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.


title: Retrospective evaluation of the effect of carotid artery stenosis on cerebral oxygen saturation during off-pump coronary artery bypasses grafting in adult patients.

text: BACKGROUND It is unknown whether cerebral oxygenation in patients with carotid artery stenosis (CAS) undergoing off-pump coronary artery bypass grafting (CABG) differs from that in patients without CAS. Thus, the effect of the presence of CAS ≥ 50 % on cerebral oxygenation during off-pump CABG in adult patients was evaluated retrospectively. METHODS Eleven patients with CAS ≥ 50% and 14 patients without CAS ≥ 50% were enrolled. Regional cerebral tissue oxygen saturation (rSO2) was quantified using near-infrared spectroscopy. Mean arterial pressure, cardiac index, central venous pressure (CVP), and rSO2 at specific points were collected, and significant changes in each parameter were detected using repeated analysis of variance. Mean rSO2 and minimum rSO2 during anastomosis were analyzed by one-way analysis of variance. Multiple logistic regression analysis was used to estimate the odds ratio (OR) with 95% confidence interval (CI) for cerebral desaturation (a decrease in rSO2 ≥ 10% from preoperative value). RESULTS Two patients with CAS ≥ 50% who received complete carotid artery stenting preoperatively were excluded from the analyses. In both patients with and without CAS, a decrease in rSO2 and cardiac index and an increase in CVP were observed during anastomosis. Mean (SD) maximum decrease in rSO2 from preoperative value was 9.2 (12.7) % on the left side and 8.1 (11.7) % on the right side in patients with CAS ≥ 50%, and 13.5 (11.3) % on the left side and 16.1 (9.8) % on the right side in patients without CAS ≥ 50% (p = 0.316). Neurological complications were not identified in both patients with and without CAS ≥ 50%. In multiple logistic regression analysis, CAS ≥ 50% was not associated with an increased risk of cerebral desaturation (OR 0.160, 95% CI 0.036-0.707, p = 0.016), and rSO2 decreased with decreasing cardiac index < 2.0 l/min/m(2) (OR 3.287, 95 % CI 2.218-5.076, p < 0.001). CONCLUSIONS CAS ≥ 50% was not an independent risk factor of cerebral desaturation during off-pump CABG. Our results suggest that maintaining cardiac output can prevent a decrease in cerebral oxygenation in both patients with and without CAS ≥ 50%.


Telerheumatology in COVID-19 era: a study from a psoriatic arthritis cohort.


title: The role of alpha defensin in prosthetic joint infection (PJI) diagnosis: a literature review.

text: Prosthetic joint infection (PJI) management is not standardized worldwide and the outcome is frequently unsatisfactory.More and more arthroplasties are now being performed. An increasing number of highly virulent and antibiotic-resistant bacteria and an ageing population of patients presenting with many comorbidities make it necessary to focus on this important topic.Diagnosis of PJI remains challenging because the clinical signs and symptoms and elevation of systemic biomarkers (C-reactive protein, erythrocyte sedimentation rate) may be unclear.In the last few years, the clinical research has focused on synovial fluid biomarkers as a possible breakthrough in the complex scenario of PJI diagnosis.Synovial biomarkers have shown encouraging results and they should be used as diagnostic adjuncts to synovial white cell count and culture bacteriology. Synovial leukocyte esterase (LE) and synovial C-reactive protein (CRP) have been evaluated as good screening measures; however, the most promising synovial fluid biomarker in terms of sensitivity and specificity for PJI seems to be alpha defensin (AD).The laboratory-based alpha defensin enzyme-linked immunosorbent assay (ELISA) test demonstrated the highest ever reported accuracy for PJI diagnosis. However, an alpha defensin lateral flow test could have its place in ruling in a suspected PJI intraoperatively because of its high specificity and rapid results. Cite this article: EFORT Open Rev 2019;4:10-13. DOI: 10.1302/2058-5241.4.180029.


title: Equitable Pandemic Preparedness and Rapid Response: Lessons from COVID-19 for Pandemic Health Equity.

text: The novel coronavirus pandemic has set in high relief the entrenched health, social, racial, political, and economic inequities within American society as the incidence of severe morbidity and mortality from the disease caused by the virus appears to be much greater in Black and other racial/ethnic minority populations, within homeless and incarcerated populations, and in lower-income communities in general. The reality is that the U.S. is ill equipped to realize health equity in prevention and control efforts for any type of health outcome, including an infectious disease pandemic. In this article, we address an important question: When new waves of the current pandemic emerge or another novel pandemic emerges, how can the U.S. be better prepared and also ensure a rapid response that reduces rather than exacerbates social and health inequities? We argue for a health equity framework to pandemic preparedness, grounded in meaningful community engagement that, while recognizing the fundamental causes of social and health inequity, has a clear focus on upstream and midstream preparedness and downstream rapid response efforts that put social and health equity at the forefront.


title: Beating the Spread: Developing a Simulation Analog for Contagious Body Fluids.

text: INTRODUCTION Effective models simulating the spread of contagion from provider to other patients, visitors, and rooms in a physically simulated emergency department setting have not been reported, and the effect of personal protective equipment (PPE) on reducing such spread in a simulated emergency department environment has not been quantified. METHODS We developed a physical model for the spread of an Ebola-like virus. The scenario involved 3 computerized mannequins. One case was a febrile patient after Ebola exposure. Four residents (group A) had only masks and gloves and were initially unaware of exposure history, whereas 4 residents (group C) had known exposure history and had full PPE present in the room. Infected mannequins and surrounding surfaces were coated with Glo Germ, a UV tracer. Fluorescence to UV light was recorded after each scenario. Both tracer groups were compared with a control group (group B) in which no tracer was used to account for background fluorescence. RESULTS There was transfer of contagion to providers, other patients, nurse and family member confederates, and other treatment rooms. Half of group C used full PPE, and half used partial PPE. There were 3 contaminations in group C with full PPE use, 15 contaminations in group C with partial PPE, and 65 contaminations in group A. CONCLUSIONS The UV tracer seems to be a useful analog of contaminated bodily fluids because it spread easily and its spread decreased with the use of barrier methods. This model could be used in future studies to measure the effectiveness of different forms of PPE and to study the effectiveness of provider education on appropriately donning and doffing PPE.


title: Prognostic Impact of Preoperative Nutritional Risk in Patients Who Undergo Surgery for Pancreatic Adenocarcinoma.

