title: Redirecting lentiviral vectors pseudotyped with Sindbis virus-derived envelope proteins to DC-SIGN by modification of N-linked glycans of envelope proteins.

text: Redirecting the tropism of viral vectors enables specific transduction of selected cells by direct administration of vectors. We previously developed targeting lentiviral vectors by pseudotyping with modified Sindbis virus envelope proteins. These modified Sindbis virus envelope proteins have mutations in their original receptor-binding regions to eliminate their natural tropisms, and they are conjugated with targeting proteins, including antibodies and peptides, to confer their tropisms on target cells. We investigated whether our targeting vectors interact with DC-SIGN, which traps many types of viruses and gene therapy vectors by binding to the N-glycans of their envelope proteins. We found that these vectors do not interact with DC-SIGN. When these vectors were produced in the presence of deoxymannojirimycin, which alters the structures of N-glycans from complex to high mannose, these vectors used DC-SIGN as their receptor. Genetic analysis demonstrated that the N-glycans at E2 amino acid (aa) 196 and E1 aa 139 mediate binding to DC-SIGN, which supports the results of a previous report of cryoelectron microscopy analysis. In addition, we investigated whether modification of the N-glycan structures could activate serum complement activity, possibly by the lectin pathway of complement activation. DC-SIGN-targeted transduction occurs in the presence of human serum complement, demonstrating that high-mannose structure N-glycans of the envelope proteins do not activate human serum complement. These results indicate that the strategy of redirecting viral vectors according to alterations of their N-glycan structures would enable the vectors to target specific cells types expressing particular types of lectins.


title: Early Electrodiagnosis in the Management of Neonatal Brachial Plexus Palsy.

text: Neonatal brachial plexus palsy (NBPP) is an important form of newborn morbidity with potentially disabling persistence. Neurosurgical intervention is indicated in selected patients. Early prognostic assessment would facilitate rational selection of those infants for surgery. We conducted a systematic literature review to determine the prognostic value of early electrodiagnosis (EDX) in NBPP. We included 16 observational studies with a total sample size of 747 children. Risk of bias and quality of evidence were rated. Wide variation was found in EDX techniques, outcome algorithms and decision making. Nevertheless, the most methodologically sound studies support the use of EDX, at standardized time frames, as key prognostic modality complementing clinical judgement and neuroimaging. An accurate knowledge of underlying anatomy of the nerve injury helps to counsel families and to guide reconstructive strategy. This article is protected by copyright. All rights reserved.


title: Advances in the Relationship Between Coronavirus Infection and Cardiovascular Diseases

text: The outbreak of coronavirus disease 2019 (COVID-19) has once again aroused people's concern about coronavirus. Seven human coronaviruses (HCoVs) have been discovered so far, including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU115, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 2. Existing studies show that the cardiovascular disease increased the incidence and severity of coronavirus infection. At the same time, myocardial injury caused by coronavirus infection is one of the main factors contributing to poor prognosis. In this review, the recent clinical findings about the relationship between coronaviruses and cardiovascular diseases and the underlying pathophysiological mechanisms are discussed. This review aimed to provide assistance for the prevention and treatment of COVID-19.


title: Mouse fibroblast L929 cells are less permissive to infection by Nelson Bay orthoreovirus compared to other mammalian cell lines.

text: In recent years, bats have been identified as a natural reservoir for a diverse range of viruses. Nelson Bay orthoreovirus (NBV) was first isolated from the heart blood of a fruit bat (Pteropus poliocephalus) in 1968. While the pathogenesis of NBV remains unknown, other related members of this group have caused acute respiratory disease in humans. Thus the potential for NBV to impact human health appears plausible. Here, to increase our knowledge of NBV, we examined the replication and infectivity of NBV using different mammalian cell lines derived from bat, human, mouse and monkey. All cell lines supported the replication of NBV; however, L929 cells showed a greater than 2 log reduction in virus titre compared with the other cell lines. Furthermore, NBV did not induce major cytopathic effects in the L929 cells, as was observed in other cell lines. Interestingly, the related Pteropine orthoreoviruses, Pulau virus (PulV) and Melaka virus (MelV) were able to replicate to high titres in L929 cells but infection resulted in reduced cytopathic effect. Our study demonstrates a unique virus-host interaction between NBV and L929 cells, where cells effectively control viral infection/replication and limit the formation of syncytia. By elucidating the molecular mechanisms that control this unique relationship, important insights will be made into the biology of this fusogenic virus.


title: Effects of sodium bicarbonate correction of metabolic acidosis on regional tissue oxygenation in very low birth weight neonates.

text: OBJECTIVE To determine the effects of sodium bicarbonate (NaHCO3) correction of metabolic acidosis on cardiopulmonary, laboratory, and cerebral, renal and splanchnic regional oxygen saturation (rSO2) and fractional tissue oxygen extraction (FTOE) in extremely premature neonates during the first postnatal week. STUDY DESIGN Observational cohort data were collected from 500 to 1250 g neonates who received NaHCO3 'half' corrections (0.3 * Weight (kg) * Base Deficit (mmol l(-1))) for presumed renal losses. RESULT Twelve subjects with normal blood pressure and heart rate received 17 NaHCO3 corrections. Mean (±s.d.) gestational age was 27±2 week and birth weight was 912±157 g. NaHCO3 corrections provided a mean (±s.d.) 4.5±1.0 ml kg(-1) fluid bolus, shifted mean (±s.d.) base deficit from 7.6±1.8 to 3.4±2.1 mmol l(-1) (P<0.05), and increased median (±s.d.) pH from 7.23±0.06 to 7.31±0.05 (P<0.05). No significant changes in blood pressure, pulse oximetry, PCO2, lactate, sodium, blood urea nitrogen, creatinine or hematocrit were observed. Cerebral, renal and splanchnic rSO2 (74%, 66% and 44%, respectively, at baseline) and FTOE (0.21, 0.29 and 0.52, respectively, at baseline) were unchanged following NaHCO3 correction. CONCLUSION NaHCO3 infusions decreased base deficits and increased pH though produced no discernible effects or benefits on cardiopulmonary parameters including rSO2 and FTOE. These findings warrant further prospective evaluation in larger populations with more significant metabolic acidosis to determine the utility of tissue oxygenation monitoring in differentiating metabolic acidosis due to oxygen delivery/consumption imbalance versus renal bicarbonate losses.


title: Reward Responsiveness Varies by Smoking Status in Women with a History of Major Depressive Disorder.

text: Major depressive disorder (MDD) and nicotine dependence are highly comorbid, with studies showing that ~50% of individuals with MDD smoke. The link between these disorders persists even after the clinical symptoms of depression subside, as indicated by high levels of nicotine dependence among individuals with remitted depression (rMDD). Recent evidence indicates that individuals with rMDD show blunted responses to reward as measured by a probabilistic reward task (PRT), which assesses the ability to modify behavior as a function of reward history. Given nicotine's ability to enhance reward responsiveness, individuals with rMDD might smoke to address this persistent reward deficit. However, it is unclear whether smokers with rMDD show enhanced reward responsiveness relative to rMDD individuals who do not smoke. To test this hypothesis, we evaluated reward responsiveness on the PRT in four groups (N=198): individuals with and without rMDD who were or were not nicotine dependent. As hypothesized, rMDD nonsmokers had lower reward responsiveness relative to both control nonsmokers and rMDD smokers; conversely, smokers with rMDD showed behavioral patterns comparable to those without a history of depression. Given nicotine's ability to enhance reward sensitivity, it is possible that nicotine normalizes the otherwise blunted reward responsiveness in individuals with rMDD. Therapies aimed at enhancing this reward-based deficit may be beneficial in the treatment of both nicotine dependence and MDD.


title: Palliative Care: Too Good to Be True?

text: INTRODUCTION Many patients and their families are hesitant to consult a palliative care (PC) team. In 2014, approximately 6,000,000 people in the United States could benefit from PC, and this number is expected to increase over the next 25 years. OBJECTIVES The purpose of this review is to shed light on the significance of PC and provide a holistic view outlining both the benefits and existing barriers. METHODS A literature search was conducted using MEDLINE (PubMed), Cochrane Central Register of Controlled Trials, and Web of Science to identify articles published in journals from 1948 to 2019. A narrative approach was used to search the grey literature. DISCUSSION Traditionally, the philosophy behind PC was based on alleviating suffering associated with terminal illnesses; PC was recommended only after other treatment options had been exhausted. However, the tenets of PC are applicable to anyone with a life-threatening illness as it is beneficial in conjunction with traditional treatments. It is now recognized that PC services are valuable when initiated alongside disease-modifying therapy early in the disease course. Studies have shown that PC decreased total symptom burden, reduced hospitalizations, and enabled patients to remain safely at home. CONCLUSION As the population ages and chronic illnesses become more widespread, there continues to be a growing need for PC programs. The importance of PC should not be overlooked despite existing barriers such as the lack of professional training and the cost of implementation. Education and open discussion play essential roles in the successful early integration of PC.


title: WEB device for endovascular treatment of wide-neck bifurcation aneurysms.

text: BACKGROUND AND PURPOSE The WEB is an intrasaccular flow disrupter dedicated to EVT of IA. We report our initial experience in a series of patients treated with this device. MATERIALS AND METHODS This prospective study was approved by the authors' ethical committees. Nineteen patients with 20 unruptured wide-neck bifurcation IAs were treated by WEB placement. Technical issues, immediate posttreatment angiographic findings, and clinical and imaging follow-up at 3, 6, and 12 months were assessed. RESULTS Failure of WEB placement occurred in 1 case because of unavailability of a suitably sized device. Embolization was successful in 18 patients with 19 IAs, and it required additional stent placement and/or coiling in 3 cases at the acute phase and in 1 case at follow-up. Two patients experienced a symptomatic complication, and 16 patients had normal neurologic examination findings at discharge. Immediate anatomic outcome showed 1 complete occlusion, 13 near-complete occlusions, and 5 incomplete occlusions. At follow-up, 17 patients had normal neurologic examination findings and 1 retained a hemiparesis. Angiographic controls were obtained in all patients (mean, 6 months), and they showed stable or improved results in all except 4 cases, including 2 complete occlusions, 15 near-complete occlusions, and 2 incomplete occlusions. CONCLUSIONS In this initial series of patients, EVT of wide-neck bifurcation IAa with the WEB was feasible. Further studies are needed to evaluate the indications, safety, and efficacy of this new technique.


title: Single-incision plus one-port laparoscopic abdominoperineal resection with bilateral pelvic lymph node dissection for advanced rectal cancer: a case report.

