title: Relevance of Microvascular Flow Assessments in Critically Ill Neonates and Children: A Systematic Review.

text: OBJECTIVES Resolution of impaired microvascular flow may lag the normalization of macrocirculatory variables. The significance of microcirculatory dysfunction in critically ill children and neonates is unknown, but microcirculatory variables can be measured using Doppler or videomicroscopy imaging techniques. We outline the current understanding of the role of the microcirculation in critical illness, review methods for its assessment, and perform a systematic review of how it has been monitored in critically ill neonates and children. DESIGN Systematic review (PROSPERO CRD42019117993). SETTING Not applicable. SUBJECTS Not applicable. INTERVENTIONS None. MEASUREMENTS AND RESULTS We systematically searched MEDLINE, EMBASE, PubMed, and Web of Science. We included studies of critically ill patients 0 to 18 years old investigating microcirculatory blood flow. Two reviewers analyzed abstracts and articles. Results were qualitatively analyzed due to study heterogeneity. A total of 2,559 abstracts met search criteria, of which 94 underwent full-text review. Of those, 36 met inclusion criteria. Seven studies investigated microcirculatory changes in critically ill children. Twenty studies investigated the microcirculatory changes in neonates with variable diagnoses compared with a diverse set of clinical endpoints. Nine studies assessed the effects of age, sex, and birth weight on microvascular flow in neonates. Across all studies, microcirculatory dysfunction was associated with poor outcomes and may not correlate with observed macrovascular function. CONCLUSIONS Assessment of microvascular flow in critically ill children and neonates is possible, although significant challenges remain. In many such patients, microvascular blood flow is disrupted despite medical management targeting normalized macrovascular variables. Future studies are needed to define normal pediatric microvascular flow variables and to assess the impact of patient and treatment factors on its function.


title: Update on non-typeable Haemophilus influenzae-mediated disease and vaccine development.

text: INTRODUCTION Non-typeable Haemophilus influenzae (NTHi) has attracted more interest in recent years due to an increased prevalence of infections caused by the pathogen. This upsurge is at least partly ascribed to the introduction of the pneumococcal conjugated vaccines that has resulted in an aetiological shift in NTHi's favor with respect to upper respiratory tract infections. Moreover, an increased antimicrobial resistance has been associated with the pathogen, a fact that further strengthens the case for novel vaccine development. AREAS COVERED A background to NTHi-mediated diseases and pathogenesis is outlined. The literature in the field of NTHi vaccine antigens and clinical trials is reviewed with focus on data added to scientific databases in the last two years. Various vaccine development strategies are conceptually discussed. EXPERT COMMENTARY Several promising vaccine antigens have been defined in recent years. A multicomponent protein-based vaccine, potentially boosted with extracellular vesicles, would constitute a suitable path going forward. Of note, however, a clinical trial investigating the efficacy of a combined NTHi/Moraxella catarrhalis vaccine to prevent infections in chronic obstructive pulmonary disease (COPD) patients has been initiated. But, as this clinical trial has not yet concluded, and its results are thus unknown, investigations of NTHi pathogenesis must determinedly continue.


title: Pain, well-being, body image and cosmesis: a comparison of single-port and four-port laparoscopic cholecystectomy.

text: BACKGROUND This study aims to compare post-operative pain, well-being, body image and cosmesis in SILS cholecystectomy and four-port laparoscopic cholecystectomy (FPLC). MATERIAL AND METHODS Forty-two consecutive patients (15 SILS, 27 FPLC) undergoing elective cholecystectomy were included in the study. Peri-operative pain, well-being, body image and cosmesis were evaluated using validated assessment tools. RESULTS Significantly lower pain scores were reported one week post-operatively in the SILS group (5.6 vs 8.3; p = 0.035). No significant difference was found in analgesic requirements, physical or mental well-being at any time interval. Significantly higher (favourable) body image questionnaire scores were reported in the SILS group at one week (5.4 v 4.5; p < 0.01), two weeks (5.6 vs 4.8; p < 0.01) and one month (5.7 vs 5.0; p < 0.01) post-operatively. CONCLUSION SILS patients have significantly reduced one-week pain scores and there was no significant difference in well-being between the two groups. Patients who underwent SILS had improved body image and cosmesis. If both techniques are found to be equivalent concerning safety, cost, learning curve and availability, SILS may play a key role in the new era of patient choice.


title: Coil embolization of overwide and undertall small intracranial aneurysms with double microcatheter technique.

text: BACKGROUND Overwide and undertall small intracranial aneurysms remain a challenge for coil embolization. The purpose of this study is to evaluate the feasibility and results of intrasaccular double microcatheter endovascular coil embolization of overwide and undertall small intracranial aneurysms. METHODS Small (<7 mm), overwide (dome-to-neck ratio [DNR] ≤1.2), and undertall (ASPECT ratio ≤1.2) aneurysms which were treated with double microcatheter technique were selected. For the double microcatheter technique, two microcatheters were selected simultaneously into the aneurysm sac and coil insertion was performed alternatingly. The initial results, ASPECT, DNR ratios, complications, and follow-up results were assessed. RESULTS Twenty small (mean, 3.8 mm), overwide (mean DNR, 1.1), and undertall (mean ASPECT, 1.0) aneurysms were treated with the double microcatheter technique. Overall, complete or near complete occlusion was achieved in 19/20 cases. This was achieved with only the double microcatheter technique in 16/20 cases (ASPECT mean, 1.0; DNR mean, 1.1). Adjuvant balloon remodeling was performed in 4/20 cases (ASPECT mean, 0.8; DNR mean, 1.1). The ASPECT ratio was significantly lower in the adjuvant balloon remodeling cases (p = 0.027). Coiling failed in one patient with both DNR and ASPECT ratio <1.0. Overall, one patient developed a focal visual field defect after the procedure. No other patients developed neurologically significant complications. CONCLUSIONS Double microcatheter technique may be a safe and effective method for the treatment of overwide and undertall small intracranial aneurysms.


title: How to reduce parental provision of unhealthy foods to 3- to 8-year-old children in the home environment? A systematic review utilizing the Behaviour Change Wheel framework.

text: BACKGROUND AND OBJECTIVE The effectiveness of obesity prevention interventions to improve children's diet can be enhanced. Deconstructing past interventions can identify components with potential to change behaviour. This systematic review using the Behaviour Change Wheel aimed to examine the behaviour change content of interventions supporting parents of 3- to 8-year olds to reduce provision of unhealthy foods to children. METHODS Ebscohost, Ovid, Scopus and Web of Science were searched. Eligible studies included controlled interventions with active parent involvement, at least one intervention strategy and outcome measure for unhealthy foods ≥3 months from baseline. Seventeen interventions were included describing 18 intervention arms. RESULTS Interventions frequently targeted parents' reflective motivation (n = 17) and psychological capability (n = 15), through education (n = 15) or enablement (n = 15) intervention functions and service provision (n = 18) policy category. Only 24 of the 93 behaviour change techniques were used with an average of five techniques used per intervention. CONCLUSIONS Existing interventions achieving small reductions in unhealthy food intake are homogenous in approach. There is potential to utilize untapped behaviour change techniques, through comprehensive intervention design and behavioural analysis guided by the Behaviour Change Wheel. Interventions targeting opportunity through persuasion, modelling or environmental restructuring, and using different policy categories are urgently needed to provide an evidence base to inform policy and practice.


title: SARS-CoV-2 and HIV coinfection: clinical experience from Rhode Island, United States.

text: INTRODUCTION Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected >6 million people worldwide since December 2019. Global reports of HIV/SARS-CoV-2 coinfection are limited. To better understand the impact of the coronavirus disease 2019 (COVID-19) pandemic on persons with HIV and improve their care, we present an outpatient and inpatient clinical experience of HIV/SARS-CoV-2 coinfection from Rhode Island, US. METHODS We describe outpatient and inpatient preparedness for the COVID-19 pandemic, and present a case series of all known patients with HIV/SARS-CoV-2 coinfection at The Miriam Hospital and Rhode Island Hospital, and The Miriam Hospital Infectious Diseases and Immunology Center, in Providence, Rhode Island, US. RESULTS AND DISCUSSION The Infectious Diseases and Immunology Center rapidly prepared for outpatient and inpatient care of persons with HIV and SARS-CoV-2. Between 30 March and 20 May 2020, 27 patients with HIV were diagnosed with SARS-CoV-2. Twenty were male, six female and one transgender female; average age was 49 years; 13/27 were Hispanic and 6/27 were African American. All had HIV viral load <200 copies/mL and were on antiretroviral therapy with CD4 count range 87 to 1441 cells/µL. Twenty-six of the 27 had common COVID-19 symptoms for one to twenty-eight days and most had other co-morbidities and/or risk factors. Nine of the 27 were hospitalized for one to thirteen days; of those, three lived in a nursing home, six received remdesivir through a clinical trial or emergency use authorization and tolerated it well; eight recovered and one died. Overall, 17% of known Center people had HIV/SARS-CoV-2 coinfection, whereas the comparable state-wide prevalence was 9%. CONCLUSIONS We highlight challenges of outpatient and inpatient HIV care in the setting of the COVID-19 pandemic and present the largest detailed case series to date from the United States on HIV/SARS-CoV-2 coinfection, adding to limited global reports. The aggregated clinical findings suggest that the clinical presentation and outcomes of COVID-19 appear consistent with those without HIV. Whether SARS-CoV-2 infection is more frequent among persons with HIV remains to be determined. More data are needed as we develop our understanding of how HIV and antiretroviral therapy are affected by or have an impact on this pandemic.


title: Differential impact of isolated psychotic symptoms on treatment outcome of major depressive disorder in the STAR*D cohort of Whites, Blacks and Latinos.

text: OBJECTIVE To determine whether isolated psychotic symptoms are more likely to be endorsed by depressed Latinos as opposed to other ethnic-racial groups; whether these symptoms affect Latinos similarly to other ethnic-racial groups in terms of treatment response; and whether they are more likely to be associated with anxiety disorders in depressed Latinos. METHODS We analyzed data from STAR*D subjects who self identified as White, Black, or Latino. Rates of isolated psychotic symptoms were assessed by the self-rated Psychiatric Diagnostic Screening Questionnaire (PDSQ) and compared between ethnic-racial groups. Depressive remission outcomes were compared within each ethnic-racial group between subjects who endorsed psychotic symptoms versus no psychotic symptoms. Associations between isolated psychotic symptoms and anxiety disorders were also examined. RESULTS Among 2597 eligible subjects with at least one post-baseline assessment and available PDSQ data excluding first-rank symptoms, the prevalence of auditory-visual hallucination was 2.5% in Whites (n=49/1928), 11.3% in Blacks (n=45/398) 6.3% in Latinos (n=17/270) (χ(2)=64.9; df=2; p<0.001). Prevalence of paranoid ideation was 15.5% in Whites (n=299/1927), 31.5% in Blacks (n=126/400), and 21.1% in Latinos (n=57/270) (χ(2)=57.3; df=2; p<0.001). Among Whites and Blacks but not Latinos, depressive remission rates were worse in subjects with auditory-visual hallucinations compared to those without them. Paranoid ideation had a significant negative impact on remission in Whites only. In all ethnic-racial groups, a significant association was found between auditory-visual hallucinations and PTSD and panic disorder. LIMITATIONS The STAR*D study did not include any structured clinician-based assessment of psychotic symptoms. CONCLUSION Latinos do not appear to have worse outcomes when treated for MDD with auditory-visual hallucinations, differently from Whites and Blacks.