text: BACKGROUND Nutritional derangements are common hallmarks of pancreatic cancer (PC). Their early detection and management are usually overlooked in routine practice. This study aimed to explore preoperative nutritional status and its prognostic value in patients undergoing surgery for PC. METHODS Data from 73 patients who underwent surgery for PC from November 2015 to January 2018 at the General and Pancreatic Surgery Unit, The Pancreas Institute, University Hospital of Verona Hospital, Verona, Italy, were retrospectively evaluated. The Nutritional Risk Screening (NRS)-2002 was used to evaluate the preoperative nutritional risk. Body composition was assessed using bioimpedance vectorial analysis (BIVA) on the day prior to surgery. The effect of clinical, pathological, and nutritional characteristics on overall survival (OS) was investigated using a Cox and logistic regression model. Kaplan-Meier curves were compared using the log-rank test. RESULTS Most patients (80.8%) were at preoperative risk of malnutrition (NRS-2002 ≥ 3) despite a mean BMI of 24.1 kg/m2(± 4.3). Twenty-four patients (32.9%) received neoadjuvant therapy prior to surgery. Preoperative NRS-2002 was significantly higher in this subset of patients (p = 0.026), with a significant difference by chemotherapy regimens (in favor of FOLFIRINOX, p = 0.035). In a multivariate analysis, the only independent prognostic factor for OS was the NRS-2002 score (HR 5.24, p = 0.013). Particularly, the likelihood of 2-year survival was higher in NRS < 3 (p = 0.009). CONCLUSIONS Our analysis confirms that preoperative malnutrition has a detrimental impact on OS in PC patients undergoing radical surgery for PC. Careful preoperative nutritional evaluation of PC patients should be mandatory, especially in those who are candidates for neoadjuvant therapy.


title: Single-incision laparoscopic splenectomy.

text: BACKGROUND AND OBJECTIVES The single-incision approach in laparoscopic surgery is a relatively new concept. This systematic review of the literature was performed to appraise the existing clinical evidence concerning the use of the single-incision technique for spleen resection. METHODS We performed a systematic search of the PubMed and Scopus databases, and the studies retrieved were included in our review. The references of the included studies were also hand searched. RESULTS Thirty-one relevant studies were found in the field including 81 patients with an age range from 0.6 to 90 years and a body mass index range from 18 to 36.7 kg/m2. Splenomegaly (44.6%), idiopathic thrombocytopenic purpura (31%), and immune thrombocytopenic purpura (6.8%) were the most common indications for the procedure. Concerning the applied port system, multiple single ports (5 to 12 mm) were used in 54.4% of patients, the SILS port (Covidien, Mansfield, Massachusetts) was used in 26.6%, the TriPort (Advanced Surgical Concepts, Wicklow, Ireland) was used in 7.6%, glove ports were used in 6.3%, and the GelPort (Applied Medical, Rancho Santa Margarita, California) was used in 5.1%. The median operative time was 125 minutes (range, 45-420 minutes), and the median quantity of blood loss was 50 mL (range, 10-450 mL). No conversion to open surgery and no transfusion were needed. The length of hospital stay was between 1 and 9 days. Low rates of complications and no patient deaths were found. The existing evidence on cosmesis is limited. CONCLUSION Single-site/single-port laparoscopic surgery is a minimally invasive procedure that seems to be a challenging alternative in the management of spleen resection.


title: Computer tomographic analysis of organ motion caused by respiration and intraoperative pneumoperitoneum in a porcine model for navigated minimally invasive esophagectomy.

text: BACKGROUND Navigation systems have the potential to facilitate intraoperative orientation and recognition of anatomical structures. Intraoperative accuracy of navigation in thoracoabdominal surgery depends on soft tissue deformation. We evaluated esophageal motion caused by respiration and pneumoperitoneum in a porcine model for minimally invasive esophagectomy. METHODS In ten pigs (20-34 kg) under general anesthesia, gastroscopic hemoclips were applied to the cervical (CE), high (T1), middle (T2), and lower thoracic (T3) level, and to the gastroesophageal junction (GEJ) of the esophagus. Furthermore, skin markers were applied. Three-dimensional (3D) and four-dimensional (4D) computed tomography (CT) scans were acquired before and after creation of pneumoperitoneum. Marker positions and lung volumes were analyzed with open source image segmentation software. RESULTS Respiratory motion of the esophagus was higher at T3 (7.0 ± 3.3 mm, mean ± SD) and GEJ (6.9 ± 2.8 mm) than on T2 (4.5 ± 1.8 mm), T1 (3.1 ± 1.8 mm), and CE (1.3 ± 1.1 mm). There was significant motion correlation in between the esophageal levels. T1 motion correlated with all other esophagus levels (r = 0.51, p = 0.003). Esophageal motion correlated with ventilation volume (419 ± 148 ml) on T1 (r = 0.29), T2 (r = 0.44), T3 (r = 0.54), and GEJ (r = 0.58) but not on CE (r = - 0.04). Motion correlation of the esophagus with skin markers was moderate to high for T1, T2, T3, GEJ, but not evident for CE. Pneumoperitoneum led to considerable displacement of the esophagus (8.2 ± 3.4 mm) and had a level-specific influence on respiratory motion. CONCLUSIONS The position and motion of the esophagus was considerably influenced by respiration and creation of pneumoperitoneum. Esophageal motion correlated with respiration and skin motion. Possible compensation mechanisms for soft tissue deformation were successfully identified. The porcine model is similar to humans for respiratory esophageal motion and can thus help to develop navigation systems with compensation for soft tissue deformation.


title: Misplacement of left-sided double-lumen tubes into the right mainstem bronchus: incidence, risk factors and blind repositioning techniques.

text: BACKGROUND Double-lumen endobronchial tubes (DLTs) are commonly advanced into the mainstem bronchus either blindly or by fiberoptic bronchoscopic guidance. However, blind advancement may result in misplacement of left-sided DLTs into the right bronchus. Therefore, incidence, risk factors, and blind repositioning techniques for right bronchial misplacement of left-sided DLTs were investigated. METHODS This was an observational cohort study performed on the data depository consecutively collected from patients who underwent intubation of left-sided DLTs for 2 years. Patients' clinical and anatomical characteristics were analyzed to investigate risk factors for DLT misplacements with logistic regression analysis. Moreover, when DLTs were misplaced into the right bronchus, the bronchial tube was withdrawn into the trachea and blindly readvanced without rotation, or with 90° or 180° counterclockwise rotation while the patient's head was turned right. RESULTS DLTs were inadvertently advanced into the right bronchus in 48 of 1135 (4.2 %) patients. DLT misplacements occurred more frequently in females, in patients of short stature or with narrow trachea and bronchi, and when small-sized DLTs were used. All of these factors were significantly inter-correlated each other (P < 0.001). In 40 of the 48 (83.3 %) patients, blind repositioning was successful. CONCLUSIONS Smaller left-sided DLTs were more frequently misplaced into the right mainstem bronchus than larger DLTs. Moreover, we were usually able to reposition the misplaced DLTs into the left bronchus by using the blind techniques. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01371773.


title: Concomitant medication use and clinical outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder.

text: BACKGROUND Repetitive Transcranial Magnetic Stimulation (rTMS) is commonly administered to Major Depressive Disorder (MDD) patients taking psychotropic medications, yet the effects on treatment outcomes remain unknown. We explored how concomitant medication use relates to clinical response to a standard course of rTMS. METHODS Medications were tabulated for 181 MDD patients who underwent a six-week rTMS treatment course. All patients received 10 Hz rTMS administered to left dorsolateral prefrontal cortex (DLPFC), with 1 Hz administered to right DLPFC in patients with inadequate response to and/or intolerance of left-sided stimulation. Primary outcomes were change in Inventory of Depressive Symptomatology Self Report (IDS-SR30) total score after 2, 4, and 6 weeks. RESULTS Use of benzodiazepines was associated with less improvement at week 2, whereas use of psychostimulants was associated with greater improvement at week 2 and across 6 weeks. These effects were significant controlling for baseline variables including age, overall symptom severity, and severity of anxiety symptoms. Response rates at week 6 were lower in benzodiazepine users versus non-users (16.4% vs. 35.5%, p = 0.008), and higher in psychostimulant users versus non-users (39.2% vs. 22.0%, p = 0.02). CONCLUSIONS Concomitant medication use may impact rTMS treatment outcome. While the differences reported here could be considered clinically significant, results were not corrected for multiple comparisons and findings should be replicated before clinicians incorporate the evidence into clinical practice. Prospective, hypothesis-based treatment studies will aid in determining causal relationships between medication treatments and outcome.