text: With regard to laparoscopic and robotic abdominoperineal resection (APR) for primary rectal malignancies, limited data have been published in the literature. Single-incision laparoscopic surgery (SLS) has been successfully introduced for treating colorectal cancer. Here we describe our experience of APR with SLS plus one port (SLS + 1) for treating advanced rectal cancer. A 65-year-old man underwent the procedure, which involved a 35-mm incision in the left side of the umbilicus for the insertion of a single multichannel port as well as the insertion of a 5-mm port into the right lower quadrant. The sigmoid colon and rectum were mobilized from the pelvic floor using a medial and lateral approach. After the rectum with the mesorectum was completely mobilized according to the total mesorectal excision, the sigmoid colon was intracorporeally transected. The specimen was removed through the perineal wound. Terminal colostomy was fashioned at the left lower trocar site. Lateral pelvic lymph node dissection was bilaterally performed. There were no perioperative complications. The total operating time was 592 minutes, and the estimated blood loss was 180 mL. To our knowledge, this is the first reported case of SLS + 1 APR with lateral pelvic lymph node dissection for treating rectal cancer. We conclude that SLS + 1 APR is a technically promising alternative method for treating selected patients with advanced rectal cancer.


title: Incidence, Predictors, and Outcomes of High-Grade Atrioventricular Block in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention (from the HORIZONS-AMI Trial).

text: High-grade atrioventricular block (HAVB) is historically considered a marker of worse outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, the predictors and prognostic impact of HAVB in the primary percutaneous coronary intervention (PCI) era remain poorly understood. We sought to describe the characteristics and predictors of HAVB in patients undergoing primary PCI in STEMI and to assess the prognostic significance of HAVB in the contemporary reperfusion era. The present analysis includes 3,115 patients presenting with STEMI from the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial who underwent primary PCI. Outcomes were examined according to the presence of HAVB on a presenting electrocardiogram, as interpreted by an independent electrocardiography core laboratory. HAVB (second-degree Mobitz II or third-degree atrioventricular block) was present at baseline in 46 patients (1.5%). Independent predictors of HAVB included increased age, diabetes mellitus, right coronary artery occlusion, sum of ST-segment deviation, and baseline Thrombolysis In Myocardial Infarction flow 0/1. Thrombolysis In Myocardial Infarction flow 3 was restored in 83.7% and 91.5% of patients with versus without baseline HAVB respectively (p = 0.06). Mortality rate was significantly higher in patients with versus without HAVB at 30-day, 1-, and 3-year follow-ups (unadjusted hazard ratio [HR] 3.83, 95% CI 1.40 to 10.48; unadjusted HR 4.37, 95% CI 2.09 to 9.38 and unadjusted HR 2.78, 95% CI 1.31 to 5.91, respectively). After covariate adjustment, mortality rate was significantly higher in patients with HAVB at 1 year (adjusted HR 2.45, 95% CI 1.09 to 5.50, p = 0.03) but not at 30 days (adjusted HR 1.70, 95% CI 0.58 to 5.01, p = 0.33) or 3 years (adjusted HR 0.71 to 3.41, p = 0.27). In conclusion, HAVB is a rare complication of STEMI but remains associated with increased mortality, even after primary PCI.


title: Transoral robotic surgery for upper airway pathology in the pediatric population.

text: OBJECTIVES/HYPOTHESIS The purpose of this study is to present one of the largest case series of pediatric transoral robotic surgery (TORS) in the upper airway demonstrating a wide range of ages and indications. STUDY DESIGN A retrospective case series at an academic tertiary referral center from August 2010 to September 2014. METHODS The da Vinci surgical robot (Intuitive Surgical, Inc., Sunnyvale, CA) was used on 16 pediatric patients for 18 procedures. A variety of upper airway pathologies and reconstructions in children with a wide range of ages and weights were treated. No lingual tonsillectomies or base-of-tongue reductions were included. RESULTS Sixteen children (6 males) underwent 18 TORS procedures, including resection of hamartoma (n = 1), repair of laryngeal cleft (n = 7), removal of saccular cyst (n = 2), release of pharyngeal or esophageal strictures (n = 2), and excision of lymphatic malformations (n = 4). Patient ages ranged from 14 days to 15 years. There were no intraoperative complications. All patients had successful robotic access, and no patients had conversions to open or traditional endoscopic surgery. Hospital courses varied with duration ranging from 1 to 20 days. The median follow up was 22 months. CONCLUSION Applying TORS to the pediatric population can be feasible and safe for appropriate airway pathologies. Because many patients are small in size, there is inherent risk in using robotic instruments and scopes transorally. Pearls in this series include a standardized two-robot experienced attending team and longitudinal airway follow-up. LEVEL OF EVIDENCE 4 Laryngoscope, 127:247-251, 2017.


title: Extracellular vesicles as an efficient nanoplatform for the delivery of therapeutics.

text: Extracellular vesicles (EVs) are membrane-derived vesicles that are enriched with RNAs, proteins and other functional molecules. We exploit the unique physical properties of EVs as a promising and advantageous nanoplatform for the delivery of therapeutic drugs and genetic materials. Early successes in the discovery of various disease-related characteristics of EVs have driven a new wave of innovation in developing nanoscale drug-delivery systems (DDSs). Nevertheless, there are several issues that need to be considered during the development of these alternative DDSs, such as standardized isolation and preservation methods, efficient drug encapsulation, mechanisms of drug release and so on. In this mini-review, we summarize the current status and progress of EV-based DDSs as an efficient nanoplatform for therapeutics delivery, followed by a discussion on their challenges and future prospects for clinical translation and applications.


title: The Utility of Near-Infrared Fluorescence and Indocyanine Green During Robotic Pulmonary Resection.

text: During minimally invasive pulmonary resection, it is often difficult to localize pulmonary nodules that are small (<2 cm), low-density/subsolid on imaging, or deep to the visceral pleura. The use of near-infrared fluorescence (NIF) imaging for localizing pulmonary nodules using indocyanine green (ICG) contrast is an emerging technology that is increasingly utilized during pulmonary resection. When administered via electromagnetic navigational bronchoscopy (ENB), ICG can accurately localize pulmonary nodules. When injected intravenously (IV), ICG can also help delineate the intersegmental plane. Research is ongoing regarding the utility of ICG for identification of the sentinel lymph node in lung cancer.


title: [The differential diagnosis for novel coronavirus pneumonia and similar lung diseases in general hospitals].

text: Novel coronavirus pneumonia was novel coronavirus infection that has dominated pulmonary infection since December 2019. The main manifestations were fever, dry cough, shortness of breath, normal or leukopenia in peripheral blood and changes in chest CT and in severe cases, multiple organ failure might occur. The National Health Commission, PRC has revised the consensus on diagnosis and treatment seven times in a short period of time, indicating the growing understanding of the disease. Patients with novel coronavirus pneumonia usually had history of travelling or living in the epidemic area including Wuhan within 14 days before onset, or have been exposed to patients who had fever or respiratory symptoms from the epidemic area, or had clustering diseases. However, novel coronavirus pneumonia was becoming more and more blurred after vanishing epidemic. The diagnosis and differential diagnosis of novel coronavirus pneumonia was facing challenges not only because of large number of tourists increasing dramatically after the relieving of epidemic, but also patients with other diseases return from different areas to search for medical care. In this article, the clinical and chest imaging features of the novel coronavirus pneumonia were reviewed and compared with other infections and non-infectious diffuse pulmonary diseases. We were trying to find the similarities and differences among them, and to identify clues to the diagnosis of novel coronavirus pneumonia, so as to ensure accurate diagnosis and treatment.


title: The Role of Emergency Endoscopy in Small Bowel Bleeding: A Review.

text: There is no consensus on the timing and management of emergency overt obscure gastrointestinal bleeding. Emergency capsule endoscopy and balloon-assisted enteroscopy have a high diagnostic and therapeutic yield in these situations. Most lesions detected by small bowel endoscopy are amenable to endoscopic haemostasis, although some lesions still require surgery or interventional radiology. The management of these patients is varied, and doubt persists about which technique should be preferred as first-line treatment. This narrative review analyses the usefulness and impact of small bowel endoscopic techniques in the emergency setting for severe overt obscure gastrointestinal bleeding.


title: Predictive factors for brace treatment outcome in adolescent idiopathic scoliosis: a best-evidence synthesis.

text: PURPOSE To evaluate predictive factors for brace treatment outcome in adolescent idiopathic scoliosis (AIS) by a systematic review of the literature. METHODS Eligible studies evaluating one or more predictive factors for brace treatment outcome were included following a systematic search in PubMed and EMBASE on October 23, 2017. Inclusion criteria were: (1) subjects diagnosed with AIS, (2) age ≤ 18 years, (3) treated with a thoraco-lumbo-sacral orthosis (TLSO), and (4) evaluated one or more predictive factors of treatment outcome (failure and/or success). The methodological quality of included studies was independently assessed by two authors. Pooling was not possible due to heterogeneity in statistical analysis. Predictive factors were presented according to a best-evidence synthesis. RESULTS The literature search identified 26 studies that met the inclusion criteria, and multiple types of TLSO braces were identified (Boston, Wilmington, Chêneau, Osaka Medical College, Dresdner Scoliosis Orthosis and SPoRT). A total of 19 radiographic and 8 clinical predictive factors were reported. Strong evidence was found that lack of initial in-brace correction is associated with treatment failure. Moderate evidence suggests that brace wear time is associated with failure and success, whereas initial curve magnitude and curve type are not. CONCLUSION The results of this review suggest that lack of initial in-brace correction is strongly associated with brace treatment failure. Future studies on the threshold for minimal immediate in-brace correction, as a potential indication for brace treatment, are recommended. These slides can be retrieved under Electronic Supplementary Material.


title: Response to avian influenza and preparedness for pandemic influenza: Thailand's experience.

text: Thailand has been struggling to control and prevent H5N1 avian influenza on both the animal health and public health fronts. Prevention and control programs for animals and humans are improving, with infections in poultry currently under control and no human cases seen in 2007. In awareness of the risk of an influenza pandemic, Thailand is joining global efforts in pandemic influenza preparedness. The national preparedness plan highlights building of national capacity for self-reliance and regional/international cooperation. Public health response to avian influenza and pandemic preparedness benefit significantly from the experience of responses to severe acute respiratory syndrome. This underlines the need to strengthen infrastructure and manpower, ensure public confidence and cooperation, secure maximum government advocacy and support, and forge multi-sector and international cooperation.


