title: Pediatric nasal injuries and management.

text: Although serious trauma injuries are uncommon in the pediatric population, nasal injuries are a more common problem. In this population, many physicians are uncomfortable managing these injuries. The evaluation and treatment of nasal trauma differ considerably in children compared with adult nasal fractures. Poor patient cooperation during the physical exam coupled with significant anatomic differences can present the nasal surgeon with a difficult diagnostic dilemma. The surgical management of pediatric nasoseptal injuries is not without controversy, as disturbing the nasal growth centers can have significant effect on future nasal and midfacial development. This article reviews the diagnostic and therapeutic challenges presented by these injuries for children and provides recommendations to successfully manage nasal injuries in this population.


title: Thrombus aspiration in primary angioplasty for ST-segment elevation myocardial infarction.

text: Mechanical reperfusion with primary percutaneous coronary intervention in acute ST-segment-elevation myocardial infarction is superior to fibrinolysis in terms of short-term and long-term outcome, provided that it can be delivered on time and by an experienced team. Balloon angioplasty and stent implantation of an occluded epicardial vessel during ST-segment-elevation myocardial infarction can cause disruption of the frail thrombus containing lesions associated with suboptimal myocardial reperfusion and microcirculatory obstruction. Distal embolization of atherothrombotic material can be prevented by thrombus aspiration during primary angioplasty. Mechanical aspiration via end-hole large-lumen thrombectomy catheters has been shown to improve Thrombolysis in Myocardial Infarction (TIMI) flow and result in a more consistent early resolution of ST-segment elevation in multiple registries. More recently, a more sophisticated quantification of the myocardial damage has been applied using myocardial scintigraphy and magnetic resonance, with no difference between patients treated with thrombectomy and patients treated with conventional therapy. The expectations in terms of lasting mortality benefit raised by the first Dutch single-center randomized trial of thrombectomy versus predilation with plain old balloon angioplasty (Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction, TAPAS) were not confirmed by a much larger Swedish trial (Thrombus Aspiration ST-Segment Elevation Myocardial Infarction, TASTE) showing no outcome changes. Although we are waiting for new trials to clarify these controversial results, thrombectomy is still used in selected patients with high thrombus load or with persistent occlusion of the infarct-related artery after wire passage. Here we review the various systems available and discuss their relative merits and the reported results.


title: Host - hepatitis C viral interactions: The role of genetics.

text: Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN)-induced genes, and a delayed induction of adaptive immune responses. There is a strong association between genetic variants in the IFNλ (IL28B) locus with the rate of spontaneous clearance. Individuals with the ancestral IFNλ4 allele capable of producing a fully active IFNλ4 are paradoxically not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability. In the chronic phase of HCV infection, the wild-type IFNλ4 genotype is strongly associated with an induction of hundreds of classical type I/type III IFN stimulated genes in hepatocytes. However, the activation of the endogenous IFN system in the liver is ineffective in clearing HCV, and is even associated with impaired therapeutic responses to pegylated (Peg)IFNα containing treatments. While the role of genetic variation in the IFNλ locus to the outcome of CHC treatment has declined, it is clear that variation not only at this locus, but also at other loci, modulate clinically important liver phenotypes, including inflammation, fibrosis progression and the development of hepatocellular cancer. In this review, we summarize current knowledge about the role of genetics in the host response to viral hepatitis and the potential future evolution of knowledge in understanding host-viral interactions.


title: Exogenous Neural Precursor Cell Transplantation Results in Structural and Functional Recovery in a Hypoxic-Ischemic Hemiplegic Mouse Model.

text: Cerebral palsy (CP) is a common pediatric neurodevelopmental disorder, frequently resulting in motor and developmental deficits and often accompanied by cognitive impairments. A regular pathobiological hallmark of CP is oligodendrocyte maturation impairment resulting in white matter (WM) injury and reduced axonal myelination. Regeneration therapies based on cell replacement are currently limited, but neural precursor cells (NPCs), as cellular support for myelination, represent a promising regeneration strategy to treat CP, although the transplantation parameters (e.g., timing, dosage, mechanism) remain to be determined. We optimized a hemiplegic mouse model of neonatal hypoxia-ischemia that mirrors the pathobiological hallmarks of CP and transplanted NPCs into the corpus callosum (CC), a major white matter structure impacted in CP patients. The NPCs survived, engrafted, and differentiated morphologically in male and female mice. Histology and MRI showed repair of lesioned structures. Furthermore, electrophysiology revealed functional myelination of the CC (e.g., restoration of conduction velocity), while cylinder and CatWalk tests demonstrated motor recovery of the affected forelimb. Endogenous oligodendrocytes, recruited in the CC following transplantation of exogenous NPCs, are the principal actors in this recovery process. The lack of differentiation of the transplanted NPCs is consistent with enhanced recovery due to an indirect mechanism, such as a trophic and/or "bio-bridge" support mediated by endogenous oligodendrocytes. Our work establishes that transplantation of NPCs represents a viable therapeutic strategy for CP treatment, and that the enhanced recovery is mediated by endogenous oligodendrocytes. This will further our understanding and contribute to the improvement of cellular therapeutic strategies.


title: Radiation exposure from CT-guided ablation of renal masses: effects on life expectancy.

text: OBJECTIVE. The purpose of this article is to project the effects of radiation exposure on life expectancy (LE) in patients who opt for CT-guided radiofrequency ablation (RFA) instead of surgery for renal cell carcinoma (RCC). MATERIALS AND METHODS. We developed a decision-analytic Markov model to compare LE losses attributable to radiation exposure in hypothetical 65-year-old patients who undergo CT-guided RFA versus surgery for small (≤ 4 cm) RCC. We incorporated mortality risks from RCC, radiation-induced cancers (for procedural and follow-up CT scans), and all other causes; institutional data informed the RFA procedural effective dose. Radiation-induced cancer risks were generated using an organ-specific approach. Effects of varying model parameters and of dose-reduction strategies were evaluated in sensitivity analysis. RESULTS. Cumulative RFA exposures (up to 305.2 mSv for one session plus surveillance) exceeded those from surgery (up to 87.2 mSv). In 65-year-old men, excess LE loss from radiation-induced cancers, comparing RFA to surgery, was 11.7 days (14.6 days for RFA vs 2.9 days for surgery). Results varied with sex and age; this difference increased to 14.6 days in 65-year-old women and to 21.5 days in 55-year-old men. Dose-reduction strategies that addressed follow-up rather than procedural exposure had a greater impact. In 65-year-old men, this difference decreased to 3.8 days if post-RFA follow-up scans were restricted to a single phase; even elimination of RFA procedural exposure could not achieve equivalent benefits. CONCLUSION. CT-guided RFA remains a safe alternative to surgery, but with decreasing age, the higher burden of radiation exposure merits explicit consideration. Dose-reduction strategies that target follow-up rather than procedural exposure will have a greater impact.


Why does the coronavirus spread so easily between people?


Can we do better?


title: Almanac 2013: novel non-coronary cardiac interventions.

text: Recent innovations in interventional cardiology have dramatically expanded the therapeutic options for patients with cardiac conditions. Interventional cardiology is no longer limited to the treatment of coronary artery disease but allows also treatment of valvular disease, stroke prevention, hypertension, etc. One of the most important new treatment options is the percutaneous treatment for aortic valve stenosis (transcatheter aortic valve implantation), since aortic valve disease is a rather common problem in elderly patients, with many of them at high risk for surgery. Similarly, mitral regurgitation is often associated with comorbidities which make surgery high risk. The MitraClip is a promising percutaneous alternative to surgical valve repair or replacement. Other procedures discussed in this review are the percutaneous left atrial appendage closure as a non-pharmacologic therapy to prevent strokes, and renal denervation for resistant hypertension. This review explains the basic principles of these procedures, the most important clinical evidence, and also provides additional recent clinical data on each of these them.


title: Protein A-conjugated iron oxide nanoparticles for separation of Vibrio cholerae from water samples.

text: Pathogen separation is of great significance for precise detection and prevention of disease outbreaks. For the first time, protein A conjugated with chitosan-coated iron oxide nanoparticles was prepared for pathogen separation at low concentrations from liquid samples. Vibrio cholerae O1 (VO1) bacteria were used for testing the effectiveness of this conjugate. Transmission electron microscopy (TEM) was used to confirm the presence of captured VO1. The results showed that, after binding with a specific antibody, the conjugate allows separation of VO1 bacteria from water samples at a concentration as low as 10 cfu mL(-1). Moreover, the conjugate can be used in parallel with conventional or modern diagnostic tests for quick and accurate detection of pathogens.


title: Proteome-wide Data Analysis Reveals Tissue-specific Network Associated with SARS-CoV-2 Infection.

text: For patients with COVID-19 caused by SARS-CoV-2, the damages to multiple organs have been clinically observed. Since most of current investigations for virus-host interaction are based on cell level, there is an urgent demand to probe tissue-specific features associated with SARS-CoV-2 infection. Based on collected proteomic datasets from human lung, colon, kidney, liver and heart, we constructed a virus-receptor network, a virus-interaction network and a virus-perturbation network. In the tissue-specific networks associated with virus-host crosstalk, both common and different key hubs are revealed in diverse tissues. Ubiquitous hubs in multiple tissues such as BRD4 and RIPK1 would be promising drug targets to rescue multi-organ injury and deal with inflammation. Certain tissue-unique hubs such as REEP5 might mediate specific olfactory dysfunction. The present analysis implies that SARS-CoV-2 could affect multi-targets in diverse host tissues, and the treatment of COVID-19 would be a complex task.


title: Experimental evaluation of immediate recanalization effect and recanalization efficacy of a new thrombus retriever for acute stroke treatment in vivo.

