutive activations were digitally captured from a laparoscope positioned to replicate the clinical setting. Plume was recognized by ImageJ software, and the percentage of pixels containing plume in each video frame was calculated. Analysis of variance statistical multi-analysis and Welch's t test were computed for all p values. RESULTS The average maximum plume produced by the Sonicision, ACE, and SonoSurg with the maximum setting were respectively 8.76% (range, 4.32-17.41%), 18.04% (range, 9.07-55.12%), and 9.46% (range, 5.68-22.12%) (p = 0.026). The deviations between the ACE and the other devices were significant (p < 0.05). The average maximum plumes produced with the coagulation setting were 4.80% (range, 0.24-19.83%) for the Sonicision, 26.63% (range, 8.12-73.50%) for the ACE, and 0.21% (range, 0.06-1.05%) for the SonoSurg (p < 0.001). The differences between all the instruments in the coagulation setting were significant. CONCLUSION To the authors' knowledge, this is the first report on a real-time digital analysis of surgical plume generation using ImageJ software. In the coagulation setting, the SonoSurg generated minimal plume. The Sonicision obstructed approximately 4%, whereas the ACE generated plume that obstructed 25% of the laparoscopic field. In the cutting setting, the SonoSurg and Sonicision generated the least obstruction, whereas the ACE caused the most obstruction.


title: SINGLE PORT LAPAROSCOPIC CHOLECYSTECTOMY: TECHNICAL ASPECTS AND RESULTS.

text: BACKGROUND The search for less traumatic surgical procedures without compromising efficacy and safety, together with the technological advances and greater experience of the teams, led to the development of operative techniques with increasingly smaller incisions, the so-called "minimally invasive surgeries". AIM To evaluate the technical aspects and results of single port cholecystectomy. METHOD Were analyzed 170 patients between 18-74 years submitted to videolaparoscopic cholecystectomies by single port, regardless of elective or urgent indication, without restriction of patient selection. RESULTS Among the 170 operations, 158 were exclusively performed by single port, and the conversion rate was 7% (inclusion of other accessory trocars or conversion to multiportal). Conversion to open surgery occurred in three cases (1.76%). The mean surgical time was 67.97 min, showing a marked decrease when was reached close to 50 cases and a stabilization after 100 surgeries. The overall complication rate was 10%, with minor complications such as: incisional pain, hematomas, granulomas, port access hernias (9.41%). CONCLUSION Single port cholecystectomy can, after standardization and surgical team training, be a safe surgical procedure associated with a recognized aesthetic advantage.


title: PAP therapy increases the risk of transmission of COVID-19.

text: Positive airway pressure (PAP) therapy is an open system that can generate contact, droplet, and airborne COVID-19 thereby increasing the risk of transmission of COVID-19 like other procedures such as tracheal intubation, noninvasive ventilation, and cardiopulmonary resuscitation. Medically prudent recommendations have been established for home use of PAP therapy in asymptomatic patients and patients with suspected or confirmed COVID-19. Recommendations for sleep clinics and sleep laboratory activities are also discussed as well as the emergency use of PAP devices as a substitute for ventilation.


title: A systematic review and meta-analysis assessing the effectiveness of alternative listening devices to conventional hearing aids in adults with hearing loss.

text: Recent technological advances have led to a rapid increase in alternative listening devices to conventional hearing aids. The aim was to systematically review the existing evidence to assess the effectiveness of alternative listening devices in adults with mild and moderate hearing loss. A systematic search strategy of the scientific literature was employed, reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) checklist. Eleven studies met eligibility for inclusion: two studies evaluated personal sound amplification products, and nine studies assessed remote microphone systems (frequency modulation, Bluetooth, wireless). The evidence in this review suggests that alternative listening devices improve behavioural measures of speech intelligibility relative to unaided and/or aided conditions. Evidence for whether alternative listening devices improve self-reported outcomes is inconsistent. The evidence was judged to be of poor to good quality and subject to bias due to limitations in study design. Our overall recommendation is that high-quality evidence (i.e. randomised controlled trials) is required to demonstrate the effectiveness of alternative listening devices. Such evidence is not currently available and is necessary to guide healthcare commissioners and policymakers when considering new service delivery models for adults with hearing loss. Review registration: Prospective Register of Systematic Reviews (PROSPERO), CRD42015029582.


title: Radiation to the Gastric Fundus Increases the Risk of Anastomotic Leakage After Esophagectomy.

text: BACKGROUND Concerns have been raised regarding the toxicity of neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer that could contribute to an increased risk of postoperative complications. The aim of this study was to determine the influence of the radiation dose to the gastric fundus on the risk of postoperative anastomotic leakage in patients undergoing nCRT followed by transthoracic esophagectomy. METHODS Between January 2012 and July 2015, 97 consecutive patients who underwent nCRT followed by transthoracic esophagectomy were included in this single-center cohort study. The gastric fundus was contoured on the pretreatment planning computed tomography. Within this contour, dose-volume histogram variables were calculated, and logistic regression analysis was used to determine their influence on the risk of anastomotic leakage. RESULTS In 25 of 97 patients (26%) anastomotic leakage occurred. The mean radiation dose to the gastric fundus was significantly higher in patients with than without leakage (median 35.6 Gy versus 24.9 Gy, respectively, p = 0.047). A mean dose more than versus less than 31.4 Gy was associated with leakage rates of 43% versus 15%, respectively. Adjusted for tumor location, clinical T stage, and radiation method, the mean radiation dose to the gastric fundus remained significantly and independently associated with an increased risk of anastomotic leakage (adjusted odds ratio 1.05 per 1-Gy increase, 95% confidence interval: 1.002 to 1.10, p = 0.043). CONCLUSIONS Efforts should be made to minimize the radiation dose to the gastric fundus when planning nCRT for esophageal cancer, because higher dose levels to the gastric fundus are associated with an increased risk of anastomotic leakage after subsequent transthoracic esophagectomy and cervical anastomosis.