Ethics and extracorporeal membrane oxygenation during coronavirus disease 2019 outbreak.


title: Laparoscopic splenectomy: operative technique and outcome in three cats.

text: CLINICAL SUMMARY: The clinical findings, treatment and outcome for three cats that underwent laparoscopic splenectomy using bipolar vessel-sealing devices for resection of diffuse splenic disease are described. In each case, a three-portal laparoscopic technique was used. The spleen was manipulated and its mesentery and associated vessels sequentially cauterized and ligated to enable removal through a portal incision with minimal hemorrhage. Each of the three patients recovered from anesthesia without incident and was able to be discharged to the owner the next day. PRACTICAL SIGNIFICANCE: Laparoscopic splenectomy may be a safe and effective alternative to celiotomy in a select group of cats requiring splenectomy.


title: A general approach for biomimetic mineralization of MOF particles using biomolecules.

text: Biomineralization of metal organic frameworks (MOFs) using biomolecules has recently attracted significant interest because of the benign process including room temperature, neutral pH and without the requirement of any other chemical reagents. Also, these biomolecule incorporated MOFs (biomolecules@MOFs) have demonstrated their potential in biomolecule encapsulation, protection and controlled release. This work aims to develop a general strategy to make biomolecules@MOFs via a biomimetic mineralization process. A library of biomolecules (peptides and proteins) with different charges were systematically studied to fundamentally understand the role of biomolecules and their proprieties in biomolecule-mediated MOF biomineralization. Biomolecule charge, amino acid sequence and stirring speed have been demonstrated to play important roles in controlling biomineralization reaction rate, particle shape and morphology.


title: Sex allocation plasticity on a transcriptome scale: Socially sensitive gene expression in a simultaneous hermaphrodite.

text: Phenotypic plasticity can enable organisms to produce optimal phenotypes in multiple environments. A crucial life history trait that is often highly plastic is sex allocation, which in simultaneous hermaphrodites describes the relative investment into the male versus female sex functions. Theory predicts-and morphological evidence supports-that greater investment into the male function is favoured with increasing group size, due to the increasing importance of sperm competition for male reproductive success. Here, we performed a genome-wide gene expression assay to test for such sex allocation plasticity in a model simultaneous hermaphrodite, the free-living flatworm Macrostomum lignano. Based on RNA-Seq data from 16 biological replicates spanning four different group size treatments, we demonstrate that at least 10% of the >75,000 investigated transcripts in M. lignano are differentially expressed according to the social environment, rising to >30% of putative gonad-specific transcripts (spermatogenesis and oogenesis candidates) and tail-specific transcripts (seminal fluid candidates). This transcriptional response closely corresponds to the expected shift away from female and towards male reproductive investment with increasing sperm competition level. Using whole-mount in situ hybridization, we then confirm that many plastic transcripts exhibit the expected organ-specific expression, and RNA interference of selected testis- and ovary-specific candidates establishes that these indeed function in gametogenesis pathways. We conclude that a large proportion of sex-specific transcripts in M. lignano are differentially expressed according to the prevailing ecological conditions and that these are functionally relevant to key reproductive phenotypes. Our study thus begins to bridge organismal and molecular perspectives on sex allocation plasticity.


Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State.


title: Long-term outcomes following microwave ablation for liver malignancies.

text: BACKGROUND Microwave ablation has emerged as a promising treatment for liver malignancies, but there are scant long-term follow-up data. This study evaluated long-term outcomes, with a comparison of 915-MHz and 2.4-GHz ablation systems. METHODS This was a retrospective review of patients with malignant liver tumours undergoing operative microwave ablation with or without liver resection between 2008 and 2013. Regional or systemic (neo)adjuvant therapy was given selectively. Local recurrence was analysed using competing-risk methods with clustering, and overall survival was determined from Kaplan-Meier curves. RESULTS A total of 176 patients with 416 tumours were analysed. Colorectal liver metastases (CRLM) comprised 81.0 per cent of tumours, hepatocellular carcinoma 8.4 per cent, primary biliary cancer 1.7 per cent and non-CRLM 8.9 per cent. Median follow-up was 20.5 months. Local recurrence developed after treatment of 33 tumours (7.9 per cent) in 31 patients (17.6 per cent). Recurrence rates increased with tumour size, and were 1.0, 9.3 and 33 per cent for lesions smaller than 1 cm, 1-3 cm and larger than 3 cm respectively. On univariable analysis, the local recurrence rate was higher after ablation of larger tumours (hazard ratio (HR) 2.05 per cm; P < 0.001), in those with a perivascular (HR 3.71; P = 0.001) or subcapsular (HR 2.71; P = 0.008) location, or biliary or non-CRLM histology (HR 2.47; P = 0.036), and with use of the 2.4-GHz ablation system (HR 3.79; P = 0.001). Tumour size (P < 0.001) and perivascular position (P = 0.045) remained significant independent predictors on multivariable analysis. Regional chemotherapy was associated with decreased local recurrence (HR 0.49; P = 0.049). Overall survival at 4 years was 58.3 per cent for CRLM and 79.4 per cent for other pathology (P = 0.360). CONCLUSION Microwave ablation of liver malignancies, either combined or not combined with liver resection, and selective regional and systemic therapy resulted in good long-term survival. Local recurrence rates were low after treatment of tumours smaller than 3 cm in diameter, and those remote from vessels.


title: Procyanidin B1 purified from Cinnamomi cortex suppresses hepatitis C virus replication.

text: BACKGROUND A combination of pegylated interferon and ribavirin is the current standard therapy for hepatitis C virus (HCV) infection, but this combination provides relatively low efficacy, especially in some patients with HCV genotype 1 infection; therefore, the development of novel therapeutic agents is required for further improvement in the treatment of chronic HCV infection. METHODS HCV pseudotype and subgenomic replicon assays were used in this study. The interaction of compounds with HCV receptors was examined using flow cytometry. Intracellular RNA levels were determined by semi-quantitative reverse transcriptase PCR. RESULTS Procyanidin B1 (PB1), a dimer of (-)-epicatechin and (+)-catechin, purified from Cinnamomi cortex, inhibits infection by vesicular stomatitis virus and HCV pseudotype virus in Huh-7 cells, with 50% effective concentrations of 29 and 15 microM, respectively. No inhibitory effects were observed in each component of PB1. We found that PB1 does not interfere with viral entry or receptor expression, but inhibits HCV RNA synthesis in a dose-dependent manner. CONCLUSIONS These results indicate that PB1 suppresses HCV RNA synthesis, possibly as a HCV RNA polymerase inhibitor. Our results might contribute towards the development of more effective inhibitors for HCV infection from natural plants.


title: Synthesis and characterization of a high-affinity NOTA-conjugated bombesin antagonist for GRPR-targeted tumor imaging.

text: The gastrin-releasing peptide receptor (GRPR/BB2) is a molecular target for the visualization of prostate cancer. This work focused on the development of high-affinity, hydrophilic, antagonistic, bombesin-based imaging agents for PET and SPECT. The bombesin antagonist analog d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 ([d-Phe(6),Sta(13),Leu(14)]bombesin[6-14]) was synthesized and conjugated to 1,4,7-triazacyclononane-N,N',N″-triacetic acid (NOTA) via a diethylene glycol (PEG2) linker. The resulting conjugate, NOTA-PEG2-[d-Phe(6),Sta(13),Leu(14)]bombesin[6-14] (NOTA-P2-RM26), was labeled with (68)Ga (T1/2 = 68 min, positron emitter) and (111)In (T1/2 = 2.8 days, gamma emitter). The labeling stability, specificity, inhibition efficiency (IC50), and dissociation constant (KD) of both labeled compounds as well as their cellular retention and internalization were investigated. The pharmacokinetics of the dual isotope ((111)In/(68)Ga)-labeled peptide in both normal NMRI mice and PC-3 tumor-bearing Balb/c nu/nu mice was also studied. NOTA-P2-RM26 was labeled with (111)In and (68)Ga at a radiochemical yield of >98%. Both conjugates were shown to have high specificity and binding affinity for GRPR. The KD value was determined to be 23 ± 13 pM for the (111)In-labeled compound in a saturation binding experiment. In addition, (nat)In- and (nat)Ga-NOTA-P2-RM26 showed low nanomolar binding inhibition concentrations (IC50 = 1.24 ± 0.29 nM and 0.91 ± 0.19 nM, respectively) in a competitive binding assay. The internalization rate of the radiolabeled conjugates was slow. The radiometal-labeled tracers demonstrated rapid blood clearance via the kidney and GRPR-specific uptake in the pancreas in normal mice. Tumor targeting and biodistribution studies in mice bearing PC-3 xenografts displayed high and specific uptake in tumors (8.1 ± 0.4%ID/g for (68)Ga and 5.7 ± 0.3%ID/g for (111)In) and high tumor-to-background ratios (tumor/blood: 12 ± 1 for (68)Ga and 10 ± 1 for (111)In) after only 1 h p.i. of 45 pmol of peptide. The xenografts were visualized by gamma and microPET cameras shortly after injection. In conclusion, the antagonistic bombesin analog NOTA-PEG2-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (NOTA-P2-RM26) is a promisindg candidate for prostate cancer imaging using PET and SPECT/CT.


title: Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe.

text: Following the emergence of a novel coronavirus1 (SARS-CoV-2) and its spread outside of China, Europe has experienced large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions such as closure of schools and national lockdowns. We study the impact of major interventions across 11 European countries for the period from the start of COVID-19 until the 4th of May 2020 when lockdowns started to be lifted. Our model calculates backwards from observed deaths to estimate transmission that occurred several weeks prior, allowing for the time lag between infection and death. We use partial pooling of information between countries with both individual and shared effects on the reproduction number. Pooling allows more information to be used, helps overcome data idiosyncrasies, and enables more timely estimates. Our model relies on fixed estimates of some epidemiological parameters such as the infection fatality rate, does not include importation or subnational variation and assumes that changes in the reproduction number are an immediate response to interventions rather than gradual changes in behavior. Amidst the ongoing pandemic, we rely on death data that is incomplete, with systematic biases in reporting, and subject to future consolidation. We estimate that, for all the countries we consider, current interventions have been sufficient to drive the reproduction number [Formula: see text] below 1 (probability [Formula: see text]< 1.0 is 99.9%) and achieve epidemic control. We estimate that, across all 11 countries, between 12 and 15 million individuals have been infected with SARS-CoV-2 up to 4th May, representing between 3.2% and 4.0% of the population. Our results show that major non-pharmaceutical interventions and lockdown in particular have had a large effect on reducing transmission. Continued intervention should be considered to keep transmission of SARS-CoV-2 under control.


title: Prognostic Value of Leukocytosis and Lymphopenia for Coronavirus Disease Severity.

text: To evaluate lymphopenia as a marker for coronavirus disease severity, we conducted a meta-analysis of 10 studies. Severe illness was associated with lower lymphocyte and higher leukocyte counts. Using these markers for early identification of patients with severe disease may help healthcare providers prioritize the need to obtain therapy.