text: BACKGROUND AND PURPOSE Currently, several new stent retriever devices for acute stroke treatment are under development and early clinical evaluation. Preclinical testing under standardized conditions is an important first step to evaluate the technical performance and potential of these devices. The aim of this study was to evaluate the immediate recanalization effect, recanalization efficacy, thrombus-device interaction, and safety of a new stent retriever intended for thrombectomy in patients with acute stroke. MATERIAL AND METHODS The pREset thrombectomy device (4 × 20 mm) was evaluated in 16 vessel occlusions in an established swine model. Radiopaque thrombi (10-mm length) were used for visualization of thrombus-device interaction during application and retrieval. Flow-restoration effect immediately after deployment and after 5-minute embedding time before retrieval, recanalization rate after retrieval, thromboembolic events, and complications were assessed. High-resolution FPCT was performed to illustrate thrombus-device interaction during the embedding time. RESULTS Immediate flow restoration was achieved in 75% of occlusions. An increase or stable percentage of recanalizations during embedding time before retrieval was seen in 56.3%; a decrease, in 12.5%; reocclusion of a previously recanalized vessel, in 18.8%; and no recanalization effect at all, in 12.5%. Complete recanalization (TICI 3) after retrieval was achieved in 93.8%; partial recanalization (TICI 2b), in 6.2%. No distal thromboembolic events were observed. High-resolution FPCT illustrated entrapment of the thrombus between the stent struts and compression against the contralateral vessel wall, leading to partial flow restoration. During retrieval, the thrombus was retained in a straight position within the stent struts. CONCLUSIONS In this experimental study, the pREset thrombus retriever showed a high recanalization rate in vivo. High-resolution FPCT allows detailed illustration of the thrombus-device interaction during embedding time and is advocated as an add-on tool to the animal model used in this study.


title: Reducing surgical site infections following craniotomy: examination of the use of topical vancomycin.

text: OBJECT Although the use of topical vancomycin has been shown to be safe and effective for reducing postoperative infection rates in patients after spine surgery, its use in cranial wounds has not been studied systematically. The authors hypothesized that topical vancomycin, applied in powder form directly to the subgaleal space during closure, would reduce cranial wound infection rates. METHODS A cohort of 150 consecutive patients who underwent craniotomy was studied retrospectively. Seventy-five patients received 1 g of vancomycin powder applied in the subgaleal space at the time of closure. This group was compared with 75 matched-control patients who were accrued over the same time interval and did not receive vancomycin. The primary outcome measure was the presence of surgical site infection within 3 months. Secondary outcome measures included tissue pH from a subgaleal drain and vancomycin levels from the subgaleal space and serum. RESULTS Vancomycin was associated with significantly fewer surgical site infections (1 of 75) than was standard antibiotic prophylaxis alone (5 of 75; p < 0.05). Cultures were positive for typical skin flora species. As expected, local measured vancomycin concentrations peaked immediately after surgery (mean ± SD 499 ± 37 μg/ml) and gradually decreased over 12 hours. Vancomycin in the circulating serum remained undetectable. Subgaleal topical vancomycin was associated with a lower incidence of surgical site infections after craniotomy. The authors attribute this reduction in the infection rate to local vancomycin concentrations well above the minimum inhibitory concentration for antimicrobial efficacy. CONCLUSIONS Topical vancomycin is safe and effective for reducing surgical site infections after craniotomy. These data support the need for a prospective randomized examination of topical vancomycin in the setting of cranial surgery.


title: Under Allocation: Critical Supply Chain Hurdles Negatively Impact the Ability of Community Hospitals to Perform Repeat SARS-CoV-2 Testing.

text: There is increasing recognition that not all SARS-CoV-2 RT-PCR assays are created equal with respect to test performance (1).….


title: Laparoscopic Repair of Small Ventral Hernias Using the "Ventralex™ Hernia Patch".

text: Laparoscopy of abdominal wall defects becomes more and more actual, considering the well-known advantages of minimally invasive surgery, and the reduced incidence of post-operative ventral infections and recurrence rates compared to the the open repair with or without mesh. We hereby present the technique of the laparoscopic repair of small ventral hernias (defect 2 centimetres), using the Ventralex mesh, which is bi-faceted, polypropylene and PTFE, circular preformed, it has 8 centimeters in diameter, fixated with 4 transparietal sutures. The mesh is created for open surgery but it is placed in the intraperitoneal cavity. This technique was used for 28 patients,16 women and 12 men, with an average age of 53,3 years (29-72 years), consisting of: 22 umbilical hernias (UH), 2 epigastric hernias (EH), one left-side Spiegelian hernia, one incisional hernia after an open surgery for an umbilical hernia with a Ventralex mesh, and 2 trocar eventrations (TE) after a laparoscopic cholecystectomy. Mean operating time was 52 minutes (42-70 minutes), post-operative hospital stay of 1,8 days (1-5 days). The main advantages are: circular preformed mesh, diameter of 8 centimeters, transfascial suture fixation, correct mesh placement and unfolding may be verified by laparoscopy, reduced costs. The technique is easy to reproduce.


title: [SECOT consensus on thromboembolisms in knee and hip replacement surgery].

text: The purpose of this paper is to develop a professional consensus that proposes, in the light of the current scientific evidence and the clinical experience of an expert panel, some clinical recommendations directed at the Orthopaedic and Trauma Surgery (OTS) specialist and with the aim of reducing the variability in the prophylactic management of venous thromboembolic disease in knee and hip arthroplasty in clinical practice. The Delphi method was used, which consisted of two rounds of an e-mail questionnaire. Of the 55 items considered, a consensus was reached in 37 (67.2%) of them. In 31 cases there was consensus with the formulation of the item, and in 6 cases there was no agreed consensus. It was observed that there was a consensus in multiple clinical recommendations that could help OTS specialists in the making of decisions in their clinical practice.


Acute Respiratory Distress Syndrome.


Safety and role of chest CT in COVID-19 patients.


Seasonal Influenza Activity During the SARS-CoV-2 Outbreak in Japan.


title: Reducing unpleasant side effects of topical 5-Fluorouracil treatment for actinic keratosis: a randomized controlled trial.

text: INTRODUCTION 5-Fluorouracil (5-FU) for prophylactic treatment of diffuse actinic keratosis results in an exuberant inflammatory reaction, contributing to patient noncompliance and dissatisfaction. DESIGN This 5-week split-faced, double-blind, randomized controlled trial involved 30 subjects with diffuse facial AK who received twice daily 5-FU treatment for 2 weeks. This was followed by pre-randomized twice daily use of one of three topical interventions on one half of the face. TEWL, pH, and hydration were assessed on each quadrant of the face at all visits. Additionally, photographs were subjectively graded by three blinded trained observers. RESULTS Thirty subjects were enrolled, and had an average 27.1 (SD 11.8, range: 13-62) palpable AKs at baseline. Average resolution of baseline AK count was 98.1% by week 4. Clobetasol propionate is best at decreasing TEWL (p = .034), while petrolatum jelly most significantly improves hydration (p = .019) and erythema (p = .014). Though controlled release skin barrier emulsion trended towards improvement in TEWL (p = .17) and hydration (p = .19), there was no significant decrease in erythema (p = .257). Patient free-text response identified erythema as the most bothersome symptom. CONCLUSIONS Given the low cost, wide availability, and ability to significantly reduce erythema, petrolatum should be used for post-5-FU treatment for diffuse AK.


title: Thermal epiphysiodesis performed with radio frequency in a porcine model.

text: BACKGROUND AND PURPOSE Current techniques for epiphysiodesis involve opening of cortical windows; use of staples, screws, and tension devices; and fusion with curettes or drills. Complications may have serious consequences. There is a need for a more reliable, precise, and less traumatic procedure that overcomes the known complications from existing techniques. We analyzed a new epiphysiodesis technique using radio-frequency ablation (RFA) in a porcine model. METHODS Six 35-kg and two 25-kg immature pigs were used. 1 hind leg of each animal was randomly selected and the proximal tibia growth plate was ablated laterally and medially. The contralateral leg was used as a control. MR images were obtained immediately after the ablation and 12 weeks later for 6 animals, and 24 weeks later for the other 2 animals. CT was done for the 2 animals that were followed for 24 weeks for proof of bone bridges. RESULTS Both tibias were equal in length initially. At the 12-week follow-up, there was an average leg length discrepancy of 3.9 mm (95% CI: 3.0-4.8), and at 24 weeks the difference was 8.4 mm and 7.5 mm. No damage to the adjacent tissue was found. Bone bridges and physeal closure were found after 24 weeks. The pigs showed no discomfort after the intervention. INTERPRETATION We found RFA to be feasible for epiphysiodesis in a pig model. The method is minimally invasive and recovery may be quick compared to conventional methods. We recommend that the method should be tested in larger-scale safety studies before clinical application.


title: The effect of using the Partners for Change Outcome Management System as feedback tool in psychotherapy-A systematic review and meta-analysis.

text: OBJECTIVE The aims of the study were to evaluate the effects of using the Partners for Change Outcome Management System (PCOMS) in psychotherapy and to explore potential moderators of the effect. METHOD A comprehensive literature search including grey literature was conducted to identify controlled outcome studies on the PCOMS, randomized (RCTs), or non-randomized trials (N-RCT). RESULTS The literature search identified 18 studies, 14 RCTs, and four N-RCTs, including altogether 2910 participants. The meta-analysis of all studies found a small overall effect of using the PCOMS on general symptoms (g = 0.27, p = .001). The heterogeneity of the results was substantial. Moderation analyses revealed no effect of the PCOMS in psychiatric settings (g = 0.10, p = .144), whereas a positive effect was found in counseling settings (g = 0.45, p < .001), although almost all of these studies were characterized by a positive researcher allegiance and using the PCOMS Outcome Rating Scale (ORS) as the only outcome measure. CONCLUSION The meta-analysis revealed a small overall effect of using the PCOMS, but no effect in psychiatric settings. The positive results in counseling settings might be biased due to researcher allegiance and use of the ORS as the only outcome measure.


title: The I in COVID: The importance of community and patient involvement in COVID-19 research.

text: The call for community and patient involvement in the COVID-19 response is yet to be heard and answered. There are practical and ethical reasons for researchers not to neglect patient and public involvement (PPI), which has become an important cornerstone of UK-based clinical research. There has been a commendable effort towards driving evidence-based research, particularly through clinical trials in the UK. This article presents a brief background to PPI and points for consideration for clinical researchers currently active in or planning COVID-19 research.


[From Tuberculosis to COVID-19: Legal and Constitutional Framework Regarding Compulsory Isolation/Treatment due to Contagious Diseases in Portugal].