title: Antiviral Cystine Knot α-Amylase Inhibitors from Alstonia scholaris.

text: Cystine knot α-amylase inhibitors are cysteine-rich, proline-rich peptides found in the Amaranthaceae and Apocynaceae plant species. They are characterized by a pseudocyclic backbone with two to four prolines and three disulfides arranged in a knotted motif. Similar to other knottins, cystine knot α-amylase inhibitors are highly resistant to degradation by heat and protease treatments. Thus far, only the α-amylase inhibition activity has been described for members of this family. Here, we show that cystine knot α-amylase inhibitors named alstotides discovered from the Alstonia scholaris plant of the Apocynaceae family display antiviral activity. The alstotides (As1-As4) were characterized by both proteomic and genomic methods. All four alsotides are novel, heat-stable and enzyme-stable and contain 30 residues. NMR determination of As1 and As4 structures reveals their conserved structural fold and the presence of one or more cis-proline bonds, characteristics shared by other cystine knot α-amylase inhibitors. Genomic analysis showed that they contain a three-domain precursor, an arrangement common to other knottins. We also showed that alstotides are antiviral and cell-permeable to inhibit the early phase of infectious bronchitis virus and Dengue infection, in addition to their ability to inhibit α-amylase. Taken together, our results expand membership of cystine knot α-amylase inhibitors in the Apocynaceae family and their bioactivity, functional promiscuity that could be exploited as leads in developing therapeutics.


title: Association of cerebral oxygenation with estimated glomerular filtration rate and cognitive function in chronic kidney disease patients without dialysis therapy.

text: BACKGROUND A decline in estimated glomerular filtration rate (eGFR) is reportedly associated with increased prevalence rates of cognitive impairment. However, data concerning the association between the cerebral saturation of oxygen (rSO2) and cognitive function of patients with chronic kidney disease (CKD) is limited. This study aimed to (i) elucidate the clinical factors associating with cerebral rSO2 and (ii) investigate the association between cerebral rSO2 and cognitive assessment in CKD patients. METHODS A total of 40 CKD patients not requiring dialysis (26 men and 14 women; mean age, 61.0 ± 2.7 years) were recruited. The numbers of patients at each CKD stage were as follows: G1, 5; G2, 8; G3a, 6; G3b, 5; G4, 11; and G5, 5. Cerebral rSO2 was monitored at the forehead using the oxygen saturation monitor INVOS 5100C. The cognitive function of each patient was confirmed using the Mini-Mental State Examination (MMSE). RESULTS Cerebral rSO2 levels were significantly higher in CKD patients than in hemodialysis patients (63.8 ± 1.5% vs. 44.9 ± 2.2%, p < 0.001). Multiple regression analysis showed that cerebral rSO2 was independently associated with eGFR (standardized coefficient: 0.530), serum albumin concentration (standardized coefficient: 0.365), and serum sodium concentration (standardized coefficient: 0.224). Furthermore, MMSE showed a significantly positive correlation with cerebral rSO2 (r = 0.624, p < 0.001). CONCLUSIONS Cerebral rSO2 was affected by eGFR and serum albumin and sodium concentrations in CKD patients. Furthermore, cerebral rSO2 monitoring, which reflected MMSE scores, might be a useful method for assessing cognitive function in CKD patients.


title: Woven Endobridge (WEB) device for endovascular treatment of complex unruptured aneurysms-a single center experience.

text: INTRODUCTION The introduction of the Woven Endobridge (WEB) device increases the feasibility of endovascular treatment of wide-neck bifurcation aneurysms with limitations given by currently available sizes and shapes of the device. Parallel to other studies, we used the new device for selected patients who were no optimal candidates for established techniques like neurosurgical clipping or endovascular coiling. We aimed to report the angiographic and clinical results of WEB implantations or combinations between WEB and coiling or intracranial stents. METHODS We reviewed the records of n = 23 interventions in 22 patients with unruptured wide-neck aneurysms (UIA) who were assigned for aneurysm treatment with the use of the WEB or adjunctive techniques. Interventional procedures and clinical and angiographic outcomes are reported for the periprocedural phase and in mid-term FU. RESULTS Of the included 22 patients, six patients needed additional coiling, intracranial stenting, or implantation of a flow diverter. WEB implantation was technically feasible in 22 out of the 23 interventions. Follow-up angiographic imaging proved total or subtotal occlusion of the aneurysm in 19 of 22 cases. Two minor recurrences remained stable during a period of 15 months. One patient with a partially thrombosed giant MCA aneurysm had a major recurrence and was retreated with a second WEB in combination with coiling. CONCLUSION Despite of unfavorable anatomic conditions, broad-based and large UIA endovascular treatment with the WEB and adjunctive techniques was feasible with a low risk of complications and promising occlusion rates in mid-term follow-up.


title: Age-dependent changes of total and differential white blood cell counts in children.

text: BACKGROUND Total and differential white blood cell counts are important for the diagnostic evaluation of suspected diseases. To facilitate the interpretation of total and differential white blood cell counts in pediatric patients, the present study investigated age-dependent changes in total and differential white blood cell counts in healthy reference children. METHODS Data were obtained from the Pediatric Reference Intervals in China study (PRINCE), which aims to establish and verify pediatric reference intervals for Chinese children based on a nationwide multicenter cross-sectional study from January 2017 to December 2018. Quantile curves were calculated using the generalized additive models for location, shape, and scale method. The 2.5th, 50th, and 97.5th quantile curves were calculated for both total and differential white blood counts. Percent of stacked area charts were used to demonstrate the proportions of differential white blood cells. All statistical analyses were performed using R software. RESULTS Both 50th and 97.5th quantiles of total white blood cell count and monocyte count were highest at birth, then rapidly decreased in the first 6 months of life; relatively slow reduction continued until 2 years of age. The lymphocyte count was low during infancy and increased to its highest level at 6 months of age; it then exhibited moderate and continuous reduction until approximately 9 years of age. The pattern of neutrophil count changed with age in a manner opposite to that of lymphocyte count. Besides, there were two inter-sections of lymphocyte count and neutrophil count during infancy and at approximately 5 years of age, based on locally weighted regression (LOESS) analysis. There were no apparent age-related changes in eosinophil or basophil counts. CONCLUSION These data regarding age-related changes in total and differential white blood cell counts can be used to assess the health of pediatric patients and guide clinical decisions.


title: Simvastatin with or without ezetimibe in familial hypercholesterolemia.