Tri-axial Biopsy Needle Cauterization During Splenic Biopsy.


title: Lopinavir/ritonavir combination therapy amongst symptomatic coronavirus disease 2019 patients in India: Protocol for restricted public health emergency use

text: As of February 29, 2020, more than 85,000 cases of coronavirus disease 2019 (COVID-19) have been reported from China and 53 other countries with 2,924 deaths. On January 30, 2020, the first laboratory-confirmed case of COVID was reported from Kerala, India. In view of the earlier evidence about effectiveness of repurposed lopinavir/ritonavir against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus (CoV), as well as preliminary docking studies conducted by the ICMR-National Institute of Virology, Pune, the Central Drugs Standard Control Organization approved the restricted public health use of lopinavir/ritonavir combination amongst symptomatic COVID-19 patients detected in the country. Hospitalized adult patients with laboratory-confirmed SARS-CoV-2 infection with any one of the following criteria will be eligible to receive lopinavir/ritonavir for 14 days after obtaining written informed consent: (i) respiratory distress with respiratory rate ≥22/min or SpO(2) of <94 per cent; (ii) lung parenchymal infiltrates on chest X-ray; (iii) hypotension defined as systolic blood pressure <90 mmHg or need for vasopressor/inotropic medication; (iv) new-onset organ dysfunction; and (v) high-risk groups - age >60 yr, diabetes mellitus, renal failure, chronic lung disease and immunocompromised persons. Patients will be monitored to document clinical (hospital length of stay and mortality at 14, 28 and 90 days), laboratory (presence of viral RNA in serial throat swab samples) and safety (adverse events and serious adverse events) outcomes. Treatment outcomes amongst initial cases would be useful in providing guidance about the clinical management of patients with COVID-19. If found useful in managing initial SARS-CoV-2-infected patients, further evaluation using a randomized control trial design is warranted to guide future therapeutic use of this combination.


Rapid Development of Resident-Led Procedural Response Teams to Support Patient Care During the Coronavirus Disease 2019 Epidemic: A Surgical Workforce Activation Team.


title: Robotic-assisted total mesorectal excision with the aid of a single-port device.

text: UNLABELLED INTRODUCTION AND INDICATIONS: Robotic surgery has numerous advantages in rectal cancer surgery. Studies have reported the advantages associated with single-port approaches, such as eliminating the need for additional incisions, as well as the difficulties inherent in this technique. The authors present a hybrid technique that they performed using a robotic total mesorectal excision with the aid of a single port-device. Materials and methods. The authors performed the technique on 2 patients using a single-port device through an umbilical incision and 3 accessory ports for the robotic arms. There was no need to place ports for the assistant's equipment or for an assistant incision. RESULTS AND COMPLICATIONS The operation time was 177.5 minutes, and there were no intraoperative or postoperative complications. Both patients were discharged 7 days after the operation. CONCLUSIONS This technical variation is an additional step forward for oncological surgery with minimal damage to the abdominal wall.


title: Phosphatidylinositol 3-kinase-, actin-, and microtubule-dependent transport of Semliki Forest Virus replication complexes from the plasma membrane to modified lysosomes.

text: Like other positive-strand RNA viruses, alphaviruses replicate their genomes in association with modified intracellular membranes. Alphavirus replication sites consist of numerous bulb-shaped membrane invaginations (spherules), which contain the double-stranded replication intermediates. Time course studies with Semliki Forest virus (SFV)-infected cells were combined with live-cell imaging and electron microscopy to reveal that the replication complex spherules of SFV undergo an unprecedented large-scale movement between cellular compartments. The spherules first accumulated at the plasma membrane and were then internalized using an endocytic process that required a functional actin-myosin network, as shown by blebbistatin treatment. Wortmannin and other inhibitors indicated that the internalization of spherules also required the activity of phosphatidylinositol 3-kinase. The spherules therefore represent an unusual type of endocytic cargo. After endocytosis, spherule-containing vesicles were highly dynamic and had a neutral pH. These primary carriers fused with acidic endosomes and moved long distances on microtubules, in a manner prevented by nocodazole. The result of the large-scale migration was the formation of a very stable compartment, where the spherules were accumulated on the outer surfaces of unusually large and static acidic vacuoles localized in the pericentriolar region. Our work highlights both fundamental similarities and important differences in the processes that lead to the modified membrane compartments in cells infected by distinct groups of positive-sense RNA viruses.


title: Endovascular thrombectomy for stroke: current best practice and future goals.

text: Endovascular thrombectomy for large vessel ischaemic stroke substantially reduces disability, with recent positive randomised trials leading to guideline changes worldwide. This review discusses in detail the evidence provided by recent randomised trials and meta-analyses, the remaining areas of uncertainty and the future directions for research. The data from existing trials have demonstrated the robust benefit of endovascular thrombectomy for internal carotid and proximal middle cerebral artery occlusions. Uncertainty remains for more distal occlusions where the efficacy of alteplase is greater, less tissue is at risk and the safety of endovascular procedures is less established. Basilar artery occlusion was excluded from the trials, but with a dire natural history and proof of principle that rapid reperfusion is effective, it seems reasonable to continue treating these patients pending ongoing trial results. There has been no evidence of heterogeneity in treatment effect in clinically defined subgroups by age, indeed, those aged >80 years have at least as great an overall reduction in disability and reduced mortality. Similarly there was no heterogeneity across the range of baseline stroke severities included in the trials. Evidence that routine use of general anaesthesia reduces the benefit of endovascular thrombectomy is increasing and conscious sedation is generally preferred unless severe agitation or airway compromise is present. The impact of time delays has become clearer with description of onset to imaging and imaging to reperfusion epochs. Delays in the onset to imaging reduce the proportion of patients with salvageable brain tissue. However, in the presence of favourable imaging, rapid treatment appears beneficial regardless of the onset to imaging time elapsed. Imaging to reperfusion delays lead to decay in the clinical benefit achieved, particularly in those with less robust collateral flow. The brain imaging options to assess prognosis have various advantages and disadvantages, but whatever strategy is employed must be fast. Ongoing trials are investigating extended time windows, using advanced brain imaging selection. There is also a need for further technical advances to maximise rates of complete reperfusion in the minimum time.