Covid-19: UK needs flexible local plans to come out of lockdown, say public health experts.


title: Pregnancy and Perinatal Outcomes of Women With Coronavirus Disease (COVID-19) Pneumonia: A Preliminary Analysis.

text: OBJECTIVE. The purpose of this study was to describe the clinical manifestations and CT features of coronavirus disease (COVID-19) pneumonia in 15 pregnant women and to provide some initial evidence that can be used for guiding treatment of pregnant women with COVID-19 pneumonia. MATERIALS AND METHODS. We reviewed the clinical data and CT examinations of 15 consecutive pregnant women with COVID-19 pneumonia in our hospital from January 20, 2020, to February 10, 2020. A semiquantitative CT scoring system was used to estimate pulmonary involvement and the time course of changes on chest CT. Symptoms and laboratory results were analyzed, treatment experiences were summarized, and clinical outcomes were tracked. RESULTS. Eleven patients had successful delivery (10 cesarean deliveries and one vaginal delivery) during the study period, and four patients were still pregnant (three in the second trimester and one in the third trimester) at the end of the study period. No cases of neonatal asphyxia, neonatal death, stillbirth, or abortion were reported. The most common early finding on chest CT was ground-glass opacity (GGO). With disease progression, crazy paving pattern and consolidations were seen on CT. The abnormalities showed absorptive changes at the end of the study period for all patients. The most common onset symptoms of COVID-19 pneumonia in pregnant women were fever (13/15 patients) and cough (9/15 patients). The most common abnormal laboratory finding was lymphocytopenia (12/15 patients). CT images obtained before and after delivery showed no signs of pneumonia aggravation after delivery. The four patients who were still pregnant at the end of the study period were not treated with antiviral drugs but had achieved good recovery. CONCLUSION. Pregnancy and childbirth did not aggravate the course of symptoms or CT features of COVID-19 pneumonia. All the cases of COVID-19 pneumonia in the pregnant women in our study were the mild type. All the women in this study-some of whom did not receive antiviral drugs-achieved good recovery from COVID-19 pneumonia.


title: [Potential antiviral therapeutics for 2019 Novel Coronavirus].

text: The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir / ritonavir, lopinavir / ritonavir combined with interferon-β, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.


Covert coronavirus infections could be seeding new outbreaks.


title: Associations Between Complex PCI and Prasugrel or Clopidogrel Use in Patients With Acute Coronary Syndrome Who Undergo PCI: From the PROMETHEUS Study.

text: BACKGROUND Potent P2Y12 inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type. METHODS PROMETHEUS was a multicentre observational study that compared clopidogrel vs prasugrel in acute coronary syndrome patients who underwent PCI (n = 19,914). Complex PCI was defined as PCI of the left main, bifurcation lesion, moderate-severely calcified lesion, or total stent length ≥ 30 mm. Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke, or unplanned revascularization. Outcomes were adjusted using multivariable Cox regression for effect of PCI complexity and propensity-stratified analysis for effect of thienopyridine type. RESULTS The study cohort included 48.9% (n = 9735) complex and 51.1% (n = 10,179) noncomplex patients. Second generation drug-eluting stents were used in 70.1% complex and 66.2% noncomplex PCI patients (P < 0.0001). Complex PCI was associated with greater adjusted risk of 1-year MACE (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.20-1.39; P < 0.001). Prasugrel was prescribed in 20.7% of complex and 20.1% of noncomplex PCI patients (P = 0.30). Compared with clopidogrel, prasugrel significantly decreased adjusted risk for 1-year MACE in complex PCI (HR, 0.79; 95% CI, 0.68-0.92) but not noncomplex PCI (HR, 0.91; 95% CI, 0.77-1.08), albeit there was no evidence of interaction (P interaction = 0.281). CONCLUSIONS Despite the use of contemporary techniques, acute coronary syndrome patients who undergo complex PCI had significantly higher rates of 1-year MACE. Adjusted magnitude of treatment effects with prasugrel vs clopidogrel were consistent in complex and noncomplex PCI without evidence of interaction.


On Masochism: A Resident's Conflict Between Sacrifice and Self-Preservation During the COVID-19 Pandemic.


title: Antiviral innate immune response of RNA interference.

text: RNA interference (RNAi) is an ancient, natural process conserved among species from different kingdoms. RNAi is a transcriptional and post-transcriptional gene silencing mechanism in which, double-stranded RNA or hairpin RNA is cleaved by an RNase III-type enzyme called Dicer into small interfering RNA duplex. This subsequently directs sequence-specific, homology dependent, Watson-Crick base-pairing post-transcriptional gene silencing by binding to its complementary RNA and initiating its elimination through degradation or by persuading translational inhibition. In plants, worms, and insects, RNAi is the main and strong antiviral defense mechanism. It is clear that RNAi silencing, contributes in restriction of viral infection in vertebrates. In a short period, RNAi has progressed to become a significant experimental tool for the analysis of gene function and target validation in mammalian systems. In addition, RNA silencing has then been found to be involved in translational repression, transcriptional inhibition, and DNA degradation. RNAi machinery required for robust RNAi-mediated antiviral response are conserved throughout evolution in mammals and plays a crucial role in antiviral defense of invertebrates, but despite these important functions RNAi contribution to mammalian antiviral innate immune defense has been underestimated and disputed. In this article, we review the literature concerning the roles of RNAi as components of innate immune system in mammals and how, the RNAi is currently one of the most hopeful new advances toward disease therapy. This review highlights the potential of RNAi as a therapeutic strategy for viral infection and gene regulation to modulate host immune response to viral infection.


title: The expanded role of extracellular matrix patch in malignant and non-malignant chest wall reconstruction in thoracic surgery.

text: OBJECTIVES The extracellular matrix (XCM Biologic Tissue Matrix) is a non-cross-linked 3D patch derived from porcine dermis. Once implanted, it is infiltrated by recipient's cells and becomes incorporated in the repair. Here, we report the first series of using this device for chest wall reconstruction. METHODS The XCM Biologic Tissue Matrix was utilized to provide the restoration of chest wall defects. It was used either alone or in conjunction with the Synthes titanium system to provide additional support. The decision was made intraoperatively. RESULTS Since April 2010, 21 (12 females) patients received the device. Average age at operation was 47 ± 17 years. Eleven (52%) patients had the patch inserted alone, while the remaining 10 received it in combination with another implantable medical device. The biological tissue matrix was used to reconstruct chest wall defects in cancer involving chest wall (n = 9), chest wall deformity (n = 6), chest wall hernia (n = 5) and chest wall repair following empyema drainage (n = 1). Complications were witnessed in 3 patients receiving the combined XCM and Synthes bar mechanisms; infection (n = 2) and bar displacement and infection (n = 1). CONCLUSIONS The XCM patch can be safely used to provide the strength required for chest wall reconstruction and to replace previously infected reconstructions.


title: Timely detection of localized excess influenza activity in Northern California across patient care, prescription, and laboratory data.

text: Timely detection of clusters of localized influenza activity in excess of background seasonal levels could improve situational awareness for public health officials and health systems. However, no single data type may capture influenza activity with optimal sensitivity, specificity, and timeliness, and it is unknown which data types could be most useful for surveillance. We compared the performance of 10 types of electronic clinical data for timely detection of influenza clusters throughout the 2007/08 influenza season in northern California. Kaiser Permanente Northern California generated zip code-specific daily episode counts for: influenza-like illness (ILI) diagnoses in ambulatory care (AC) and emergency departments (ED), both with and without regard to fever; hospital admissions and discharges for pneumonia and influenza; antiviral drugs dispensed (Rx); influenza laboratory tests ordered (Tests); and tests positive for influenza type A (FluA) and type B (FluB). Four credible events of localized excess illness were identified. Prospective surveillance was mimicked within each data stream using a space-time permutation scan statistic, analyzing only data available as of each day, to evaluate the ability and timeliness to detect the credible events. AC without fever and Tests signaled during all four events and, along with Rx, had the most timely signals. FluA had less timely signals. ED, hospitalizations, and FluB did not signal reliably. When fever was included in the ILI definition, signals were either delayed or missed. Although limited to one health plan, location, and year, these results can inform the choice of data streams for public health surveillance of influenza.


Neutrophil-to-lymphocyte ratio predicts the clearance of SARS-CoV-2 RNA in mild COVID-19 patients - a retrospective analysis from Dongxihu Fangcang Hospital in Wuhan, China.


title: Standardization of operative equipment reduces cost.

text: BACKGROUND We hypothesize that standardizing operative equipment, and reducing variability can safely achieve cost reduction. METHODS We retrospectively measured supply costs, operative time, intra-operative complications, and length of stay in a cohort of 145 patients at a children's hospital who underwent a laparoscopic appendectomy. A standardized preference card for laparoscopic appendectomy was developed and implemented. Data were prospectively collected on 101 consecutive patients and compared to the retrospective cohort using multiple linear regression. A survey assessing the perception of surgeons, nurses and scrub technologists of the impact of standardization on patient safety, patient care, OR efficiency, and cost was conducted. Wilcoxon rank sum test was used to evaluate associations between clinical role and years of experience with the total level of agreement on the survey. RESULTS A 20% average reduction was achieved in supply cost per case, with no significant change in operative time (p=0.14), total time in OR (p=0.15), or length of stay (p=0.60). No intra-operative complications were identified in either group. Survey participants agreed that standardization improves cost and safety. Nurses tended to have greater agreement that standardization improved efficiency and patient care compared to other roles (p=0.06). CONCLUSIONS Standardization of operative equipment can result in a significant cost reduction without impacting quality or delivery of care. Based on average case number per year, a total annual cost savings of >$41,000 could be realized. Survey participants agree that standardization improves cost and patient safety, yet perceptions regarding the impact on efficiency and patient care varied by occupation.


title: IRE1α promotes viral infection by conferring resistance to apoptosis.