text: BACKGROUND Ezetimibe, a cholesterol-absorption inhibitor, reduces levels of low-density lipoprotein (LDL) cholesterol when added to statin treatment. However, the effect of ezetimibe on the progression of atherosclerosis remains unknown. METHODS We conducted a double-blind, randomized, 24-month trial comparing the effects of daily therapy with 80 mg of simvastatin either with placebo or with 10 mg of ezetimibe in 720 patients with familial hypercholesterolemia. Patients underwent B-mode ultrasonography to assess the intima-media thickness of the walls of the carotid and femoral arteries. The primary outcome measure was the change in the mean carotid-artery intima-media thickness, which was defined as the average of the means of the far-wall intima-media thickness of the right and left common carotid arteries, carotid bulbs, and internal carotid arteries. RESULTS The primary outcome, the mean (+/-SE) change in the carotid-artery intima-media thickness, was 0.0058+/-0.0037 mm in the simvastatin-only group and 0.0111+/-0.0038 mm in the simvastatin-plus-ezetimibe (combined-therapy) group (P=0.29). Secondary outcomes (consisting of other variables regarding the intima-media thickness of the carotid and femoral arteries) did not differ significantly between the two groups. At the end of the study, the mean (+/-SD) LDL cholesterol level was 192.7+/-60.3 mg per deciliter (4.98+/-1.56 mmol per liter) in the simvastatin group and 141.3+/-52.6 mg per deciliter (3.65+/-1.36 mmol per liter) in the combined-therapy group (a between-group difference of 16.5%, P<0.01). The differences between the two groups in reductions in levels of triglycerides and C-reactive protein were 6.6% and 25.7%, respectively, with greater reductions in the combined-therapy group (P<0.01 for both comparisons). Side-effect and safety profiles were similar in the two groups. CONCLUSIONS In patients with familial hypercholesterolemia, combined therapy with ezetimibe and simvastatin did not result in a significant difference in changes in intima-media thickness, as compared with simvastatin alone, despite decreases in levels of LDL cholesterol and C-reactive protein. (ClinicalTrials.gov number, NCT00552097 [ClinicalTrials.gov].).


title: Uterus-sparing vaginolaparoscopic sacrocolpopexy for apical pelvic organ prolapse.

text: INTRODUCTION AND HYPOTHESIS Our aim was to evaluate the safety, feasibility, and effectiveness of a vaginolaparoscopic sacrocolpopexy (VLS) technique for treating apical pelvic organ prolapse (POP). MATERIALS AND METHODS This was a prospective interventional case series (design classification: Canadian Task Force II3) performed in the endoscopic unit of a tertiary care referral facility and university hospital. We assessed 15 symptomatic parous women with stage ≥2 apical POP according to the POP Quantification (POP-Q) classification. Interventions comprised posterior colpotomy with mesh fixation to the uterosacral ligaments and the back of the uterus that was further fixed to the anterior longitudinal ligament of the sacrum using a tacker via laparoscopy. RESULTS The main outcome was a significant postoperative improvement in prolapse and resultant improvement in quality of life (QoL) after VLS. Six patients required concomitant reconstructive procedures. Mean operative time for the vaginal phase was 8.54 ± 3.10 (7-12) min and 32.36 ± 8.2 (27-41) min. for the laparoscopic phase Mean duration of VLS ranged from 30 to 50 min. At the 6-months follow-up, the procedure was successful in 14 of 15 patients (93.34%); one woman (6.66%) presented with recurrence at a lower stage. Neither mesh complications nor sacral ostitis were encountered. There was significant improvement in vaginal symptoms, sexual well-being, QoL, and clinical staging after the procedure. CONCLUSION By eliminating all forms of intraperitoneal suturing, performing a posterior colpotomy, and the advent of tackers without evidence of sacral ostitis, VLS seems to be a simple, feasible, effective, and fast approach for treating POP.


title: Vedolizumab Induces Long-term Mucosal Healing in Patients With Crohn's Disease and Ulcerative Colitis.

text: Introduction Vedolizumab has proven efficacy in inflammatory bowel disease [IBD], but long-term mucosal healing in Crohn's disease [CD], as well as the incidence of colorectal neoplasia in IBD, among patients treated with vedolizumab have not been studied. We aimed to document mucosal healing and to explore the risk of colorectal neoplasia with vedolizumab maintenance therapy. Methods Surveillance colonoscopy was prospectively scheduled for patients with longstanding ulcerative coltis [UC] or CD at a tertiary referral centre, in the open-label extension phase (vedolizumab 300 mg intravenously [IV] every 4 weeks) of the Gemini studies [GEMINI LTS, study number NCT00790933]. Mayo score ≤ 1 or ulcer disappearance [in CD] was defined as mucosal healing. Targeted biopsies were graded for inflammation and dysplasia. Results Of 68 patients [29 CD/39 UC] treated for ≥ 1 year [median 3.2 years, range 1.1-6.1], 58 [24 CD/34 UC] were endoscopically monitored. Durable endoscopic healing corrected by non-responder imputation was found in 7/24, 29% [CD] and 17/34, 50% [UC]. Combined histological and mucosal healing was observed in 5/24 [CD] and 11/34 [UC] of those with endoscopic healing. Low-grade dysplasia was detected in 10% of patients and high-grade dysplasia in the resection specimen of one patient with biopsy-proven low-grade dysplasia. Conclusions Long-term endoscopic and histological healing was observed in a proportion of patients treated with vedolizumab long-term. The dysplasia risk with vedolizumab deserves further study.


title: Identification of respiratory viruses in asymptomatic subjects: asymptomatic respiratory viral infections.

text: The medical literature of the past 4 decades was searched regarding respiratory virus detection by polymerase chain reaction and conventional methods (culture, antigen detection, serology) in asymptomatic subjects in an attempt to determine the prevalence and clinical significance of such viruses in normal persons.


title: Clinical utility of PCR for common viruses in acute respiratory illness.

text: BACKGROUND Acute respiratory illness (ARI) accounts for a large proportion of all visits to pediatric health facilities. Quantitative real-time polymerase chain reaction (qPCR) analyses allow sensitive detection of viral nucleic acids, but it is not clear to what extent specific viruses contribute to disease because many viruses have been detected in asymptomatic children. Better understanding of how to interpret viral findings is important to reduce unnecessary use of antibiotics. OBJECTIVE To compare viral qPCR findings from children with ARI versus asymptomatic control subjects. METHODS Nasopharyngeal aspirates were collected from children aged ≤5 years with ARI and from individually matched, asymptomatic, population-based control subjects during a noninfluenza season. Samples were analyzed by using qPCR for 16 viruses. RESULTS Respiratory viruses were detected in 72.3% of the case patients (n = 151) and 35.4% of the control subjects (n = 74) (P = .001). Rhinovirus was the most common finding in both case patients and control subjects (47.9% and 21.5%, respectively), with a population-attributable proportion of 0.39 (95% confidence interval: 0.01 to 0.62). Metapneumovirus, parainfluenza viruses, and respiratory syncytial virus were highly overrepresented in case patients. Bocavirus was associated with ARI even after adjustment for coinfections with other viruses and was associated with severe disease. Enterovirus and coronavirus were equally common in case patients and control subjects. CONCLUSIONS qPCR detection of respiratory syncytial virus, metapneumovirus, or parainfluenza viruses in children with ARI is likely to be causative of disease; detection of several other respiratory viruses must be interpreted with caution due to high detection rates in asymptomatic children.


title: Pre-operative quantification of pulmonary function using hybrid-SPECT/low-dose-CT: A pilot study.