Social solidarity and the right to health: essential elements for people-centred health systems.


The COVID-19 Pandemic in the US: A Clinical Update.


title: Stereotactic irradiation of the resection cavity after surgical resection of brain metastases - when is the right timing?

text: Purpose: This study aimed to evaluate whether an early beginning of the adjuvant stereotactic radiotherapy after macroscopic complete resection of 1-3 brain metastases is essential or whether longer intervals between surgery and radiotherapy are feasible. Material and methods: Sixty-six patients with 69 resection cavities treated with HFSRT after macroscopic complete resection of 1-3 brain metastases between 2009 and 2016 in our institution were included in this study. Overall survival, local recurrence and locoregional recurrence were evaluated depending on the time interval from surgery to the start of radiation therapy. Results: Patients that started radiotherapy within 21 days from surgery had a significantly decreased OS compared to patients treated after a longer interval from surgery (p < .01). There was no significant difference between patients treated ≥ 34 and 22-33 days from surgery (p = .210). In the univariate analysis, local control was superior for patients starting treatment 22-33 days from surgery compared to a later start (p = .049). This effect did not prevail in a multivariate model. There was no significant difference between patients treated within 21 days and patients treated more than 33 days after surgery (p = .203). Locoregional control was not influenced by RT timing (p = .508). Conclusion: A short delay in the start of radiotherapy does not seem to negatively impact the outcome in patients with resected brain metastases. We even observed an unexpected reduction in OS in patients treated within 21 days from surgery. Further studies are needed to define the optimal timing of postoperative radiotherapy to the resection cavity.


title: Evidence of protective effect of hydroxychloroquine to prevent COVID-19.

text: We would like to share ideas on the report on "Hydroxychloroquine in Patients with Rheumatic Disease Complicated by COVID-19: Clarifying Target Exposures and the Need for Clinical Trials [1]."Balevic noted that "well-designed clinical trials that include patients with rheumatic disease are urgently needed to characterize the efficacy, safety, and target exposures for hydroxychloroquine [1]."


title: Patient selection for stroke endovascular therapy--DWI-ASPECTS thresholds should vary among age groups: insights from the RECOST study.

text: BACKGROUND AND PURPOSE The purpose of this study was to evaluate the benefits of endovascular intervention in large-vessel occlusion strokes, depending on age class. MATERIALS AND METHODS A clinical management protocol including intravenous treatment and mechanical thrombectomy was instigated in our center in 2009 (Prognostic Factors Related to Clinical Outcome Following Thrombectomy in Ischemic Stroke [RECOST] study). All patients with acute ischemic stroke with an anterior circulation major-vessel occlusion who presented within 6 hours were evaluated with an initial MR imaging examination and were analyzed according to age subgroups (younger than 50 years, 50-59 years, 60-69 years, 70-79 years; 80 years or older). The mRS score at 3 months was the study end point. RESULTS One hundred sixty-five patients were included in the analysis. The mean age was 67.4 years (range, 29-90 years). The mean baseline NIHSS score was 17.24 (range, 3-27). The mean DWI-derived ASPECTS was 6.4. Recanalization of TICI 2b/3 was achieved in 80%. At 3 months, 41.72% of patients had a good outcome, with a gradation of prognosis depending on the age subgroup and a clear cutoff at 70 years. Only 19% of patients older than 80 years had a good outcome at 3 months (mean ASPECTS = 7.4) with 28% for 70-79 years (mean ASPECTS = 6.8), but 58% for 60-69 years (mean ASPECTS = 6), 52% for 50-59 years (mean ASPECTS = 5.91), and 72% for younger than 50 years (mean ASPECTS = 6.31). In contrast, the mortality rate was 35% for 80 years and older, and 26% for 70-79 versus 5%-9% for younger than 70 years. CONCLUSIONS The elderly may benefit from thrombectomy when their ischemic core volume is low in comparison with younger patients who still benefit from acute recanalization despite larger infarcts. Stroke volume thresholds should, therefore, be related and adjusted to the patient's age group.


title: Demonstration of Ornithobacterium rhinotracheale in pheasants (Phasianus colchicus) with pneumonia and airsacculitis.

text: Outbreaks of respiratory disease were investigated in reared pheasants (Phasianus colchicus) aged approximately 18 to 32 weeks, released into the semi-wild on four shooting estates in southern England. The clinical signs in the affected birds included swelling of the face and eyes, loss of condition, gasping respirations and coughing. The gross pathology findings included sinusitis, airsacculitis, pleural oedema and lung lesions. The histopathological findings in the affected lungs were characterized by a granulomatous pneumonia. Ornithobacterium rhinotracheale (ORT) was isolated from respiratory tract tissues, and 16S rRNA gene sequencing on three isolates revealed two distinct genotypes, one previously associated with some electrophoretic type (ET) 1 strains and the other a novel genotype that clustered among sequences previously associated with ET 3, ET 4, ET 5 and ET 6 isolates. The localization of ORT within the lung tissue was demonstrated by fluorescent in-situ hybridization in the bronchial exudate of three cases, although not within the granulomatous lesions themselves. In each case, ORT was identified as part of a complex of other respiratory agents including avian paramyxovirus type 2, avian coronavirus, Mycoplasma gallisepticum, Mycoplasma synoviae and other Mycoplasma species, Escherichia coli, Pasteurella multocida, other Pasteurellaceae and Syngamus trachea, suggesting synergism with other agents. Exposure to other intercurrent factors, including adverse weather conditions and internal parasitism, may also have exacerbated the severity of disease.


title: Acute stroke chameleons in a university hospital: Risk factors, circumstances, and outcomes.

text: OBJECTIVE To identify risk factors, circumstances, and outcomes for individuals with acute ischemic stroke (AIS) chameleons (AIS-C) arriving in the emergency department of a university hospital. METHODS We retrospectively reviewed all patients with AIS from the prospectively constructed Acute Stroke Registry and Analysis of Lausanne during 8.25 years. AIS-C were defined as a failure to suspect stroke or as incorrect exclusion of stroke diagnosis. They were compared with patients diagnosed correctly at the time of admission. RESULTS Forty-seven of 2,200 AIS were missed (2.1%). These AIS-C were either very mild or very severe strokes. Multivariate analysis showed a younger age in patients with AIS-C (odds ratio [OR] per year 0.98, p < 0.01), less prestroke statin treatment (OR 0.29, p = 0.04), and lower diastolic admission blood pressure (OR 0.98 p = 0.04). They showed less eye deviation (OR 0.21, p = 0.04) and more cerebellar strokes (OR 3.78, p < 0.01). AIS-C were misdiagnosed as other neurologic (42.6% of cases) or nonneurologic (17.0%) disease, as unexplained decreased level of consciousness (21.3%), and as concomitantly present disease (19.1%). At 12 months, patients with AIS-C had less favorable outcomes (adjusted OR 0.21, p < 0.01) and higher mortality (adjusted OR 4.37, p < 0.01). CONCLUSIONS AIS are missed in patients with younger age with a lower cerebrovascular risk profile and may be masked by other acute conditions. Patients with chameleons present more often with milder strokes or coma, fewer focal signs and cerebellar strokes, and have higher disability and mortality rates at 12 months. These findings may be used to raise awareness in emergency departments to recognize and treat such patients appropriately.


title: Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury.

text: INTRODUCTION Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. METHODS We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. RESULTS Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. CONCLUSIONS Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. TRIAL REGISTRATION ClinicalTrials.gov number NCT01209169.


A Research Agenda on the Sexual and Reproductive Health Dimensions of the COVID-19 Pandemic in Africa.


title: Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age.

text: T cell-dependent B-cell responses decline with age, suggesting defective CD4 T-cell function. CD4 memory T cells from individuals older than 65 y displayed increased and sustained transcription of the dual-specific phosphatase 4 (DUSP4) that shortened expression of CD40-ligand (CD40L) and inducible T-cell costimulator (ICOS) (both P < 0.001) and decreased production of IL-4, IL-17A, and IL-21 (all P < 0.001) after in vitro activation. In vivo after influenza vaccination, activated CD4 T cells from elderly individuals had increased DUSP4 transcription (P = 0.002), which inversely correlated with the expression of CD40L (r = 0.65, P = 0.002), ICOS (r = 0.57, P = 0.008), and IL-4 (r = 0.66, P = 0.001). In CD4 KO mice reconstituted with DUSP4 OT-II T cells, DUSP4 had a negative effect on the expansion of antigen-specific B cells (P = 0.003) and the production of ova-specific antibodies (P = 0.03) after immunization. Silencing of DUSP4 in memory CD4 T cells improved CD40L (P < 0.001), IL-4 (P = 0.007), and IL-21 (P = 0.04) expression significantly more in the elderly than young adults. Consequently, the ability of CD4 memory T cells to support B-cell differentiation that was impaired in the elderly (P = 0.004) was restored. Our data suggest that increased DUSP4 expression in activated T cells in the elderly in part accounts for defective adaptive immune responses.


title: Pretreatment with and ongoing use of omega-3 fatty acid ethyl esters reduce the slow-flow phenomenon and prevent in-stent restenosis in patients undergoing carotid artery stenting.