text: The unfolded protein response (UPR) is an ancient cellular pathway that detects and alleviates protein-folding stresses. The UPR components X-box binding protein 1 (XBP1) and inositol-requiring enzyme 1α (IRE1α) promote type I interferon (IFN) responses. We found that Xbp1-deficient mouse embryonic fibroblasts and macrophages had impaired antiviral resistance. However, this was not because of a defect in type I IFN responses but rather an inability of Xbp1-deficient cells to undergo viral-induced apoptosis. The ability to undergo apoptosis limited infection in wild-type cells. Xbp1-deficient cells were generally resistant to the intrinsic pathway of apoptosis through an indirect mechanism involving activation of the nuclease IRE1α. We observed an IRE1α-dependent reduction in the abundance of the proapoptotic microRNA miR-125a and a corresponding increase in the amounts of the members of the antiapoptotic Bcl-2 family. The activation of IRE1α by the hepatitis C virus (HCV) protein NS4B in XBP1-proficient cells also conferred apoptosis resistance and promoted viral replication. Furthermore, we found evidence of IRE1α activation and decreased miR-125a abundance in liver biopsies from patients infected with HCV compared to those in the livers of healthy controls. Our results reveal a prosurvival role for IRE1α in virally infected cells and suggest a possible target for IFN-independent antiviral therapy.


title: Risk of distal embolization with stent retriever thrombectomy and ADAPT.

text: BACKGROUND There is a discrepancy in clinical outcomes and the achieved recanalization rates with stent retrievers in the endovascular treatment of ischemic stroke. It is our hypothesis that procedural release of embolic particulate may be one contributor to poor outcomes and is a modifiable risk. The goal of this study is to assess various treatment strategies that reduce the risk of distal emboli. METHODS Mechanical thrombectomy was simulated in a vascular phantom with collateral circulation. Hard fragment-prone clots (HFC) and soft elastic clots (SECs) were used to generate middle cerebral artery (MCA) occlusions that were retrieved by the Solitaire FR devices through (1) an 8 Fr balloon guide catheter (BGC), (2) a 5 Fr distal access catheter at the proximal aspect of the clot in the MCA (Solumbra), or (3) a 6 Fr guide catheter with the tip at the cervical internal carotid artery (guide catheter, GC). Results from mechanical thrombectomy were compared with those from direct aspiration using the Penumbra 5MAX catheter. The primary endpoint was the size distribution of emboli to the distribution of the middle and anterior cerebral arteries. RESULTS Solumbra was the most efficient method for reducing HFC fragments (p<0.05) while BGC was the best method for preventing SEC fragmentation (p<0.05). The risk of forming HFC distal emboli (>1000 µm) was significantly increased using GC. A non-statistically significant benefit of direct aspiration was observed in several subgroups of emboli with size 50-1000 µm. However, compared with the stent-retriever mechanical thrombectomy techniques, direct aspiration significantly increased the risk of SEC fragmentation (<50 µm) by at least twofold. CONCLUSIONS The risk of distal embolization is affected by the catheterization technique and clot mechanics.


title: The development and reform of public health in China from 1949 to 2019.

text: BACKGROUND Public health system plays a vital role in the development of health sector in China and protects the health of Chinese people. However, there are few comprehensive reviews and studies focusing on its evolution and reform. It is worthwhile to pay attention to the public health development in China, given that the history and structure of public health system have their own characteristics in China. METHODS The study is a retrospective review of the development public health over seven decades in China. It presents the findings from some national or provincial survey data, interviews with key informants, reviews of relevant published papers and policy contents. RESULTS This study identified four key stages that public health experienced in China: the initial stage centering on prevention, the stage of deviation with more attention to treatment but little to prevention, the recovery stage after SARS(Severe Acute Respiratory Syndromes) Crisis, and the new stage to an equitable and people-centered system. In the latest stage, the National Basic Public Health Service Program (NBPHSP) is implemented to respond the threat of noncommunicable diseases (NCDs) and has achieved some initial results, while there are still many challenges including service quality, poor integration among service items and IT system, lack of quality professionals and insufficient intersectoral endeavor. DISCUSSION There are unique Chinese wisdom and remarkable achievements as well as twists and turns on the development of China's public health. Prevention-first, flexible structure of the system, multi-agency collaboration and mass mobilization and society participation are the main experience of public health in early stage. Despite twists and turns since 1980s, public health system in China shows substantial resilience which may be from the government's continuous commitment to social development and people's livelihoods and its flexible governance. In 2010s, in order to achieve the well-off society, Chinese government pays unprecedented attention to health sector, which bring a new wave of opportunities to public health such as remaining the NBPHSP for priority. The evolution and reform of China's public health is based on its national condition, accumulates rich experience but also faces many common worldwide challenges. Getting this development and reform right is important to China's social and economic development in future, and China's experience in public health may provide many lessons for other countries. CONCLUSION Public health in China needs to focus on prevention, strengthen multi-agency coordination mechanism, improve the quality of public health services in the future.


title: Ethics of Outbreaks Position Statement. Part 2: Family-Centered Care.

text: OBJECTIVES Continue the dialogue presented in Ethics of Outbreaks Position Statement. Part 1, with a focus on strategies for provision of family-centered care in critical illness during Pubic Health Emergency of International Concern. DESIGN Development of a Society of Critical Care Medicine position statement using literature review, expert consensus from the Society of Critical Care Medicine Ethics Committee. A family member of a patient who was critically ill during a natural disaster served on the writing panel and provided validation from a family perspective to the recommendations. SETTING Provision of family-centered care and support for patients who are critically ill or who have the potential of becoming critically ill, and their families, during a Pubic Health Emergency of International Concern. INTERVENTIONS Communication; family support. MEASUREMENTS AND MAIN RESULTS Family-centered interventions during a Pubic Health Emergency of International Concern include understanding how crisis standards may affect regional and local traditions. Transparently communicate changes in decision-making authority and uncertainty regarding treatments and outcomes to the family and community. Assess family coping, increase family communication and support, and guide families regarding possible engagement strategies during crisis. Prepare the public to accept survivors returning to the community.


title: [Intensive Care During a Global Epidemic].

text: The global spread of coronavirus disease 2019 (COVID-19) is rapidly increasing the number of patients who are critically ill with this disease, with the related rate of mortality expected to peak in 2020 (Alhazzani et al., 2020). As severe acute respiratory syndrome is the major cause of mortality after COVID-19 infection, patients with COVID-19 who are prone to severe acute respiratory problems may require mechanical ventilation or extracorporeal membrane oxygenation (ECMO; Alhazzani et al., 2020). Ongoing advances in intensive care medicine are continuing to improve survival in critically ill patients (Kaukonen, Bailey, Suzuki, Pilcher, & Bellomo, 2014). However, intensive care unit (ICU) survivors may experience complications and problems related to their disease and treatment such as critical illness polyneuropathy, critical illness myopathy, and post intensive care syndrome (PICS; Alhazzani et al., 2020). Harvey (2012) reported that 85%-95% of ICU patients have ICU-acquired weakness after ICU discharge and 74% of ICU patients with acute respiratory distress syndrome have cognitive impairment after ICU discharge. Physical disabilities, cognitive impairment, and mental or psychological distress (e.g., anxiety, depression, and post-traumatic stress disorder) after ICU discharge may be symptoms of PICS, and may continue to affect surviving patients for several years after ICU discharge (Elliott et al., 2014; Held & Moss, 2019; Jackson et al., 2014; Jubran et al., 2010). Efforts to prevent and treat COVID-19 in Taiwan have proven more effective compared to most other places in the world. In addition to the low number of diagnosed cases, the mortality rate (seven of 440 confirmed cases) in Taiwan has been significantly lower than in most other countries (Taiwan Centers for Disease Control, ROC, 2020, May 14). However, post-discharge care for ICU survivors, especially those hospitalized after a sudden onset of severe disease symptoms and then discharged after a long ICU stay or after receiving mechanical ventilation, require specialized care to minimize PICS. Nurses are responsible not only for treating patients with the disease but also for preventing the further spread of disease. Therefore, providing continued care to patients discharged from the ICU is essential. Specifically, interventions to avoid PICS must be implemented rapidly by multidisciplinary medical teams during and immediately after ICU discharge.


title: Architecture and self-assembly of the SARS-CoV-2 nucleocapsid protein.

text: The COVID-2019 pandemic is the most severe acute public health threat of the twenty-first century. To properly address this crisis with both robust testing and novel treatments, we require a deep understanding of the life cycle of the causative agent, the SARS-CoV-2 coronavirus. Here, we examine the architecture and self-assembly properties of the SARS-CoV-2 nucleocapsid protein, which packages viral RNA into new virions. We determined a 1.4 å resolution crystal structure of this protein's N2b domain, revealing a compact, intertwined dimer similar to that of related coronaviruses including SARS-CoV. While the N2b domain forms a dimer in solution, addition of the C-terminal spacer B/N3 domain mediates formation of a homotetramer. Using hydrogen-deuterium exchange mass spectrometry, we find evidence that at least part of this putatively disordered domain is structured, potentially forming an α-helix that self-associates and cooperates with the N2b domain to mediate tetramer formation. Finally, we map the locations of amino acid substitutions in the N protein from over 38,000 SARS-CoV-2 genome sequences. We find that these substitutions are strongly clustered in the protein's N2a linker domain, and that substitutions within the N1b and N2b domains cluster away from their functional RNA binding and dimerization interfaces. Overall, this work reveals the architecture and self-assembly properties of a key protein in the SARS-CoV-2 life cycle, with implications for both drug design and antibody-based testing. This article is protected by copyright. All rights reserved.


title: Calculation of the Respiratory Modulation of the Photoplethysmogram (DPOP) Incorporating a Correction for Low Perfusion.

text: DPOP quantifies respiratory modulations in the photoplethysmogram. It has been proposed as a noninvasive surrogate for pulse pressure variation (PPV) used in the prediction of the response to volume expansion in hypovolemic patients. The correlation between DPOP and PPV may degrade due to low perfusion effects. We implemented an automated DPOP algorithm with an optional correction for low perfusion. These two algorithm variants (DPOPa and DPOPb) were tested on data from 20 mechanically ventilated OR patients split into a benign "stable region" subset and a whole record "global set." Strong correlation was found between DPOP and PPV for both algorithms when applied to the stable data set: R = 0.83/0.85 for DPOPa/DPOPb. However, a marked improvement was found when applying the low perfusion correction to the global data set: R = 0.47/0.73 for DPOPa/DPOPb. Sensitivities, Specificities, and AUCs were 0.86, 0.70, and 0.88 for DPOPa/stable region; 0.89, 0.82, and 0.92 for DPOPb/stable region; 0.81, 0.61, and 0.73 for DPOPa/global region; 0.83, 0.76, and 0.86 for DPOPb/global region. An improvement was found in all results across both data sets when using the DPOPb algorithm. Further, DPOPb showed marked improvements, both in terms of its values, and correlation with PPV, for signals exhibiting low percent modulations.