text: RATIONALE Pre-operative lobar function is estimated by scintigraphy in patients with pulmonary malignancies and compromised function. This study compared the lobar perfusion determined by scintigraphy (PS) with data from SPECT/low-dose-CT (SPECT/ldCT) analyzed manually and semi-automatic. METHODS Retrospective analysis on 39 patients (m/f = 25/14; age: 72.5 [22-89] years) with indication for pulmonary perfusion scintigraphy. Imaging was performed using SPECT/ldCT. Data was analyzed manually and by semi-automatic software. Readers' confidence in 3D-segmentation was scored by two independent readers. Interrater agreement was calculated. In addition, Spearman's rank correlation and Wilcoxon's test were used. RESULTS Results from PS differed significantly from SPECT/ldCT processed manually or semi-automatically in 4/5 lobes (total difference ≤21.6%; rho ≥0.44) and in 3/5 (total difference 21.6%; rho ≥0.37), respectively. Readers' confidence in 3D-segmentation showed a perfect interrater agreement (κ = 0.98). CONCLUSION Quantification of lobar perfusion by SPECT/ldCT differs significantly from planar scintigraphy (e.g., with potential influence on therapy). The semi-automatic software analysis provides an applicable methodology.


title: A Pilot Study of Pulmonary Segmentectomy With Indocyanine Green Near-Infrared Angiography.

text: OBJECTIVES Video-assisted thoracoscopic surgery (VATS) pulmonary segmentectomy is commonly used in treating small ground-glass opacity (GGO) nodules in lung. The identification of the intersegmental plane is one of the challenges. In this pilot study, we aimed to evaluate the feasibility of indocyanine green (ICG) angiography in VATS segmentectomy. METHODS Nineteen GGO patients were enrolled, and VATS segmentectomy with ICG near-infrared angiography were performed between July 2017 and December 2017. Conventional 3-port VATS was used. ICG was injected intravenously after dominant arties were ligated. Intersegmental plane was identified and divided by stapler and electrocautery. RESULTS All patients had perfect intersegmental plane visualization. The mean operation time was 140.8 minutes, and the mean blood loss was 23.7 mL. No complications due to ICG occurred. The mean chest tube duration was 4.6 days. No severe complications occurred in the perioperative period. The mean chest tube drainage duration was 4.6 days. Prolonged postoperative air leak (>5 days), which required no surgical intervention, occurred in 2 cases. There were no severe complications or in-hospital deaths. CONCLUSIONS VATS segmentectomy with ICG near-infrared angiography is a reasonable treatment option to treat small GGO in lung, especially due to its good surgical view maintenance.


title: Targeting CXCR4-dependent immunosuppressive Ly6Clow monocytes improves antiangiogenic therapy in colorectal cancer.

text: Antiangiogenic therapy with antibodies against VEGF (bevacizumab) or VEGFR2 (ramucirumab) has been proven efficacious in colorectal cancer (CRC) patients. However, the improvement in overall survival is modest and only in combination with chemotherapy. Thus, there is an urgent need to identify potential underlying mechanisms of resistance specific to antiangiogenic therapy and develop strategies to overcome them. Here we found that anti-VEGFR2 therapy up-regulates both C-X-C chemokine ligand 12 (CXCL12) and C-X-C chemokine receptor 4 (CXCR4) in orthotopic murine CRC models, including SL4 and CT26. Blockade of CXCR4 signaling significantly enhanced treatment efficacy of anti-VEGFR2 treatment in both CRC models. CXCR4 was predominantly expressed in immunosuppressive innate immune cells, which are recruited to CRCs upon anti-VEGFR2 treatment. Blockade of CXCR4 abrogated the recruitment of these innate immune cells. Importantly, these myeloid cells were mostly Ly6Clow monocytes and not Ly6Chigh monocytes. To selectively deplete individual innate immune cell populations, we targeted key pathways in Ly6Clow monocytes (Cx3cr1-/- mice), Ly6Chigh monocytes (CCR2-/- mice), and neutrophils (anti-Ly6G antibody) in combination with CXCR4 blockade in SL4 CRCs. Depletion of Ly6Clow monocytes or neutrophils improved anti-VEGFR2-induced SL4 tumor growth delay similar to the CXCR4 blockade. In CT26 CRCs, highly resistant to anti-VEGFR2 therapy, CXCR4 blockade enhanced anti-VEGFR2-induced tumor growth delay but specific depletion of Ly6G+ neutrophils did not. The discovery of CXCR4-dependent recruitment of Ly6Clow monocytes in tumors unveiled a heretofore unknown mechanism of resistance to anti-VEGF therapies. Our findings also provide a rapidly translatable strategy to enhance the outcome of anti-VEGF cancer therapies.


title: Contrast-Enhanced Nanofocus X-Ray Computed Tomography Allows Virtual Three-Dimensional Histopathology and Morphometric Analysis of Osteoarthritis in Small Animal Models.

text: OBJECTIVE One of the early hallmarks of osteoarthritis (OA) is a progressive degeneration of the articular cartilage. Early diagnosis of OA-associated cartilage alterations would be beneficial for disease prevention and control, and for the development of disease-modifying treatments. However, early diagnosis is still hampered by a lack of quantifiable readouts in preclinical models. DESIGN In this study, we have shown the potency of contrast-enhanced nanofocus x-ray computed tomography (CE-nanoCT) to be used for virtual 3-dimensional (3D) histopathology in established mouse models for OA, and we compared with standard histopathology. RESULTS We showed the equivalence of CE-nanoCT images to histopathology for the modified Mankin scoring of the cartilage structure and quality. Additionally, a limited set of 3D cartilage characteristics measured by CE-nanoCT image analysis in a user-independent and semiautomatic manner, that is, average and maximum of the noncalcified cartilage thickness distribution and loss in glycosaminoglycans, was shown to be predictive for the cartilage quality and structure as can be evaluated by histopathological scoring through the use of an empirical model. CONCLUSIONS We have shown that CE-nanoCT is a tool that allows virtual histopathology and 3D morphological quantification of multitissue systems, such as the chondro-osseous junction. It provides faster and more quantitative data on cartilage structure and quality compared with standard histopathology while eliminating user bias. CE-nanoCT thus should allow capturing subtle differences in cartilage characteristics, carefully mapping OA progression and, ultimately, asses the beneficial changes when testing a candidate disease-modifying treatment.


title: Early dinner or "dinner like a pauper": Evidence, the habitual time of the largest meal of the day - dinner - is predisposing to severe COVID-19 outcome - death.

text: COVID-19 and metabolic syndrome are devastating pandemics. Effective control of metabolic parameters and their dysfunction may help prevent or minimize the acute and devastating effects of SARS-CoV-2 by reducing the local inflammatory response and blocking the entry of the virus into cells. With such consideration in mind, we gathered data from dietary surveys conducted in nine European countries to explore the relationship between actual clock hour of the large dinner meal and also interval in minutes between it and sunset in the respective countries and death rate above the median rate of per one million people as an index of mortality due to COVID-19 infection. Clock time of the dinner meal varied between 16:00 and 21:00 h across the European counties sampled, and the correlation between dinner mealtime and death rate was strongly correlated, R = 0.7991 (two-tailed p = 0.0098), with R 2 explaining 63% of the variation within the data. This strong linear positive correlation indicates that the later the clock time of the dinner meal, the higher is the death rate (and vice versa). The relationship between meal timing in reference to sunset, utilized as a gross surrogate marker of the activity/rest synchronizer of circadian rhythms, and death rate was negative and even slightly stronger, R = -0.8025 (two-tailed p = 0.0092), with R 2 explaining 64% of the variation within the data. This strong linear negative correlation indicates that the shorter the interval between the dinner meal and sunset, i.e., the closer the time of the largest meal of the day to bedtime, the greater is the death rate (and vice versa). Our preliminary approach to nighttime eating, in terms of the day's largest caloric intake, as a risk factor for the predisposing conditions of obesity, metabolic syndrome, type 2 diabetes, and other commonly associated comorbidities of being overweight, and death from COVID-19 infection reveals strong correlation with the time of the dinner meal, both in terms of its actual clock and circadian time.