title: Robotic Roux-en-Y duodenojejunostomy for superior mesenteric artery syndrome: operative technique.

text: BACKGROUND Superior mesenteric artery (SMA) syndrome, also known as Wilkie's syndrome, is a rare condition characterized by vascular compression of the duodenum that leads to intestinal obstruction. While there have been a few recent case reports of laparoscopic duodenojejunostomy performed as an option for surgical treatment, the role of the da Vinci(®) robot in superior mesenteric syndrome has been underestimated. The authors report a robotic Roux-en-Y duodenojejunostomy for the treatment of SMA syndrome. MATERIALS AND METHODS A 39-year-old man with a history of Amyotrophic lateral sclerosis presented with an upper gastrointestinal obstruction with distended abdomen. A computed tomography scan showed a transition in the third portion of the duodenum where the SMA vessels crossed over, with a decompressed jejunum. He was identified as a candidate for a duodenojejunostomy. The da Vinci Surgical System was used to mobilize the colon and duodenum, and a Roux-en-Y duodenojejunostomy was performed with hand-sewn anastomosis. RESULTS There were no intraoperative complications. The blood loss was minimal and operative time was 120 minutes. The postoperative course was uneventful with resolution of intestinal obstruction. CONCLUSION Robotic Roux-en-Y duodenojejunostomy as a surgical option for treatment of SMA syndrome is safe, feasible, and a valid alternative to open surgery with the added benefits of a minimally invasive approach.


title: The neutralizing human recombinant antibodies to pathogenic Orthopoxviruses derived from a phage display immune library.

text: A panel of recombinant human antibodies to orthopoxviruses was isolated from a combinatorial phage display library of human scFv antibodies constructed from the Vh and Vl genes cloned from the peripheral blood lymphocytes of Vaccinia virus (VACV) immune donors. Plaque-reduction neutralization tests showed that seven selected phage-displaying scFv antibodies (pdAbs) neutralized both CPXV and VACV, and five of them neutralized Monkeypox virus (MPXV). Western blot analysis of VACV and CPXV proteins demonstrated that seven neutralizing antibodies recognized a 35 kDa protein. To identify this target protein, we produced a recombinant J3L protein of CPXV and showed that all the selected neutralizing antibodies recognized this protein. Neutralizing pdAb b9 was converted into fully human mAb b9 (fh b9), and scFv b9 displayed high binding affinities (K(d) of 0.7 and 3.2 nM). The fh b9 reduced VACV plaque formation in a dose-dependent manner.


title: Immunogenicity and protection efficacy of monomeric and trimeric recombinant SARS coronavirus spike protein subunit vaccine candidates.

text: Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease, and an effective vaccine is not available. In this study, we compared the immunogenicity and protection efficacy of recombinant proteins corresponding to different domains of the SARS-coronavirus spike protein. Trimeric recombinant proteins were created by fusing the foldon domain derived from T4 bacteriophage to the carboxy-termini of individual domains of the spike protein. While the full-length ectodomain (S) of the spike protein, the full-length ectodomain fused to foldon (S-foldon), the S1 domain (S1), S1-foldon, and the S2 domain(S2) antigens all elicited comparable antibody titers as measured by ELISA, S-foldon induced a significantly higher titer of neutralizing antibody and S2 protein did not elicit virus neutralizing antibodies. When tested in a mouse virus replication model, all the mice vaccinated with the S1, S1-foldon, S, or S-foldon were completely protected.


title: Continuous monitoring of changes in plasma nitrite following cerebral ischemia in a rabbit embolic stroke model.

text: In this proof-of-concept study, we investigated direct, continuous monitoring of plasma nitrite as an indicator of cerebral ischemia following clot embolization of rabbits via an indwelling carotid catheter. Two groups of rabbits were studied to compare the effects of embolization on nitrite levels. In the control group, blood was continuously obtained from a jugular venous catheter. The blood was immediately passed through an ultrafiltration filter; the filtrate was chemically reduced to convert free nitrite to nitric oxide (NO) and then measured using a NO-specific electrode. In the embolized group, after a baseline nitrite level was achieved, blood clots were injected into the brain via the carotid artery catheter, and then nitrite levels were continuously measured from jugular venous blood. The stroke group showed a significantly greater increase in nitrite as compared to controls (p=0.017). Using the area-under-the-curve (AUC) method, results reached statistical significance (p<0.05) within 3 min of embolization. In embolized rabbits, NO(2) levels increased 424±256% compared to baseline. This study shows that nitrite can be measured immediately following a stroke and that our system measures nitrite independent of the extent of the stroke. This study provides evidence for the feasibility of using nitrite as a marker of ischemic stroke.


title: A Newly Isolated Bacillus subtilis Strain Named WS-1 Inhibited Diarrhea and Death Caused by Pathogenic Escherichia coli in Newborn Piglets.

text: Bacillus subtilis is recognized as a safe and reliable human and animal probiotic and is associated with bioactivities such as production of vitamin and immune stimulation. Additionally, it has great potential to be used as an alternative to antimicrobial drugs, which is significant in the context of antibiotic abuse in food animal production. In this study, we isolated one strain of B. subtilis, named WS-1, from apparently healthy pigs growing with sick cohorts on one Escherichia coli endemic commercial pig farm in Guangdong, China. WS-1 can strongly inhibit the growth of pathogenic E. coli in vitro. The B. subtilis strain WS-1 showed typical Bacillus characteristics by endospore staining, biochemical test, enzyme activity analysis, and 16S rRNA sequence analysis. Genomic analysis showed that the B. subtilis strain WS-1 shares 100% genomic synteny with B. subtilis with a size of 4,088,167 bp. Importantly, inoculation of newborn piglets with 1.5 × 1010 CFU of B. subtilis strain WS-1 by oral feeding was able to clearly inhibit diarrhea (p < 0.05) and death (p < 0.05) caused by pathogenic E. coli in piglets. Furthermore, histopathological results showed that the WS-1 strain could protect small intestine from lesions caused by E. coli infection. Collectively, these findings suggest that the probiotic B. subtilis strain WS-1 acts as a potential biocontrol agent protecting pigs from pathogenic E. coli infection. Importance: In this work, one B. subtilis strain (WS-1) was successfully isolated from apparently healthy pigs growing with sick cohorts on one E. coli endemic commercial pig farm in Guangdong, China. The B. subtilis strain WS-1 was identified to inhibit the growth of pathogenic E. coli both in vitro and in vivo, indicating its potential application in protecting newborn piglets from diarrhea caused by E. coli infections. The isolation and characterization will help better understand this bacterium, and the strain WS-1 can be further explored as an alternative to antimicrobial drugs to protect human and animal health.


title: Emergence of a novel drug resistant H7N9 influenza virus: evidence based clinical potential of a natural IFN-α for infection control and treatment.

text: The novel avian H7N9 influenza virus has caused more than 130 human infections with 43 deaths (as of September, 2013) in China. Because of the lack of existing immunity against H7 subtype influenza viruses in the human population and the absence of a licensed commercial vaccine, antiviral drugs are critical tools for the treatment of infection with this novel H7N9. Both M2-ion channel blockers and neuraminidase inhibitors are used as antiviral drugs for influenza infections of humans. The emerging H7N9 viruses are resistant to the M2-ion channel blockers because of a S31N mutation in the M2 protein; additionally, some H7N9 isolates have gained neuraminidase R292K substitution resulting in broad resistance to neuraminidase inhibitors. In this study we report that Alferon N can inhibit wild type and 292K H7N9 viruses replication in vitro. Since Alferon N is approved for clinical use, this would allow a rapid regulatory approval process for this drug under pandemic threat.


Emlékezés Robicsek Ferenc professzorra.


docid: fxoythew

title: Endovascular treatment of wide-necked intracranial aneurysms using the novel Contour Neurovascular System: a single-center safety and feasibility study.

text: BACKGROUND AND PURPOSE Wide-necked bifurcation aneurysms pose a significant challenge to the treating clinician. The Contour Neurovascular System embolization device is a novel tool for the treatment of such intracranial aneurysms. We report on our experience with this device. METHODS Prospective clinical and radiological data were collected for all patients treated with the Contour device at our center. All our patients were treated on an elective basis. RESULTS We have treated 11 patients successfully with the Contour device to date. All patients were women with a mean (SD) age of 65.0 (6.4) years. In total, four basilar tip, two internal carotid artery, three middle cerebral artery, one anterior communicating artery, and one superior cerebellar artery aneurysms were treated. At 1-year follow-up, complete occlusion (Raymond Class 1) was seen in 55.56% (5/9) of cases, with 44.44% (4/9) having small neck remnants (Raymond Class 2). One patient declined 1-year catheter angiography and another had no further follow-up due to an unrelated medical condition. For six patients, 2-year radiological follow-up is available and shows stability. At 6 weeks, nine of the 11 patients had a modifed Rankin Scale score of 0, with two patients scoring 1 for headaches. Two patients had thromboembolic events, but there were no complications leading to permanent neurological disability or death. We additionally had three patients where the Contour device was attempted but was unable to be successfully used. CONCLUSION Initial results are promising although larger case numbers and longer follow-up are necessary to draw further conclusions on the utility and risk profile of this new device.


title: Simulation of late inspiratory rise in airway pressure during pressure support ventilation.

text: BACKGROUND Late inspiratory rise in airway pressure (LIRAP, Paw/ΔT) caused by inspiratory muscle relaxation or expiratory muscle contraction is frequently seen during pressure support ventilation (PSV), although the modulating factors are unknown. METHODS We investigated the effects of respiratory mechanics (normal, obstructive, restrictive, or mixed), inspiratory effort (-2, -8, or -15 cm H2O), flow cycle criteria (5-40% peak inspiratory flow), and duration of inspiratory muscle relaxation (0.18-0.3 s) on LIRAP during PSV using a lung simulator and 4 types of ventilators. RESULTS LIRAP occurred with all lung models when inspiratory effort was medium to high and duration of inspiratory muscle relaxation was short. The normal lung model was associated with the fastest LIRAP, whereas the obstructive lung model was associated with the slowest. Unless lung mechanics were normal or mixed, LIRAP was unlikely to occur when inspiratory effort was low. Different ventilators were also associated with differences in LIRAP speed. Except for within the restrictive lung model, changes in flow cycle level did not abolish LIRAP if inspiratory effort was medium to high. Increased duration of inspiratory relaxation also led to the elimination of LIRAP. Simulation of expiratory muscle contraction revealed that LIRAP occurred only when expiratory muscle contraction occurred sometime after the beginning of inspiration. CONCLUSIONS Our simulation study reveals that both respiratory resistance and compliance may affect LIRAP. Except for under restrictive lung conditions, LIRAP is unlikely to be abolished by simply lowering flow cycle criteria when inspiratory effort is strong and relaxation time is rapid. LIRAP may be caused by expiratory muscle contraction when it occurs during inspiration.