title: Antithrombotic therapy use in patients with atrial fibrillation before the era of non-vitamin K antagonist oral anticoagulants: the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) Phase I cohort.

text: AIMS The introduction of non-VKA oral anticoagulants (NOACs), which differ from the earlier vitamin K antagonist (VKA) treatments, has changed the approach to stroke prevention in atrial fibrillation (AF). GLORIA-AF is a prospective, global registry programme describing the selection of antithrombotic treatment in newly diagnosed AF patients at risk of stroke. It comprises three phases: Phase I, before the introduction of NOACs; Phase II, during the time of the introduction of dabigatran, the first NOAC; and Phase III, once NOACs have been established in clinical practice. METHODS AND RESULTS In Phase I, 1063 patients were eligible from the 1100 enrolled (54.3% male; median age 70 years); patients were from China (67.1%), Europe (EU; 27.4%), and the Middle East (ME; 5.6%). The majority of patients using VKAs had high stroke risk (CHA2DS2-VASc ≥ 2; 86.5%); 13.5% had moderate risk (CHA2DS2-VASc = 1). Vitamin K antagonist use was higher for persistent/permanent AF (47.7%) than that for paroxysmal (23.9%). Most patients in China were treated with antiplatelet agents (53.7%) vs. 27.1% in EU and 28.8% in ME. In China, 25.9% of patients had no antithrombotic therapy, vs. 8.6% in EU and 8.5% in ME. CONCLUSION Phase I of GLORIA-AF shows that VKAs were mostly used in patients with persistent/permanent (vs. paroxysmal) AF and in those with high stroke risk. Furthermore, there were meaningful geographical differences in the use of VKA therapy in the era before the availability of NOACs, including a much lower use of VKAs in China, where most patients either received antiplatelet agents or no antithrombotic treatment.


title: A review on human influenza A H5N1 infections in Hong Kong.

text: Avian influenza A H5N1 remains the most threatening virus that may cause another devastating pandemic in the foreseeable future. In 1997, Hong Kong was the first place to detect human infections due to this virus originated from birds. The experience and lessons learnt provide important information for controlling further outbreaks caused by avian influenza viruses.


Adrenal Vascular Changes in COVID-19 Autopsies.


title: Etiology and seasonality of viral respiratory infections in rural Honduran children.

text: BACKGROUND Limited data are available in Honduras that describe the etiology and seasonality of respiratory infections, especially in rural outpatient settings. Better data may lead to improved therapeutic and preventive strategies. The goal of our study was to determine the viral etiology and seasonality of acute respiratory infections in a rural Honduran population of children. METHODS Prospective clinic surveillance was conducted to identify children < 5 years of age presenting with respiratory symptoms of < 5 days duration. We obtained data on age, sex, medical history, breastfeeding history, symptoms, risk factors, household setting, temperature, respiratory rate and chest examination findings. To assess the association between specific viruses and weather, regional meteorological data were collected. Nasopharyngeal samples were tested for 16 respiratory viruses using a multiplex polymerase chain reaction panel. RESULTS From February 2010 through June 2011, 345 children < 5 years of age were enrolled; 17%, 23%, 30% and 31% were <6, 6-11, 12-23 and 24-60 months old, respectively. Including all clinics in the region, 44.5% of patients < 5 years of age with documented respiratory diagnoses were enrolled. At least 1 virus was identified in 75.4% children, of which 7.5% were coinfections; 13.3% were positive for parainfluenza, 11.9% for influenza, 8.1% for human metapneumovirus and 7.5% for respiratory syncytial virus. Rainfall correlated with parainfluenza (P < 0.0001), influenza (P < 0.0001), human metapneumovirus (P = 0.0182) and respiratory syncytial virus (P < 0.0001). CONCLUSIONS These results suggest that the spectrum of viruses in ill, rural, Honduran children is similar to that in North and Central America, although the seasonality is typical of some tropical regions.


Policy opportunities to enhance sharing for pandemic research.


title: Phage-derived fully human antibody scFv fragment directed against human vascular endothelial growth factor receptor 2 blocked its interaction with VEGF.

text: Vascular endothelial growth factor receptor 2 (VEGFR-2) plays a critical role in tumor angiogenesis. None therapeutic antibodies targeting VEGFR-2 are available in clinical use. Herein, we describe the screening of a new single-chain antibody fragment (scFv) targeting extracellular domain 3 of human VEGFR-2 (kinase insert domain-containing receptor [KDR]3) from Griffin phage display scFv library. A comprehensive sequence analysis was performed to assign the framework and complementary-determining regions. The scFv exerted particular binding sites to KDR3 on molecular docking, and the binding affinity was further convinced by binding analysis both in quantitative ELISA and real-time kinetic determination by biosensors (K(D) = 40 nM). Finally, the scFv was revealed to inhibit VEGF-stimulated proliferation of human umbilical vein endothelial cells (HUVECs; IC(50) = 5 nM) and to inhibit HUVEC migration significantly at 17 nM. Taken together, our results indicate that we have successfully isolated a scFv which differentially recognizes KDR3 and has potential clinical applications in the treatment of angiogenesis related diseases.