text: OBJECTIVE Carotid artery stenting (CAS) is a less invasive alternative to carotid endarterectomy, but it is essential to prevent thromboembolic complications during CAS and to suppress in-stent restenosis (ISR) after CAS because of the relatively high risk of periprocedural and follow-up stroke events. Clinical trials have demonstrated the strong relationship of carotid plaque vulnerability with the subsequent risk of ipsilateral ischemic stroke and thromboembolic complications during CAS. Recent studies demonstrated that both low eicosapentaenoic acid (EPA) and low docosahexaenoic acid (DHA) levels were significantly associated with lipid-rich coronary and carotid plaques, but little is known about the effect of administration of omega-3 fatty acids (O-3FAs) containing EPA and DHA before and after CAS for stabilizing carotid plaque, preventing thromboembolic complications, and suppressing ISR. In this study, the efficacy of pretreatment with and ongoing daily use of O-3FA in addition to statin treatment was evaluated in patients undergoing CAS. METHODS This study was a nonrandomized prospective trial with retrospective analysis of historical control data. From 2012 to 2015, there were 100 consecutive patients with hyperlipidemia undergoing CAS for carotid artery stenosis who were divided into two groups. Between 2012 and 2013 (control period), 47 patients were treated with standard statin therapy. Between 2014 and 2015 (O-3FA period), patients were treated with statin therapy and add-on oral O-3FA ethyl esters containing 750 mg/d DHA and 1860 mg/d EPA from 4 weeks before CAS, followed by ongoing daily use for at least 12 months. In all patients, the plaque morphology by virtual histology intravascular ultrasound, the incidence of new ipsilateral ischemic lesions on the day after CAS, the slow-flow phenomenon during CAS, and ISR within 12 months after CAS were compared between the periods. RESULTS The slow-flow phenomenon during CAS with filter-type embolic protection devices decreased in the O-3FA period (1 of 53 patients [2%]) compared with the control period (7 of 47 patients [15%]; P = .02). Furthermore, ISR for 12 months after CAS was significantly decreased in the O-3FA period (1 of 53 patients [2%]) compared with the control period (10 of 47 patients [21%]; P = .01). On virtual histology intravascular ultrasound analysis, the fibrofatty area was significantly smaller and the fibrous area was significantly greater in the O-3FA period. On multivariate logistic regression analysis, a low EPA/arachidonic acid ratio and a symptomatic lesion were the factors related to vulnerable plaque (P = .01 [odds ratio, 5.24; 95% confidence interval, 1.65-16.63] and P = .01 [odds ratio, 11.72; 95% confidence interval, 2.93-46.86], respectively). CONCLUSIONS Pretreatment with O-3FA reduces the slow-flow phenomenon generated by plaque vulnerability during CAS, and on-going daily use of O-3FA suppresses ISR after CAS.


Poor adoption of hemodynamic optimization during major surgery: are we practicing substandard care?


Annals for Hospitalists Inpatient Notes - Preparing for Battle: How Hospitalists Can Manage the Stress of COVID-19.


title: [Psychological intervention in oral patients in novel coronavirus pneumonia outbreak period].

text: Public health emergencies have an impact on the public mental health. The outbreak of the novel coronavirus has affected the normal diagnosis and treatment services in oral medical institutions across the country. Delay of non-emergency dental service will have a potential impact on the experience, cognition, treatment and rehabilitation of patients with oral diseases. Through literature review, this paper reviewed the oral psychosomatic diseases closely related to patients' psychological state, such as oral mucosal disease, temporomandibular joint disease, bruxism, periodontal disease and so on. It was believed that these patients might be more susceptible to the impact of stress events, and dental specialists should pay more attention to them. At the same time, this paper analyzes the possible psychological stress symptoms of patients with different oral diseases, and puts forward suggestions for remote consultation and emergency treatment of dentists. From the perspective of social role, dentists not only played the role of expert in dental home professional guidance, but also played the role of psychological counseling for patients.


title: Case report: COVID-19 Masquerading as an Acute Surgical Abdomen.

text: SARS-CoV-2 infection can present with various clinical features, among which gastrointestinal manifestations such as nausea, diarrhea, vomiting, and mild abdominal pain have been reported. Recognition of rare presentations of SARS-CoV-2 infection has increased over time. These atypical and rare presentations may lead to difficulties in establishing the diagnosis in a timely manner; furthermore, they may lead to unnecessary investigations, extended hospital stays, adverse outcomes, and more strain on healthcare resources. We present three cases admitted to our hospital with a picture that mimicked an acute abdomen, necessitating surgical assessment and evaluation. All cases turned out to be SARS-CoV-2 positive and did not require surgical management. We discuss the management course, highlight the importance of abdominal symptoms in the setting of COVID-19, and discuss the implications of this association for medical practice amid the current pandemic in both resource-rich and resource-limited settings.


title: Microcirculation: Physiology, Pathophysiology, and Clinical Application.

text: This paper briefly reviews the physiological components of the microcirculation, focusing on its function in homeostasis and its central function in the realization of oxygen transport to tissue cells. Its pivotal role in the understanding of circulatory compromise in states of shock and renal compromise is discussed. Our introduction of hand-held vital microscopes (HVM) to clinical medicine has revealed the importance of the microcirculation as a central target organ in states of critical illness and inadequate response to therapy. Technical and methodological developments have been made in hardware and in software including our recent introduction and validation of automatic analysis software called MicroTools, which now allows point-of-care use of HVM imaging at the bedside for instant availability of functional microcirculatory parameters needed for microcirculatory targeted resuscitation procedures to be a reality.


title: Laparoscopic resection of a lymphangiomatous cyst of the colon: a case report.

text: INTRODUCTION Lymphangiomatous cysts are submucosal masses that are rarely found in the gastrointestinal tract and more often in the neck, oral cavity, and skin. These cysts are benign tumors and mostly clinically silent. Symptoms include abdominal pain, diarrhea, and rectal bleeding. Their pathogenesis remains unclear. CASE PRESENTATION During a routine ultrasound examination of a Caucasian 25-year-old woman, a structure that raised our suspicions of an ovarian cyst was found. MRI showed a 4.5 cm cystic lesion in the cecal region. Laparoscopic exploration revealed unexpected contact with the ascending colon. The cyst, including its base and of portion of the colon, was resected laparoscopically. The histological examination revealed cystic lymphangioma. CONCLUSION Lymphangiomatous cysts of the colon are very rare lesions. Although their pathology is benign, the recommended treatment is resection, which can be performed with minimal invasiveness.


title: Changes in obesity-related diseases and biochemical variables after laparoscopic sleeve gastrectomy: a two-year follow-up study.

text: BACKGROUND To evaluate changes in obesity-related diseases and micronutrients after laparoscopic sleeve gastrectomy (LSG). METHODS We started the procedure in May 2007, and by December 2011, 117 patients could be evaluated for a two year follow-up. Comparisons of preoperative status with 12 and 24 months postoperative status were made for body mass index (BMI), obesity-related diseases and micronutrients. RESULTS Major complications included bleeding requiring transfusion at 5.1%, leak at 1.7% and abscess without a visible leak at 0.9%. Mean BMI was reduced from 46.6 (standard deviation (SD) 6.0) kg/m2 to 30.6 (SD 5.6) kg/m2 at two years, and resolution occurred for 80.7% of patients with type 2 diabetes, 63.9% with hypertension, 75.8% with hyperlipidemia, 93.0% with sleep apnea, 31.4% with musculoskeletal pain, 85.4% with snoring and 73.3% with urinary incontinence. Amenorrhea resolved in all premenopausal females. The proportion of patients with symptomatic gastroesophageal reflux disease increased from 12.8% to 27.4%. The prevalence of patients with low ferritin-levels increased, while 25-hydroxyvitamin D (25(OH)D) deficiency decreased postoperatively. CONCLUSIONS LSG is an effective procedure for morbid obesity and obesity-related diseases, but the technique should be further explored particularly to avoid gastroesophageal reflux.


title: Two critical N-terminal epitopes of the nucleocapsid protein contribute to the cross-reactivity between porcine epidemic diarrhea virus and porcine transmissible gastroenteritis virus.

text: Both porcine epidemic diarrhoea virus (PEDV) and porcine transmissible gastroenteritis virus (TGEV), which cause high mortality in piglets and produce similar clinical symptoms and histopathological morphology, belong to the genus Alphacoronavirus. Serological diagnosis plays an important role in distinguishing pathogen species. Together with the spike (S) protein, the nucleocapsid (N) protein is one of the immunodominant regions among coronaviruses. In this study, two-way antigenic cross-reactivity between the N proteins of PEDV and TGEV was observed by indirect immunofluorescence assay (IFA) and Western blot analysis. Furthermore, the PEDV N protein harbouring truncations of amino acids (aa) 1 to 170 or aa 125 to 301 was demonstrated to cross-react with the anti-TGEV N polyclonal antibody (PAb), whereas the truncation-expressing aa 302 to 401 resulted in a specific reaction with the anti-PEDV N PAb but not with the anti-TGEV N PAb. Mutants of the PEDV N protein were generated based on sequence alignment and structural analysis; we then confirmed that the N-terminal residues 58-RWRMRRGERIE-68 and 78-LGTGPHAD-85 contributed to the cross-reactivity. All the results provide vital clues for the development of precise diagnostic assays for porcine coronaviruses.


title: Endovascular Stroke Treatment Outcomes After Patient Selection Based on Magnetic Resonance Imaging and Clinical Criteria.

text: IMPORTANCE Which imaging modality is optimal to select patients for endovascular stroke treatment remains unclear. OBJECTIVE To evaluate the effectiveness of specific magnetic resonance imaging (MRI) and clinical criteria in the selection of patients with acute ischemic stroke for thrombectomy. DESIGN, SETTING, AND PARTICIPANTS In this observational, single-center, prospective cohort study, we studied 72 patients with middle cerebral artery or terminal internal carotid artery occlusion using computed tomographic angiography, followed by core infarct volume determination by diffusion weighted MRI, who underwent thrombectomy after meeting institutional criteria from January 1, 2012, through December 31, 2014. In this period, 31 patients with similar ischemic strokes underwent endovascular treatment without MRI and are categorized as computed tomography only and considered in a secondary analysis. INTERVENTIONS Patients were prospectively classified as likely to benefit (LTB) or uncertain to benefit (UTB) using diffusion-weighted imaging lesion volume and clinical criteria (age, National Institutes of Health Stroke Scale score, time from onset, baseline modified Rankin Scale [mRS] score, life expectancy). MAIN OUTCOMES AND MEASURES The 90-day mRS score, with favorable defined as a 90-day mRS score of 2 or less. RESULTS Forty patients were prospectively classified as LTB and 32 as UTB. Reperfusion (71 of 103 patients) and prospective categorization as LTB (40 of 103 patients) were associated with favorable outcomes (P < .001 and P < .005, respectively). Successful reperfusion positively affected the distribution of mRS scores of the LTB cohort (P < .001). Reperfusion was achieved in 27 LTB patients (67.5%) and 24 UTB patients (75.0%) (P = .86). Favorable outcomes were obtained in 21 (52.5%) and 8 (25.0%) of LTB and UTB patients who were treated, respectively (P = .02). Favorable outcomes were observed in 20 of the 27 LTB patients (74.1%) who had successful reperfusion compared with 8 of the 24 UTB patients (33.3%) who had successful reperfusion (P = .004). The ratio of treated to screened patients was 1:3. CONCLUSIONS AND RELEVANCE Prospective classification as LTB by MRI and clinical criteria is associated with likelihood of favorable outcome after thrombectomy, particularly if reperfusion is successful. Selection of patients using MRI compares favorably with selection using computed tomographic techniques with the distinction that a higher proportion of screened patients were treated.