COVID-19 Global Pandemic: Options for Management of Gynecologic Cancers.


title: Initial experience with the new double-lumen scepter balloon catheter for treatment of wide-necked aneurysms.

text: OBJECTIVE A new double-lumen balloon catheter was being developed for the treatment of cerebral aneurysms. The purpose of this study is to report our initial experience of a double-lumen balloon catheter for the treatment of wide-necked aneurysms. MATERIALS AND METHODS Seventeen patients (mean age, 63 years; range, 45-80 years) with wide-necked, with or without a branch-incorporated aneurysms, (10 ruptured and 9 unruptured) were treated with balloon-assisted coil embolization using a double-lumen balloon catheter (Scepter C™ or Scepter XC™) for 7 months after being introduced to our country. Locations of the aneurysms were posterior communicating artery (n = 7), anterior communicating artery or A2 (n = 7), middle cerebral artery (MCA) bifurcation (n = 3), basilar artery tip (n = 1) and anterior choroidal artery (n = 1). The initial clinical and angiographic outcomes were retrospectively evaluated. RESULTS Coil embolization was successfully completed in all 19 aneurysms, resulting in complete occlusions (n = 18) or residual neck (n = 1). In one procedure, a thrombus formation was detected at the neck portion of the ruptured MCA bifurcation aneurysm near to the end of the procedure. It was completely resolved with an intra-arterial infusion of Glycoprotein IIb/IIIa inhibitor (Tirofiban, 1.0 mg) without any clinical sequela. There were no treatment-related events in the remaining 18 aneurysms. At discharge, functional neurological state improved in 11 patients (10 patients with ruptured aneurysm and 1 with unruptured aneurysm presenting with mass symptoms) and 6 patients with unruptured aneurysms had no newly developed symptoms. CONCLUSION In this preliminary case series, the newly developed double-lumen Scepter balloon appears to be a safe and convenient device for coil embolization of wide-necked aneurysms.


title: Mutagenesis of Coronavirus nsp14 Reveals Its Potential Role in Modulation of the Innate Immune Response.

text: UNLABELLED Coronavirus (CoV) nonstructural protein 14 (nsp14) is a 60-kDa protein encoded by the replicase gene that is part of the replication-transcription complex. It is a bifunctional enzyme bearing 3'-to-5' exoribonuclease (ExoN) and guanine-N7-methyltransferase (N7-MTase) activities. ExoN hydrolyzes single-stranded RNAs and double-stranded RNAs (dsRNAs) and is part of a proofreading system responsible for the high fidelity of CoV replication. nsp14 N7-MTase activity is required for viral mRNA cap synthesis and prevents the recognition of viral mRNAs as "non-self" by the host cell. In this work, a set of point mutants affecting different motifs within the ExoN domain of nsp14 was generated, using transmissible gastroenteritis virus as a model of Alphacoronavirus Mutants lacking ExoN activity were nonviable despite being competent in both viral RNA and protein synthesis. A specific mutation within zinc finger 1 (ZF-C) led to production of a viable virus with growth and viral RNA synthesis kinetics similar to that of the parental virus. Mutant recombinant transmissible gastroenteritis virus (TGEV) ZF-C (rTGEV-ZF-C) caused decreased cytopathic effect and apoptosis compared with the wild-type virus and reduced levels of dsRNA accumulation at late times postinfection. Consequently, the mutant triggered a reduced antiviral response, which was confirmed by evaluating different stages of the dsRNA-induced antiviral pathway. The expression of beta interferon (IFN-β), tumor necrosis factor (TNF), and interferon-stimulated genes in cells infected with mutant rTGEV-ZF-C was reduced compared to the levels seen with the parental virus. Overall, our data revealed a potential role for CoV nsp14 in modulation of the innate immune response. IMPORTANCE The innate immune response is the first line of antiviral defense that culminates in the synthesis of interferon and proinflammatory cytokines to control viral replication. CoVs have evolved several mechanisms to counteract the innate immune response at different levels, but the role of CoV-encoded ribonucleases in preventing activation of the dsRNA-induced antiviral response has not been described to date. The introduction of a mutation in zinc finger 1 of the ExoN domain of nsp14 led to production of a virus that induced a weak antiviral response, most likely due to the accumulation of lower levels of dsRNA in the late phases of infection. These observations allowed us to propose a novel role for CoV nsp14 ExoN activity in counteracting the antiviral response, which could serve as a novel target for the design of antiviral strategies.


title: Comprehensive radiolabeling, stability, and tissue distribution studies of technetium-99m single amino acid chelates (SAAC).

text: Technetium tricarbonyl chemistry has been a subject of interest in radiopharmaceutical development over the past decade. Despite the extensive work done on developing chelates for Tc(I), a rigorous investigation of the impact of changing donor groups and labeling conditions on radiochemical yields and/or distribution has been lacking. This information is crucially important if these platforms are going to be used to develop molecular imaging probes. Previous studies on the coordination chemistry of the {M(CO)(3)}(+) core have established alkylamine, aromatic nitrogen heterocycles, and carboxylate donors as effective chelating ligands. These observations led to the design of tridentate ligands derived from the amino acid lysine. Such amino acid analogues provide a tridentate donor set for chelation to the metal and an amino acid functionality for conjugation to biomolecules. We recently developed a family of single amino acid chelates (SAAC) that serve this function and can be readily incorporated into peptides via solid-phase synthesis techniques. As part of these continuing studies, we report here on the radiolabeling with technetium-99m ((99m)Tc) and stability of a series of SAAC analogues of lysine. The complexes studied include cationic, neutral, and anionic complexes. The results of tissue distribution studies with these novel complexes in normal rats demonstrate a range of distribution in kidney, liver, and intestines.


title: Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline.

text: 1 ESGE/EASL recommend that, as the primary diagnostic modality for PSC, magnetic resonance cholangiography (MRC) should be preferred over endoscopic retrograde cholangiopancreatography (ERCP).Moderate quality evidence, strong recommendation. 2 ESGE/EASL suggest that ERCP can be considered if MRC plus liver biopsy is equivocal or contraindicated in patients with persisting clinical suspicion of PSC. The risks of ERCP have to be weighed against the potential benefit with regard to surveillance and treatment recommendations.Low quality evidence, weak recommendation. 6 ESGE/EASL suggest that, in patients with an established diagnosis of PSC, MRC should be considered before therapeutic ERCP.Weak recommendation, low quality evidence. 7 ESGE/EASL suggest performing endoscopic treatment with concomitant ductal sampling (brush cytology, endobiliary biopsies) of suspected significant strictures identified at MRC in PSC patients who present with symptoms likely to improve following endoscopic treatment.Strong recommendation, low quality evidence. 9 ESGE/EASL recommend weighing the anticipated benefits of biliary papillotomy/sphincterotomy against its risks on a case-by-case basis.Strong recommendation, moderate quality evidence.Biliary papillotomy/sphincterotomy should be considered especially after difficult cannulation.Strong recommendation, low quality evidence. 16 ESGE/EASL suggest routine administration of prophylactic antibiotics before ERCP in patients with PSC.Strong recommendation, low quality evidence. 17 EASL/ESGE recommend that cholangiocarcinoma (CCA) should be suspected in any patient with worsening cholestasis, weight loss, raised serum CA19-9, and/or new or progressive dominant stricture, particularly with an associated enhancing mass lesion.Strong recommendation, moderate quality evidence. 19 ESGE/EASL recommend ductal sampling (brush cytology, endobiliary biopsies) as part of the initial investigation for the diagnosis and staging of suspected CCA in patients with PSC.Strong recommendation, high quality evidence.


Clarifying the role of lung ultrasonography in COVID-19 respiratory disease.


title: Factors which influence concordance among measurements obtained by different pulse oximeters currently used in some clinical situations.

text: AIMS AND OBJECTIVES To evaluate both concordance among those measurements obtained by three different pulse oximeters currently used by nursing professionals in hospital units and the factors which can influence this concordance. BACKGROUND Many models of wireless pulse oximeters in the present market do not offer possibility of calibration and, therefore, they do not ensure patients' safety in daily clinical practice. DESIGN This is a descriptive and cross-sectional study. The sample of patients (140) was selected from such hospital units, and all of them had to fulfil inclusion and exclusion criteria for participation. METHODS The instruments used to carry out this research were a monitor (calibrated), two models of portable wireless pulse oximeters (used for 3 years by the nursing staff, without being calibrated), a tympanic thermometer and a weather meter. The concordance correlation coefficient (CCC) was used to establish the concordance, whereas the Landis-Koch criteria were used to interpret the results. RESULTS The concordance among the three devices was considered as "good" (CCC: 0.925 and 0.974 (95%)). The CCC (0.925) for saturation measures was regarded as "very good"/"almost perfect," and the pulse measure was considered as "very good" CCC 0.974, providing in both cases a high level of concordance (CCC > 0.91). CONCLUSIONS The overall concordance as regards pulse and oxygen saturation among the three pulse oximeters analysed is considered as "very good" according to the Landis-Koch criteria. RELEVANCE TO CLINICAL PRACTICE There exists a "very good" concordance among two wireless oximeters which have been used by the health staff for 3 years and which did not offer any possibility of calibration and one monitor which belongs to the healthcare institution. This aspect is of crucial importance in daily clinical practice, and it is also relevant to ensure patient's safety.


title: Gaps in the evidence for treatment decisions in cystic fibrosis: a systematic review.