title: Intraoperative experiments combined with gait analyses indicate that active state rather than passive dominates the spastic gracilis muscle's joint movement limiting effect in cerebral palsy.

text: BACKGROUND In cerebral palsy, spastic muscle's passive forces are considered to be high but have not been assessed directly. Although activated spastic muscle's force-joint angle relations were studied, this was independent of gait relevant joint positions. The aim was to test the following hypotheses intraoperatively: (i) spastic gracilis passive forces are high even in flexed knee positions, (ii) its active state forces attain high amplitudes within the gait relevant knee angle range, and (iii) increase with added activations of other muscles. METHODS Isometric forces (seven children with cerebral palsy, gross motor function classification score = II) were measured during surgery from knee flexion to full extension, at hip angles of 45° and 20° and in four conditions: (I) passive state, after gracilis was stimulated (II) alone, (III) simultaneously with its synergists, and (IV) also with an antagonist. FINDINGS Directly measured peak passive force of spastic gracilis was only a certain fraction of the peak active state forces (maximally 26%) measured in condition II. Conditions III and IV caused gracilis forces to increase (for hip angle = 45°, by 32.8% and 71.9%, and for hip angle = 20°, by 24.5% and 45.1%, respectively). Gait analyses indicated that intraoperative data for knee angles 61-17° and 33-0° (for hip angles 45° and 20°, respectively) are particularly relevant, where active state force approximates its peak values. INTERPRETATION Active state muscular mechanics, rather than passive, of spastic gracilis present a capacity to limit joint movement. The findings can be highly relevant for diagnosis and orthopaedic surgery in individuals with cerebral palsy.


title: A prospective, multi-institutional study of flexible ureteroscopy for proximal ureteral stones smaller than 2 cm.

text: PURPOSE Flexible ureteroscopy is rapidly becoming a first line therapy for many patients with renal and ureteral stones. However, current understanding of treatment outcomes in patients with isolated proximal ureteral stones is limited. Therefore, we performed a prospective, multi-institutional study of ureteroscopic management of proximal ureteral stones smaller than 2 cm to better define clinical outcomes associated with this approach. MATERIALS AND METHODS Adult patients with proximal ureteral calculi smaller than 2 cm were prospectively identified. Patients with concomitant ipsilateral renal calculi or prior ureteral stenting were excluded from study. Flexible ureteroscopy, holmium laser lithotripsy and ureteral stent placement was performed. Ureteral access sheath use, laser settings and other details of perioperative and postoperative management were based on individual surgeon preference. Stone clearance was determined by the results of renal ultrasound and plain x-ray of the kidneys, ureters and bladder 4 to 6 weeks postoperatively. RESULTS Of 71 patients 44 (62%) were male and 27 (38%) were female. Mean age was 48.2 years. ASA(®) score was 1 in 12 cases (16%), 2 in 41 (58%), 3 in 16 (23%) and 4 in 2 (3%). Mean body mass index was 31.8 kg/m(2), mean stone size was 7.4 mm (range 5 to 15) and mean operative time was 60.3 minutes (range 15 to 148). Intraoperative complications occurred in 2 patients (2.8%), including mild ureteral trauma. Postoperative complications developed in 6 patients (8.7%), including urinary tract infection in 3, urinary retention in 2 and flash pulmonary edema in 1. The stone-free rate was 95% and for stones smaller than 1 cm it was 100%. CONCLUSIONS Flexible ureteroscopy is associated with excellent clinical outcomes and acceptable morbidity when applied to patients with proximal ureteral stones smaller than 2 cm.


title: More stapler firings increase the risk of perioperative morbidity after laparoscopic sleeve gastrectomy.

text: Introduction Staple-line bleeding and leakage are the most common serious complications of laparoscopic sleeve gastrectomy. The relationship between multiple stapler firings and higher risk of postoperative complications is well defined in colorectal surgery but has not been addressed in bariatric procedures so far. Identification of new factors such as "the numbers of stapler firings used during laparoscopic sleeve gastrectomy (LSG)" as a predictor for complications can lead to optimization of the patient care at bariatric centers. Aim To determine the association between perioperative morbidity and the number of stapler firings during laparoscopic sleeve gastrectomy. Material and methods This observational study was based on retrospective analysis of prospectively collected data in patients operated on for morbid obesity in a teaching hospital/tertiary referral center for general surgery. The patients who underwent LSG were analyzed in terms of the number of stapler firings used as a new potential risk predictor for postoperative complications after surgery, adjusting for other patient- and treatment-related factors. The study included 333 patients (209 women, 124 men, mean age: 40 ±11). Results During the first 30 days after surgery, complications were observed in 18 (5.41%) patients. Multivariate analysis showed that prolonging operative time increased morbidity (every minute, OR = 1.01; 95% CI: 1.00-1.02) and the complication rate increased with the number of stapler firings (every firing, OR = 1.91; 95% CI: 1.09-3.33; p = 0.023). Conclusions Additional stapler firings above the usual number and a prolonged operation should alert a surgeon and the whole team about increased risk of postoperative complications.


title: Genome-wide analysis of transcript isoform variation in humans.

text: We have performed a genome-wide analysis of common genetic variation controlling differential expression of transcript isoforms in the CEU HapMap population using a comprehensive exon tiling microarray covering 17,897 genes. We detected 324 genes with significant associations between flanking SNPs and transcript levels. Of these, 39% reflected changes in whole gene expression and 55% reflected transcript isoform changes such as splicing variants (exon skipping, alternative splice site use, intron retention), differential 5' UTR (initiation of transcription) use, and differential 3' UTR (alternative polyadenylation) use. These results demonstrate that the regulatory effects of genetic variation in a normal human population are far more complex than previously observed. This extra layer of molecular diversity may account for natural phenotypic variation and disease susceptibility.


title: Use of humanized severe combined immunodeficient mice for human vaccine development.

text: The severe combined immunodeficient (SCID) mouse has no adaptive immunity, lacking mature T and B cells in the peripheral blood or the lymphoid organs. It has been used extensively in biomedical research as a valuable translational model for xeno-engraftment of human tissues and cells. This review focuses on the engraftment of human peripheral blood cells and tissues in SCID mice, as well as in the newly established and more permissive SCID mice deficient in the IL-2 receptor gamma-chain. Human immune responses could be elicited and assessed in these humanized SCID mice upon vaccination or sensitization with allogeneic tissues. A translational model is proposed to attain preclinical data for testing human vaccines.


title: Plasma levels of receptor for advanced glycation end products, blood transfusion, and risk of primary graft dysfunction.

text: RATIONALE The receptor for advanced glycation end products (RAGE) is an important marker of lung epithelial injury and may be associated with impaired alveolar fluid clearance. We hypothesized that patients with primary graft dysfunction (PGD) after lung transplantation would have higher RAGE levels in plasma than patients without PGD. OBJECTIVES To test the association of soluble RAGE (sRAGE) levels with PGD in a prospective, multicenter cohort study. METHODS We measured plasma levels of sRAGE at 6 and 24 hours after allograft reperfusion in 317 lung transplant recipients at seven centers. The primary outcome was grade 3 PGD (Pa(O(2))/Fi(O(2)) < 200 with alveolar infiltrates) within the first 72 hours after transplantation. MEASUREMENTS AND MAIN RESULTS Patients who developed PGD had higher levels of sRAGE than patients without PGD at both 6 hours (median 9.3 ng/ml vs. 7.5 ng/ml, respectively; P = 0.028) and at 24 hours post-transplantation (median 4.3 ng/ml vs. 1.9 ng/ml, respectively; P < 0.001). Multivariable logistic regression analyses indicated that the relationship between levels of sRAGE and PGD was attenuated by elevated right heart pressures and by the use of cardiopulmonary bypass. Median sRAGE levels were higher in subjects with cardiopulmonary bypass at both 6 hours (P = 0.003) and 24 hours (P < 0.001). sRAGE levels at 6 hours were significantly associated with intraoperative red cell transfusion (Spearman's rho = 0.39, P = 0.002 in those with PGD), and in multivariable linear regression analyses this association was independent of confounding variables (P = 0.02). CONCLUSIONS Elevated plasma levels of sRAGE are associated with PGD after lung transplantation. Furthermore, plasma sRAGE levels are associated with blood product transfusion and use of cardiopulmonary bypass.


title: The Battle against COVID 19 Pandemic: What we Need to Know Before we "Test Fire" Ivermectin.

text: The world is faced with the dire challenge of finding an effective treatment against the rampaging COVID 19 pandemic. Amidst the crisis, reports of in vitro inhibitory activity of ivermectin, an approved anthelmintic, against the causative SARSCoV2 virus, have generated lot of optimism. In this article, we have fished and compiled the needed information on the drug, that will help readers and prospective investigators in having a quick overview. Though the primordial biological action of the drug is allosteric modulation of helminthic ion channel receptor, its in vitro activity against both RNA and DNA viruses is known for almost a decade. In the past two years, efficacy study in animal models of pseudorabies and zika virus was found to be favourable and unfavourable respectively. Only one clinical study evaluated the drug in dengue virus infection without any clinical efficacy. However, the proposed mechanism of drug action, by inhibiting the importin family of nucleus-cytoplasmic transporters along with favourable pharmacokinetics, warrants exploration of its role in COVID 19 through safely conducted clinical trials. Being an available and affordable drug, enlisted in WHO List of Essential Medicine, and a long track record of clinical safety, the drug is already in clinical trials the world over. As the pandemic continues to ravage human civilisation with unabated intensity, the world eagerly waits for a ray of hope emanating from the outcome of the ongoing trials with ivermectin as well as other drugs.


title: Dissecting mammalian immunity through mutation.

text: Although mutation and natural selection have given rise to our immune system, a well-placed mutation can also cripple it, and within an expanding population we are recognizing more and more cases of single-gene mutations that compromise immunity. These mutations are an ideal tool for understanding human immunology, and there are more ways than ever to measure their physiological effects. There are also more ways to create mutations in the laboratory, and to use these resources to systematically define the function of every gene in our genome. This review focuses on the discovery and creation of mutations in the context of mammalian immunity, with an emphasis on the use of genome-wide chemical and CRISPR/Cas9 mutagenesis to reveal gene function.