title: Transcriptomic correlates of organ failure extent in sepsis.

text: OBJECTIVES Sepsis is characterised by the frequent presence of organ failure and marked immunologic alterations. We studied the association between the extent of organ failure and the transcriptomic response of septic patients. METHODS Gene expression profiles in the blood of 74 surgical patients with sepsis were compared with those of 30 surgical patients with no sepsis. Differentially expressed genes were assessed for their correlation with the sequential organ failure (SOFA) score. RESULTS The expression levels of a group of genes participating in the cell cycle (HIST1H1C, CKS2, CCNA2, CDK1, CCNB2, CIT, CCNB1, AURKA, RAD51), neutrophil protease activity (ELANE, ADORA3, MPO, MMP8, CTSG), IL-1R and IL-18R response correlated directly with SOFA and mortality. Genes involved in T cell (LCK, CD3G, CD3D, ZAP70, ICOS, CD3E, CD28, IL2RB, CD8B, CD8A, CD40LG, IL23A, CCL5, SH2D1A, ITK, CD247, TBX21, GATA3, CCR7, LEF1, STAT4) and NK cell immunity (CD244, KLRK1, KLRD1) were inversely associated with SOFA and mortality. CONCLUSIONS The extent of organ failure in sepsis correlates directly with the existence of imbalanced innate and adaptive responses at the transcriptomic level. Quantification of the expression levels of the genes identified here could contribute to the simultaneous assessment of disease severity and immunological alterations in sepsis.


title: TMPRSS2 is a host factor that is essential for pneumotropism and pathogenicity of H7N9 influenza A virus in mice.

text: UNLABELLED Cleavage of the hemagglutinin (HA) by host proteases is essential for the infectivity of influenza viruses. Here, we analyzed the role of the serine protease TMPRSS2, which activates HA in the human respiratory tract, in pathogenesis in a mouse model. Replication of the human H7N9 isolate A/Anhui/1/13 and of human H1N1 and H3N2 viruses was compared in TMPRSS2 knockout (TMPRSS2(-/-)) and wild-type (WT) mice. Knockout of TMPRSS2 expression inhibited H7N9 influenza virus replication in explants of murine tracheas, bronchi, and lungs. H1N1 virus replication was also strongly suppressed in airway explants of TMPRSS2(-/-) mice, while H3N2 virus replication was only marginally affected. H7N9 and H1N1 viruses were apathogenic in TMPRSS2(-/-) mice, whereas WT mice developed severe disease with mortality rates of 100% and 20%, respectively. In contrast, all H3N2 infected TMPRSS2(-/-) and WT mice succumbed to lethal infection. Cleavage analysis showed that H7 and H1 are efficiently activated by TMPRSS2, whereas H3 is less susceptible to the protease. Our data demonstrate that TMPRSS2 is a host factor that is essential for pneumotropism and pathogenicity of H7N9 and H1N1 influenza virus in mice. In contrast, replication of H3N2 virus appears to depend on another, not yet identified protease, supporting the concept that human influenza viruses differ in protease specificity. IMPORTANCE Cleavage of the hemagglutinin (HA) by host proteases is essential for the infectivity of influenza virus, but little is known about its relevance for pathogenesis in mammals. Here, we show that knockout mice that do not express the HA-activating protease TMPRSS2 are resistant to pulmonary disease with lethal outcome when infected with influenza A viruses of subtypes H7N9 and H1N1, whereas they are not protected from lethal H3N2 virus infection. These findings demonstrate that human influenza viruses differ in protease specificity, and that expression of the appropriate protease in respiratory tissues is essential for pneumotropism and pathogenicity. Our observations also demonstrate that HA-activating proteases and in particular TMPRSS2 are promising targets for influenza therapy.


title: Bidirectional barbed suture in laparoscopic myomectomy: clinical features.

text: OBJECTIVE To compare bidirectional knotless barbed suture versus standard sutures, with either extracorporeal or intracorporeal knots, and to assess the feasibility, safety, and rapidity in repairing a uterine wall defect after laparoscopic myomectomy. SUBJECTS AND METHODS This was a randomized clinical study having a Canadian Task Force Classification of I. In tertiary-care university-based teaching hospitals, 117 women who underwent laparoscopic myomectomy were enrolled. In accord with randomization, uterine wall defects were closed with either extracorporeal (poliglecaprone 25; Monocryl™-1; Ethicon Inc., Somerville, NJ) or intracorporeal (polyglactin 910; Vicryl™-1; Ethicon Inc.) knots or a bidirectional knotless barbed suture (Quill™-0; Angiotech Pharmaceuticals, Inc., Vancouver, BC, Canada). RESULTS Time required to suture was significantly lower in the group operated on with a bidirectional suture than in groups with traditional sutures (P<.001). No significant difference was observed in operative time among the study groups. The degree of surgical difficulty was significantly lower in the Quill group than in the other groups. CONCLUSIONS Use of barbed sutures reduces the time required to repair a uterine wall defect during laparoscopic myomectomy. In a follow-up of patients carried out at 3 months, 6 months, and 1 year after the surgery, there were no wound dehiscence, no bleeding, and no other potential major complications.


title: The value of iterative metal artifact reduction algorithms during antenna positioning for CT-guided microwave ablation.