text: INTRODUCTION Cystic fibrosis (CF) is a multisystem disorder. Treatment is complex and evidence for treatment decisions may be absent. Characterising gaps in the research evidence will highlight treatment uncertainties and help prioritise research questions. We systematically identified the evidence gaps for treatment decisions in CF. METHODS We searched for systematic reviews and guidelines on treatment interventions in CF. Two researchers identified eligible reviews with arbitration from a third. Using a structured framework, we extracted and characterised evidence gaps. RESULTS There were 73 reviews and 21 guidelines that met our inclusion criteria. From these, we identified 148 evidence gaps across a range of treatment areas. We found 111 evidence gaps through systematic reviews and a further 37 from guidelines. The reason for an evidence gap could only be reliably characterised for systematic reviews. In most cases, there was more than one explanation-most commonly few or no trials (97/111 evidence gaps). Other important factors leading to evidence gaps were small sample size (49/111), inadequate duration of follow-up (38/111) or intervention (37/111) and factors relating to outcomes (35/111). Evidence gaps from both systematic reviews and guidelines fell into the following categories: Respiratory (91); Gastrointestinal (20); PhysiotherapyandExercise (16); Musculoskeletal (6); Endocrine (4); Basic defect of CF (8); Psychosocial (2); Ears, Nose and Throat (1). CONCLUSIONS We have compiled an up-to-date list of treatment uncertainties in CF and the reasons for these uncertainties. These can be used as a resource to aid researchers and funders when planning future trials. PROSPERO REGISTRATION NUMBER Pre-results; CRD42015030111.


title: Information Overload: A Method to Share Updates among Frontline Staff during the COVID-19 Pandemic.

text: Since COVID-19 was classified as a pandemic, the stream of important information from multiple sources is constant and always changing. As the pandemic evolves, the need to report relevant information to frontline providers remains crucial. A 1-page centralized document termed a "quicksheet" was developed to include guidelines, policies, and practical information and to serve as a reference tool for our clinicians. It was updated and distributed frequently, up to once daily. It was initially embraced as an important resource for resident physicians and then quickly adopted by the entire department as a necessary reference and communication tool during the ongoing crisis. The quicksheet has been a beneficial tool to distill and organize the most important and relevant information for frontline staff, and we hope that it can serve as a template for departments and health care workers in other hospital systems to adopt.


Interference with BISTM values from a forced-air warming device.


title: Persistent vegetative state and minimally conscious state: a systematic review and meta-analysis of diagnostic procedures.

text: BACKGROUND Acute brain damage can cause major disturbances of consciousness, ranging all the way to the persistent vegetative state (PVS), which is also known as "unresponsive wakefulness syndrome". PVS can be hard to distinguish from a state of minimal preserved consciousness ("minimally conscious state," MCS); the rate of misdiagnosis is high and has been estimated at 37-43%. In contrast, PVS is easily distinguished from brain death. We discuss the various diagnostic techniques that can be used to determine whether a patient is minimally conscious or in a persistent vegetative state. METHODS This article is based on a systematic review of pertinent literature and on a quantitative meta-analysis of the sensitivity and specificity of new diagnostic methods for the minimally conscious state. RESULTS We identified and evaluated 20 clinical studies involving a total of 906 patients with either PVS or MCS. The reported sensitivities and specificities of the various techniques used to diagnose MCS vary widely. The sensitivity and specificity of functional MRI-based techniques are 44% and 67%, respectively (with corresponding 95% confidence intervals of 19%-72% and 55%-77%); those of quantitative EEG are 90% and 80%, respectively (95% CI, 69%-97% and 66%-90%). EEG, event-related potentials, and imaging studies can also aid in prognostication. Contrary to prior assumptions, 10% to 24% of patients in PVS can regain consciousness, sometimes years after the event, but only with marked functional impairment. CONCLUSION The basic diagnostic evaluation for differentiating PVS from MCS consists of a standardized clinical examination. In the future, modern diagnostic techniques may help identify patients who are in a subclinical minimally conscious state.


title: Synthesis and biochemical evaluation of thiochromanone thiosemicarbazone analogues as inhibitors of cathepsin L.

text: A series of 36 thiosemicarbazone analogues containing the thiochromanone molecular scaffold functionalized primarily at the C-6 position were prepared by chemical synthesis and evaluated as inhibitors of cathepsins L and B. The most promising inhibitors from this group are selective for cathepsin L and demonstrate IC50 values in the low nanomolar range. In nearly all cases, the thiochromanone sulfide analogues show superior inhibition of cathepsin L as compared to their corresponding thiochromanone sulfone derivatives. Without exception, the compounds evaluated were inactive (IC50 > 10000 nM) against cathepsin B. The most potent inhibitor (IC50 = 46 nM) of cathepsin L proved to be the 6,7-difluoro analogue 4. This small library of compounds significantly expands the structure-activity relationship known for small molecule, nonpeptidic inhibitors of cathepsin L.


title: Single-port cholecystectomy with the TransEnterix SPIDER: simple and safe.

text: INTRODUCTION Single-port or single-incision cholecystectomy with current rigid laparoscopic devices is limited by in-line visualization, restricting the ability to approach the surgical site with proper angles and instrumentation. A single-port access system with articulating arms and strong instrumentation should minimize these issues. The TransEnterix system may facilitate safe and straightforward single-port surgery. METHODS The TransEnterix single-port surgery system was used in both survival and nonsurvival porcine laparoscopic cholecystectomies under animal use committee approval. Nonsurvival procedures compared four standard laparoscopic with four single-port cholecystectomies from a histologic perspective. Five single-port swine laparoscopic cholecystectomy procedures were completed in sterile conditions, and all animals survived for 1 week postoperatively. Standard surgical clips were used for both cystic duct and artery ligation. At sacrifice, both gross and microscopic histology were obtained for assessment of surgical complications. RESULTS All cholecystectomies were successfully completed with the TransEnterix single-port system. Operative time for the survival procedures averaged 39.4 (range 18-66) min. Histology of the acute specimens showed less inflammation at the single-port site compared with the trocar sites from the standard cholecystectomy. At sacrifice, no complications were identified. CONCLUSIONS The TransEnterix system is safe and straightforward for completing single-port cholecystectomy in this limited porcine series. Port site inflammation is reduced compared with standard laparoscopic trocars.


Evaluation of current devices in single-incision laparoscopic colorectal surgery.


The physician as public health professional in the 21st century.


title: Adaptation of low-resolution methods for the study of yeast microsomal polytopic membrane proteins: a methodological review.

text: Most integral membrane proteins of yeast with two or more membrane-spanning sequences have not yet been crystallized and for many of them the side on which the active sites or ligand-binding domains reside is unknown. Also, bioinformatic topology predictions are not yet fully reliable. However, so-called low-resolution biochemical methods can be used to locate hydrophilic loops or individual residues of polytopic membrane proteins at one or the other side of the membrane. The advantages and limitations of several such methods for topological studies with yeast ER integral membrane proteins are discussed. We also describe new tools that allow us to better control and validate results obtained with SCAM (substituted cysteine accessibility method), an approach that determines the position of individual residues with respect to the membrane plane, whereby only minimal changes in the primary sequence have to be introduced into the protein of interest.


Are Powered Air Purifying Respirators a Solution for Protecting Healthcare Workers from Emerging Aerosol-Transmissible Diseases?


title: Characteristics of regional cerebral oxygen saturation levels in patients with out-of-hospital cardiac arrest with or without return of spontaneous circulation: A prospective observational multicentre study.

text: AIM Our study aimed at filling the fundamental knowledge gap on the characteristics of regional brain oxygen saturation (rSO2) levels in out-of-hospital cardiac arrest (OHCA) patients with or without return of spontaneous circulation (ROSC) upon arrival at the hospital for estimating the quality of cardiopulmonary resuscitation and neurological prognostication in these patients. METHODS We enrolled 1921 OHCA patients from the Japan - Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry and measured their rSO2 immediately upon arrival at the hospital by near-infrared spectroscopy using two independent forehead probes (right and left). We also assessed the percentage of patients with a good neurological outcome (defined as cerebral performance categories 1 or 2) 90 days post cardiac arrest. RESULTS After 90 days, 79 (4%) patients had good neurological outcomes and a median lower rSO2 level of 15% (15-20%). Compared to patients without ROSC upon arrival at the hospital, those with ROSC had significantly higher rSO2 levels (56% [39-65%] vs. 15% [15-17%], respectively; P<0.01), and significantly correlated right- and left-sided regional brain oxygen saturation levels (R=0.94 vs. 0.66, respectively). In both groups, the percentage of patients with a good 90-day neurological outcome increased significantly in proportion to their rSO2 levels upon arrival at the hospital (P<0.01). CONCLUSION Our data indicate that measuring rSO2 levels might be effective for both monitoring the quality of resuscitation and neurological prognostication in patients with OHCA.


title: Acute respiratory tract infections: a potential trigger for the acute coronary syndrome.

text: Clinical studies suggest that acute respiratory tract infection (ARTI) may be a risk factor for the acute coronary syndrome (ACS). ARTI is associated with an increased risk for ACS up to 2 weeks prior to a cardiac event. The mechanism that may underlie this association is unclear. Infections are thought to play a role in the progression and instability of atherosclerotic plaques, resulting in plaque rupture, sudden constriction, and/or blockage of coronary arteries. Inflammation, endothelial dysfunction and thrombotic activation seem to play an important role in this. Influenza vaccination may reduce the risk of ACS in patients with coronary artery disease. Future studies will provide more information about the underlying mechanisms of infection-related ACS.