title: Histopathologic host response to polypropylene-based surgical mesh materials in a rat abdominal wall defect model.

text: Composite polypropylene-based surgical mesh materials including various synthetic polymers and naturally occurring biomaterials have been developed to ameliorate device-associated inflammatory response and associated reduced compliance of pure polypropylene meshes. This study evaluated the histomorphologic response of three composite polypropylene-based surgical meshes, Revive™, a polycarbonate polyurethane reinforced monofilamentous polypropylene scaffold, Assure™, a polycarbonate polyurethane reinforced monofilamentous polypropylene scaffold with a resorbable anti-adhesion layer of lactide caprolactone copolymer, and Proceed™, a polypropylene mesh modified with oxidized cellulose, in a soft tissue repair model in the rat. The host inflammatory response and neotissue formation were evaluated by semiquantitative histologic scoring including the amount of cellular infiltration, angiogenesis, presence of multinucleate giant cells, fibrous connective tissue formation, and host neo-extracellular matrix deposition for up to 26 weeks. All three composite surgical mesh materials showed good integration with host tissue as indicated by rapid cellular infiltration, abundant neo-vascularization, minimal shrinkage, and the lack of visible mesh degradation. The devices elicited a similar inflammatory response and the presence of a mild foreign body response in spite of the different composition and morphology of these composite mesh materials.


title: Robotic Sacrocolpopexy for Treatment of Apical Compartment Prolapse.

text: Abdominal sacrocolpopexy is the gold-standard treatment for apical compartment prolapse, as it is more effective and durable than the transvaginal approach. In the current era of minimally invasive surgery, laparoscopic sacrocolpopexy techniques have been described, but have not gained popularity due to their complexity and steep learning curves. To overcome this problem, robotic sacrocolpopexy was introduced, and has shown equivalent outcomes and safety compared to open and laparoscopic sacrocolpopexy based on findings that have been accumulated over 15 years.


title: Burden and prevalence of prognostic factors for severe COVID-19 in Sweden

text: The World Health Organization and European Centre for Disease Prevention and Control suggest that individuals over the age of 70 years or with underlying cardiovascular disease, cancer, chronic obstructive pulmonary disease, asthma, or diabetes are at increased risk of severe COVID-19. However, the prevalence of these prognostic factors is unknown in many countries. We aimed to describe the burden and prevalence of prognostic factors of severe COVID-19 at national and county level in Sweden. We calculated the burden and prevalence of prognostic factors for severe COVID-19 based on records from the Swedish national health care and population registers for 3 years before 1st January 2016. 9,624,428 individuals were included in the study population. 22.1% had at least one prognostic factor for severe COVID-19 (2,131,319 individuals), and 1.6% had at least three factors (154,746 individuals). The prevalence of underlying medical conditions ranged from 0.8% with chronic obstructive pulmonary disease (78,516 individuals) to 7.4% with cardiovascular disease (708,090 individuals), and the county specific prevalence of at least one prognostic factor ranged from 19.2% in Stockholm (416,988 individuals) to 25.9% in Kalmar (60,005 individuals). We show that one in five individuals in Sweden is at increased risk of severe COVID-19. When compared with the critical care capacity at a local and national level, these results can aid authorities in optimally planning healthcare resources during the current pandemic. Findings can also be applied to underlying assumptions of disease burden in modelling efforts to support COVID-19 planning. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10654-020-00646-z) contains supplementary material, which is available to authorized users.


title: Feature sensitivity criterion-based sampling strategy from the Optimization based on Phylogram Analysis (Fs-OPA) and Cox regression applied to mental disorder datasets.

text: Digital datasets in several health care facilities, as hospitals and prehospital services, accumulated data from thousands of patients for more than a decade. In general, there is no local team with enough experts with the required different skills capable of analyzing them in entirety. The integration of those abilities usually demands a relatively long-period and is cost. Considering that scenario, this paper proposes a new Feature Sensitivity technique that can automatically deal with a large dataset. It uses a criterion-based sampling strategy from the Optimization based on Phylogram Analysis. Called FS-opa, the new approach seems proper for dealing with any types of raw data from health centers and manipulate their entire datasets. Besides, FS-opa can find the principal features for the construction of inference models without depending on expert knowledge of the problem domain. The selected features can be combined with usual statistical or machine learning methods to perform predictions. The new method can mine entire datasets from scratch. FS-opa was evaluated using a relatively large dataset from electronic health records of mental disorder prehospital services in Brazil. Cox's approach was integrated to FS-opa to generate survival analysis models related to the length of stay (LOS) in hospitals, assuming that it is a relevant aspect that can benefit estimates of the efficiency of hospitals and the quality of patient treatments. Since FS-opa can work with raw datasets, no knowledge from the problem domain was used to obtain the preliminary prediction models found. Results show that FS-opa succeeded in performing a feature sensitivity analysis using only the raw data available. In this way, FS-opa can find the principal features without bias of an inference model, since the proposed method does not use it. Moreover, the experiments show that FS-opa can provide models with a useful trade-off according to their representativeness and parsimony. It can benefit further analyses by experts since they can focus on aspects that benefit problem modeling.


title: Depicting medullary thyroid cancer recurrence: the past and the future of nuclear medicine imaging.

text: CONTEXT Inherited and sporadic medullary thyroid cancer (MTC) is an uncommon and medically challenging malignancy. Even if the extent of initial surgery is deemed adequate, the recurrence rate remains high, up to 50% in most series. Measurement of serum calcitonin is important in the follow-up of patients with MTC, and reliably reflects the existence of the disease. EVIDENCE ACQUISITION There is no single sensitive diagnostic imaging method to reveal all MTC recurrences or metastases. Conventional morphologic imaging methods (U/S, CT, and MRI) and several methods of nuclear medicine have been used for this purpose with variable accuracy. RESULTS The main role of nuclear medicine imaging is the detection of residual or recurrent tumor in the postoperative follow-up. In this review we present the radiopharmaceuticals used in the diagnosis of MTC recurrence, and comparison among them. CONCLUSIONS The most used radiopharmaceuticals labelled with γ emitters are: Metaiodobenzylguanidine (MIBG), labelled with (131)I or (123)I, (111)In-pentetreotide (Octreoscan), 99mTc-pentavalent dimercaptosuccinic acid ((99m)Tc(V)-DMSA), and (99m)Tc-EDDA/HYNIC-Tyr3-Octreotide ( Tektrotyd). The radiopharmaceuticals labelled with a positron-emitting radionuclide (β+), suitable for positron emission tomography (PET) imaging are: (18)F-fluorodeoxyglucose ((18)F-FDG), (18)F-fluorodihydroxyphenylalanine (18F-DOPA), and 68Ga-labelled somatostatin analogues (68Ga-DOTATATE or DOTATOC).


A hard time to die: grief and the coronavirus: Michael Boland.


Pharmacy, employee health lead health system's exposure response.


Covid-19: US cases soar as Trump pushes for schools to open.


title: Production of antigen-specific human IgGs by in vitro immunization.

text: BACKGROUND We previously developed in vitro immunization based on a fusion protein containing the transcriptional transactivator (Tat) of human immunodeficiency virus and a double domain, called ZZ, derived from protein A of Staphylococcus aureus. In this approach, naïve human peripheral blood mononuclear cells (PBMCs) trigger a specific IgM antibody (Ab) response in the presence of ZZTat. In the present study, we attempted to raise a specific IgG Ab response. RESULTS We found that PBMCs incubated with ZZTat and a mixture containing anti-CD40, IL4 and IL21 secrete anti-Tat IgG Abs in their supernatants, indicating that the cytokine cocktail provides an isotypic switch. Then, we deciphered the Tat determinant involved in the phenomenon and found that it is located in the region 22-57 and that, within this region, the cysteine-rich domain and the basic residues play a crucial role. Finally, we prepared a fusion protein containing a fragment derived from the NY-ESO-1 cancer/testis antigen (Ag) and showed that PBMCs incubated with ZZfNY-ESO-1Tat trigger a specific anti-fNY-ESO-1 IgG Ab response, which demonstrates the possibility of transferring immunizing ability to an Ag unrelated to Tat. CONCLUSION Our ZZTat-based in vitro immunization approach that offers the possibility to raise an IgG Ab response against NY-ESO-1 might represent a valuable first stage for the generation of fully human IgG specific Abs.


title: What is behind the remarkable increase in esophageal adenocarcinoma?

text: Esophageal adenocarcinoma has undergone a marked increase in incidence in Western cultures. The cause of this rise is unclear, and multiple putative causal factors have been implicated in the literature. Although data regarding some of these factors are suggestive, none appear to completely explain the observed trends. Given the complexity of cancer biology, the variety of causative and protective factors involved, and the difficulty in accurate measurement of exposures and outcomes, isolating one or few causative factors is challenging. Understanding the driving force(s) behind these trends may require a better understanding of the interaction between risk factors, as well as the multiple ways in which a single risk factor may affect the pathogenesis of the tumor.


title: Interventional approaches to deep vein thrombosis.

text: The last decade has seen increased use of aggressive, catheter-based methods of treating deep vein thrombosis (DVT). In this article, we outline the risks, benefits, and uncertainties surrounding endovascular DVT therapies, describe clinical situations in which endovascular treatment options should reasonably be considered, and update the reader on new outcome data that pertains to catheter-based DVT interventions. Endovascular thrombolytic therapy is reasonable to perform for selected patients with DVT causing acute limb-threatening circulatory compromise, acute inferior vena cava occlusion, or acute iliofemoral DVT for the purposes of limb salvage and relief of presenting DVT symptoms, and appears likely to prevent post-thrombotic syndrome (PTS) in patients with proximal DVT. A multicenter randomized trial, the ATTRACT Study, is currently underway in the United States to determine whether pharmacomechanical catheter-directed thrombolysis (PCDT) is sufficiently safe and effective to be recommended for routine use in proximal DVT patients. Selected patients with established moderate-to-severe PTS in association with an occluded iliac vein or a refluxing saphenous vein may also be amenable to endovascular intervention to reduce venous hypertension, alleviate symptoms, and improve limb function and quality of life. Pending the results of further studies, an individualized approach to patient selection for interventional DVT therapies is recommended.