Managing chronic pain patients at the time of COVID-19 pandemic.


title: Integration of care for HIV and opioid use disorder: a systematic review of interventions in clinical and community-based settings.

text: OBJECTIVE We sought to identify optimal strategies for integrating HIV- and opioid use disorder-(OUD) screening and treatment in diverse settings. DESIGN Systematic review. METHODS We searched Ovid MEDLINE, PubMed, Embase, and PsycINFO and pre-identified websites. Studies were included if they were published in English on or after 2002 through May 2017, and evaluated interventions that integrated, at an organizational level, screening and/or treatment for HIV and OUD in any care setting in any country. RESULTS Twenty-nine articles met criteria for inclusion, including 23 unique studies: six took place in HIV care settings, 12 in opioid treatment settings, and five elsewhere. Eight involved screening strategies, 22 involved treatment strategies, and seven involved strategies that encompassed screening and treatment. Randomized controlled studies demonstrated low to moderate risk of bias and observational studies demonstrated fair to good quality. Studies in HIV care settings (n = 6) identified HIV- and OUD-related clinical benefits with the use of buprenorphine/naloxone for OUD. No studies in HIV care settings focused on screening for OUD. Studies in opioid treatment settings (n = 12) identified improving HIV screening uptake and clinical benefits with antiretroviral therapy when provided on-site. Counseling intensity for OUD medication adherence or HIV-related risk reduction was not associated with clinical benefits. CONCLUSION Screening for HIV can be effectively delivered in opioid treatment settings, yet there is a need to identify optimal OUD screening strategies in HIV care settings. Strategies integrating the provision of medications for HIV and for OUD should be expanded and should not be contingent on resources available for behavioral interventions. REGISTRATION A protocol for record eligibility was developed a priori and was registered in the PROSPERO database of systematic reviews (registration number CRD42017069314).


docid: mhbedmpx

title: A proposed grading system for endovascular treatment of cerebral arteriovenous malformations: Buffalo score.

text: BACKGROUND The Spetzler-Martin arteriovenous malformation (AVM) grading system has proven to be useful in guiding treatment of cerebral AVMs with craniotomy. It is based on anatomical characteristics each of which makes surgical resection of an AVM more difficult, namely, deep venous drainage, eloquence of surrounding tissue, and large nidus size. A higher score correlates with more complications after treatment. Although this grading system has proven reliable over time, it does not reflect the major determinants of risk associated with endovascular treatment. The authors developed a grading system unique to endovascular treatment of cerebral AVMs. METHODS The proposed grading system accounts for the principal AVM anatomical and physiological features that make endovascular embolization more difficult and, thus, the likelihood of complications greater. These include number of arterial pedicles, diameter of arterial pedicles, and eloquent location of AVM nidus. The proposed grading system was retrospectively applied to 50 patients undergoing endovascular AVM embolization, and its ability to predict complications was compared to the Spetzler-Martin grading system. RESULTS Perioperative complications among the 50 patients included 4 major and 9 minor complications. The proposed grading system was predictive of complication risk, with an increasing rate of perioperative complications associated with an increasing AVM grade. An improved correlation of perioperative complication incidence was noted with the proposed system (P = 0.002), when compared with the Spetzler-Martin grading system (P = 0.33). CONCLUSION This grading system for the endovascular treatment of AVMs is simple, easily reproduced, and clinically valuable.


title: Influence of anatomic landmarks in the virtual environment on simulated angled laparoscope navigation.

text: BACKGROUND The aim of this study is to investigate the influence of the presence of anatomic landmarks on the performance of angled laparoscope navigation on the SimSurgery SEP simulator. METHODS Twenty-eight experienced laparoscopic surgeons (familiar with 30° angled laparoscope, >100 basic laparoscopic procedures, >5 advanced laparoscopic procedures) and 23 novices (no laparoscopy experience) performed the Camera Navigation task in an abstract virtual environment (CN-box) and in a virtual representation of the lower abdomen (CN-abdomen). They also rated the realism and added value of the virtual environments on seven-point scales. RESULTS Within both groups, the CN-box task was accomplished in less time and with shorter tip trajectory than the CN-abdomen task (Wilcoxon test, p < 0.05). No significant differences were found between the performances of the experienced participants and the novices on the CN tasks (Mann-Whitney U test, p > 0.05). In both groups, the CN tasks were perceived as hard work and more challenging than anticipated. CONCLUSIONS Performance of the angled laparoscope navigation task is influenced by the virtual environment surrounding the exercise. The task was performed better in an abstract environment than in a virtual environment with anatomic landmarks. More insight is required into the influence and function of different types of intrinsic and extrinsic feedback on the effectiveness of preclinical simulator training.


title: [Ebola virus disease].

text: The current Ebola outbreak in Western Africa differs from previous ones due to its extent. Serious shortcomings in the on-site management in Africa are obvious. In addition to the situation in the countries affected media and medical interests also focus on detection and management of imported cases in Germany. From the experience with such patients already treated in Germany the existing medical concepts have been updated and expanded. This overview addresses not only the latest clinical knowledge and epidemiological developments but also outlines the key measures as well as the practical procedure when there is a suspected case.


title: Suppression of host gene expression by nsp1 proteins of group 2 bat coronaviruses.

text: nsp1 protein of severe acute respiratory syndrome coronavirus (SARS-CoV), a group 2b CoV, suppresses host gene expression by promoting host mRNA degradation and translation inhibition. The present study analyzed the activities of nsp1 proteins from the group 2 bat CoV strains Rm1, 133, and HKU9-1, belonging to groups 2b, 2c, and 2d, respectively. The host mRNA degradation and translational suppression activities of nsp1 of SARS-CoV and Rm1 nsp1 were similar and stronger than the activities of the nsp1 proteins of 133 and HKU9-1. Rm1 nsp1 expression in trans strongly inhibited the induction of type I interferon (IFN-I) and IFN-stimulated genes in cells infected with an IFN-inducing SARS-CoV mutant, while 133 and HKU9-1 nsp1 proteins had relatively moderate IFN-inhibitory activities. The results of our studies suggested a conserved function among nsp1 proteins of SARS-CoV and group 2 bat CoVs.


title: Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread.