Donald Trump: a political determinant of covid-19.


title: A Randomized Controlled Trial Comparing Novel Triple-Cuffed Double-Lumen Endobronchial Tubes with Conventional Double-Lumen Endobronchial Tubes for Lung Isolation.

text: Placing a double-lumen endobronchial tube (DLT) in an appropriate position to facilitate lung isolation is essential for thoracic procedures. The novel ANKOR DLT is a DLT developed with three cuffs with a newly added carinal cuff designed to prevent further advancement by being blocked by the carina when the cuff is inflated. In this prospective study, the direction and depth of initial placement of ANKOR DLT were compared with those of conventional DLT. Patients undergoing thoracic surgery (n = 190) with one-lung ventilation (OLV) were randomly allocated into either left-sided conventional DLT group (n = 95) or left-sided ANKOR DLT group (n = 95). The direction and depth of DLT position were compared via fiberoptic bronchoscopy (FOB) after endobronchial intubation between the groups. There was no significant difference in the number of right mainstem endobronchial intubations between the two groups (p = 0.468). The difference between the initial depth of DLT placement and the target depth confirmed by FOB was significantly lower in the ANKOR DLT group than in the conventional DLT group (1.8 ± 1.8 vs. 12.9 ± 9.7 mm; p < 0.001). In conclusion, the ANKOR DLT facilitated its initial positioning at the optimal depth compared to the conventional DLT.


title: Retrospective Screening for SARS-CoV-2 RNA in California, USA, Late 2019.

text: To investigate the possibility of earlier cases of severe acute respiratory syndrome coronavirus 2 infection than previously recognized, we retrospectively tested pooled samples from 1,700 persons with respiratory signs/symptoms seen at Stanford Health Care, Palo Alto, California, USA, during the last 2 months of 2019. We found no evidence of earlier infection.


title: Short-term mesh exposure after robotic sacrocolpopexy with and without concomitant hysterectomy.

text: OBJECTIVES The primary objective of this study was to compare the short-term rate of mesh exposure after a robotic sacrocolpopexy (RSCP) compared with those after RSCP with a concomitant hysterectomy. Secondary objectives included a comparison of mesh exposure from total hysterectomies (TH) versus supracervical hysterectomies (SCH) and determination of risk factors for mesh exposure. METHODS This was a retrospective cohort study of women who underwent RSCP between January 2009 and December 2011 at one academic center. The primary outcome was mesh exposure at 6 weeks postoperation. Subjects were divided into two groups: those with concomitant hysterectomy and those with RSCP alone. The hysterectomy group was subdivided into TH versus SCH. Mesh exposures and mesh revision procedures were identified using International Classification of Diseases-9 and CPT codes, respectively, and confirmed by chart review. RESULTS There were 230 eligible women who underwent RSCP during the study period and were followed up at a 6-week postoperative visit; 118 (51.7%) had RSCP only and 112 (48.7%) had a concomitant hysterectomy. Of those who underwent hysterectomy, 79 patients (70.5%) had TH and 33 (29.5%) had SCH. There were nine (3.9%) mesh exposures attributed to RSCP. The difference between the RSCP + hysterectomy group and the RSCP-only group was 2.7% versus 5.1% (P = 0.50). The 2.7% of mesh exposures in the hysterectomy group were associated with TH and none with SCH, but this difference was not significant (P = 0.55). CONCLUSIONS Although mesh exposure with RSCP is low, serious morbidity can be associated with mesh use and appropriate preoperative counseling is critical.


title: Optimization and Standardization of the Immunodeficient Mouse Model for Assessing Fat Grafting Outcomes.

text: BACKGROUND Animal models are often used to assess interventions that might improve fat grafting outcomes; however, there is great variability in the models. The authors sought to determine the predictive value of the immunocompromised mouse model for fat grafting so that experiments could be standardized and optimized. METHODS Human lipoaspirate injections at different volumes and time points were assessed in a nude mouse model and compared with control injections of nonviable fat. Volume retention and explant histologic score were compared. In a separate study, interanimal reproducibility was determined by implanting a highly consistent hydrogel and measuring variability in volume retention. RESULTS Injection volume significantly affects adipose resorption kinetics at 6 and 12 weeks. Masson trichrome staining revealed that macrophages were unable to infiltrate large (1 ml) grafts, and oil cysts were not absorbed by 18 weeks, which interfered with interpretation of volume retention data. Nonviable tissue was resorbed when grafts were 0.3 ml, and quantification of graft histologic viability correlated well with graft retention at all study time points. Interanimal variability was measured to be 8.44 percent of the mean retention volume for small graft volumes. CONCLUSIONS Human fat graft retention in the immunodeficient mouse correlates with graft viability in small, 0.3-ml-volume grafts. However, centralized oil cysts in nonviable 1.0-ml grafts were not resorbed by 18 weeks and thus volume measurements were confounded and not significantly different from viable samples. In addition, tissue injury scores increased in initially healthy fat grafts at 18 weeks, possibly because of a delayed immune reaction.


title: Medical Education Adaptations During a Pandemic: Transitioning to Virtual Student Support.

text: Student pastoral support is crucial throughout medical training and is often conducted via face to face meetings with academic personal tutors or mentors. However, the sudden introduction of social distancing measures designed to stem the spread of the virus resulted in a national switch to online teaching and removed the ability to provide students with support in-person. This rapid and unexpected change of circumstances and loss of structure left many students socially isolated and struggling to cope with massive uncertainty.


title: Anti-TNF-α treatment for pelvic pain associated with endometriosis.

text: BACKGROUND Endometriosis is a chronic, recurring condition that can develop during the reproductive years. It is characterised by the development of endometrial tissue outside the uterine cavity. It is the most common cause of pelvic pain in women. This endometrial tissue development is dependent on oestrogen produced primarily by the ovaries and, therefore, traditional management has focused on suppression of ovarian function. Mounting evidence shows that altered immune function plays a crucial role in the genesis and development of endometriosis. In this review we considered modulation of the inflammation as an alternative approach. OBJECTIVES To determine the effectiveness and safety of anti-tumour necrosis factor-α (anti-TNF-α) treatment in the management of endometriosis in premenopausal women. SEARCH METHODS For the first publication of this review, we searched for trials in the following databases (from their inception to August 2009): Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINAHL, and PsycINFO. In addition, we searched all reference lists of included trials and contacted experts in the field in an attempt to locate trials. We reran this search to 3 September 2012 for this update. SELECTION CRITERIA Randomised controlled trials (RCTs) comparing anti-TNF-α drugs with placebo, no treatment, medical treatment, or surgery for pelvic pain associated with endometriosis were included. DATA COLLECTION AND ANALYSIS Two review authors independently selected trials for inclusion, assessed trial quality, and extracted data using data extraction forms. The domains assessed for risk of bias were sequence generation, allocation concealment, blinding, incomplete outcome data, and selective outcome reporting. We used risk ratios (RR) for reporting dichotomous data with 95% confidence intervals (CI), whilst we expressed continuous data as mean differences (MD). We assessed statistical heterogeneity using the I(2) statistic. MAIN RESULTS Only one trial involving 21 participants was included. The results showed no evidence of an effect of infliximab, one of the known anti-TNF-α drugs, on pelvic pain reduction using the Biberoglu-Behrman (BB) score (0 to 3 scale) for participants (MD -0.14, 95% CI -0.43 to 0.15), the BB score for clinicians (MD -0.14, 95% CI -0.39 to 0.11), or a visual analogue pain score (VAS, 100 mm scale) (MD -5.60, 95% CI -16.10 to 4.90), or on the use of pain killers (ibuprofen, g/day) (MD -0.10, 95% CI -0.30 to 0.10). There was no evidence of an increase in adverse events in the infliximab group compared with placebo (RR 3.73, 95% CI 0.22 to 63.66). We found no evidence of clinical benefits of infliximab for endometriotic lesions, dysmenorrhoea, dyspareunia, or pelvic tenderness. To date, there is no trial that has reported a cost-effectiveness analysis of anti-TNF-α drugs, or the odds of recurrence. AUTHORS' CONCLUSIONS This review was updated in 2012. The results of the original review published in 2010 remain unchanged. There is still not enough evidence to support the use of anti-TNF-α drugs in the management of women with endometriosis for the relief of pelvic pain.


title: Recurrence of varicose veins after endovenous ablation of the great saphenous vein in randomized trials.

text: BACKGROUND Recurrence of varicose veins after surgery (REVAS) for saphenous incompetence has been well described after ligation and stripping (L&S) but not after the now most frequently performed method of saphenous ablation, endovenous ablation (EVA). The purpose of this study was to define the overall incidence of REVAS as well as both the sites of reflux and the causes of REVAS through a systematic review and meta-analysis of randomized controlled trials (RCTs) for EVA. These studies have the advantage of prospectively collected data and a uniform duplex follow-up. METHODS We searched databases (January 1, 2000 through July 1, 2014) for published RCTs evaluating EVA treatment of great saphenous vein (GSV) incompetence that employed endovenous laser ablation or radiofrequency ablation. RCTs were eliminated that (1) did not have follow-up of at least 2 years, (2) did not obtain postoperative duplex scans, (3) did not clearly report the incidence of recurrent varicosities after GSV ablation, and (4) treated the small saphenous or anterior accessory saphenous veins. RESULTS Of the 68 studies screened, 20 RCTs that employed EVA of the GSV were identified. Eight had a follow-up of at least 2 years, but one was eliminated because of lack of information on both the site and cause of REVAS. The resultant seven RCTs provided eight comparisons (one study compared both types of EVA to a comparator arm): three used radiofrequency ablation, and five employed endovenous laser ablation. Overall recurrent varicose veins developed in 125 limbs after EVA (22%), with no difference in the incidence vs the L&S group (22%) based on the number of limbs available at the time of the development of recurrence for both groups, but this incidence is dependent on the length of follow-up after the initial treatment. The two studies with serial follow-up showed an approximate doubling of REVAS over time for both EVA and L&S. By contrast, the cause of REVAS was different between the two methods. Neovascularization occurred in only two limbs (2%) after EVA vs 18 (18%) in the L&S group. Recanalization was the most common cause of REVAS for EVA (32%; 40 of 125 limbs), followed by the development of anterior accessory saphenous vein incompetence (19%; 23 of 125 limbs). In contrast to other reports, incompetent calf perforating veins were an infrequent cause of REVAS (7%; eight of 125). CONCLUSIONS There is no difference in the incidence of REVAS for EVA vs L&S, but the causes of REVAS are different with L&S, which has important implications for treatment.


title: A descriptive analysis of occupational health exposures in an urban emergency medical services system: 2007-2009.

text: INTRODUCTION Prehospital providers are exposed to various infectious disease hazards. Examining specific infectious exposures would be useful in describing their current trends as well as guidance with appropriate protective measures an emergency medical services (EMS) system should consider. OBJECTIVE To describe the types of infectious occupational health exposures and associated outcomes reported at an urban EMS system. METHODS A retrospective review of all reported exposures was performed for a three-year period from January 1, 2007, to December 31, 2009. Descriptive analysis was performed on data such as provider demographics, types of exposures reported, confirmation of exposure based on patient follow-up information, and outcomes. RESULTS Three hundred ninety-seven exposure reports were filed with the designated infection control officer (ICO), resulting in an overall exposure rate of 1.2 per 1,000 EMS incidents. The most common exposure was to possible meningitis (n = 131, 32.9%), followed by tuberculosis (TB) (n = 68, 17.1%), viral respiratory infections (VRIs) such as influenza or H1N1 (n = 61, 15.4%), and body fluid splashes to skin or mucous membranes (n = 56, 14.1%). Body fluid splashes involving the eyes accounted for 41 cases (10.3%). Only six cases (1.5%) of needlestick injuries were reported. Three hundred thirty-two of all cases (83.6%) were considered true exposures to an infectious hazard, of which 177 (53.3%) were actually confirmed. Half of all exposures required only follow-up with the ICO (52.6%). One hundred twenty-seven cases (31.9%) required follow-up at a designated occupational health services or emergency department. Of these, only 23 cases (18.1%) required treatment. There was a significant trend of increasing incidence of VRI exposures from 2008 to 2009 (6.3% vs. 26.8%, p < 0.001), while a significant decrease in TB exposures was experienced during the same year (22.9% vs. 8.2%, p = 0.002). CONCLUSIONS Trends in our data suggest increasing exposures to viral respiratory illnesses, whereas exposures to needlestick injuries were relatively infrequent. Efforts should continue to focus on proper respiratory protection to include eye protection in order to mitigate these exposure risks.