title: Providing Re-Essure-ance to the Nickel-Allergic Patient Considering Hysteroscopic Sterilization.

text: Essure is a popular method of permanent sterilization that offers a minimally invasive approach that avoids the risks of traditional sterilization procedures in the operating room. Despite the rarity of complications, there has been concern in the popular media over the safety of Essure. We describe the third reported case of systemic contact dermatitis due to the nickel component of the device, with a resolution of symptoms following surgical removal of the inserts. Despite these cases, we believe that extremely rare complications such as this should not dissuade patients from choosing this safe, effective method of sterilization.


title: Long-Term Outcomes of Obesity Surgery and Implications for Health System Planning.

text: Weight loss surgery is currently the only treatment that offers significant and sustained weight loss for those with severe and complex obesity. Obesity levels have reached a sustained high, whereby several percent of a country's population would qualify for surgery based upon current national guidelines. Worldwide, the provision of surgery is highly variable and to treat all the affected population, it would require at least a 100-fold increase in the provision of services. This has important cost and commissioning implications for health-care planners. Reliable level 1 evidence of the long-term effects of obesity surgery is still lacking, and the long-term complication profiles and re-operation rates unclear, which could have significant impact on health-care systems in the future. The chronic disease management of obesity in a population must be integrated with education and prevention and the brief intervention of weight loss surgery and the management of its sequelae, to prevent significant future morbidity and mortality.


title: Effects of respiratory viruses on febrile neutropenia attacks in children.

text: Respiratory tract viruses have an important effect on morbidity and mortality in patients with febrile neutropenia (FN). The aim of this study was to determine frequency and clinical influence of viral respiratory viruses as potential etiologic agents in episodes of FN in children. A total of 100 children (62 boys, 38 girls) with 166 FN episodes were included in this prospective study. Nasopharyngeal aspirate samples were analyzed for respiratory viral agents using multiplex real-time polymerase chain reaction. The origin of the fever could be defined in 111 (67%) of the episodes. We detected viral agents in 86 (51.8%), bacterial agents in 19 (11.4%), and fungal agents in 5 (3%) of the episodes. The most common detected viruses were rhinovirus (n= 27), respiratory syncytial virus (n=17), and coronavirus (n=16). Parainfluenza virus, influenza A and B, adenovirus, human metapneumovirus, enterovirus, bocavirus and parechovirus were the remaining detected agents. More than one virus positivity occurred in 13 FN episodes. Forty-three patients had multiple FN episodes. Only four patients had the same viral agent in consecutive attacks. Respiratory symptoms (cough, nasal discharge and congestion, sneezing, wheezing), physical examination signs (rales and rhonchi) and radiological findings were significantly more common in viral agent positive patients (p < 0.05). This study showed that respiratory viruses make a substantial contribution on the etiology of FN episodes in children. Identifying viral agents may help to constitute individualized infection-management algorithms in these patients.


title: Impact of a vendor-specific motion-correction algorithm on image quality, interpretability, and diagnostic performance of daily routine coronary CT angiography: influence of heart rate on the effect of motion-correction.

text: To investigate the impact of a vendor-specific motion-correction algorithm on morphological assessment of coronary arteries using coronary CT angiography (cCTA) and to evaluate the influence of heart rate (HR) on the motion-correction effect of this algorithm. Eighty-four patients (mean age 56.3 ± 11.4 years; 53 males) were divided into two groups with a HR of ≥65 and <65 bpm during cCTA, respectively. Images were assigned quality scores (graded 1-4) on coronary segments. Interpretability was defined as a grade >1. Catheter angiography was used to determine the diagnostic accuracy of cCTA for detecting significant stenosis (≥50 %). We compared the image quality, interpretability and diagnostic accuracy between the standard and motion-correction reconstructions in both groups. The motion-correction reconstructions showed significantly (p < 0.05) higher image quality in the proximal and middle right coronary artery (RCA) in the low HR group (57.2 ± 5.0 bpm; n = 51) and proximal-to-distal RCA, posterior descending artery, and proximal and distal left circumflex artery in the high HR group (71.1 ± 4.6 bpm; n = 33). The per-segment interpretability was significantly higher using motion-correction algorithm in the middle RCA in the low HR group and in the proximal and middle RCA in high HR group. Overall, the image quality and interpretability were improved using motion-correction reconstructions in both groups (p < 0.05). Motion-correction reconstruction demonstrated higher (p < 0.05) diagnostic accuracy in 25 patients from both groups. Use of the motion-correction algorithm improves the overall image quality and interpretability of cCTA in both groups. However, it may be more beneficial to the patients with a higher HR.


title: Survey of Telehealth Adoption by Neuro-ophthalmologists During the COVID-19 Pandemic: Benefits, Barriers and Utility.

text: BACKGROUND During the COVID-19 pandemic tele-health modalities have come to prominence as a strategy for providing patient care when in-person care provision opportunities are limited. The degree of adoption by neuro-ophthalmologists has not been quantified. METHODS Telehealth utilization pre- and peri-COVID-19 was surveyed among practicing neuro-ophthalmologists in and outside the US using an on-line platform. Demographics, perceived benefits, barriers, and utility for different neuro-ophthalmic conditions were collected. Data collection occurred over a 2-week period in May, 2020. RESULTS 208 practicing neuro-ophthalmologists (81.3% US, 50.2% female, age range < 35 to > 65, mode 35-44 years) participated in the survey. Utilization of all telehealth modalities increased from pre-COVID to peri-COVID (video visit 3.9% to 68.3%, p<0.0005, remote interpretation of testing 26.7% to 32.2%, p=0.09, on-line second opinion 7.9% to 15.3%, p=0.001, interprofessional e-consult 4.4% to 18.7%, p<0.0005, McNemar). The majority selected access, continuity, and patient efficiency of care as benefits and data quality as a barrier. Telehealth was felt to be most helpful for conditions relying on history, external exam, and previously collected ancillary testing and not helpful for conditions requiring funduscopic exam. CONCLUSIONS Telehealth modality usage by neuro-ophthalmologists increased during the COVID-19 pandemic. Identified benefits have relevance both during and beyond COVID-19. Further work is needed to address barriers in their current and future states to maintain these modalities as viable care delivery options.


title: Sepsis, a 2020 review for the internist.

text: Sepsis is an overwhelming reaction to infection that comes with high morbidity and mortality, that requires urgent interventions in order to improve outcomes. Surviving Sepsis is an international campaign that aims to improve sepsis outcomes. The 2016 guideline modifies the previous definition of sepsis and proposes some specific diagnostic and therapeutic measures, such as the protocolized use of fluid resuscitation and antibiotics. We aim to summarize the main recommendations of the 2016 guideline that are relevant to the internist and evidence-base update them to the year 2020. In the current context, this review doesn't address patients affected by SARS-COV2 induced disease.


title: Middle East respiratory syndrome coronavirus in healthcare settings.

text: PURPOSE OF REVIEW Attracting global attention, Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause sporadic cases and a potential risk of healthcare-associated infections. In this review, we highlight what is known about the risk of transmission within healthcare facilities and discuss interventions to halt its transmission within healthcare. RECENT FINDINGS MERS-CoV causes a wide range of infections from asymptomatic infections, mild or moderately symptomatic cases, to fatal disease. Two years after the initial reported case, MERS-CoV has caused limited disease outside the Arabian Peninsula with several cases in Europe, Asia, and the United States. Epidemiologically, these infections are linked to exposures from the region and their diagnosis outside is related to travel. Several reported clusters of disease report multiple transmissions of MERS-CoV within healthcare settings that have been attributed to poor compliance with the basic infection control measures. Factors contributing to the spread and control of MERS-CoV within healthcare settings have not been elucidated so far. Data suggest the overcrowding, late recognition of MERS-CoV cases, and inadequate infection control practices contribute significantly to the transmission. SUMMARY Understanding factors contributing to the spread and the dynamic of MERS-CoV transmission within healthcare settings would further enhance the control of the disease in and outside the healthcare setting.


title: Cadaver study of oesophageal insufflation with supraglottic airway devices during positive pressure ventilation in an obstructed airway.

text: BACKGROUND Supraglottic airway devices (SADs) play an increasing role in airway management in clinical anaesthesia and emergency medicine. Until now, no data exist concerning the extent of oesophageal insufflation when oropharyngeal leak pressures are exceeded. METHODS Laryngeal masks LMA-Supreme™ and LMA-ProSeal™, laryngeal tubes LTS-D and LTS II, Combitube™, and I-Gel were inserted into unfixed human cadavers. The oesophagus was connected to a volumeter, while the trachea was closed surgically to simulate complete airway obstruction. Volumes of oesophageal insufflation resulting from pressure-controlled ventilation at inspiratory pressures of 20, 40, and 60 mbar were measured. RESULTS No oesophageal insufflation could be detected at a ventilation pressure of 20 mbar in any device. Using inspiratory pressures of 40 and 60 mbar, oesophageal insufflation occurred in all devices, with significantly higher volumes of intraoesophageal air for both laryngeal tubes. CONCLUSIONS The use of SADs with inspiratory pressures of 20 mbar appears to be safe regarding the risk of intragastric insufflation. Higher inspiratory pressures should be strictly avoided.