text: Objectives: To compare image quality between filtered back projection (FBP) and iterative reconstruction algorithm and dedicated metal artifact reduction (iMAR) algorithms during antenna positioning for computed tomography-guided microwave ablation (MWA).Materials and methods: An MWA antenna was positioned in the liver of five pigs under CT guidance. Different exposure settings (120kVp/200mAs-120kVp/50mAs) and image reconstruction techniques (FBP, iterative reconstruction with and without iMAR) were applied. Quantitative image analysis included density measurements in six positions (e.g., liver in extension of the antenna [ANTENNA] and liver >3 cm away from the antenna [LIVER-1]). Qualitative image analysis included assessment of overall quality, image noise, artifacts at the antenna tip, artifacts in liver parenchyma bordering antenna tip and newly generated artifacts. Two independent observers performed the analyses twice and interreader agreement was compared with Bland-Altman analysis.Results: For all exposure and reconstruction settings, density measurements for ANTENNA were significantly higher for the I30-1 iMAR compared with FBP and I30-1 (e.g., 8.3-17.2HU vs. -104.5 to 155.1HU; p ≤ 0.01, respectively). In contrast, for all exposure settings, density measurements for LIVER-1 were comparable between FBP and I30-1 iMAR (e.g., 49.4-50.4HU vs. 50.1-52.5U, respectively). For all exposure and reconstruction settings, subjective image quality for LIVER-1 was better for the I30-1 iMAR algorithm compared with FBP and I30-1. Bland-Altman interobserver agreement was from -0.2 to 0.2 for FBP and iMAR, and Cohen's kappa was 0.74.Conclusion: Iterative algorithms I30-1 with iMAR algorithm improves image quality during antenna positioning and placement for CT-guided MWA and is applicable over a range of exposure settings.


title: In vivo electroporation of developing mouse retina.

text: The functional characterization of genes expressed during mammalian retinal development remains a significant challenge. Gene targeting to generate constitutive or conditional loss of function knockouts remains cost and labor intensive, as well as time consuming. Adding to these challenges, retina expressed genes may have essential roles outside the retina leading to unintended confounds when using a knockout approach. Furthermore, the ability to ectopically express a gene in a gain of function experiment can be extremely valuable when attempting to identify a role in cell fate specification and/or terminal differentiation. We present a method for the rapid and efficient incorporation of DNA plasmids into the neonatal mouse retina by electroporation. The application of short electrical impulses above a certain field strength results in a transient increase in plasma membrane permeability, facilitating the transfer of material across the membrane (1,2,3,4). Groundbreaking work demonstrated that electroporation could be utilized as a method of gene transfer into mammalian cells by inducing the formation of hydrophilic plasma membrane pores allowing the passage of highly charged DNA through the lipid bilayer (5). Continuous technical development has resulted in the viability of electroporation as a method for in vivo gene transfer in multiple mouse tissues including the retina, the method for which is described herein (6, 7, 8, 9, 10). DNA solution is injected into the subretinal space so that DNA is placed between the retinal pigmented epithelium and retina of the neonatal (P0) mouse and electrical pulses are applied using a tweezer electrode. The lateral placement of the eyes in the mouse allows for the easy orientation of the tweezer electrode to the necessary negative pole-DNA-retina-positive pole alignment. Extensive incorporation and expression of transferred genes can be identified by postnatal day 2 (P2). Due to the lack of significant lateral migration of cells in the retina, electroporated and non-electroporated regions are generated. Non-electroporated regions may serve as internal histological controls where appropriate. Retinal electroporation can be used to express a gene under a ubiquitous promoter, such as CAG, or to disrupt gene function using shRNA constructs or Cre-recombinase. More targeted expression can be achieved by designing constructs with cell specific gene promoters. Visualization of electroporated cells is achieved using bicistronic constructs expressing GFP or by co-electroporating a GFP expression construct. Furthermore, multiple constructs may be electroporated for the study of combinatorial gene effects or simultaneous gain and loss of function of different genes. Retinal electroporation may also be utilized for the analysis of genomic cis-regulatory elements by generating appropriate expression constructs and deletion mutants. Such experiments can be used to identify cis-regulatory regions sufficient or required for cell specific gene expression (11). Potential experiments are limited only by construct availability.


title: A score to estimate 30-day mortality after intensive care admission after cardiac surgery.

text: OBJECTIVE Several risk-scoring systems have been developed to predict surgical mortality and complications in cardiac surgical patients, but none of the current systems include factors related to the intraoperative period. The purpose of this study was to develop a score that incorporates both preoperative and intraoperative factors so that it could be used for patients admitted to a cardiac surgical intensive care unit (ICU) immediately after surgery. METHOD Preoperative and intraoperative data from 30,350 patients in four hospitals were used to build a multiple logistic regression model estimating 30-day mortality after cardiac surgery. Sixty percent of the patients were used as a derivation group and forty percent as a validation group. RESULTS Mortality occurred in 2.6% of patients (n = 790). Preoperative factors identified in the model were age, female sex, emergency status, pulmonary hypertension, peripheral vascular disease, renal dysfunction, diabetes, peptic ulcer disease, history of alcohol abuse, and refusal of blood products. Intraoperative risk factors included the need for an intra-aortic balloon pump, ventricular assist device or extracorporeal membrane oxygenation leaving the operating room, presence of any intraoperative complication reported by the surgeon, the use of inotropes, high-dose vasopressors, red blood cell transfusion, and cardiopulmonary bypass time. When used after surgery at ICU admission, the model had C-statistics of 0.86 in both derivation and validation sets to estimate the 30-day mortality. CONCLUSIONS Preoperative and intraoperative variables can be used on admission to a cardiac surgical ICU to estimate 30-day mortality. The score could be used for risk stratification after cardiac surgery and evaluation of performance of cardiac surgical ICUs.