title: Inferior Vena Cava Filters: Indications, Outcomes, and Evidence.

text: OPINION STATEMENT Filter technology seems relatively stable, although absorbable devices are an area of investigational interest. The indications for filter placement remain controversial, with wide variations in adherence to guidelines, and relatively poor quality of data about the specific prophylactic indications of trauma or bariatric surgery. The outcomes of filters are not well-defined despite widespread clinical use, and good data remains difficult to obtain. Several larger database and institutional retrospective studies support the notions that while filters prevent pulmonary embolism, they may be associated with venous thrombotic complications. Some subsets of cancer patients may be at increased risk of these complications, but whether the filter or the underlying hypercoagulable state is the cause is not clear. Lastly, although the benefits of filter retrieval are widely assumed (but not proven), filter retrieval rates remain lower than expected. The single most influential factor in improving filter retrieval rates is dedicated follow-up with intent to retrieve the filter.


title: End-of-Treatment Positron Emission Tomography After Uniform First-Line Therapy of B-Cell Posttransplant Lymphoproliferative Disorder Identifies Patients at Low Risk of Relapse in the Prospective German PTLD Registry.

text: BACKGROUND Fluorine-18 fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET) is a recommended standard in the staging and response assessment of 18F-FDG-avid lymphoma. Posttransplant lymphoproliferative disorder (PTLD) can be detected by 18F-FDG-PET at diagnosis with high sensitivity and specificity. However, the role of response assessment by end-of-treatment (EOT) PET has only been addressed in small case series. METHODS We performed a retrospective, multicenter study of 37 patients with CD20-positive PTLD after solid organ transplantation treated with uniform, up-to-date, first-line protocols in the prospective German PTLD registry who had received EOT 18F-FDG-PET between 2006 and 2014. Median follow-up was 5.0 years. Any nonphysiological 18F-FDG uptake (Deauville score greater 2) was interpreted as PET-positive. RESULTS By computed tomography (CT) final staging, 18 of 37 patients had a complete response, 18 had a partial response and 1 patient had stable disease. EOT PET was negative in 24 of 37 patients and positive in 13 of 37 patients. The positive predictive value of EOT PET for PTLD relapse was 38%, and the negative predictive value was 92%. Time to progression (TTP) and progression-free-survival were significantly longer in the PET negative group (P = 0.019 and P = 0.013). In the 18 patients in a partial response by CT staging, we noted highly significant differences in overall survival (P = 0.001), time to progression (P = 0.007), and progression-free survival (P < 0.001) by EOT PET. CONCLUSIONS Even without baseline imaging, EOT PET in PTLD identifies patients at low risk of relapse and offers clinically relevant information, particularly in patients in a partial remission by CT staging.


South Korea scrambles to contain MERS virus.


title: Performance of CURB-65 in predicting mortality of patients with community-acquired pneumonia in Saudi Arabia.

text: INTRODUCTION Various objective scoring systems were developed to standardize the approach to the designation of severity of community-acquired pneumonia (CAP). There is limited data on the use of CURB-65 among admitted CAP patients in Saudi Arabia. METHODOLOGY: The retrospective study included CAP patients, admitted to a general hospital in Eastern Saudi Arabia. The CURB-65 was extracted from the available medical records. RESULTS During the study period, from 2013 to 2016, a total of 1786 adults were admitted with a mean age of 63.9 ± 21.7 (range 14-108 years). The majority of the patients (51.7%) had CURB-65 score 0 or 1 followed by the score 2, 3 and 4/5 (29%, 15.2%, and 4.1%, respectively). The mean CURB-65 was 1.4 ± 1.12 for those who survived and 2.27 ± 1.03 for those who died (p < 0.001). The mean age was 63.01± 21.9 years for survived patients and 75.1 ± 15.58 years for fatal cases (p < 0.001). The overall 30-day crude mortality rate was 7.6%. The mortality rates for CURB-65 scores 0, 1, 2, 3, and 4/5 were 1.8%, 4.3%, 10.2%, 14%, and 21.9%, respectively. CONCLUSIONS The mortality rates of admitted patients with CAP did not differ from those reported in the literature. However, the utilization of CURB-65 score was low and there is a need for wider implementation of pneumonia severity index for patients presenting with CAP.


title: Conventional blood tests in predicting influenza A (H1N1) rapidly.

text: PURPOSE Although real-time reverse transcriptase-polymerase chain reactions (rRT-PCR) are gold standard for the diagnosis of influenza A (H1N1), the results can be delayed up to several days, which is problematic during a pandemic. Because of this limitation of rRT-PCR, clinicians have often had to set a treatment plan that was solely based on clinical suspicion. We investigated the hematological and biochemical factors that are associated with rRT-PCR results, in order to help clinicians deal with acute febrile patients during influenza pandemics. METHODS We conducted a retrospective, cross-sectional study of 465 emergency department patients who underwent both rRT-PCR and blood tests at the same time. Hematological and biochemical findings were compared between the rRT-PCR-positive group and rRT-PCR-negative group. RESULTS Levels of leukocytes, hemoglobin, platelets, blood urea nitrogen (BUN), total bilirubin, lactate dehydrogenase, serum glucose, C-reactive protein (CRP), and procalcitonin were significantly different between the two groups in the univariate analyses. In the multivariate analyses, leukocyte counts ≤ 10.8 (× 10(9))/L [odd ratio (OR) = 8.2, sensitivity = 93.7%, NPV = 85.3%], BUN levels ≤ 7.1 μmol/L (OR = 3.0, sensitivity = 93.7%, NPV = 85.3%), and CRP levels ≤ 60 mg/L (OR = 2.4, sensitivity = 93.7%, NPV = 85.3%) were independently associated with positive rRT-PCR results. CONCLUSIONS Leukocyte counts, BUN levels and CRP levels were important predictors of rRT-PCR-positive results for 2009 influenza A (H1N1) in adults.


title: Diverse novel astroviruses identified in wild Himalayan marmots.

text: With advances in viral surveillance and next-generation sequencing, highly diverse novel astroviruses (AstVs) and different animal hosts had been discovered in recent years. However, the existence of AstVs in marmots had yet to be shown. Here, we identified two highly divergent strains of AstVs (tentatively named Qinghai Himalayanmarmot AstVs, HHMAstV1 and HHMAstV2), by viral metagenomic analysis in liver tissues isolated from wild Marmota himalayana in China. Overall, 12 of 99 (12.1 %) M. himalayana faecal samples were positive for the presence of genetically diverse AstVs, while only HHMAstV1 and HHMAstV2 were identified in 300 liver samples. The complete genomic sequences of HHMAstV1 and HHMAstV2 were 6681 and 6610 nt in length, respectively, with the typical genomic organization of AstVs. Analysis of the complete ORF 2 sequence showed that these novel AstVs are most closely related to the rabbit AstV, mamastrovirus 23 (with 31.0 and 48.0 % shared amino acid identity, respectively). Phylogenetic analysis of the amino acid sequences of ORF1a, ORF1b and ORF2 indicated that HHMAstV1 and HHMAstV2 form two distinct clusters among the mamastroviruses, and may share a common ancestor with the rabbit-specific mamastrovirus 23. These results suggest that HHMAstV1 and HHMAstV2 are two novel species of the genus Mamastrovirus in the Astroviridae. The remarkable diversity of these novel AstVs will contribute to a greater understanding of the evolution and ecology of AstVs, although additional studies will be needed to understand the clinical significance of these novel AstVs in marmots, as well as in humans.


title: Heparin-binding protein as a biomarker of gastrointestinal dysfunction in critically ill patients: a retrospective cross-sectional study in China.

text: OBJECTIVE To investigate the association of plasma heparin-binding protein (HBP) with the development of acute gastrointestinal injury (AGI) in critically ill patients. DESIGN Clinical retrospective cross-sectional study. SETTING A general teaching hospital in China. PARTICIPANTS Adult patients (age ≥18 years) admitted to our department with an intensive care unit (ICU) stay ≥5 days. MAIN OUTCOME MEASURES HBP levels were recorded twice or more within 5 days after admission. The initial AGI grades and the worst AGI grades within 5 days after admission, the number of patients receiving total enteral nutrition (TEN) and the number of patients with feeding intolerance (FI) and with sepsis were also recorded, along with some clinical severity and outcome variables. RESULTS From June 2018 to May 2019, 221 patients were enrolled in this study. We divided patients into four groups based on the HBP values: HBP ≤20 ng/mL, 20100 ng/mL. Significant differences were found in the ratios of AGI deterioration and TEN and the incidence rates of FI and sepsis among the four groups. Differences were also found among the groups regarding the worst AGI grades. The area under receiver operating characteristic curves for AGI deterioration, severe AGI (grades II or above), TEN and FI were 0.738 (p=0.001), 0.774 (p<0.001), 0.810 (p<0.001) and 0.729 (p=0.001), respectively. The optimal HBP cut-off values for AGI deterioration and severe AGI were 53.27 ng/mL and 41.26 ng/mL, respectively. However, no differences in ICU duration or 28-day mortality were found. CONCLUSIONS HBP levels were associated with gastrointestinal dysfunction in critically ill patients. Increased HBP was positively correlated with sepsis but it was not correlated with 28-day mortality.


title: Mapping the Specific Amino Acid Residues That Make Hamster DPP4 Functional as a Receptor for Middle East Respiratory Syndrome Coronavirus.

text: UNLABELLED The novel emerging coronavirus Middle East respiratory syndrome coronavirus (MERS-CoV) binds to its receptor, dipeptidyl peptidase 4 (DPP4), via 14 interacting amino acids. We previously showed that if the five interacting amino acids which differ between hamster and human DPP4 are changed to the residues found in human DPP4, hamster DPP4 does act as a receptor. Here, we show that the functionality of hamster DPP4 as a receptor is severely decreased if less than 4 out of 5 amino acids are changed. IMPORTANCE The novel emerging coronavirus MERS-CoV has infected >1,600 people worldwide, and the case fatality rate is ∼36%. In this study, we show that by changing 4 amino acids in hamster DPP4, this protein functions as a receptor for MERS-CoV. This work is vital in the development of new small-animal models, which will broaden our understanding of MERS-CoV and be instrumental in the development of countermeasures.