text: The HA of influenza virus is a receptor-binding and fusion protein that is required to initiate infection. The HA receptor-binding domain determines the species of sialyl receptors recognized by influenza viruses. Here, we demonstrate that changes in the HA receptor-binding domain alter the ability of the H5N1 virus to spread systemically in mice. The A/Vietnam/1203/04 (VN1203) and A/Hong Kong/213/03 (HK213) viruses are consistently lethal to domestic chickens but differ in their pathogenicity to mammals. Insertion of the VN1203 HA and neuraminidase (NA) genes into recombinant HK213 virus expanded its tissue tropism and increased its lethality in mice; conversely, insertion of HK213 HA and NA genes into recombinant VN1203 virus decreased its systemic spread and lethality. The VN1203 and HK213 HAs differ by 10 aa, and HK213 HA has shown greater binding affinity for synthetic alpha2,6-linked sialyl receptor. Introduction of an S227N change and removal of N-linked glycosylation at residue 158 increased the alpha2,6-binding affinity of VN1203 HA. Recombinant VN1203 virus carrying the S227N change alone or with the residue-158 glycosylation site removed showed reduced lethality and systemic spread in mice but not in domestic chickens. Wild-type VN1203 virus exhibited the greatest efficiency in systemic spread after intramuscular inoculation and in infection of mouse bone marrow-derived dendritic cells and conventional pulmonary dendritic cells. These results show that VN1203 HA glycoprotein confers pathogenicity by facilitating systemic spread in mice; they also suggest that a minor change in receptor binding domain may modulate the virulence of H5N1 viruses.


Covid-19 infection in kidney transplant recipients: endocrine and metabolic issues.


title: Finding Alternate Resources for Completing Senior Design Projects During the Current COVID-19 Pandemic.

text: At this time many (if not all) colleges and universities are on lockdown, students have returned home, and classes have transitioned to online instruction. Students in capstone design courses around the country have no access to their school's maker spaces and test equipment. Their prototype parts may be stored in a locked maker space, making it difficult to build, test, and deliver prototypes to sponsors or clients at the end of the semester.z.


title: Laparoscopic sacrocolpopexy: demonstration of a nerve-sparing technique.

text: Laparoscopic sacrocolpopexy is a well-established technique to treat apical vaginal prolapse. De novo micturition disorders, pelvic pain, and defecation disorders have been reported and may be due to intraoperative compromise of the superior hypogastric plexus. The video demonstrates our technique for nerve-sparing laparoscopic sacrocolpopexy. The patient is a 62-year-old woman with symptomatic stage III posthysterectomy vaginal vault prolapse. Key steps of the procedure are opening the peritoneum at the level of the promontory, identification of the fibers of the superior hypogastric plexus, deep anterior and posterior dissection with attachment of the mesh to the vagina, displacement of the nerve fibers to the left side during suturing of the mesh to the longitudinal ligament, and complete peritonealization. This technique of the identification and protection of relevant nerve structures appears to be reproducible and can be considered by surgeons who perform laparoscopic sacrocolpopexy.


title: Erratum to "A feasibility study of a complete low-cost consumer-grade brain-computer interface system" [Heliyon 6 (3) (March 2020) e03425].

text: [This corrects the article DOI: 10.1016/j.heliyon.2020.e03425.].


title: Acute dissection of the descending aorta: a case report and review of the literature.

text: Cardiovascular disease is the leading cause of death worldwide. Acute aortic syndromes, which include aortic dissection, intramural hematoma, and penetrating aortic ulcer, represent the most morbid presentations of aortic disease and can be difficult to diagnose. Recent advances in imaging have allowed for more rapid and accurate diagnosis of acute aortic syndromes and the options for management are expanding. This case report and review presents the case of a 43-year-old man with acute type B aortic dissection who underwent two endovascular procedures for malperfusion syndrome. The review focuses on the presentation, diagnosis, medical management, and procedural options for acute dissection of the descending aorta.


docid: qlaaddtu

title: Functional Duration of Closure Systems Used in Partial Nephrectomy.

text: PURPOSE We determined the functional life of various configurations of partial nephrectomy closure systems. MATERIALS AND METHODS Sutures were prepared using standard techniques for sutured renorrhaphy during partial nephrectomy. Tested systems included knot/Hem-o-Lok®, Lapra-Ty®/Hem-o-Lok and Hem-o-Lok/Hem-o-Lok combinations. The saline filled tank was maintained at 37C. Vicryl®, Stratafix™ polyglycolic acid-polycaprolactone or V-Loc™ 180 sutures were suspended at 4 or 2 N. Suture material breakage or slippage was considered failure. RESULTS At 4 N 20% of sutures terminated with knot/Hem-o-Lok failed by 3 weeks compared to 56% and 100% terminated with Lapra-Ty/Hem-o-Lok and Hem-o-Lok/Hem-o-Lok, respectively (p <0.0001). The 55% and 100% of failures with Lapra-Ty/Hem-o-Lok and Hem-o-Lok/Hem-o-Lok, respectively, were generally due to slippage vs 11% with knot/Hem-o-Lok (p <0.0001). Overall failure rates with Lapra-Ty/Hem-o-Lok for zero to 4-zero sutures were 41% with Vicryl, 82% with polyglycolic acid-polycaprolactone and 24% with V-Loc 180 (p <0.0001). The only sutures without failure at 4 N with Lapra-Ty/Hem-o-Lok and knot/Hem-o-Lok closure systems were Vicryl zero, and V-Loc 2-zero and 3-zero. At 2 N Lapra-Ty/Hem-o-Lok failure (17.5% vs 0%, p = 0.039) and Hem-o-Lok/Hem-o-Lok failure (39% vs 16%, p = 0.074) were more common with polyglycolic acid-polycaprolactone than with V-Loc sutures. CONCLUSION Hem-o-Lok/Hem-o-Lok and Lapra-Ty/Hem-o-Lok combinations resulted in more frequent failures at 3 weeks or greater than knot/Hem-o-Lok. For all sutures tested knots were superior to Lapra-Tys to backstop Hem-o-Loks at 4 N. Preferably, Vicryl zero or V-Loc 2-zero/3-zero sutures should be used in combination with knots or Lapra-Tys at 4 N. Under these experimental conditions the Lapra-Ty/Hem-o-Lok combination did not reliably suspend the other sutures tested for 3 weeks. If Lapra-Ty/Hem-o-Lok or Hem-o-Lok/Hem-o-Lok combinations are used, we recommend closure at lesser tension and/or the use of appropriate sutures.


title: Sedation options for the morbidly obese intensive care unit patient: a concise survey and an agenda for development.

text: BACKGROUND We offer some perspectives and commentary on the sedation of obese patients in the intensive care unit (ICU). DISCUSSION Sedation in morbidly obese patients should conform to the same broad principles now current in ICU practice. These include a general presumption against benzodiazepines as first-line agents. Opioids should be avoided in any situation where spontaneous breathing is required. Remifentanil is the preferred agent where continuous stable opioid levels using an infusion are required, because of its lack of context-sensitive accumulation. Volatile anaesthetics may be an option for the same reason but there are no substantial, controlled demonstrations of effectiveness/safety in short-term use in the ICU setting. Propofol is a valuable resource in the morbidly obese patients but the duration of continuous sedation should not exceed 6 days, in order to avoid propofol infusion syndrome. Alpha-2 agonists offer a range of theoretically positive features for the sedation of morbidly obese patients, but at present there is a lack of pharmacokinetic data and a critical mass of high-grade clinical data. Dexmedetomidine has the attraction of not causing respiratory depression or obstructive breathing during sedation and its sympatholytic effects should help deliver stable blood pressure and heart rate. Ketamine has a poor tolerability profile in adults so its use in the ICU context is largely confined to paediatrics. CONCLUSION None of the agents currently available is ideal for every situation encountered in the management of morbidly obese patients. This article identifies additional research needed to place sedation practice of obese patients on a more systematic footing.