Ethics and Resource Scarcity: ASCO Recommendations for the Oncology Community During the COVID-19 Pandemic.


title: Evaluating developmental motor plasticity with paired afferent stimulation.

text: AIM Brain plasticity mechanisms are probably different in children but remain poorly understood. Paired afferent stimulation (PAS) combines peripheral sensory stimulation with transcranial magnetic stimulation (TMS) of primary motor cortex to induce rapid, reversible, topographically specific increases in primary motor cortex excitability suggestive of long-term potentiation in adults. Our aim was to determine frequency, characteristics, age effects, and reproducibility of PAS in school-age children. METHOD Typically developing right-handed children (6-18y) were recruited. Median nerve stimulation was delivered 25ms before suprathreshold primary motor cortex stimulation (0.2Hz, 7.5min). Primary outcome was changed in the amplitude of motor evoked potentials (MEPs) at five time points after PAS (0, 15, 30, 45, 75min) expressed as area under the curve. Reproducibility was evaluated. Secondary outcomes included stimulus response curves and safety/tolerability. RESULTS Of 28 children (20 males, mean age 12y), 64% demonstrated PAS effects (11 definite, seven probable). PAS effects were sustained across all time points to 75min (p=0.004). Stimulus response curve scores increased after PAS (n=9, p=0.02). PAS effect and age were not correlated. PAS was highly reproducible (p=0.925, r=0.283). Tolerability was favorable without adverse events. INTERPRETATION PAS effects are present and reproducible in children. Pediatric PAS paradigms appear safe and tolerable. PAS may provide insight into endogenous developmental plasticity, informing future studies in children with cerebral palsy and other motor disorders.


title: Culture Matters in Communicating the Global Response to COVID-19.

text: Current communication messages in the COVID-19 pandemic tend to focus more on individual risks than community risks resulting from existing inequities. Culture is central to an effective community-engaged public health communication to reduce collective risks. In this commentary, we discuss the importance of culture in unpacking messages that may be the same globally (physical/social distancing) yet different across cultures and communities (individualist versus collectivist). Structural inequity continues to fuel the disproportionate impact of COVID-19 on black and brown communities nationally and globally. PEN-3 offers a cultural framework for a community-engaged global communication response to COVID-19.


title: The potential impacts of obesity on COVID-19.

text: Obese patients are at increased risk of exacerbations from viral respiratory infections. During the H1N1 pandemic, obesity was associated with an increased risk of influenza-associated intensive care unit (ICU) admission and death, longer duration of mechanical ventilation, and longer duration of ICU and hospital length of stay compared with the non-obese. These observations have raised a concern about the correlation between obesity and the current COVID-19 pandemic. In this review, we have outlined the potential impacts of obesity on respiratory physiology and the function of both innate and adaptive immune responses. Also, it has been clearly illustrated that obese patients are potentially more vulnerable to COVID-19 and more contagious than lean patients. The comorbidities associated with obesity were found to be correlated with a severe clinical course of COVID-19 and increased mortality and high BMI has been shown to be correlated with hospitalisation, the need for mechanical ventilation and non-survival. The review also sheds light on the challenges that obese patients pose for healthcare providers inside and outside ICUs.


title: Renal denervation in patients with resistant hypertension: six-month results.

text: INTRODUCTION Increased activation of the sympathetic nervous system plays a central role in the pathophysiology of hypertension (HTN). Catheter-based renal denervation (RDN) was recently developed for the treatment of resistant HTN. AIM To assess the safety and efficacy of RDN for blood pressure (BP) reduction at six months in patients with resistant HTN. METHODS In this prospective registry of patients with essential resistant HTN who underwent RDN between July 2011 and May 2013, the efficacy of RDN was defined as ≥ 10 mm Hg reduction in office systolic blood pressure (SBP) six months after the intervention. RESULTS In a resistant HTN outpatient clinic, 177 consecutive patients were evaluated, of whom 34 underwent RDN (age 62.7 ± 7.6 years; 50.0% male). There were no vascular complications, either at the access site or in the renal arteries. Of the 22 patients with complete six-month follow-up, the response rate was 81.8% (n=18). The mean office SBP reduction was 22 mm Hg (174 ± 23 vs. 152 ± 22 mm Hg; p<0.001) and 9 mm Hg in diastolic BP (89 ± 16 vs. 80 ± 11 mm Hg; p=0.006). The number of antihypertensive drugs (5.5 ± 1.0 vs. 4.6 ± 1.1; p=0.010) and pharmacological classes (5.4 ± 0.7 vs. 4.6 ± 1.1; p=0.009) also decreased significantly. Of the 24-hour ambulatory BP monitoring and echocardiographic parameters analyzed, there were significant reductions in diastolic load (45 ± 29 vs. 27 ± 26%; p=0.049) and in left ventricular mass index (174 ± 56 vs. 158 ± 60 g/m(2); p=0.014). CONCLUSION In this cohort of patients with resistant HTN, RDN was safe and effective, with a significant BP reduction at six-month follow-up.


Attitude to telemedicine in the times of COVID 19 pandemic: Opinion of medical practitioners from India.


title: Pressure stability with CPAP devices: A bench evaluation.

text: BACKGROUND Continuous positive airway pressure (CPAP) maintains a constant pressure to reduce the patient's work of breathing (WOB). The aim of this study was to measure the additional WOB imposed by four current CPAP devices during simulation of a difficult but commonly encountered clinical situation. METHOD Flow contour, respiratory system compliance and total lung-airway resistance of a patient under CPAP were simulated. The devices were tested at a CPAP of 15cm H(2)O with a heated humidifier and a nasal pillow, which increased circuitry resistance and with and without a simulated unintentional leak. RESULTS With no leak, positive end-expiratory pressure (PEEP) at the interface varied across devices from 14.0 to 15.3cm H(2)O. With a leak of 1L/s, PEEP varied from 11.5 to 17.1cm H(2)O. Imposed inspiratory WOB ranged from less than 0.1J/min to 0.45J/min with no leak, and the range broadened with leaking. Findings were similar for the imposed expiratory WOB. CONCLUSION The performances of CPAP devices are variable. The device that calibrated for the pressure loss in the circuitry under dynamic conditions and made appropriate pressure adjustments outperformed the other devices.