Mycoplasma bovis infection causing arthritis and pneumonia in cattle.


title: The safety and effectiveness of the retrievable option inferior vena cava filter: a United States prospective multicenter clinical study.

text: PURPOSE To evaluate the safety and effectiveness of the retrievable Option inferior vena cava (IVC) filter in patients at risk for pulmonary embolism (PE). MATERIALS AND METHODS This was a prospective, multicenter, single-arm clinical trial. Subjects (N = 100) underwent implantation of the IVC filter and were followed for 180 days; subjects whose filters were later removed were followed for 30 days thereafter. The primary objective was to determine whether the one-sided lower limit of the 95% CI for the observed clinical success rate was at least 80%. Clinical success was defined as technical success (deployment of the filter such that it was judged suitable for mechanical protection from PE) without subsequent PE, significant filter migration or embolization, symptomatic caval thrombosis, or other complications. RESULTS Technical success was achieved in 100% of subjects. There were eight cases of recurrent PE, two cases of filter migration (23 mm), and three cases of symptomatic caval occlusion/thrombosis (one in a subject who also experienced filter migration). No filter embolization or fracture occurred. Clinical success was achieved in 88% of subjects; the one-sided lower limit of the 95% CI was 81%. Retrieval was successful at a mean of 67.1 days after implantation (range, 1-175 d) for 36 of 39 subjects (92.3%). All deaths (n = 17) and deep vein thromboses (n = 18) were judged to have resulted from preexisting or intercurrent illnesses or interventions and unrelated to the filter device; all deaths were judged to be unrelated to PE. CONCLUSIONS Placement and retrieval of the Option IVC filter were performed safely and with high rates of clinical success.


title: Prediction of optimal endotracheal tube cuff volume from tracheal diameter and from patient height and age: a prospective cohort trial.

text: PURPOSE Endotracheal tube intra-cuff pressure should be maintained between 20 and 30 cmH(2)O to prevent damage to the tracheal wall. However, cuff pressure is rarely measured, and clinicians estimate cuff pressure poorly. The goal of the present study was to predict the cuff volume that produces optimal cuff pressure either from tracheal diameter or from patient height and age. METHODS In the development phase, initial cuff pressure and cuff volume were measured in 240 patients. Optimal cuff volume, defined as the volume halfway between the volumes required to produce cuff pressures of 20 and 30 cmH(2)O, was determined in each patient. Then, regression equations relating optimal cuff volume to tracheal diameter on chest X-ray, and between optimal cuff volume and a combination of height and age, were calculated. The primary outcome was the proportion of patients in a validation set (n = 104) who achieved a cuff pressure of 20-30 cmH(2)O when cuff volume was selected by each regression formula. RESULTS Only 28% of the cuffs were optimally inflated using clinical criteria during the development phase. There was good correlation between optimal cuff volume and tracheal diameter and moderate correlation between optimal cuff volume and both height and age. Predicted cuff volume was more likely to provide optimal cuff pressure when based on tracheal diameter (65% of patients) than when based on both height and age (45% of patients). CONCLUSIONS Optimal cuff volume was better estimated from tracheal diameter and patient height and age than from the manual palpation method.


title: Single-incision transperitoneal laparoscopic left adrenalectomy.

text: BACKGROUND Laparoscopic adrenalectomy via three or four trocars is a well-established procedure. This report describes the initial experience with single-incision laparoscopic surgery (SILS) using the transperitoneal approach for left adrenalectomy. METHODS Between April 2010 and August 2011, all consecutive patients with adrenal masses, including Conn's syndrome, Cushing's adenoma, and nonfunctional adrenal tumors, who agreed to undergo SILS adrenalectomy were included in a prospective study. The left 2.5-cm subcostal incision was the sole point of entry. Data of patients who underwent SILS adrenalectomy were compared with those from an uncontrolled group of patients who underwent conventional laparoscopic adrenalectomy during the same study period. RESULTS There were 20 patients in each study group (20 men, 20 women; mean age [SD] = 50 [6.5] years). SILS was successfully performed and none of the patients required conversion to an open procedure. In one case of SILS procedure, an additional lateral 5-mm port was needed for retraction of the kidney. The mean (SD) duration of the operation was 95 (20) min in the SILS group and 80 (8) min in the conventional laparoscopic adrenalectomy group (p = 0.052). There were no intraoperative or postoperative complications. There were no differences between the two study groups with respect to postoperative pain, number of patients who resumed oral intake within the first 24 h, final pathologic diagnosis, and length of hospital stay. CONCLUSION SILS left adrenalectomy is a technically feasible and safe procedure in carefully selected patients. The definitive clinical, aesthetic and functional advantages of this technique require further analysis.


title: Targeting obstetric providers in interventions for obesity and gestational weight gain: A systematic review.

text: BACKGROUND Providers need to be comfortable addressing obesity and gestational weight gain so they may give appropriate care; however, health care providers lack guidelines for the most effective educational strategies to assist in providing optimal care. OBJECTIVE To identify studies that involved the obstetric provider in interventions for either the perinatal management of obesity and/or gestational weight gain in a systematic review. SEARCH STRATEGY A keyword search of databases was performed up to April 2017. SELECTION CRITERIA Obstetric providers who participated in an intervention with the aim to change a provider's clinical practice, knowledge, and/or satisfaction with the intervention in relation to the perinatal management of obesity or gestational weight gain were included. Provider intervention could include training or education, changes in systems or organization of care, or resources to support practice. PROSPERO database #42016038921. DATA COLLECTION AND ANALYSIS Bias was assessed according to the validated Mixed Methods Appraisal Tool. The following variables were synthesized: study location and setting, provider and patient characteristics, intervention features, outcomes and efficacy, and strengths and weakness. MAIN RESULTS Of the 6,821 abstracts screened, seven studies (4 quantitative, 3 mixed-methods) with a total of 335 providers met the inclusion criteria; two of which focused on the management of obesity, three focused on gestational weight gain, and two focused on both topics. Interventions that incorporated motivational interviewing skills (n = 2), required additional training for the research study and addressed specific knowledge deficits such as nutrition and exercise (n = 3), and interfaced with the electronic medical record (n = 1) demonstrated the greatest impact on provider outcomes. Provider reported satisfaction scores were generally favorable, but none addressed provider-level efficacy in practice change. CONCLUSIONS Given the limited number of studies, varying range of provider participation, and lack of provider-level efficacy, further evaluation of provider training and involvement in interventions for perinatal obesity or gestational weight gain is indicated to determine best practices for provider and patient outcomes.


docid: kifgxtze

title: The Hip Fracture Surgery in Elderly Patients (HIPELD) study: protocol for a randomized, multicenter controlled trial evaluating the effect of xenon on postoperative delirium in older patients undergoing hip fracture surgery.

text: BACKGROUND Strategies to protect the brain from postoperative delirium (POD) after hip fracture are urgently needed. The development of delirium often is associated with the loss of independence, poor functional recovery, and increased morbidity, as well as increases in length of hospital stay, discharges to nursing facilities, and healthcare costs. We hypothesize that xenon may reduce the burden of POD, (i) by avoiding the need to provide anesthesia with a drug that targets the γ-amino-butyric acid (GABA)A receptor and (ii) through beneficial anesthetic and organ-protective effects. METHODS AND DESIGN An international, multicenter, phase 2, prospective, randomized, blinded, parallel group and controlled trial to evaluate the incidence of POD, diagnosed with the Confusion Assessment Method (CAM), in older patients undergoing hip fracture surgery under general anesthesia with xenon or sevoflurane, for a period of 4 days post surgery (primary outcome) is planned. Secondary objectives are to compare the incidence of POD between xenon and sevoflurane, to evaluate the incidence of POD from day 5 post surgery until discharge from hospital, to determine the time to first POD diagnosis, to evaluate the duration of POD, to evaluate the evolution of the physiological status of the patients in the postoperative period, to evaluate the recovery parameters, to collect preliminary data to evaluate the economical impact of POD in the postoperative period and to collect safety data. Patients are eligible if they are older aged (≥ 75 years) and assigned to a planned hip fracture surgery within 48 h after the hip fracture. Furthermore, patients need to be willing and able to complete the requirements of this study including the signature of the written informed consent. A total of 256 randomized patients in the 10 participating centers will be recruited, that is, 128 randomized patients in each of the 2 study groups (receiving either xenon or sevoflurane). TRIAL REGISTRATION EudraCT Identifier: 2009-017153-35; ClinicalTrials.gov Identifier: NCT01199276.


title: Safety and immunogenicity of recombinant Rift Valley fever MP-12 vaccine candidates in sheep.

text: The safety and immunogenicity of two authentic recombinant (ar) Rift Valley fever (RVF) viruses, one with a deletion in the NSs region of the S RNA segment (arMP-12ΔNSs16/198) and the other with a large deletion of the NSm gene in the pre Gn region of the M RNA segment (arMP-12ΔNSm21/384) of the RVF MP-12 vaccine virus were tested in crossbred ewes at 30-50 days of gestation. First, we evaluated the neutralizing antibody response, measured by plaque reduction neutralization (PRNT(80)), and clinical response of the two viruses in groups of four ewes each. The virus dose was 1×10(5)plaque forming units (PFU). Control groups of four ewes each were also inoculated with a similar dose of RVF MP-12 or the parent recombinant virus (arMP-12). Neutralizing antibody was first detected in 3 of 4 animals inoculated with arMP-12ΔNSm21/384 on Day 5 post inoculation and all four animals had PRNT(80) titers of ≥1:20 on Day 6. Neutralizing antibody was first detected in 2 of 4 ewes inoculated with arMP-12ΔNSs16/198 on Day 7 and all had PRNT(80) titers of ≥1:20 on Day 10. We found the mean PRNT(80) response to arMP-12ΔNSs16/198 to be 16- to 25-fold lower than that of ewes inoculated with arMP-12ΔNSm21/384, arMP-12 or RVF MP-12. No abortions occurred though a single fetal death in each of the arMP-12 and RVF MP-12 groups was found at necropsy. The poor PRNT(80) response to arMP-12ΔNSs16/198 caused us to discontinue further testing of this candidate and focus on arMP-12ΔNSm21/384. A dose escalation study of arMP-12ΔNSm21/384 showed that 1×10(3)plaque forming units (PFU) stimulate a PRNT(80) response comparable to doses of up to 1×10(5)PFU of this virus. With further study, the arMP-12ΔNSm21/384 virus may prove to be a safe and efficacious candidate for a livestock vaccine. The large deletion in the NSm gene may also provide a negative marker that will allow serologic differentiation of naturally infected animals from vaccinated animals.


title: A Rabbit Corneal Endothelial Dysfunction Model Using Endothelial-Mesenchymal Transformed Cells.

text: Unlike humans, rabbit corneal endothelial wounds are known to spontaneously heal. The current study was aimed to develop a new rabbit bullous keratopathy model using corneal endothelial cells that were induced to undergo endothelial-mesenchymal transformation (EMT). EMT was induced in rabbit corneal endothelial cells (RCECs) by culturing with TGFβ and basic FGF Supplemented Medium. The corneal endothelia in recipient rabbits were mechanically scraped from the corneal endothelial surface inside an 8 mm mark. Then, a suspension of EMT-induced RCECs (EMT-RCECs) was injected into the anterior chamber. Eyes injected with freshly isolated RCECs (Fresh RCECs group) and eyes that were scraped without injection of cells (Scrape group) were used as controls. Immediately following operation, subepithelial and stromal edema was observed with increased central corneal thickness and corneal opacity in all groups. In the EMT-RCECs group, bullous keratopathy persisted for 42 days up to the end of the study. In the Fresh-RCECs and Scrape groups, corneal transparency and thickness recovered by 7 days after treatment and was maintained up to 42 days. The activated fibroblast marker, α-SMA, was observed spanning from corneal endothelium to corneal stroma in the EMT-RCECs group. Interestingly, α-SMA was upregulated in the Scrape-group as well. In all groups, there was no damage to other intraocular structures, and intraocular pressure was normal throughout the observation period. Transplanting a fresh donor cornea effectively treated corneal edema due to bullous keratopathy. This model is a promising tool for pre-clinical trials in the development of new therapies against corneal endothelial dysfunction.