Pressure Cooker Technique for the Treatment of a Pelvic Arteriovenous Malformation Associated with a Giant Venous Aneurysmal Dilatation.


title: Multifunctional immune responses of HMBPP-specific Vγ2Vδ2 T cells in M. tuberculosis and other infections.

text: Vγ2Vδ2 T (also known as Vγ9Vδ2 T) cells exist only in primates, and in humans represent a major γδ T-cell sub-population in the total population of circulating γδ T cells. Results from recent studies suggest that while (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) phosphoantigen from Mycobacterium tuberculosis (Mtb) and other microbes activates and expands primate Vγ2Vδ2 T cells, the Vγ2Vδ2 T-cell receptor (TCR) recognizes and binds to HMBPP on antigen-presenting cells (APC). In response to HMBPP stimulus, Vγ2Vδ2 TCRs array to form signaling-related nanoclusters or nanodomains during the activation of Vγ2Vδ2 T cells. Primary infections with HMBPP-producing pathogens drive the evolution of multieffector functional responses in Vγ2Vδ2 T cells, although Vγ2Vδ2 T cells display different patterns of responses during the acute and chronic phases of Mtb infection and in other infections. Expanded Vγ2Vδ2 T cells in primary Mtb infection can exhibit a broader TCR repertoire and a greater clonal response than previously assumed, with different distribution patterns of Vγ2Vδ2 T-cell clones in lymphoid and non-lymphoid compartments. Emerging in vivo data suggest that HMBPP activation of Vγ2Vδ2 T cells appears to impact other immune cells during infection.


title: A Narrative Review of Cardiovascular Abnormalities After Spontaneous Intracerebral Hemorrhage.

text: BACKGROUND The recommended cardiac workup of patients with spontaneous intracerebral hemorrhage (ICH) includes an electrocardiogram (ECG) and cardiac troponin. However, abnormalities in other cardiovascular domains may occur. We reviewed the literature to examine the spectrum of observed cardiovascular abnormalities in patients with ICH. METHODS A narrative review of cardiovascular abnormalities in ECG, cardiac biomarkers, echocardiogram, and hemodynamic domains was conducted on patients with ICH. RESULTS We searched PubMed for articles using MeSH Terms "heart," "cardiac," hypertension," "hypotension," "blood pressure," "electro," "echocardio," "troponin," "beta natriuretic peptide," "adverse events," "arrhythmi," "donor," "ICH," "intracerebral hemorrhage." Using Covidence software, 670 articles were screened for title and abstracts, 482 articles for full-text review, and 310 extracted. A total of 161 articles met inclusion and exclusion criteria, and, included in the manuscript. Cardiovascular abnormalities reported after ICH include electrocardiographic abnormalities (56% to 81%) in form of prolonged QT interval (19% to 67%), and ST-T changes (19% to 41%), elevation in cardiac troponin (>0.04 ng/mL), and beta-natriuretic peptide (BNP) (>156.6 pg/mL, up to 78%), echocardiographic abnormalities in form of regional wall motion abnormalities (14%) and reduced ejection fraction. Location and volume of ICH affect the prevalence of cardiovascular abnormalities. Prolonged QT interval, elevated troponin-I, and BNP associated with increased in-hospital mortality after ICH. Blood pressure control after ICH aims to preserve cerebral perfusion pressure and maintain systolic blood pressure between 140 and 179 mm Hg, and avoid intensive blood pressure reduction (110 to 140 mm Hg). The recipients of ICH donor hearts especially those with reduced ejection fraction experience increased early mortality and graft rejection. CONCLUSIONS Various cardiovascular abnormalities are common after spontaneous ICH. The workup of patients with spontaneous ICH should involve 12-lead ECG, cardiac troponin-I, as well as BNP, and echocardiogram to evaluate for heart failure. Blood pressure control with preservation of cerebral perfusion pressure is a cornerstone of hemodynamic management after ICH. The perioperative implications of hemodynamic perturbations after ICH warrant urgent further examination.


Putting the IMPACT study into perspective: should CMV prophylaxis be extended to 6 months for high risk transplants?


title: Efficacy of flattening-filter-free beam in stereotactic body radiation therapy planning and treatment: A systematic review with meta-analysis.

text: A linear accelerator with the flattening-filter removed generates a non-uniform dose profile beam. We aimed to analyse and compare plan quality and treatment time between flattened beam (FB) and flattening-filter-free (FFF) beam to assess the efficacy of FFF beam for stereotactic body radiation therapy (SBRT). The search strategy was based around 3 concepts; radiation therapy, flattening-filter-free and treatment delivery. The years searched were restricted from 2010 to date of review (October 2015). All plan quality comparisons were between FFF and FB plans from the same data sets. We identified 210 potential studies based on the three searched concepts. All articles were screened by two authors for title and abstract and by three authors for full text. Ten studies met the eligibility criteria. Plan quality was evaluated using conformity index (CI), heterogeneity index (HI) and gradient index (GI). Dose to organs-at-risk (OAR) and healthy tissues were compared. Differences between beam-on-time (BOT) and treatment time (T × T) were also analysed. Normalized percentage ratios of CI and HI demonstrated no clinical differences among the studied articles. GI displayed small variations between the articles favouring FFF beam. The BOT with FFF is substantially reduced, and appears to impact the frequency of intra-fraction imaging which, in turn, affects total treatment time. Based on planning tumour volume (PTV) coverage, dose to OAR and healthy tissue sparing, FFF beam is clinically effective for the treatment of cancer patients using SBRT. We recommend the use of FFF beam for SBRT based on these factors and the reported overall treatment time reduction.


title: Endovascular treatment of fusiform intracranial vertebral artery aneurysms using reconstructive techniques.

text: OBJECTIVE To report our single center experience in the treatment of fusiform aneurysms involving the intracranial vertebral arteries using reconstructive endovascular techniques. PATIENTS AND METHODS The neurointerventional database of our institution was retrospectively reviewed from June 2010 to February 2013. Patients who underwent endovascular treatment of fusiform intracranial vertebral artery aneurysms using reconstructive techniques were included in the analysis. Clinical presentation, size, reconstructive technique used, procedural complication, and clinical and angiographic follow-ups were included in the analysis. RESULTS Nine patients, aged 41-76 years (mean 54.8 years), were included. Mean angiographic diameter of unruptured aneurysms was 8.4 mm (range 4-14) while ruptured aneurysms averaged 6 mm (range 5-7 ). Two patients (two women) presented with acute subarachnoid hemorrhage (SAH). One patient with a large partially thrombosed aneurysm was treated with stent reconstruction requiring deployment of two stents (no coiling). There was one asymptomatic procedural complication (non-flow limiting cervical vertebral dissection). All patients had good clinical outcomes (modified Rankin Scale score of 0 or ≤1) including the two patients that presented with SAH (Hunt and Hess grades 2 and 3). There were no late hemorrhages at a mean clinical follow-up of 12 months (6-24 months). Eight patients had angiographic follow-up (6-18 months, mean 10.5 months) and six demonstrated aneurysm occlusion with complete vessel reconstruction at the angiographic follow-up. CONCLUSIONS The use of reconstructive techniques in the endovascular treatment of unruptured fusiform intracranial vertebral artery aneurysms is feasible, safe, and effective in the mid term. In patients presenting with SAH, however, the safety and effectiveness of these techniques remain unclear.


title: Antiviral treatment using the adenosine nucleoside analogue GS-441524 in cats with clinically diagnosed neurological feline infectious peritonitis.

text: Feline infectious peritonitis (FIP) is caused by a mutant biotype of the feline enteric coronavirus. The resulting FIP virus (FIPV) commonly causes central nervous system (CNS) and ocular pathology in cases of noneffusive disease. Over 95% of cats with FIP will succumb to disease in days to months after diagnosis despite a variety of historically used treatments. Recently developed antiviral drugs have shown promise in treatment of nonneurological FIP, but data from neurological FIP cases are limited. Four cases of naturally occurring FIP with CNS involvement were treated with the antiviral nucleoside analogue GS-441524 (5-10 mg/kg) for at least 12 weeks. Cats were monitored serially with physical, neurologic, and ophthalmic examinations. One cat had serial magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis (including feline coronavirus [FCoV]) titers and FCoV reverse transcriptase [RT]-PCR) and serial ocular imaging using Fourier-domain optical coherence tomography (FD-OCT) and in vivo confocal microscopy (IVCM). All cats had a positive response to treatment. Three cats are alive off treatment (528, 516, and 354 days after treatment initiation) with normal physical and neurologic examinations. One cat was euthanized 216 days after treatment initiation following relapses after primary and secondary treatment. In 1 case, resolution of disease was defined based on normalization of MRI and CSF findings and resolution of cranial and caudal segment disease with ocular imaging. Treatment with GS-441524 shows clinical efficacy and may result in clearance and long-term resolution of neurological FIP. Dosages required for CNS disease may be higher than those used for nonneurological FIP.


title: Identification of herpesvirus proteins that contribute to G1/S arrest.

text: UNLABELLED Lytic infection by herpesviruses induces cell cycle arrest at the G1/S transition. This appears to be a function of multiple herpesvirus proteins, but only a minority of herpesvirus proteins have been examined for cell cycle effects. To gain a more comprehensive understanding of the viral proteins that contribute to G1/S arrest, we screened a library of over 200 proteins from herpes simplex virus type 1, human cytomegalovirus, and Epstein-Barr virus (EBV) for effects on the G1/S interface, using HeLa fluorescent, ubiquitination-based cell cycle indicator (Fucci) cells in which G1/S can be detected colorimetrically. Proteins from each virus were identified that induce accumulation of G1/S cells, predominantly tegument, early, and capsid proteins. The identification of several capsid proteins in this screen suggests that incoming viral capsids may function to modulate cellular processes. The cell cycle effects of selected EBV proteins were further verified and examined for effects on p53 and p21 as regulators of the G1/S transition. Two EBV replication proteins (BORF2 and BMRF1) were found to induce p53 but not p21, while a previously uncharacterized tegument protein (BGLF2) was found to induce p21 protein levels in a p53-independent manner. Proteomic analyses of BGLF2-interacting proteins identified interactions with the NIMA-related protein kinase (NEK9) and GEM-interacting protein (GMIP). Silencing of either NEK9 or GMIP induced p21 without affecting p53 and abrogated the ability of BGLF2 to further induce p21. Collectively, these results suggest multiple viral proteins contribute to G1/S arrest, including BGLF2, which induces p21 levels likely by interfering with the functions of NEK9 and GMIP. IMPORTANCE Most people are infected with multiple herpesviruses, whose proteins alter the infected cells in several ways. During lytic infection, the viral proteins block cell proliferation just before the cellular DNA replicates. We used a novel screening method to identify proteins from three different herpesviruses that contribute to this block. Several of the proteins we identified had previously unknown functions or were structural components of the virion. Subsets of these proteins from Epstein-Barr virus were studied for their effects on the cell cycle regulatory proteins p53 and p21, thereby identifying two proteins that induce p53 and one that induces p21 (BGLF2). We identified interactions of BGLF2 with two human proteins, both of which regulate p21, suggesting that BGLF2 induces p21 by interfering with the functions of these two host proteins. Our study indicates that multiple herpesvirus proteins contribute to the cell proliferation block, including components of the incoming virions.