title: Incidence of perforated gastrojejunal anastomotic ulcers after laparoscopic gastric bypass for morbid obesity and role of laparoscopy in their management.

text: BACKGROUND Laparoscopic Roux-en-Y gastric bypass (RYGB) is a well-established procedure to treat morbid obesity. Gastrojejunal anastomotic (GJA) ulcers can develop after surgery with subsequent perforation. Our aim was to evaluate the incidence, presentation and outcome of management of perforated GJA ulcer disease after laparoscopic RYGB. METHODS The database of all patients at the senior author's bariatric institutions was retrospectively reviewed. The results are presented as mean (range). RESULTS From April 2002 to April 2010, 1213 patients underwent laparoscopic RYGB, which included 1184 primary and 29 revision procedures. The operative mortality was .15%. Ten patients developed perforated GJA ulcers (.82%) at a mean of 13.5 (6-19) months. The patients who presented to bariatric surgeons (n = 5) were treated with laparoscopic closure and an omental patch, and those who presented to nonbariatric surgeons (n = 5) were treated with laparotomy. The morbidity and mortality rate was 30% and 10%, respectively, and the mean postoperative hospital stay for the survivors was 14 (5-44) days. CONCLUSION Perforated GJA ulcers can develop in 1 of 120 patients after laparoscopic RYGB and can be effectively managed by laparoscopic repair with an omental patch, if expertise is available.


Endotherapy for Barrett's Esophagus.


title: Perseverance in a pandemic: A unique pharmacy residency learning experience.

text: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.


title: Single incision laparoscopic hepatectomy: Advances in laparoscopic liver surgery.

text: BACKGROUND Laparoscopic liver surgery is now an established practice in many institutions. It is a safe and feasible approach in experienced hands. Single incision laparoscopic surgery (SILS) has been performed for cholecystectomies, nephrectomies, splenectomies and obesity surgery. However, the use of SILS in liver surgery has been rarely reported. We report our initial experience in seven patients on single incision laparoscopic hepatectomy (SILH). PATIENTS AND METHODS From October 2010 to September 2012, seven patients underwent single-incision laparoscopic liver surgery. The abdomen was approached through a 25 mm periumbilical incision. No supplemental ports were required. The liver was transected using a combination of LigaSure™ (Covidien-Valleylab. Boulder. USA), Harmonic Scalpel and Ligaclips (Ethicon Endo-Surgery, Inc.). RESULTS Liver resection was successfully completed for the seven patients. The procedures consisted of two partial resections of segment three, two partial resections of segment five and three partial resections of segment six. The mean operative time was 98.3 min (range: 60-150 min) and the mean estimated blood loss was 57 ml (range: 25-150 ml). The postoperative courses were uneventful and the mean hospital stay was 5.1 days (range: 1-13 days). Pathology identified three benign and four malignant liver tumours with clear margins. CONCLUSION SILH is a technically feasible and safe approach for wedge resections of the liver without oncological compromise and with favourable cosmetic results. This surgical technique requires relatively advanced laparoscopic skills. Further studies are needed to determine the potential advantages of this technique, apart from the better cosmetic result, compared to the conventional laparoscopic approach.


title: Endocrinology in the time of COVID-19: Management of neuroendocrine neoplasms (NENs).

text: In viral pandemics, most specifically Covid-19, many patients with neuroendocrine neoplasms (NENs), including phaeochromocytomas, paragangliomas and medullary thyroid carcinoma, may develop Covid-19 in a mild or severe form, or be concerned about the influence of viral infection relative to their anti-tumoral therapy. In general, newly-presenting patients should be assessed, and patients recently receiving chemotherapy, targeted therapy or radionuclide therapy, or showing tumour growth, should be closely followed. For previously diagnosed patients, who have indolent disease, some delay in routine follow-up or treatment may not be problematic. However, patients developing acute secretory syndromes due to functional neuroendocrine neoplasms (such as of the pancreas, intestine or lung), phaeochromocytomas and paragangliomas, will require prompt treatment. Patients with life-threatening Covid-19-related symptoms should be urgently treated and long-term anti-tumoral treatments may be temporarily delayed. In patients with especially aggressive NENs, a careful judgement should be made regarding the severity of any Covid-19 illness, tumour grade, and the immunosuppressant effects of any planned chemotherapy, immunotherapy, targeted therapy or related treatment. In other cases, especially patients with completely resected NENs, or who are under surveillance for a genetic disorder, a telephone or delayed consultation may be in order, balancing the risk of a delay against that of the possible development of Covid-19.


title: Epidemiology, Natural History, and Clinical Presentation of Large Vessel Ischemic Stroke.

text: Large vessel occlusions (LVOs), variably defined as blockages of the proximal intracranial anterior and posterior circulation, account for approximately 24% to 46% of acute ischemic strokes. Commonly refractory to intravenous tissue plasminogen activator (tPA), LVOs place large cerebral territories at ischemic risk and cause high rates of morbidity and mortality without further treatment. Over the past few years, an abundance of high-quality data has demonstrated the efficacy of endovascular thrombectomy for improving clinical outcomes in patients with LVOs, transforming the treatment algorithm for affected patients. In this review, we discuss the epidemiology, pathophysiology, natural history, and clinical presentation of LVOs as a framework for understanding the recent clinical strides of the endovascular era.


title: Training in Neurology: Adoption of resident teleneurology training in the wake of COVID-19: Telemedicine crash course.

text: The current COVID-19 pandemic has changed the way we engage patient care, with a move toward telemedicine-based healthcare encounters. Teleneurology is now being rapidly embraced by neurologists in clinics and hospitals nationwide but for many, this paradigm of care is unfamiliar. Exposure to telemedicine in neurology training programs is scarce despite previous calls to expand teleneurology education. Programs that do provide a teleneurology curriculum have demonstrated increased proficiency, accuracy, and post-training utilization among their trainees. With the current changes in healthcare, broad incorporation of teleneurology education in resident and fellow training after this pandemic dissipates will only serve to improve trainee preparedness for independent practice.The current COVID-19 pandemic is forcing a reckoning of current healthcare delivery and expediting a rapid transition to telemedicine-based care. Even in 2017, the Telemedicine Work Group of the American Academy of Neurology (AAN) recommended a teleneurology curriculum as an elective rotation for trainees1 How long ago 2017 seems now as we all hastily work to create operational teleneurology infrastructure in our clinics and hospitals. Although prior exposure in teleneurology is advantageous in tackling the complexities of moving to telehealth-based care, most of the neurology workforce is not formally trained in telemedicine. While we are far from fully understanding the long-term sequelae of this pandemic on our healthcare systems, broader exposure and increased comfort with teleneurology is imperative to prepare our trainees for the new world of medicine they will face after this current pandemic dissipates.