title: Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis.

text: OBJECTIVE To evaluate the efficacy and safety of artificial pancreas treatment in non-pregnant outpatients with type 1 diabetes. DESIGN Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES Medline, Embase, Cochrane Library, and grey literature up to 2 February 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomised controlled trials in non-pregnant outpatients with type 1 diabetes that compared the use of any artificial pancreas system with any type of insulin based treatment. Primary outcome was proportion (%) of time that sensor glucose level was within the near normoglycaemic range (3.9-10 mmol/L). Secondary outcomes included proportion (%) of time that sensor glucose level was above 10 mmol/L or below 3.9 mmol/L, low blood glucose index overnight, mean sensor glucose level, total daily insulin needs, and glycated haemoglobin. The Cochrane Collaboration risk of bias tool was used to assess study quality. RESULTS 40 studies (1027 participants with data for 44 comparisons) were included in the meta-analysis. 35 comparisons assessed a single hormone artificial pancreas system, whereas nine comparisons assessed a dual hormone system. Only nine studies were at low risk of bias. Proportion of time in the near normoglycaemic range (3.9-10.0 mmol/L) was significantly higher with artificial pancreas use, both overnight (weighted mean difference 15.15%, 95% confidence interval 12.21% to 18.09%) and over a 24 hour period (9.62%, 7.54% to 11.7%). Artificial pancreas systems had a favourable effect on the proportion of time with sensor glucose level above 10 mmol/L (-8.52%, -11.14% to -5.9%) or below 3.9 mmol/L (-1.49%, -1.86% to -1.11%) over 24 hours, compared with control treatment. Robustness of findings for the primary outcome was verified in sensitivity analyses, by including only trials at low risk of bias (11.64%, 9.1% to 14.18%) or trials under unsupervised, normal living conditions (10.42%, 8.63% to 12.2%). Results were consistent in a subgroup analysis both for single hormone and dual hormone artificial pancreas systems. CONCLUSIONS Artificial pancreas systems are an efficacious and safe approach for treating outpatients with type 1 diabetes. The main limitations of current research evidence on artificial pancreas systems are related to inconsistency in outcome reporting, small sample size, and short follow-up duration of individual trials.


title: Hepatocellular carcinoma: concomitant sorafenib promotes necrosis after radiofrequency ablation--propensity score matching analysis.

text: PURPOSE To retrospectively compare radiofrequency ablation (RFA) combined with the multikinase inhibitor sorafenib (hereafter, sorafenib-RFA) and RFA alone in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. Between January 2007 and December 2011, 16 patients (mean age, 72.8 years; age range 52-84 years; 10 men, six women) with HCC tumors less than 3 cm in diameter were included in the sorafenib-RFA group, and 136 patients (mean age, 72.1 years; age range, 51-86 years; 92 men, 44 women) with HCC tumors less than 3 cm in diameter were included in the RFA alone (control) group. Mean diameters of the greatest long-axis dimensions of HCC were 22.8 mm ± 4.6 (standard deviation) in the sorafenib-RFA group and 18.1 mm ± 4.4 in the control group. RFA was performed immediately after the 7-day administration of sorafenib. Propensity score matching analysis was used to adjust for potential biases. RESULTS Fifteen of the 16 patients in the sorafenib-RFA group and 30 of the 136 patients in the control group were selected during propensity score matching. No significant differences between the sorafenib-RFA group (n = 15) and the control group (n = 30) were observed with regard to age, sex, etiology, Child-Pugh class, tumor size, puncture number, needle size, location at the liver margin, or location adjacent to a main vessel. The respective mean diameters of the greatest long- and short-axis dimensions of the RFA-induced ablated area were 46.3 mm ± 10.3 and 33.0 mm ± 6.9 in the sorafenib-RFA group and 32.9 mm ± 7.6 and 25.6 mm ± 5.7 in the control group; both of these dimensions were significantly larger in the sorafenib-RFA group (both P < .001). CONCLUSION Sorafenib-RFA may be superior to standard RFA alone in the treatment of HCC tumors smaller than 3 cm in diameter.


title: Does targeted neonatal echocardiography affect hemodynamics and cerebral oxygenation in extremely preterm infants?

text: OBJECTIVE To investigate the effect of targeted neonatal echocardiography (TnEcho) on heart rate, arterial oxygen saturation (SPO2), cerebral regional oxygen saturation (CrSO2) and cerebral fractional oxygen extraction (CFOE) in extremely preterm infants during the first 3 postnatal days. STUDY DESIGN s a nested study in a prospective observational study, we acquired continuous data on heart rate, SPO2, CrSO2 and CFOE. Data averaged for the duration of TnEcho study were compared with the data collected during a baseline period immediately before the start of echocardiography. The duration of the baseline and study periods was the same. TnEcho evaluation included assessment of preload, afterload, contractility, left and right ventricular output, patent ductus arteriosus and foramen ovale. RESULT We analyzed 138 data pairs before and during TnEcho in 22 extremely preterm infants (gestational age 25.9 ± 1.2 weeks; range 23 to 27). There was no significant difference in heart rate between baseline and TnEcho period. There was a statistical, but clinically negligible, difference between baseline and TnEcho in SPO2 (median (quartile) 91.4% (88.9, 94.2) vs 91.3% (88.9, 94), P = 0.048), CrSO2 (76.8% (70.7, 81.5) vs 74.9% (69.5, 80.1), P<0.0001) and CFOE (15.8% (9.8, 23.6) vs 17.5% (11.3, 24.7), P<0.0001). The changes in the parameters monitored were similar in preterm infants who developed peri/intraventricular hemorrhage and in those who did not. CONCLUSION Although there were statistically significant changes in SPO2, CrSO2 and CFOE, the alterations were minimal and unlikely of clinical relevance. Thus, cerebral hemodynamics and systemic and cerebral oxygenation are not perturbed during TnEcho and the procedure is well tolerated by the extremely preterm infants during the postnatal transitional period.


docid: rurrljcz

title: Funders' Efforts: Aging And Health, COVID-19.


title: Serology for SARS-CoV-2: Apprehensions, opportunities, and the path forward.

text: Serological testing for SARS-CoV-2 has enormous potential to contribute to COVID-19 pandemic response efforts. However, the required performance characteristics of antibody tests will critically depend on the use case (individual-level vs. population-level).