title: An Analysis of the Growth in Uptake of OpenWHO's Online Learning Resources for COVID-19.

text: From 26 January - 21 April 2020, 9 online courses for COVID-19 were published on OpenWHO.org. The courses are available in 18 different languages, totalling 53 learning resources and more than 1.5 million course enrolments. This paper analyses key trends in the growth of enrolments in these resources. The number of enrolments increased significantly between 26 January and 21 April, with distinct spikes in growth preceded by important global milestones in the timeline of the outbreak. The surge in users demonstrates that the platform is serving as a source of digitized learning for COVID-19, helping meet the broad demand for outbreak-related information.


title: Generation, collection and transportation, disposal and recycling of kitchen waste: a case study in Shanghai.

text: With respect to waste sorting, Shanghai sets an example for other Chinese cities on the standardized treatment of kitchen waste (KW) in China. According to the results of investigation, about 560 kilo tons of KW from different sources in Shanghai were produced in 2011. Of this, 45.6% (255.6 kilo tons) was collected and transported properly by a comprehensive and formal collection and transportation system. Landfilling and incineration, which are the traditional treatment technologies used, show downward trends because of increasing environmental awareness and land restrictions. Feed production, composting and biodiesel refining play increasingly important roles in the recycling of KW. Safe disposal, reduced KW quantity, public education, and technological innovation are still problematic issues and need to be considered in future waste management in Shanghai.


title: Telemedicine for Delivery of Care in Frontotemporal Lobar Degeneration During COVID-19 Pandemic: Results from Southern Italy.

text: BACKGROUND The COVID-19 pandemic is changing clinical practice in neurology, after the governments decided the introduction of social distancing and interruption of medical non-emergency services in many countries. Teleneurology is an effective tool for the remote evaluation of patients but its adoption for frontotemporal lobar dementia (FTD) is in a preliminary stage. OBJECTIVE We evaluated multidisciplinary assessment of patients with FTD using telehealth during the COVID-19 pandemic. METHODS All patients received a diagnosis of FTD during 2018-2019 according to international criteria. A structured questionnaire and Clinical Dementia Rating Scale (CDR)-FTD were used by the neurologist with patients and/or caregivers. Index symptoms of COVID-19 infection were searched. RESULTS Twenty-eight clinical interviews were completed with caregivers and four with both patients/caregivers. Most patients and caregivers were satisfied with the neurological interview and expressed their willingness to continue to be included in remote evaluation programs (90%). Fifty percent of patients experienced significant worsening of clinical picture and quality of life since the start of social distancing. The CDR-FTD scale revealed a significant worsening of behavior (p = 0.01) and language functions (p = 0.009), compared to the last in-person evaluation at the center. One patient presented index symptoms of COVID-19 infection and was confirmed to be positive for COVID-19 with pharyngeal swab. CONCLUSION The study was conducted in Italy, one of the countries hit particularly hard by the COVID-19 pandemic, with interruption of all non-emergency medical services. Our study indicates that telemedicine is a valid tool to triage patients with FTD to increase practice outreach and efficiency.


title: Novel device and technique for minimally invasive intracerebral hematoma evacuation in the same setting of a ruptured intracranial aneurysm: combined treatment in the neurointerventional angiography suite.

text: BACKGROUND The presence of intracerebral hematoma from aneurysm rupture is an indication for craniotomy for clot evacuation and aneurysm clipping. Some centers have begun securing aneurysms with coil embolization followed by clot evacuation in the operating room. This approach requires transporting a patient from the angiography suite to the operating room, which can take valuable time and resources. OBJECTIVE To report our experience with 3 cases in which a novel technique for minimally invasive evacuation of intracerebral hematomas after endovascular treatment of ruptured intracranial aneurysms was used. The Penumbra Apollo system can be used in the angiography suite in conjunction with neuroendovascular techniques to simultaneously address a symptomatic hematoma associated with a ruptured aneurysm. METHODS Standard preoperative computed tomography angiography was performed on arrival to the emergency department. The patients underwent diagnostic cerebral angiography followed by balloon-assisted coil embolization and then remained in the neurointerventional suite for intracerebral hematoma evacuation with the Apollo system. RESULTS All patients tolerated coil embolization and hematoma evacuation well. The combined procedures lasted <3 hours in both cases. Two patients were eventually discharged to acute rehabilitation facilities less than a month after their initial insult, and 1 has been cleared to return to work. The other patient was transferred to hospice care. CONCLUSION The Apollo aspiration system appears to be a safe and effective minimally invasive option for intracerebral hematoma evacuation, particularly when coupled with endovascular embolization of ruptured intracranial aneurysms. Future work will address which patient population is most likely to benefit from this promising technique.


title: Learning from the severe acute respiratory syndrome (SARS) epidemic.

text: AIMS AND OBJECTIVES This study uses two models of nursing practice, conventional and modular design, to compare nursing activities, hand hygiene, time efficiency and nurse-patient satisfaction in medical and surgical wards. Background. Learning from the SARS epidemic pointed to the importance of quality nursing practice considerations that minimize cross-transmission of infection while maximizing patient-focused care. Hence, a modular nursing model was adopted. DESIGN AND METHOD This study comprised pre- and postintervention phases. Data collection tools to evaluate modular nursing practice included a work sampling observation checklist, focused group interviews with nurses, questionnaires addressing nurses' perceived competence and caring attributes, a patient satisfaction questionnaire, and a hand hygiene audit. A series of education sessions were conducted between the two phases. Quantitative and qualitative analyses were used for data triangulation. RESULTS Modular nursing practice, focusing on continuity of care, led to changes in the nature of direct care activities and improvement in patient/family education frequency. Also, a general increase in nurses' hand washing frequency was noted. However, when nurses perceived time pressure, a lapse in hand hygiene compliance was found. Because of human resource and inefficiency issues, some nurses in the studied wards did not embrace geographical separation for infection control. Positive correlations were found for nurses' perceived infection control practice competence and their perceived caring attributes. RELEVANCE TO CLINICAL PRACTICE In examining nursing practice models within complex clinical situations, the significance lies not only in the model's effects but also in other operational outcomes.


title: Geographic Differences in COVID-19 Cases, Deaths, and Incidence - United States, February 12-April 7, 2020.

text: Community transmission of coronavirus disease 2019 (COVID-19) was first detected in the United States in February 2020. By mid-March, all 50 states, the District of Columbia (DC), New York City (NYC), and four U.S. territories had reported cases of COVID-19. This report describes the geographic distribution of laboratory-confirmed COVID-19 cases and related deaths reported by each U.S. state, each territory and freely associated state,* DC, and NYC during February 12-April 7, 2020, and estimates cumulative incidence for each jurisdiction. In addition, it projects the jurisdiction-level trajectory of this pandemic by estimating case doubling times on April 7 and changes in cumulative incidence during the most recent 7-day period (March 31-April 7). As of April 7, 2020, a total of 395,926 cases of COVID-19, including 12,757 related deaths, were reported in the United States. Cumulative COVID-19 incidence varied substantially by jurisdiction, ranging from 20.6 cases per 100,000 in Minnesota to 915.3 in NYC. On April 7, national case doubling time was approximately 6.5 days, although this ranged from 5.5 to 8.0 days in the 10 jurisdictions reporting the most cases. Absolute change in cumulative incidence during March 31-April 7 also varied widely, ranging from an increase of 8.3 cases per 100,000 in Minnesota to 418.0 in NYC. Geographic differences in numbers of COVID-19 cases and deaths, cumulative incidence, and changes in incidence likely reflect a combination of jurisdiction-specific epidemiologic and population-level factors, including 1) the timing of COVID-19 introductions; 2) population density; 3) age distribution and prevalence of underlying medical conditions among COVID-19 patients (1-3); 4) the timing and extent of community mitigation measures; 5) diagnostic testing capacity; and 6) public health reporting practices. Monitoring jurisdiction-level numbers of COVID-19 cases, deaths, and changes in incidence is critical for understanding community risk and making decisions about community mitigation, including social distancing, and strategic health care resource allocation.


title: The significant impact of framing coils on long-term outcomes in endovascular coiling for intracranial aneurysms: how to select an appropriate framing coil.

text: OBJECTIVE The importance of a framing coil (FC)-the first coil inserted into an aneurysm during endovascular coiling, also called a lead coil or a first coil-is recognized, but its impact on long-term outcomes, including recanalization and retreatment, is not well established. The purposes of this study were to test the hypothesis that the FC is a significant factor for aneurysmal recurrence and to provide some insights on appropriate FC selection. METHODS The authors retrospectively reviewed endovascular coiling for 280 unruptured intracranial aneurysms and gathered data on age, sex, aneurysm location, aneurysm morphology, maximal size, neck width, adjunctive techniques, recanalization, retreatment, follow-up periods, total volume packing density (VPD), volume packing density of the FC, and framing coil percentage (FCP; the percentage of FC volume in total coil volume) to clarify the associated factors for aneurysmal recurrence. RESULTS Of 236 aneurysms included in this study, 33 (14.0%) had recanalization, and 18 (7.6%) needed retreatment during a mean follow-up period of 37.7 ± 16.1 months. In multivariate analysis, aneurysm size (odds ratio [OR] = 1.29, p < 0.001), FCP < 32% (OR 3.54, p = 0.009), and VPD < 25% (OR 2.96, p = 0.015) were significantly associated with recanalization, while aneurysm size (OR 1.25, p < 0.001) and FCP < 32% (OR 6.91, p = 0.017) were significant predictors of retreatment. VPD as a continuous value or VPD with any cutoff value could not predict retreatment with statistical significance in multivariate analysis. CONCLUSIONS FCP, which is equal to the FC volume as a percentage of the total coil volume and is unaffected by the morphology of the aneurysm or the measurement error in aneurysm length, width, or height, is a novel predictor of recanalization and retreatment and is more significantly predictive of retreatment than VPD. To select FCs large enough to meet the condition of FCP ≥ 32% is a potential relevant factor for better long-term outcomes. These findings support our hypothesis that the FC is a significant factor for aneurysmal recurrence.


title: Design of prodrugs to enhance colonic absorption by increasing lipophilicity and blocking ionization.

text: Prodrugs are chemistry-enabled drug delivery modifications of active molecules designed to enhance their pharmacokinetic, pharmacodynamic and/or biopharmaceutical properties. Ideally, prodrugs are efficiently converted in vivo, through chemical or enzymatic transformations, to the active parent molecule. The goal of this work is to enhance the colonic absorption of a drug molecule with a short half-life via a prodrug approach to deliver sustained plasma exposure and enable once daily (QD) dosing. The compound has poor absorption in the colon and by the addition of a promoiety to block the ionization of the molecule as well as increase lipophilicity, the relative colonic absorption increased from 9% to 40% in the retrograde dog colonic model. A combination of acceptable solubility and stability in the gastrointestinal tract (GI) as well as permeability was used to select suitable prodrugs to optimize colonic absorption.