The World Glaucoma Association during the COVID-19 Pandemic.


Cuff leakage caused by automatic cuff pressure monitor and water condensation in the inflation tube of Microcuff® endotracheal tube.


docid: vxzwgpgv

title: Clinical and computed tomographic (CT) images characteristics in the patients with COVID-19 infection: What should radiologists need to know?

text: OBJECTIVE To evaluate the clinical and computed tomographic (CT) features in the patients with COVID-19 pneumonia confirmed by the real-time reverse transcriptase polymerase chain reaction (rRT-PCR) amplification of the viral DNA from a sputum sample. MATERIAL AND METHODS Clinical information and CT findings of a total of 14 patients with COVID-19 infection (age range, 12-83 years; females 6) were analyzed retrospectively. The clinical information includes the history of exposure, laboratory results, and the symptoms (such as fever, cough, headache, etc.); CT findings of chest include the extension and distribution of lesion, the ground-glass opacity (GGO), consolidation, bronchovascular enlarged, irregular linear appearances, pleural effusion, and lymphadenopathy. RESULTS Eight patients had the exposure history for recent travel to Wuhan of Hubei province (8/14, 57%), 6 had the exposure to patients with COVID-19 infection. Significant statistical differences were observed in lymphocyte percentage decreased and C-reactive protein elevated (p = 0.015). Seven patients had fever, 7 had cough, 2 had headache, 3 had fatigue, 1 had body soreness, 3 had diarrhea, and 2 had no obvious symptoms. In chest CT examination, 10 patients were positive (10/14, 71.43%). Among these patients, 9 had lesions involving both lungs (9/10, 90%), 8 had lesions involving 4 to 5 lobes (8/10, 80%). Most of lesions were distributed peripherally and the most significant lesions were observed in the right lower lobe in 9 patients (9/10, 90%). Nodules were observed in 5 patients (5/10, 50%); GGO, consolidation, and bronchovascular enlarged were shown in 9 patients (9/10, 90%); irregular linear appearances were revealed in 7 patients (7/10, 70%); and pleural effusions were exhibited in 2 patients (2/10, 20%). Last, no patients showed lymphadenopathy. CONCLUSION There were some typical CT features for diagnosis of COVID-19 pneumonia. The radiologists should know these CT findings and clinical information, which could help for accurate analysis in the patients with 2019 novel coronavirus infection.


title: Discovering potent inhibitors against the beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) of Helicobacter pylori: structure-based design, synthesis, bioassay, and crystal structure determination.

text: The discovery of HpFabZ inhibitors is now of special interest in the treatment of various gastric diseases. In this work, three series of derivatives (compounds 3, 4, and 5) were designed, synthesized, and their biological activities were investigated as potential HpFabZ inhibitors in a two phased manner. First, we designed and synthesized two series of derivatives (3a-r and 4a-u) and evaluated the enzyme-based assay against HpFabZ. Five compounds (3i-k, 3m, and 3q) showed potential inhibitory activity, with IC(50) values less than 2 muM. Second, a focused combinatorial library containing 280 molecules was designed employing the LD1.0 program. Twelve compounds (5a-l) were selected and synthesized. The activity of the most potent compound 5h (IC(50) = 0.86 muM) was 46 times higher than that of the hit 1. The high hit rate and the potency of the new HpFabZ inhibitors demonstrated the efficiency of the strategy for the focused library design and virtual screening.


title: The management of chest tubes after pulmonary resection.

text: Most patients who undergo pulmonary resection can have one chest tube and have it removed by postoperative day 3. Air leaks are probably best treated with water seal (passive suction) for most patients with small leaks. If they develop a new or enlarging pneumothorax or subcutaneous emphysema, some suction (active suction) is needed and alternating suction at night with waters seal during the day may be best. Most patients with persistent air leaks can be discharged home safely on an outpatient device and have their tubes removed in 2 to 3 weeks even if they still have an air leak.


title: Deformable three-dimensional model architecture for interactive augmented reality in minimally invasive surgery.

text: BACKGROUND Surgical procedures have undergone considerable advancement during the last few decades. More recently, the availability of some imaging methods intraoperatively has added a new dimension to minimally invasive techniques. Augmented reality in surgery has been a topic of intense interest and research. METHODS Augmented reality involves usage of computer vision algorithms on video from endoscopic cameras or cameras mounted in the operating room to provide the surgeon additional information that he or she otherwise would have to recognize intuitively. One of the techniques combines a virtual preoperative model of the patient with the endoscope camera using natural or artificial landmarks to provide an augmented reality view in the operating room. The authors' approach is to provide this with the least number of changes to the operating room. Software architecture is presented to provide interactive adjustment in the registration of a three-dimensional (3D) model and endoscope video. RESULTS Augmented reality including adrenalectomy, ureteropelvic junction obstruction, and retrocaval ureter and pancreas was used to perform 12 surgeries. The general feedback from the surgeons has been very positive not only in terms of deciding the positions for inserting points but also in knowing the least change in anatomy. CONCLUSIONS The approach involves providing a deformable 3D model architecture and its application to the operating room. A 3D model with a deformable structure is needed to show the shape change of soft tissue during the surgery. The software architecture to provide interactive adjustment in registration of the 3D model and endoscope video with adjustability of every 3D model is presented.


title: Endovascular management of arteriovenous malformations of the brain.

text: Arteriovenous malformations (AVMs) of the brain are rare, complex, vascular lesions that can result in significant morbidity and mortality. Modern treatment of brain AVMs is a multimodality endeavor, requiring a multidisciplinary team with expertise in cerebrovascular neurosurgery, endovascular intervention, and radiation therapy in order to provide all therapeutic options and determine the most appropriate treatment regimen depending on patient characteristics and AVM morphology. Current therapeutic options include microsurgical resection, radiosurgery (focused radiation), and endovascular embolization. Endovascular embolization is primarily used as a preoperative adjuvant before microsurgery or radiosurgery. Palliative embolization has been used successfully to reduce the risk of hemorrhage, alleviate clinical symptoms, and preserve or improve neurological function in inoperable or nonradiosurgical AVMs. Less frequently, embolization is used as 'primary therapy' particularly for smaller, surgically difficult lesions. Current embolic agents used to treat brain AVMs include both solid and liquid agents. Liquid agents including N-butyl cyanoacrylate and Onyx are the most commonly used agents. As newer embolic agents become available and as microcatheter technology improves, the role of endovascular treatment for brain AVMs will likely expand.


title: Maternal complications following open and fetoscopic fetal surgery: A systematic review and meta-analysis.

text: OBJECTIVE To establish maternal complication rates for fetoscopic or open fetal surgery. METHODS We conducted a systematic literature review for studies of fetoscopic or open fetal surgery performed since 1990, recording maternal complications during fetal surgery, the remainder of pregnancy, delivery, and after the index pregnancy. RESULTS One hundred sixty-six studies were included, reporting outcomes for open fetal (n = 1193 patients) and fetoscopic surgery (n = 9403 patients). No maternal deaths were reported. The risk of any maternal complication in the index pregnancy was 20.9% (95%CI, 15.22-27.13) for open fetal and 6.2% (95%CI, 4.93-7.49) for fetoscopic surgery. For severe maternal complications (grades III to V Clavien-Dindo classification of surgical complications), the risk was 4.5% (95% CI 3.24-5.98) for open fetal and 1.7% (95% CI, 1.19-2.20) for fetoscopic surgery. In subsequent pregnancies, open fetal surgery increased the risk of preterm birth but not uterine dehiscence or rupture. Nearly one quarter of reviewed studies (n = 175, 23.3%) was excluded for failing to report the presence or absence of maternal complications. CONCLUSIONS Maternal complications occur in 6.2% fetoscopic and 20.9% open fetal surgeries, with serious maternal complications in 1.7% fetoscopic and 4.5% open procedures. Reporting of maternal complications is variable. To properly quantify maternal risks, outcomes should be reported consistently across all fetal surgery studies.


title: Anti-thrombotic therapy in patients with atrial fibrillation and intracranial hemorrhage.

text: Patients with atrial fibrillation have an increased risk of ischemic stroke that can be dramatically lowered by treatment with anticoagulants. The annual rate of major bleeds with warfarin averages about 2%. The rates of intracerebral and intracranial bleeds are significantly reduced with the use of the novel direct oral anticoagulants (DOACs) compared with warfarin. Treatment of anticoagulation-related intracerebral hemorrhage is based on the results of case series and small trials. Resumption of anticoagulation in patients with atrial fibrillation who had an intracerebral bleed depends on the etiology and location of the bleeding and the absolute rate of stroke in the absence of anticoagulation.


title: Endovascular management and treatment of acute ischemic stroke.

text: Endovascular intra-arterial therapy is reserved for strokes from large vessel occlusion. This article reviews the critical role of the location of the occlusion, extent and characteristics of the occlusive thrombus on noninvasive imaging, and identification of ischemic core and salvageable tissue on perfusion imaging for proper patient selection. The advantages of stentrievers over other mechanical thrombectomy approaches are discussed and the role of the aspiration thrombectomy approach in modern clinical practice is reviewed. Finally, the implications of the results of recent randomized trials of endovascular therapy on the future of intra-arterial revascularization therapies are discussed.