Reply: S-shaped brachioplasty: an effective technique to correct excess skin and fat of the upper arm.


title: How does an inventor find an investor or partner? Raising funds to start a company.

text: Rudy Mazzocchi has over 25 years of senior executive management, technology and intellectual property development, and financing experience in the medical-technology/biotechnology industries. He serves currently as cofounder/chief executive officer of ELENZA, Inc, an ophthalmology company that has developed an electro-active, autofocusing, implantable lens; executive chairman of Establishment Labs; executive chairman of LAFORGE Optical; and executive chairman of OptiSTENT, Inc. He served previously as managing director of Accuitive Medical Ventures and The Innovation Factory; cofounder/chief executive officer of Image-Guided NEUROLOGICS, acquired by Medtronic in 2005; and founding chief executive officer of MICROVENA Corporation, which became "eV3," acquired by Covidien. He was formerly cofounder/director of Vascular Science, acquired by St Jude Medical in 1996, and cofounder/chairman of CytoGenesis, one of the first United States stem cell companies that was merged with BresaGen and listed on the Australian public exchange. He is the recipient of the Technology Leadership Award, the Businessman of the Year Award, the Ernst & Young Entrepreneur of the Year Award in Healthcare, and Global Entrepreneur of the Year Award. He has also authored more than 70 patents; 2 published, award-winning novels (medical thrillers); and a top-selling business book on entrepreneurism.


title: Optimal number of samples to test for institutional respiratory infection outbreaks in Ontario.

text: The objective of this study was to determine the optimal number of respiratory samples per outbreak to be tested for institutional respiratory outbreaks in Ontario. We reviewed respiratory samples tested for respiratory viruses by multiplex PCR as part of outbreak investigations. We documented outbreaks that were positive for any respiratory viruses and for influenza alone. At least one virus was detected in 1454 (85∙2%) outbreaks. The ability to detect influenza or any respiratory virus increased as the number of samples tested increased. When analysed by chronological order of when samples were received at the laboratory, percent positivity of outbreaks testing positive for any respiratory virus including influenza increased with the number of samples tested up to the ninth sample, with minimal benefit beyond the fourth sample tested. Testing up to four respiratory samples per outbreak was sufficient to detect viral organisms and resulted in significant savings for outbreak investigations.


title: Near-infrared spectroscopy can predict the onset of cerebral hyperperfusion syndrome after carotid endarterectomy.

text: BACKGROUND Cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy (CEA) is a potential life-threatening complication. Therefore, early identification and treatment of patients at risk is essential. CHS can be predicted by a doubling of postoperative transcranial Doppler (TCD)-derived mean middle cerebral artery blood velocity (V(mean)) compared to preoperative values. However, in approximately 15% of CEA patients, an adequate TCD signal cannot be obtained due to an insufficient temporal bone window. Moreover, the use of TCD requires specifically skilled personnel. An alternative and promising technique of noninvasive cerebral monitoring is relative frontal lobe oxygenation (rSO(2)) measured by near-infrared spectroscopy (NIRS), which offers on-line information about cerebral oxygenation without the need for specialized personnel. In this study, we assess whether NIRS and perioperative TCD are related to the onset CHS following CEA. METHODS Patients who underwent CEA under general anesthesia and had a sufficient TCD window were prospectively included. The V(mean) and rSO(2) measured before induction of anesthesia were compared to measurements performed in the first postoperative hour (ΔV(mean), ΔrSO(2), respectively). Logistic regression analysis was performed to determine the relationship between ΔV and ΔrSO(2) and the occurrence of CHS. Subsequently, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values. Diagnostic values were shown as positive and negative predictive values (PPV and NPV). RESULTS In total, 151 patients were included, of which 7 patients developed CHS. The ΔV(mean) and ΔrSO(2) differed between CHS and non-CHS patients (median, interquartile range), i.e. 74% (67-103) versus 16% (-2 to 41), p = 0.001, and 7% (4-15) versus 1% (-6 to 7), p = 0.009, respectively. The mean arterial blood pressure did not change. Postoperative ΔV(mean) and ΔrSO(2) were significantly related to the occurrence of CHS [odds ratio (OR) 1.40 (95% CI 1.02-1.93) per 30% increase in V(mean) and OR 1.82 (95% CI 1.11-2.99) per 5% increase in rSO(2)]. ROC curve analysis showed an area under the curve of 0.88 (p = 0.001) for ΔV(mean) and an optimal cutoff value of 67% increase (PPV 38% and NPV 99%), and an area under the curve of 0.79 (p = 0.009) for ΔrSO(2) and an optimal cutoff value of 3% rSO(2) increase (PPV 11% and NPV 100%). The combination of both monitoring techniques provided a PPV of 58% and an NPV of 99%. CONCLUSIONS Both TCD and NIRS measurements can be used to safely identify patients not at risk of developing CHS. It appears that NIRS is a good alternative when a TCD signal cannot be obtained.