Intraoperative radiation therapy for breast cancer: a patient's view.


title: Sex-Specific Modulation of Blood Pressure and the Renin-Angiotensin System by ACE (Angiotensin-Converting Enzyme) 2.

text: We showed ACE (angiotensin-converting enzyme) 2 is higher in the kidney of male compared with female mice. To further investigate this sex difference, we examined the role of ACE2 in Ang-[1-8] (angiotensin [1-8])-induced hypertension and regulation of the renin-angiotensin system in the kidney of WT (wild type) and Ace2 KO (knockout) mice. Mean arterial pressure rose faster in WT male than WT female mice after Ang-[1-8] infusion. This sex difference was attenuated in ACE2 KO mice. Ang-[1-8] infusion reduced glomerular AT1R (angiotensin type 1 receptor) binding in WT female mice by 30%, and deletion of Ace2 abolished this effect. In contrast, Ang-[1-8] infusion increased glomerular AT1R binding in WT male mice by 1.2-fold, and this effect of Ang-[1-8] persisted in Ace2 KO male mice (1.3-fold). ACE2 also had an effect on renal protein expression of the neutral endopeptidase NEP (neprilysin), the enzyme that catabolizes Ang-[1-10] (angiotensin [1-10]), the precursor of Ang-[1-8]. Ang-[1-8] infusion downregulated NEP protein expression by 20% in WT male, whereas there was a slight increase in NEP expression in WT female mice. Deletion of Ace2 resulted in lowered NEP expression after Ang-[1-8] infusion in both sexes. These findings suggest sex-specific ACE2 regulation of the renin-angiotensin system contributes to female protection from Ang-[1-8]-induced hypertension. These findings have ramifications for the current coronavirus disease 2019 (COVID-19) pandemic, especially in hypertension since ACE2 is the SARS-CoV-2 receptor and hypertension is a major risk factor for poor outcomes.


title: Evaluation of the histological variability of core and wedge biopsies in nonalcoholic fatty liver disease in bariatric surgical patients.

text: BACKGROUND Liver biopsy remains the gold standard for characterizing and evaluating treatment response in nonalcoholic fatty liver disease (NAFLD). Liver heterogeneity and sampling variability can affect the reliability of results. This study aimed to compare histological variability of intraoperative wedge and core liver biopsies from different lobes in bariatric patients, to better inform surgeons on biopsy method and guide interpretation of results. METHODS We prospectively recruited bariatric surgical patients. Intraoperative core biopsies were taken from the left and right lobe, with a wedge biopsy taken from the left. All biopsies were graded by a specialist liver pathologist, blinded to clinical details and biopsy site. Concordance of histological findings between sites was evaluated. RESULTS There were 91 participants (72.2% female), mean age 46.8 ± 12.0 years, body mass index 45.9 ± 9.4 kg/m2. There was no significant pattern for up- or down-grading disease dependent on biopsy technique. Moderate to strong agreement was seen in the presence of NAFLD and nonalcoholic steatohepatitis (NASH, κ = 0.609-0.865, p < 0.001) between biopsy sites. Individual components (steatosis, inflammation, ballooning) showed weaker agreement (κ = 0.386-0.656, p < 0.01). Fibrosis showed particularly poor agreement (κ = 0.223-0.496, p < 0.01). Detection of pathology improved with a combination of biopsy techniques, compared to a single biopsy method. CONCLUSION Overall diagnosis of NAFLD or NASH shows good agreement between biopsy sites, but individual components, particularly fibrosis stage, vary significantly. Clinicians should consider biopsies from varied sites, to better assess liver disease severity. These data have important implications in fibrosis assessment of NAFLD and are relevant in the interpretation of histological efficacy of investigational pharmacotherapies. TRIAL REGISTRATION ACTRN12615000875505 (Australian Clinical Trials Register).


title: Modeling infectious disease dynamics.

text: The spread of the coronavirus SARS-CoV-2 has predictable features.


title: Global oncology pharmacy response to COVID-19 pandemic: Medication access and safety.

text: Response, action, and adaptation of the way health services are delivered will impact our ability to provide optimized and continuity of care while acting within resource constraints imposed by COVID-19. Care for patients with cancer is particularly important given increased infection rates and worse outcomes from COVID-19 in this patient population, as well as potential adverse outcomes if treatment pathways need to be compromised. In this commentary, we provide a global oncology pharmacy perspective (including both developed and developing nations) on how COVID-19 has impacted access to and delivery of cancer therapies. This perspective was prepared by the International Society of Oncology Pharmacy Practitioners, with input from national and regional oncology pharmacy practice groups (42 practice leaders from 28 countries and regions) who contributed to a snapshot survey between 10 and 22 April 2020. Specifically, we highlight challenges related to safe handling of hazardous drugs and maintaining high-quality medication safety standards that have impacted various stakeholders.


title: Greening and legume-supported crop rotations: An impacts assessment on Italian arable farms

text: Abstract Since the 1990s, the European Union has progressively and structurally reformed the Common Agricultural Policy with a gradual integration of environmental objectives. For the period post-2020, one of the most relevant changes could be the upgrading of the crops diversification, imposing it as an obligation to rotate crops by introducing legumes in the cropping patterns. This paper proposes an assessment of the possible effects of such obligation on the arable crops sector in Italy. The analysis uses a mathematical programming model calibrated and validated by way positive approach and is conducted on data of about 2800 Italian farms of the Farm Accountancy Data Network. Moreover, the analysis is structured by geographical area and altimetric level in order to consider typical specificities of Italian farms according to their localization. Our results show the legume-supported crop rotations reduce the general environmental pressure of agricultural activities and affect a large part of the arable land, against reduced economic impacts. In the majority of farms the lost income per hectare is lower than the national average value of the decoupled payments. Yet, the legume-supported crop rotations determine a reduction in the production of main crops and, especially in some areas, negative economic and social impacts. All this suggests that the legume-supported crop rotations are an opportunity to adopting sustainable agricultural practices and that Member States could implement the agronomic practice differently for areas and use additional instruments to meet the EU's objectives. Especially the decoupled and coupled payments are needed to limit economic losses and incentivize farmers towards virtuous behaviour.


title: Plaster: our orthopaedic heritage: AAOS exhibit selection.

text: BACKGROUND Plaster has been used for centuries as a stiffening agent to treat fractures and other musculoskeletal conditions that require rest, immobilization, or correction of a deformity. Despite modern metallurgy and internal stabilization, plaster casts and splints remain an important means of external stabilization. Casting is a dying art as modern internal and external fixation replace external immobilization. Proper casting technique is paramount. This manuscript outlines the history and chemistry of immobilization materials and techniques as well as the differences among them and the advantages and disadvantages of each. METHODS Historical references, peer-reviewed journals, textbooks, and primary sources were reviewed to provide data for this review. RESULTS The history of immobilization reveals a progressive development and refinement of materials that culminated in Mathijsen's plaster bandage in 1851. In 1798, calcium sulfate (plaster of Paris) was introduced. By 1927, crinoline rolls dipped in plaster treated with binding agents facilitated application. Synthetic casting "tapes" (45% polyurethane resin and 55% fiberglass) were introduced in the 1970s. Splinting techniques are ancient, with development spurred by treatment of war wounds. Plaster relies on soft-tissue contact to maintain rigidity. There are well-known advantages, disadvantages, and complications of plaster management. Casting materials all create an exothermic reaction. Burns are associated with water temperatures of >24°C, more than eight layers (ply), and inadequate ventilation. The maximum water temperature must be lower with fiberglass casts. Plaster was the definitive management for most fractures for over 100 years until it was replaced by modern surgical techniques involving internal fixation in the latter part of the twentieth century. CONCLUSIONS Plaster casts and splints remain an important treatment method for acute and chronic orthopaedic conditions.


title: Ocular oncology practice guidelines during COVID-19 pandemic-An expert consensus.

text: The outbreak of rapidly spreading COVID-19 pandemic in December 2019 has witnessed a major transformation in the health care system worldwide. This has led to the re-organization of the specialty services for the effective utilization of available resources and ensuring the safety of patients and healthcare workers. Suspension of oncology services will have major implications on cancer care due to delayed diagnosis and treatment leading to irreversible adverse consequences. Therefore various oncology organizations have called for a continuation of cancer care during this crisis with diligence. The COVID-19 pandemic has forced the clinicians to transform the components of care from screening to outpatient care and primary management. The purpose of this article is to establish guidelines and recommendations for ocular oncology in the management of ocular tumors set by a multidisciplinary team of experts including ocular, medical and radiation oncologists, and pathologists. As the pandemic is evolving fast, it will require constant updates and reformation of health strategies and guidelines for safe and quality health care.


title: Effects of Changes in Arterial Carbon Dioxide and Oxygen Partial Pressures on Cerebral Oximeter Performance.

text: BACKGROUND Cerebral oximetry (cerebral oxygen saturation; ScO2) is used to noninvasively monitor cerebral oxygenation. ScO2 readings are based on the fraction of reduced and oxidized hemoglobin as an indirect estimate of brain tissue oxygenation and assume a static ratio of arterial to venous intracranial blood. Conditions that alter cerebral blood flow, such as acute changes in PaCO2, may decrease accuracy. We assessed the performance of two commercial cerebral oximeters across a range of oxygen concentrations during normocapnia and hypocapnia. METHODS Casmed FORE-SIGHT Elite (CAS Medical Systems, Inc., USA) and Covidien INVOS 5100C (Covidien, USA) oximeter sensors were placed on 12 healthy volunteers. The fractional inspired oxygen tension was varied to achieve seven steady-state levels including hypoxic and hyperoxic PaO2 values. ScO2 and simultaneous arterial and jugular venous blood gas measurements were obtained with both normocapnia and hypocapnia. Oximeter bias was calculated as the difference between the ScO2 and reference saturation using manufacturer-specified weighting ratios from the arterial and venous samples. RESULTS FORE-SIGHT Elite bias was greater during hypocapnia as compared with normocapnia (4 ± 9% vs. 0 ± 6%; P < 0.001). The INVOS 5100C bias was also lower during normocapnia (5 ± 15% vs. 3 ± 12%; P = 0.01). Hypocapnia resulted in a significant decrease in mixed venous oxygen saturation and mixed venous oxygen tension, as well as increased oxygen extraction across fractional inspired oxygen tension levels (P < 0.0001). Bias increased significantly with increasing oxygen extraction (P < 0.0001). CONCLUSIONS Changes in PaCO2 affect cerebral oximeter accuracy, and increased bias occurs with hypocapnia. Decreased accuracy may represent an incorrect assumption of a static arterial-venous blood fraction. Understanding cerebral oximetry limitations is especially important in patients at risk for hypoxia-induced brain injury, where PaCO2 may be purposefully altered.


title: Sleep and sleep disordered breathing in hospitalized patients.

text: Sleep is a fundamental physiological process necessary for recovery from acute illness. Unfortunately for hospitalized patients, sleep is often short, fragmented, and poor in quality, and may be associated with adverse outcomes including inpatient delirium. Many factors contribute to poor sleep in the hospital setting, including preexisting sleep deprivation, sleep disordered breathing, environmental noise and light, patient care activities, and medications. Sleep disordered breathing increases the risk of potentially life-threatening cardiovascular, respiratory, and metabolic consequences, and therefore should be diagnosed and treated in hospitalized patients. Mitigating the sequelae associated with poor sleep quality and sleep disordered breathing requires early identification of modifiable factors impacting a patient's sleep, including engagement of a multidisciplinary team. In this article, we review the current knowledge of sleep in hospitalized patients with a detailed focus on patients with sleep disordered breathing.


title: Association between Brain and Kidney Near-Infrared Spectroscopy and Early Postresuscitation Mortality in Asphyxiated Newborn Piglets.

text: BACKGROUND Early outcome predictors after delivery room cardiopulmonary resuscitation (CPR) of asphyxiated newborns are needed. OBJECTIVES To investigate if cerebral (rScO2) and renal (rSrO2) tissue oxygen saturation 30 min after return of spontaneous circulation (ROSC) are different between surviving versus nonsurviving piglets with asphyxia-induced cardiac arrest and CPR. Further, to investigate the relationship of rScO2 and rSrO2 to cardiac output (CO), blood pressure (BP), and biochemical variables 30 min and 4 h after ROSC. METHODS Anesthetized, mechanically ventilated piglets (1-3 days, 1.7-2.4 kg) were used. rScO2, rSrO2, SpO2, right common carotid artery flow, and arterial BP were measured continuously. CO was measured with echocardiography. The piglets were asphyxiated until cardiac arrest and resuscitated. Piglets that survived 4 h after ROSC (n = 12) were compared with piglets that died before planned euthanasia at 4 h (n = 13). Left ventricular, and kidney and brain tissue lactate were analyzed. Correlations between variables were assessed. RESULTS Thirty minutes after ROSC, median rSrO2 (43% [n = 10] vs. 25% [n = 2], p = 0.003) but not rScO2 (46% [41-55] [n = 10] vs. 40% [22-45] [n = 5], p = 0.08) was higher in survivors than in nonsurvivors. Arterial lactate was negatively correlated and pH positively correlated with rScO2 and rSrO2. Left ventricular, but not kidney or brain lactate was negatively correlated with rScO2 and rSrO2. There was no correlation between CO or BP and rScO2 or rSrO2. CONCLUSIONS Despite satisfactory CO and BP vital organ oxygenation can be poor. Tissue oxygen saturation, pH, and lactate, as measures of anaerobic metabolism, may reflect vital organ oxygenation and outcome.


title: [Pathogenic characteristics of hospitalized severe acute respiratory infections in Shanghai, China, 2015-2017].

text: Objective: To understand the epidemiological and pathogenic characteristics of hospitalized severe acute respiratory infections (SARI) in Shanghai, China. Methods: From 2015 to 2017, one Tertiary hospital and one Secondary hospital were chosen as the surveillance sites. Two respiratory tract specimens per case were collected from SARI cases aged 15 years and older. One specimen was tested for 22 respiratory pathogens by RT-PCR, and the other specimen was cultured for 6 respiratory bacteria. Results: A total of 287 SARI cases were enrolled for sampling and lab testing. 70.73% of the cases were aged 60 years and older, with 41.46% (119/287) were positive for at least one pathogen. Influenza virus was the predominant pathogen, accounting for 17.77% (51/287) of all SARI cases. Human rhinovirus/Enterovirus and Coronavirus were both accounting for 7.32% (21/287), followed by Mycoplasma pneumoniae (5.57%, 16/287). The positive rates of parainfluenza virus, bocavirus, adenovirus, respiratory syncytial virus and human metapneumo virus were all less than 5%. Bacterial strains were identified in seven SARI cases, including Klebsiella pneumoniae (3 strains), Staphylococcus aureus (2 strains), Streptococcus pneumoniae (1 strain) and Pseudomonas aeruginosa (1 strain). Two or Three pathogens were co-detected from 40 cases, accounting for 33.61% of 119 positive cases. The most common co-detected pathogens were influenza virus and Mycoplasma pneumoniae (10 cases). Influenza cases peaked in winter-spring and summer. Mycoplasma pneumoniae peaked in winter-spring season and overlapped with influenza. The positive rates of pathogens were not significantly different between different age groups. Conclusions: Various respiratory pathogens can be detected from SARI cases aged 15 years and older. Influenza virus was the predominant pathogen and the co-detection of influenza virus with Mycoplasma pneumoniae the most common one.


title: Impact of Prior Hepatectomy History on Local Tumor Progression after Percutaneous Ablation of Colorectal Liver Metastases.

text: PURPOSE To test the hypothesis that, given the current resection eligibility criteria for colorectal liver metastasis (CLM), prior hepatectomy would be associated with improved local tumor control and survival after percutaneous ablation of CLMs. MATERIALS AND METHODS This single-institution retrospective study included 82 consecutive patients with 97 CLMs treated with ablation (radiofrequency ablation, microwave ablation, or cryoablation) from January 2005 to December 2014. Local tumor progression-free survival (LTPFS), recurrence-free survival (RFS) at any organ, and overall survival (OS) were calculated using the Kaplan-Meier method from the time of ablation and compared between patients with (n = 49) and without (n = 33) prior hepatectomy. Cox regression models were used to identify LTPFS predictors. RESULTS Median overall follow-up period was 28 months (range, 4.5-132 months). Three-year actuarial LTPFS (patient level: 73% vs 34%, P < .001) was significantly higher in patients with than without prior hepatectomy, respectively. Similarly, 3-year RFS (23% vs 9.1%, P = .026) and OS (78% vs 48%, P = .003) were improved in patients with prior hepatectomy. At multivariate analysis, predictors of worse LTPFS were: no prior hepatectomy (hazard ratio [HR] 2.35, 95% confidence interval [CI] 1.02-5.45; P = .045), minimal ablation margin < 5 mm (HR 2.4, 95% CI 1.18-4.87; P = .016), and RAS-mutant tumor (HR 2.65, 95% CI 1.18-5.94; P = .019). CONCLUSIONS Prior hepatectomy for CLMs is associated with improved local tumor control after percutaneous ablation of post-resection-developed CLMs.


title: Cytokine expression in the visceral adipose tissue after laparoscopic and conventional surgery in a rodent model.

text: BACKGROUND Laparoscopic Surgery has become a worldwide standard procedure for a variety of indications. This has been attributed to a milder postoperative inflammatory response by the innate immune system potentially mediated through immune mediators released by the visceral adipose tissue (VAT). However, an in vivo experimental evidence is lacking and is the issue of our present study. METHODS Male Wistar rats (N = 24) underwent standardized surgical procedures of conventional cecum resection (CCR), conventional sham operation, laparoscopic cecum resection (LCR), or laparoscopic sham operation. Cytokine expression of leptin, resistin, and IL-6 was analyzed in VAT before and after resection by quantitative RT-PCR. RESULTS Postoperative leptin gene expression was reduced in the CCR and LCR groups, while expression was not significantly affected in both sham groups compared to the preoperative levels. In contrast, IL-6 expression was not affected in the LCR group, but was significantly elevated in the CCR cohort. The IL-6 expression was significantly higher in CCR compared to LCR. Resistin expression levels did not differ between all groups. CONCLUSIONS Our study underlines the role of immunological involvement of VAT in the postoperative phase. Low leptin levels seem to act as a stimulator for energy uptake in order to cope with postoperative stress. A lower IL-6 expression in the LCR compared to the CCR group may indicate a weaker inflammatory activity potentially adding to the clinical benefits observed in patients undergoing LS.


When and how to update systematic reviews: consensus and checklist.


title: Effective repair of articular cartilage using human pluripotent stem cell-derived tissue.

text: In an effort to develop an effective source of clinically relevant cells and tissues for cartilage repair a directed differentiation method was used to generate articular chondrocytes and cartilage tissues from human embryonic stem cells (hESCs). It has previously been demonstrated that chondrocytes derived from hESCs retain a stable cartilage-forming phenotype following subcutaneous implantation in mice. In this report, the potential of hESC-derived articular-like cartilage to repair osteochondral defects created in the rat trochlea was evaluated. Articular cartilage-like tissues were generated from hESCs and implanted into the defects. After 6 and 12 weeks, the defects were evaluated histologically and immunohistochemically, and the quality of repair was assessed using a modified ICRS II scoring system. Following 6 and 12 weeks after implantation, hESC-derived cartilage tissues maintained their proteoglycan and type II collagen-rich matrix and scored significantly higher than control defects, which had been filled with fibrin glue alone. Implants were found to be well integrated with native host tissue at the basal and lateral surfaces, although implanted human cells and host cells remained regionally separated. A subset of implants underwent a process of remodeling similar to endochondral ossification, suggesting the potential for a single cartilaginous implant to promote the generation of new subchondral bone in addition to repair of the articular cartilage. The ability to create cartilage tissues with integrative and reparative properties from an unlimited and robust cell source represents a significant advance for cartilage repair that can be further developed in large animal models before clinical- setting application.